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CopyrlghL © AceCrganlcChem.com 2009, all rlghL reserved
lS8n978-144939482
WlLhouL llmlLlng Lhe rlghL under copyrlghL reserved above, no parL of Lhls publlcaLlon may
be reproduced, sLored ln or lnLroduced lnLo a reLrleval sysLem, or LransmlLLed ln any form
or by any means (elecLronlc, mechanlcal, phoLocopylng, or oLherwlse) wlLhouL express
wrlLLen consenL of AceCrganlcChem.com or lLs deslgnee and Lhe publlsher of Lhls book.
Þ a g e | 4

1ab|e of Contents
What |s AceCrgan|cChem.com?
Introduct|on - now to use th|s book.
Ded|cat|on
Chapter 1: Sett|ng ¥ourse|f Up for Success
#1- WaLch ouL for Lhe ºllunklng Þrofessor".
#2- SLudy ln packs-Lhere ls safeLy ln numbers.
#3-1ake Lhe course aL a more opporLune Llme.
#4- CeL away from Lhe pre-meds.
#3- uon'L over-emphaslze Lhe lab secLlon.

Chapter 2: Introductory Concepts
#6- Memorlze your nomenclaLure and essenLlal vocabulary.
#7- Wouldn'L formaldehyde by a dlfferenL name smell [usL as sweeL? 1he
dlfference beLween common names and luÞAC nomenclaLure.
#8- know Lhe ºnormal" sLaLe for common organlc aLoms.
#9- llscher pro[ecLlons are a black Lle affalr.
#10- ls lL really LhaL ºLZ"? ueLermlnlng alkene geomeLry.
#11- MasLer 8esonance.
#12- ?ou Spln Me 8lghL 8ound 8aby, 8lghL 8ound, Llke a 8ecord 8aby
#13- Slze MaLLers: 8esonance beLween equlvalenL aLoms means equal bond
lengLhs.
#14- Cood for noLhlng alkanes. Lousy molecules.
#13- ln organlc chemlsLry, llkes dlssolve llkes.
#16- 8eware of Lhe bad acld Lrlp: MeeL your sLrong aclds.
#17- MeeL your sLrong nucleophlles.
#18- 1hey have worn ouL Lhelr welcome: know your leavlng groups.
#19- lf you don'L sLarL wlLh chlrallLy, you can'L end wlLh lL.
#20- Markovnlkov was a llar. A dlrLy, smelly llar.
#21- A dlfferenL Lype of chemlsLry LesL. luncLlonal group LesLs
#22- ls lL L1, L2, Sn1, Sn2?
#23- Why you should noL sLay on Lhe sLralghL and narrow (lf you are counLlng
carbon chalns).
#24- Arrows wlll polnL Lhe way.
#23- 1here are only 3 dlfferenL mechanlsms Lo know. 1haL's lL, [usL 3 (klnda).
#26- º1hey have Lhe lnLerneL on compuLers now??"
Þ a g e | S


Chapter 3: Crgan|c Chem|stry Strategy
#27- Co Lo Lhe hardware sLore and geL a chemlsLry Loolbox.
#28- lL Lakes alkynes Lo make Lhe world go 'round (and Lo reacL wlLh epoxldes)
#29- lour organomeLalllcs Lo rule Lhem all
#30- ulels-Alder 8eacLlon-ÞarL 1: An lnLroducLlon
#31- LeL's go reLro: 8eLrosynLheLlc analysls
#32- Cverall LAS sLraLegy
#33- LAS sLraLegy: 1urn a meLa lnLo orLho/para and vlce-versa.
#34- LAS sLraLegy: Converslon of alkyl groups Lo carboxyllc aclds.
#33- LAS sLraLegy: ln fooLball, you need good blockers. SC
3
and x are our blocklng
groups
#36- LAS sLraLegy: Long chaln alkyl groups from Wolff-klshner or reducLlon
#37- LAS sLraLegy: SubsLlLuLed Loluenes came from Loluene. uuh

Chapter 4: ne|pfu| keact|ons, n|nts, C|ues
#38: WanL Lo lmpress your lnsLrucLor? SLarL dropplng names.
#39- LnanLlomers are slbllngs, dlasLereomers are couslns whlch makes roLomers
your dlngy aunL.
#40- 8enzyllc and allyllc leavlng groups are beLLer Lhan Lhey look.
#41- 8efore you dle, you see Lhe [aromaLlc] rlng.
#42- ºL[ecL! L[ecL! L[ecL!" Carbonyls wlLh an e[ecLable group are added Lo Lwlce.
#43- PlnL: ºh!" means a radlcal ls brewlng.
#44- 1-buLyl groups on cyclohexane means no rlng fllps..klnda.
#43- Llke !erry Lewls asklng for money, Lewls aclds are always asklng for elecLron
denslLy.
#46- P
2
SC
4
and PnC
3
: 1he good-cop/bad-cop of nlLraLlons.
#47- 1he lncredlble 8ulk: 8ulky bases.
#48- Poffman vs. ZalLsev: 1he ellmlnaLlon.
#49- uude, where's my carbocaLlon?
#30- lree 8adlcal PalogenaLlon: 1he Molecular Pandle.
#31- My 1hree 8educLlons: 8educLlon MeLhods lor Alkynes
#32- ls a Palogen SquaLLlng on ?our Molecule? 8emovlng Lhe unwanLed halogen.
#33- ?ou don'L wanL a ºu" on your LranscrlpL, buL you mlghL wanL one on your
molecule.
#34- ulels-Alder ÞarL 2: 8eglochemlsLry and sLereochemlsLry
#33- ulels-Alder ÞarL 3: WhaL makes a good ulels-Alder reacLlon
#36- lL's an urban legend LhaL S
n
1 reacLlons glve !"#$%&'&%( racemlc producLs.
#37- ºWhaL do you 'Amlne' you're geLLlng rld of me?"--Pow Lo ellmlnaLe an amlne.
Þ a g e | 6

#38- ºWhy dldn'L you say were sendln' Lhe wolf?"-1he Wolff-klshner reducLlon
#39- lL Lakes a 8aeyer-vllllger Lo ralse a chlld
#60- SymmeLrlc dlols came lrom Lhe Þlnacol reacLlon
#61- ConverL a nlLro group lnLo Lhe aldehyde or keLone.
#62- 1he McMurry reacLlon: A ºreverse" ozonolysls.
#63- 8ole reversal: nlLrlle hydraLlon and Lhe LeLLs nlLrlle SynLhesls
#64- 8ole reversal: ulhydroxylaLlon and Lhe Corey-WlnLer CleflnaLlon
#63- 8ole reversal: Palogens and carboxyllc Aclds
#66- Muslcal double bonds: uslng caLalyLlc l
2
.
#67- !usL llke Lhe SecreL Servlce, proLecLlng groups are chemlcal bodyguards
#68- uon'L hydrogenaLe LhaL aryl rlng! ?ou'll klll us all!
#69- lL's as easy as 1,2 addlLlon. Cr ls lL 1,4 addlLlon?
#70- Pere's Lo you're annulaLlon, Mrs. 8oblnson: Muslngs on Lhe 8oblnson
AnnulaLlon.
#71- klneLlc vs. Lhermodynamlc enolaLes: ?ou choose Lhe wlnner of Lhls flghL.
#72- ºWhere's Aldol?": Maklng an aldol reacLlon work for you.
#73- AceLoaceLlc LsLer SynLhesls: WhaL you need Lo know ln one page or less.
#74- µ-keLo esLers came from a Clalsen CondensaLlon (nC1 Lhe Clalsen
8earrangemenL)
#73- ConverL keLones Lo epoxldes fasL
#76- 1wo ways Lo open one epoxlde

Chapter S: Spectroscopy
#77- SCuA8 ls noL [usL a drlnk mlxer anymore
#78- SpllLLlng should be auLomaLlc, aL leasL wlLh nM8
#79- C, M, Þ from Lhe aromaLlc reglon of an nM8
#80- LveryLhlng ?ou Lver WanLed Lo know AbouL a
13
C nM8, 8uL Were Afrald Lo
Ask
#81- 1here are Cnly lour lmporLanL l8 Þeaks.
#82- Check CuL Lhe Cleavage Cn 1haL Molecule
#83- 1he nlLrogen PlnL (noL a 8ule)

Chapter 6: Study 1|ps and Suggest|ons
#84- Are ?ou a Learner Llke SocraLes or a Memorlzer Llke a Super CompuLer?
#83- WhaL a 1angled Web We Weave.
#86- 8e a ChaLLy ÞaLLy and 1alk CuL ?our 8eacLlons.

Þ a g e | 7

What |s AceCrgan|cChem.com and how can |t he|p me??
AceCrganlcChem.com ls a webslLe deslgned Lo help you navlgaLe Lhe Lreacherous waLers
LhaL comprlse undergraduaLe organlc chemlsLry. Cn Lhe slLe, we have:
- Crganlc chemlsLry course revlew vldeos
- A LesL bank of old exams from schools around Lhe counLry, classlfled by dlfflculLy
- LlecLronlc flash cards
- Mechanlsm movles and oLher aldes
- Pelp for your MCA1
- Crganlc ChemlsLry º8esL of Lhe Web" llsLlng for oLher helpful webslLes
- Scholarshlp lnformaLlon
- 8ecommended organlc chemlsLry help books
- Crganlc chemlsLry lab help, wlLh free vldeos.
Many servlces are free of charge and are deslgned by former lnsLrucLors Lo help you geL
Lhe besL grade posslble. vlslL Lhe slLe and help yourself earn Lhe grade you deserve.


Þ a g e | 8

Introduct|on: now to use th|s book effect|ve|y.
1here are many Lhlngs LhaL Lhls book can be for you. 8uL flrsL, we should dlscuss whaL Lhls
book ls noL. 1hls ls noL meanL Lo be a comprehenslve LreaLlse on organlc chemlsLry. CulLe
Lhe opposlLe acLually, Lhls book ls meanL Lo be a shorL supplemenL Lo Lhe organlc chemlsLry
LexL LhaL you are already uslng ln your class. 1here are some very |mportant concepts |n
organ|c chem|stry that th|s book w||| not even touch. 1haL does noL mean LhaL Lhey wlll
noL be on your exam, lL [usL means LhaL we were Lrylng Lo hlL on Loplcs where Lhere are
Lrlcks LhaL can be learned Lo make LhaL Loplc easler.
1haL belng sald, here ls how Lo use Lhls book mosL effecLlvely:
1) 1ry to understand the top|c from your text f|rst, Lhen refer Lo Lhls book as a
supplemenL Lo see lf Lhere ls an easler way Lo learn lL.

2) Determ|ne what grade you want then study to get that grade. All Loo ofLen, Lhe
sLudenLs who only wanL a ºC" spend way Loo much Llme sLudylng Lhe hardesL
concepLs of organlc chemlsLry and don'L masLer Lhe maLerlal LhaL wlll geL Lhem
LhaL C. 1hls book breaks each Llp down by dlfflculLy:
Lx:

1hree SLars: MaLerlal for Lhe ºA" sLudenLs. 1hese are Lhe mosL
dlfflculL concepLs or Lrlcks. Some of Lhem may noL even be LaughL ln
your class. 1hese are meanL for Lhe Lrue organlc masLers.
1wo SLars: MosL undergraduaLe sLudenLs wlll be LaughL Lhese
concepLs. 1he Lrlcks and Llps LhaL we wlll glve you wlLh Lhese
concepLs are meanL for almosL all sLudenLs. SLudenLs who wanL a
grade of ºC" or beLLer should become famlllar wlLh Lhese concepLs.
Cne SLar: 1he very baslcs. 1hese are Lhe bedrock of organlc
chemlsLry, and should be learned lnslde ouL ln order Lo ensure a good
grade ln organlc chemlsLry. lf you are havlng Lrouble wlLh Lhese
concepLs, lL ls golng Lo be a very long semesLer for you.
3) If one of the tr|cks does not make sense to you, !"#$% use |t. ?our mlsslon ls for
you Lo learn organlc chemlsLry, whaLever way you can. lf one of Lhese Lrlcks does
noL make sense Lo you, [usL learn lL anoLher way.
1haL belng sald, Lhls book wlll glve you some nlce maLerlal LhaL you may noL easlly flnd ln
oLher places. use lL Lo your advanLage, sLudy hard and you wlll geL Lhe grade you wanL.
Crgo II, D|ff|cu|ty:
Þ a g e | 9


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1o my lovely (and undersLandlng) wlfe and wonderful daughLer.







Þ a g e | 11











Chapter 1: Sett|ng ¥ourse|f up for Success
Þ a g e | 12

#1- Watch out for the "I|unk|ng Þrofessor".
8ecause Lhe sclences have become so popular ln recenL years, many of Lhe larger
unlverslLles have several professors Leachlng organlc chemlsLry, whlch means ln flnanclal
Lerms, Lhls ls a buyer's markeL. ?ou have cholces on whose class you Lake and whose class
you avold. Cf course Lhe besL way Lo learn who ls good, who ls bad, and who ls ugly ls Lo
ask Lhe boys and glrls who have already Laken Lhe class. ln lleu of LhaL, here are a couple of
Lell-Lale slgns LhaL you are abouL Lo enLer Lhe realm of ºÞrofessor llunks-aloL":
1) Cn Lhe flrsL day, Lhe professor brags abouL how many sLudenLs fall/drop Lhe class.
2) 1he professor ls anLl-medlcal school. (Crganlc chemlsLry ls a blg med school prep
sub[ecL)
3) 1he professor does noL have a degree ln organlc chemlsLry, some schools, due Lo
sLafflng needs, wlll run someone ouL Lhere wlLh a degree ln anoLher fleld of chemlsLry, or
worse-a blology degree.
4) 1he professor ls noL recepLlve Lo sLudenL quesLlons ln offlce hours.
3) 1he professor does noL lncorporaLe examples of more recenL organlc chemlsLry lnLo Lhe
lecLures. 1hls ls a Lrlcky one. lL mlghL show LhaL Lhe lnsLrucLor ls a llLLle ouL of Louch, or
doesn'L care enough Lo flnd more lnLeresLlng examples Lo presenL.
6) 1he professor focuses a loL on physlcal organlc chemlsLry (orblLals and such). llrsL, Lhls
ls noL Lhe maln parL of organlc chemlsLry, whlch roLaLes around Lhe synLhesls of new
molecules. Second, lL ls very borlng.
lf you deLermlne LhaL you have a bad professor, Lhe flrsL Lhlng Lo declde ls lf Lhere ls a
beLLer one ouL Lhere, preferably Leachlng Lhe course Lhls semesLer. lf lL ls easy, and you
feel comforLable, swlLch Lo Lhe oLher class. lf you conslder yourself a masochlsL, Lough
guy, or [usL can'L swlLch, Lhen slL back and make Lhe besL of lL.
lf you really need Lo geL ouL and can spend a llLLle exLra money, many unlverslLles wlll
accepL a [unlor college Lransfer credlL. Call Lhe reglsLrar's offlce aL your school, ask lf Lhey
wlll accepL organlc chemlsLry from Lhe local communlLy college and Lake lL Lhere. More
ofLen Lhan noL, Lhe communlLy college wlll offer a slmpler verslon of Lhe course, whlch you
can Lake back wlLh you Lo avold Lhe whole mess of a [erk professor.
Þ a g e | 13

#2- Study |n packs¬there |s safety |n numbers.
1hls remlnds me of my favorlLe vldeo on ?ou1ube
(hLLp://www.youLube.com/waLch?v=Lu8uu?z68kM). ?ou are a pack of wlldebeesL, [usL
chllllng ouL by Lhe waLer, Lrylng Lo score a good grade ln organlc chemlsLry. 8uL you are
belng hunLed by prlde of hungry llons (your professors) who would llke noLhlng beLLer Lo
make a qulck snack of Lhe weakesL one of you. AfLer crouchlng ln Lhe brush, Lhe llons
suddenly pounce (pop qulz) and grab a hold of Lhe smallesL one of you (Lhe sLudenL wlLh
Lhe hardesL course load).
1wo Lhlngs can happen aL Lhls polnL: LlLher Lhe resL of Lhe pack of wlldebeesL wlll cuL Lhelr
losses and Lry Lo save Lhemselves or Lhey can go back and herolcally baLLle Lhe llons Lo save
Lhelr fallen colleague. l am noL golng Lo ruln Lhe vldeo lf you have noL already vlewed lL,
buL l Lhlnk you already know whaL happens.
SLudylng ln packs presenLs a number of beneflLs oLher Lhan [usL alLrulsLlcally helplng a
lesser sLudenL:
1) SLudles have shown over and over LhaL sLudylng ln groups dlrecLly leads Lo hlgher
grades for all parLlclpanLs.

2) SLudylng ln groups ls generally more en[oyable for people, whlch leads Lo more
Llme spenL on Lhe sub[ecL.

3) lf you are weaker ln one area of Lhe course, you have Lhe opporLunlLy Lo have a
peer explaln lL Lo you. Many sLudenLs are more llkely Lo undersLand a peer's
explanaLlon over a sLuffy professor's.

4) lf you are sLronger ln one area of Lhe course, you wlll sLrengLhen your overall
undersLandlng of chemlsLry by Leachlng lL Lo someone else.
Cf course, when you are chooslng sLudy parLners on Lhe SerengeLl, you need Lo be very
careful Lo sLay away from Lhe [ackals. 1hese are Lhe sLudenLs LhaL are more paraslLe Lhan
human and wlll [usL leach off of your LalenLs. 1hey wlll come Lo sLudy sesslons unprepared
and expecL you Lo Leach Lhe enLlre course Lo Lhem. 1hey are more succubus Lhan man and
wlll noL help you much. We suggesL flndlng sLudy parLners LhaL are lnLeresLed ln a good
grade and are wllllng Lo puL ln Lhe Llme necessary Lo achleve a good grade ln Lhe course.
Þ a g e | 14

#3-1ake the course at a more opportune t|me.
A useful sLraLegy LhaL many sLudenLs have used ls Lo Lake chemlsLry ln Lhe ºoff season".
1hls means LhaL Lhey have Laken Crganlc l ln Lhe sprlng and Lhen followed wlLh Crganlc ll ln
Lhe nexL fall. 1hls presenLs a number of advanLages, lncludlng LhaL slnce you are ºouL of
sequence" Lhe class slzes wlll mosL llkely be smaller, Lhls wlll usually provlde for a beLLer
learnlng envlronmenL.
Many wlll ask lf Lhey should Lake lL ln Lhe summer. 1hls ls noL an easy "yes or no" quesLlon,
and deflnlLely depends on Lhe sLudenL. Pere are some of Lhe conslderaLlons for summer
classes:
1he Good:
1. lL ls only usually 3 weeks long.
2. lf you are noL worklng LhaL summer, lL ls much beLLer Lhan [usL slLLlng around dolng
noLhlng.
3. lf you are noL ma[orlng ln chemlsLry and don'L wanL Lo go Lo medlcal school, lL ls a greaL
way Lo geL organlc chemlsLry ouL of Lhe way qulckly.
1he 8ad:
1. lf you A8L ma[orlng ln chemlsLry, lL ls very easy Lo forgeL everyLhlng LhaL you learned ln
Lhe class because you crammed lL all lnLo 3 weeks.
2. Classes are usually aL leasL 3 hours per day, plus homework every nlghL and an exam
once a week. 1hls can be overwhelmlng.
1he Ug|y:
1. lf you geL a bad professor, keep Lhe hemlock close.

Þ a g e | 1S

#4- Get away from the Þre-Meds.
?es, we reallze LhaL many of you LhaL are Laklng organlc chemlsLry dream of golng Lo
medlcal school someday. Lverybody needs docLors, and Lhe [ob pays well, so good for you.
Powever, Lhere ls a seeLhlng underbelly Lo Lhe pre-med world. Some horrlble Lhlngs LhaL
nobody wanLs Lo Lalk abouL are:

1) Þre-Meds are noLorlously cuLLhroaL. 8y Lhls, we mean LhaL Lhey would sllL your
LhroaL lf lL would geL Lhem anoLher polnL on LhaL qulz. We have seen pre-med
sLudenLs Lear essenLlal pages ouL of LexLbooks ln Lhe llbrary because Lhey dldn'L
wanL Lhe oLher sLudenLs Lo geL LhaL help. We have seen pre-meds sLeal Lhe exam
answer key off of Lhe wall (mosL answer keys are onllne now, so LhaL helps), so LhaL
?Cu don'L know whaL Lhe correcL answers were.

2) 1hey can be curve-wreckers. lL ls noL unusual Lo flnd a professor who has Lhe
average grade ln hls class be a 30 ouL of 100 polnLs. 1hls means LhaL anyLhlng
above LhaL llne ls a º8" and anyLhlng below ls a ºC". Þre-med sLudenLs are llke Lhe
1ermlnaLor: Lhey don'L feel plLy, Lhey don'L feel remorse, and Lhey are relenLless ln
Lhelr sLudles. 1he average grade ln a class full of pre-meds ls golng Lo be much
hlgher Lhan one wlLh only a few of Lhem.



Þ a g e | 16

#S- Don't over-emphas|ze the |ab sect|on.
Cne of Lhe blggesL complalnLs LhaL mosL 1As hear ls LhaL Lhe laboraLory secLlon of organlc
chemlsLry ls a loL of work for [usL one credlL. 1here are no Lwo ways abouL lL, Lhls ls a Lrue
sLaLemenL. 1hlnk abouL lL. lf you were Lo do everyLhlng mosL 1As requlre for Lhe lab, you
would spend aL leasL one hour prlor Lo Lhe lab preparlng for lL, Lhree hours ln Lhe lab lLself,
and Lwo hours analyzlng your daLa and wrlLlng your reporL. 1hls equals slx hours of work
per week for one lousy credlL. Compare Lhls Lo your organlc chemlsLry lecLure class, whlch
ls usually Lhree hours of class for Lhree credlLs.
We can'L change Lhe sysLem, buL we can learn how Lo work lL Lo our advanLage. WlLh
respecL Lo Lhe pre-lab preparaLlon, one Lrlck we have found LhaL works well ls Lo geL
LogeLher wlLh a group of labmaLes and spllL Lhe work on Lhe lab preparaLlon by alLernaLlng
who does Lhe lab prep for LhaL week. Some 1As wanL Lo you Lo have Lhe MSuS sheeLs for
all chemlcals Lo be used, ln addlLlon Lo answerlng pre-lab quesLlons abouL whaL you are
golng Lo do ln lab LhaL day. 8y alLernaLlng who does LhaL each week, you could save hours
of Llme LhaL could be devoLed Lo Lhe lecLure porLlon lnsLead.
1he reporL Lo be wrlLLen afLer each lab exerclse ls anoLher place LhaL many sLudenLs wasLe
counLless hours. 8emember LhaL Lhe mosL lmporLanL parL of Lhe lab ls Lo do Lhe
calculaLlons correcLly. lL does noL maLLer LhaL your daLa ls crappy, lL maLLers whaL you do
wlLh LhaL crappy daLa. Second, do noL spend a Lon of Llme on Lhe narraLlve porLlon.
Conclsely wrlLe whaL you dld and leave lL. uon'L fool yourself lnLo Lhlnklng LhaL your 1A ls
golng Lo go over Lhls wlLh a flne-LooLh comb.
Many wlll flnd Lhls Lo be a conLroverslal sLaLemenL, buL we have found LhaL a º8" ln Lhe lab
secLlon ls noL golng Lo preclude you from golng furLher ln sclence, wheLher LhaL be Lo a
graduaLe degree or medlcal school. 1he one credlL from Lhe lab secLlon does noL facLor
LhaL heavlly lnLo your ºsclence CÞA" or overall CÞA. lf you could spend Lhree hours less
per week on Lhe lab and focus LhaL Llme lnLo sLudylng Lhe lecLure porLlon, you are much
more llkely Lo see a Langlble beneflL down Lhe road. lurLher, would lL be worLh spendlng
LhaL exLra Lhree hours on Lhe lab porLlon lf lL were only golng Lo ralse your lab grade a llLLle
blL? (lor example, from a º8" Lo a º8+") 1hls ls even more Lrue lf all you wanL ls Lo pass
Lhe lab secLlon and don'L care abouL Lhe grade.
uo noL mlsLake whaL we are saylng here, as Lhe lab porLlon can be a fun and rewardlng
experlence. We are only advocaLlng LhaL for some sLudenLs lL may be helpful Lo noL over-
emphaslze a class LhaL ls only worLh one credlL.


Þ a g e | 17










Chapter 2: Introductory Concepts
Þ a g e | 18

Crgo I, D|ff|cu|ty:
#6- Memor|ze your nomenc|ature and essent|a| vocabu|ary.
Learnlng organlc chemlsLry ls llke Lrylng Lo work ln a forelgn counLry, lf you don'L know Lhe
language, lL ls golng Lo be very dlfflculL Lo learn how Lo do your [ob. lmaglne LhaL you have
[usL been LransporLed Lo Lhe myLhlcal counLry of ºochemla", a small lsland naLlon ln Lhe
souLh Þaclflc, where your [ob ls Lo wrlLe chemlsLry reacLlons.
lrequenLly, ln a chemlsLry lecLure, professors sLarL Losslng ouL sLrange organlc chemlsLry
Lerms far Loo qulckly. 8ecause sLudenLs aren'L fluenL ln ºochemla" yeL, Lhey need Lo
LranslaLe each word ln Lhelr head Lo undersLand whaL Lhe lnsLrucLor has [usL sald. 8y Lhe
Llme Lhls menLally LranslaLlon ls done, Lhe sLudenL has [usL mlssed Lhe nexL senLence and
has losL half of Lhe lecLure. Cur goal ls Lo geL as fluenL as we can ln Lhe language of
chemlsLry as qulckly as we can. Pere are some Lerms lL wlll be helpful Lo memorlze so LhaL
you don'L have Lo do a menLal LranslaLlon when you hear Lhem:
MeLh = 1
LLh= 2
Þrop = 3
8uL = 4
ÞenL = 3
Pex = 6
PepL = 7
CcL = 8
non = 9
uec = 10



nucleophlle = has elecLrons, has a
negaLlve or parLlal negaLlve charge
Palogen = l, Cl, 8r, l
AproLlc solvenLs = do noL conLaln CP or
nP bonds
ÞroLlc solvenLs = conLaln CP or nP bonds
Lewls Acld = elecLron accepLor
Lewls 8ase = elecLron donor
Carbonyl group = (C=C)
Cls = same slde of a double bond or rlng
1rans = opposlLe sldes of a double bond
or rlng
LlecLrophlle = wanLs elecLrons, has a
poslLlve or parLlal poslLlve charge



Þ a g e | 19

#7-Wou|dn't forma|dehyde by a d|fferent name sme|| [ust as sweet?
1he d|fference between common names and IUÞAC nomenc|ature.
We all have nlcknames. 1hls ls noL LarLh-shaLLerlng lnformaLlon, and chemlcal compounds
are no dlfferenL. ?our [ob ls Lo deLermlne whlch compound ls belng dlscussed when your
professor refers Lo lL by Lhree dlfferenL names.
As shown below, Lhe same compound can have a couple of dlfferenL names. 1here are
some compounds LhaL we never use Lhe sysLemaLlc name for. 1,3,3-cyclohexaLrlene would
be one of Lhose, as we never use LhaL name, we always refer Lo lL as benzene. lurLher,
mosL sLudenLs are noL famlllar wlLh 2-propanone, buL mosL of us know whaL aceLone ls.
So whaL ls Lhe rlghL sLraLegy Lo use so as noL Lo confuse Lhese compounds? We belleve LhaL
you can )%#"*' never go wrong uslng Lhe luÞAC name of a compound. 1he reason Lhe
luÞAC nomenclaLure was developed was Lo ellmlnaLe confuslon wlLh lnformal names of
chemlcal compounds. 1haL belng sald, you should be aware of some common names also.
WlLh subsLlLuenL groups and many large molecules, lL wlll be much easler Lo refer Lo Lhe
compound by lLs common name. 8elow, we glve some molecules LhaL you should know
by Lhelr common names:
Structure IUÞAC name Common name
C H
3
H
O

MeLhanal lormaldehyde
C H
3
CH
3
OH

2-propanol lsopropanol
C H CH

LLhyne AceLylene
C H
3
CH
3
O

2-propanone AceLone
C H
3
OH
O

LLhanolc Acld AceLlc Acld
OH

2-meLhyl 2-propanol L-buLyl alcohol

1ake nome Message: Use the IUÞAC name for a|most a|| mo|ecu|es, except for a
few that you shou|d know the common names.

Crgo I, D|ff|cu|ty:
Þ a g e | 20

#8- know the "norma|" state for common organ|c atoms.
SLrucLures of molecules can be dlfflculL Lo plece LogeLher aL flrsL when you are [usL sLarLlng
ln an organlc chemlsLry class. Cne of Lhe Lrlcks LhaL can greaLly help wlLh Lhls ls Lo know
Lhe uncharged or ºnormal" sLaLe for aLoms LhaL are commonly found ln organlc molecules.
Pere ls a Lable of Lhe mosL common of Lhose:
ln an unCPA8CLu sLaLe:
- C has four bonds (and no lone palrs)
- n has Lhree bonds (and one lone palr)
- Palogens have one bond (and Lhree lone palrs)
- C has Lwo bonds (and Lwo lone palrs)
- P has one bond (and no lone palrs)

1hree more rules:
! C, n, C are cenLral aLoms, meanlng LhaL Lhey wlll always be ln Lhe mlddle of
your molecule, never as a Lermlnal aLom (ll Lhey are neuLral)
! P and halogens are Lermlnal aLoms, meanlng LhaL Lhey wlll only have one
bond and be aL Lhe ends of molecules.
! WlLh Lhe excepLlon of P, aLoms ln group l & group ll are only counLerlons
(+1 or +2 charge and noL lnvolved ln resonance).

8emember, Lhese rules are for when Lhe aLom ls uncharged, Lhls +"&* -"' apply Lo charged
aLoms. lor example, a carbocaLlon (a poslLlvely charged carbon aLom) wlll have only Lhree
bonds wlLh no lone palrs whlle a carbanlon (a negaLlvely charged carbon aLom) wlll have
Lhree bonds wlLh one lone palr.

noLlce LhaL all of Lhese aLoms sLlll follow Lhe ocLeL rule. Powever, beware of aLoms LhaL do
noL follow Lhe ocLeL rule, as phosphorus ls an example of an aLom LhaL can have more Lhan
an ocLeL of elecLrons. Shown below ls Lrlphenylphosphlne oxlde, a byproducL of Lhe WlLLlg
reacLlon.

P
O


LlemenLs wlLh open d-subshells, llke phosphorous and sulfur, do noL always follow Lhe
ocLeL rule. More examples of Lhls are Sl
6
and ÞCl
3
. Powever, carbon, nlLrogen and oxygen
wlll follow Lhe ocLeL rule.
Crgo I, D|ff|cu|ty:
Þ a g e | 21

#9- I|scher pro[ect|ons are a b|ack t|e affa|r.
Lmll llscher ls consldered by many Lo be Lhe greaLesL organlc chemlsL Lo ever llve. Pls
problem was LhaL he creaLed a way of looklng aL organlc molecules LhaL ls very confuslng
Lo undergraduaLes. 1hese sLrucLures are necessary Lo learn and are very helpful when
looklng aL cerLaln molecules (such as carbohydraLes), buL Lhey are also very easy Lo [umble.
1hls ls because llscher sLrucLures are drawn as crosses, whlch could lead one Lo
erroneously Lhlnk LhaL Lhe cenLral carbon ls flaL, when lL ls acLually sLlll LeLrahedral.
1he easlesL way Lo look aL Lhese ls Lo Lhlnk of Lhem as bowLles LhaL have been sLrung
LogeLher:

CH
3
CH
3
CH
2
CH
3
O H
Br H
CI H CI H
Br H
CH
2
CH
3
O H
CH
3
CH
3
is equaI to


3-dlmenslonally speaklng, Lhe subsLlLuenLs LhaL are on Lhe sldes of Lhe sLrucLure are
deplcLed aL Lhe end of Lhe bowLle and are represenLed as ºcomlng ouL of Lhe paper". 1he
backbone ls composed of dashed llnes, whlch are meanL Lo represenL LhaL Lhose porLlons
ºare golng lnLo Lhe paper". 1hls ls now a much easler way Lo vlew Lhese sLrucLures, as lL ls
more apparenL whaL area each subsLlLuenL occuples.
1he useful parL of Lhe bowLle pro[ecLlon ls LhaL lL ls now easler Lo assess Lhe
sLereochemlsLry aL each chlral cenLer. lL should be much easler Lo vlsuallze LhaL Lhe
boLLom chlral cenLer ls º8". 1hls was noL as obvlous when vlewlng Lhe llscher pro[ecLlon as
a cross.
CI H
Br H
CH
2
CH
3
O H
CH
3
CH
3


ChlrallLy = º8"
1he ºbowLle"
Crgo I, D|ff|cu|ty:
Þ a g e | 22

#10- Is |t rea||y that "L2"? Determ|n|ng a|kene geometry.
Way back when you were [usL an organlc chemlsLry lnfanL, you learned LhaL alkenes exlsLed
and LhaL Lhey could be labeled elLher a as cls alkene or a Lrans alkene. lL was nlce, and you
were happy noL knowlng LhaL Lhere were oLher, more slnlsLer, alkenes ouL Lhere LhaL dld
noL wanL Lo fall lnLo such neaL llLLle caLegorles. Cne of Lhese dlabollcal oleflns (anoLher
name for an alkene) ls below:
CH
3

lurLher lnLo your organlc chemlsLry odyssey, you are golng Lo worry abouL how you mlghL
synLheslze Lhls molecule. 8lghL now, you are merely concerned wlLh whaL Lo name lL. ls
Lhls a cls or Lrans alkene? unforLunaLely, cls and Lrans do noL apply Lo more complex
alkenes, so we need a new sysLem of nomenclaLure. LnLer Lhe Cahn/lngold/Þrelog sysLem
for namlng double bonds.
1he sysLem lLself ls slmple: asslgn Lhe aLom connecLed Lo Lhe olefln a prlorlLy based on lLs
aLomlc number Lhen deLermlne wheLher Lhe Lwo hlghesL prlorlLy groups are on Lhe same
slde of Lhe double bond, or on opposlLe sldes. lor example:
H
CH
3
F
CI

ln Lhe above example, we compare Cl Lo l and qulckly deLermlne Lhe Cl ls of greaLer
prlorlLy based on lLs aLomlc number. When Lhe same comparlson ls made for P and CP
3
,
we deLermlne LhaL C ls Lhe hlgher prlorlLy. 1hus, Lhe alkene above ls an ºL" alkene.
lurLher, Lhere ls a nlce mnemonlc used Lo remember whlch leLLer goes wlLh whlch alkene:
! ºZ" alkenes are on Lhe ºZAML slde"
! ºL" alkenes are far ºL-WA?" from each oLher.

Whlle flgurlng ouL whlch Lype of alkene ls presenL ls easy when Lhere are four dlfferenL
aLoms connecLed Lo Lhe alkene, we have Lo ask whaL would happen lf Lhere was a Lle
because Lhere were Lwo of Lhe same aLom on Lhe alkene.
Crgo I, D|ff|cu|ty:
Þ a g e | 23


ln Lhe above alkene, we are posed wlLh Lhe problem of four carbon aLoms bound Lo Lhe
double bond. Pere, we can use Lhe AceCrganlcChem.com meLhod for deLermlnlng
prlorlLy. lor each subsLlLuenL on Lhe alkene, wrlLe ouL Lhe aLom aLLached dlrecLly Lo Lhe
alkene and each of Lhe Lhree aLoms aLLached Lo lL, ln order of aLomlc number. lor
example, -CP
3
would be C (P, P, P), and -CP
2
CP
3
would be C (C, P, P). lf we were Lo say
whaL we were wrlLlng, an eLhyl group of C (C, P, P) would LranslaLe Lo ºa carbon wlLh one
carbon and Lwo hydrogens aLLached Lo lL". Slnce Lhey are already ln Lhe parenLheses ln
order of aLomlc number, Lles are easy Lo [udge. lf Lhe flrsL aLoms ln Lhe parenLheses are
Lhe same, [usL go Lo Lhe second aLom Lo break Lhe Lle. 1hus, an lsopropyl group wlLh C (C,
C, P) ouLranks an eLhyl group wlLh C (C, P, P)
now, our molecule looks llke Lhls:
C (C, C, H)
C (C, C, C)
C (C, H, H)
C (H, H, H)

lL can now easlly be seen LhaL Lhls ls an ºL" alkene. 1hls meLhod can also be applled Lo
oLher funcLlonallLles common found aLLached Lo oleflns:

Þ a g e | 24

O
H
AIdehyde C (O, O, H)
O
OH
CarboxyIic acid C (O, O, O)
O
CI
Acid haIide C (CI, O, O)
C
N
NitriIe C (N, N, N)
C
CH
AIkyne C (C, C, C)
O
OMe
Ester C (O, O, O)
CH
3
AIkane C (H, H, H)
Increasing
Priority

1he Lrlck Lo looklng aL Lhese groups ls Lo recognlze LhaL a double bond on Lhe subsLlLuenL ls
equal Lo Lwo of LhaL Lype of aLom. lor example, a cyano group would be equal Lo C (n, n,
n). AnoLher example of Lhls would be as follows:
C H
3
O
OH
O
CI
MeO
C (O, O, CI)
C (O, O, O)
O (C)
C (H, H, H)

1he only oLher Lrlck Lo be aware of ls a problem LhaL has lsoLopes of Lhe same aLom. lor
example, deuLerlum ls a hlgher prlorlLy Lhan hydrogen because lL ls heavler. 1herefore, Lhe
example below would be a ºZ" alkene.


Þ a g e | 2S

D
H H
C H
3

1ake nome Message: When determ|n|ng L]2 conf|gurat|on of an a|kene, use the
C (k, k, k) method for determ|n|ng pr|or|ty, and remember that "2" |s the "2AML
s|de" and "L" |s far "L-way" the other group.















Þ a g e | 26

#11- Master kesonance.
8esonance ls one of Lhose lssues LhaL you wlll have Lo deal wlLh for boLh semesLer l & ll of
organlc chemlsLry. lL ls much beLLer Lo have a solld undersLandlng of lL now, raLher Lhan
have Lo worry abouL lL laLer. 1he baslc goal of resonance sLrucLures ls Lo show LhaL
molecules can move elecLrons and charges onLo dlfferenL aLoms on Lhe molecule. 1hls
makes Lhe molecule generally more sLable because Lhe charge ls now delocallzed and noL
ºforced" on an aLom LhaL does noL wanL lL.
8elow are some handy rules of resonance. lf you learn Lhese and Lhlnk abouL Lhem when
Lackllng dlfferenL resonance problems, you wlll be able Lo handle whaLever ls Lhrown aL
you.
1) know each aLom's ºnaLural sLaLe", see Llp #8. ?ou need Lo recognlze whaL each aLom
generally looks llke, ln an uncharged sLaLe. 1hls wlll help you Lo consLrucL Lhe Lewls uoL
sLrucLure on whlch you wlll base your resonance sLrucLures. 8emember LhaL halogens and
hydrogens are always Lermlnal, meanlng LhaL are aL Lhe end of Lhe molecule and only have
one bond, and Lherefore, Lhey wlll noL parLlclpaLe ln resonance.
2) ALom poslLlons wlll noL change. Cnce you have deLermlned LhaL an aLom ls bonded Lo
anoLher aLom, lL wlll noL change ln a resonance sLrucLure. lf Lhey do change, lL ls no longer
a resonance sLrucLure, buL ls now a consLlLuLlonal lsomer.
3) Check Lhe sLrucLure you have creaLed Lo make sure LhaL lL follows Lhe ocLeL rule. 1hls
wlll become much easler once you have a beLLer handle on Lhe ºnaLural sLaLe" of aLoms.
4) When Lwo or more resonance sLrucLures can be drawn, Lhe one wlLh Lhe fewesL
LoLal charges ls Lhe mosL sLable. ln Lhe example below, A ls more sLable Lhan 8.

C H
3
N
CH
3
O
CH
3
C H
3
N
+
CH
3
O
CH
3
A B

3) When Lwo or more resonance sLrucLures can be drawn, Lhe more sLable has Lhe
negaLlve charge on Lhe more elecLronegaLlve aLom. ln Lhe example below, A ls more sLable
Lhan 8.
Crgo I, D|ff|cu|ty:
Þ a g e | 27


C H
3
N
O
CH
3
C H
3
N
O
CH
3
A B

6) ln Lhe end, each resonance sLrucLure should have Lhe same overall charge and
LoLal number of elecLrons (bonds + lone palrs) as when you sLarLed.

1ake nome Message: kesonance |s ||ke te|emarketers. It |s never go|ng to go
away, so you need to |earn how to do |t we||.

Þ a g e | 28

#12- ¥ou Sp|n Me k|ght kound 8aby, k|ght kound, L|ke a kecord 8aby.
3-u vlsuallzaLlon ls one of Lhe hardesL aspecLs of organlc chemlsLry for new sLudenLs Lo
learn and undersLand. Cne of Lhe greaL aldes ln Lhls area ls a molecular modellng seL,
whlch wlll allow you Lo hold a represenLaLlon of a LeLrahedral carbon ln your hands and
roLaLe lL yourself.
Along Lhose llnes, asslgnlng 8/S conflguraLlon Lo a chlral carbon can be made more dlfflculL
lf Lhe lowesL prlorlLy group ls noL ln Lhe rear. lor example:
CI
H
CH
3
Br

lL noL compleLely obvlous LhaL Lhls ls ln Lhe 8 conflguraLlon from Lhls vlew. 1here are a
couple of Lhlngs LhaL we can do Lo Lhls molecule Lo make Lhe conflguraLlon more apparenL.
llrsL, we could Lhlnk of Lhls as a newman pro[ecLlon lnsLead of Lhe sLandard LeLrahedral
carbon.
CI
H
CH
3
Br
CH
3
Br
CI
H
is the same as

1he oLher (easler) way Lo do Lhls ls Lo [usL roLaLe Lhe LeLrahedral carbon. 1he way Lo do
Lhls ls Lo freeze one of Lhe groups and roLaLe Lhe oLher Lhree. As long as Lhey are roLaLed
and noL swlLched, (Lhey can be roLaLed ln elLher dlrecLlon, clockwlse or counLerclockwlse)
lL wlll be Lhe same molecule.
CI
H
CH
3
Br
is the
same as
HoId
is the
same as
CI
Br
H
CH
3
HoId
CI
C H
3
Br
H
HoId

Any of Lhe four groups can be held ln place whlle Lhe oLher Lhree are roLaLed. Cnce
roLaLed Lo a polnL where Lhe lowesL prlorlLy group ls ln Lhe back, lL becomes much easler Lo
asslgn 8/S conflguraLlon. lurLher, Lhls meLhod ls noL [usL conflned Lo small molecules, as
shown below.
Crgo I, D|ff|cu|ty:
Þ a g e | 29

is the
same as
HoId
is the
same as
HoId HoId
CH
3
Br
CI
Br
CI
CH
3
CI
C H
3
Br

ln Lhe example above, CP
3
ls Lhe lowesL prlorlLy group. 8y keeplng Lhe alkyl chaln
sLaLlonary, we can roLaLe Lhe oLher groups clockwlse ln order Lo place Lhe meLhyl group ln
back. now lL ls more apparenL LhaL lL ls ln Lhe 8 conflguraLlon.

1ake nome Message: Don't get angry. Iust rotate your mo|ecu|e to p|ace the
|owest pr|or|ty group |n back.
Þ a g e | 30

#13- S|ze Matters: kesonance between equ|va|ent atoms means equa|
bond |engths.
Cnce mosL sLudenLs hear Lhls Llp, lL makes perfecL sense Lo Lhem, buL lL lsn'L one LhaL you
mlghL Lhlnk abouL on your own. 1ake a look aL Lhe sLrucLure below, and ask yourself: are
Lhe Lwo n-C bonds Lhe same lengLh?
N
+
O
O

Slnce freshman chemlsLry, we have been Lold LhaL double bonds beLween Lwo aLoms are
shorLer Lhan a slngle bond beLween Lhe same Lwo aLoms. Pence, Lhe n-C double bond
should be shorLer Lhan Lhe n-C slngle bond. 8uL leL's look aL some resonance forms:
N
+
O
O
N
+
O
O
N
+
O
O
_
1 2 3

Pere, we can more clearly see LhaL Lhe nlLro group ls movlng beLween Lhe Lhree resonance
sLrucLures. SLrucLure 3, where Lhe charge ls spread evenly beLween Lhe Lwo oxygens ls a
valld sLrucLure and shows LhaL Lhe bond Lwo oxygen aLoms ln Lhe molecule are equlvalenL
and have Lhe same bond lengLh (124 pm).
We care abouL Lhls prlnclple when lL can be applled Lo more complex organlc molecules
where lL ls noL obvlous LhaL Lhe aLoms are equlvalenL. 1ake Lhe cyclopenLadlene anlon:
C


AL flrsL glance, Lhls appears Lo have Lhree dlfferenL carbon aLoms. Powever, once you sLarL
looklng aL resonance sLrucLures, you can see LhaL Lhe anlon can be moved Lo any of Lhe
carbons ln Lhe rlng. 1hls makes Lhem all equlvalenL, vla resonance. 1hls ls conflrmed
Lhrough analyLlcal sLudles whlch show LhaL all C-C bonds are approxlmaLely 137pm long.
AddlLlonally, as Lhls flLs Puckel's rule of 4n+2, Lhe molecule ls also aromaLlc.
C

C

C

C

C


1ake nome Message: If you see symmetry or aromat|c|ty, th|nk equ|va|ent atoms
Crgo I, D|ff|cu|ty:
Þ a g e | 31

#14- Good for noth|ng a|kanes. Lousy mo|ecu|es.
LeL's face facLs: alkanes don'L have many uses. ln real llfe, Lhey are non-polar solvenLs,
larger-chalned ones can be used Lo make wax, and Lhey are good for burnlng/Lhey make
good fuels. As far as organlc chemlsLry goes, alkanes are very borlng. 1hey have only Lhree
uses ln your class:
1. SolvenLs: Alkanes are very good non-polar solvenLs. See Llp #13 for more
lnformaLlon on Lhls.

2. PalogenaLlon: Alkanes can be reacLed wlLh bromlne or chlorlne under free-radlcal
condlLlons Lo obLaln an alkyl hallde. See Llp #43 for more lnformaLlon on Lhls.

3. CombusLlon: 1hls ls Lhe fuel parL. CompleLe combusLlon ls an alkane reacLlon wlLh
oxygen Lo obLaln CC
2
and waLer, as shown ln Lhe followlng example: C
3
P
8
+3C
2
!
3CC
2
+ 4P
2
C + PeaL

1here ls only a small posslblllLy LhaL you wlll see a combusLlon reacLlon on one of your
exams. 1herefore, Lhe only real uses for alkanes ln your undergraduaLe organlc chemlsLry
class wlll be as a solvenL or ln a halogenaLlon reacLlon. Pence, lf you have an alkane ln one
of your exam reacLlons, lL should be very slmple Lo deLermlne lLs role. lf Lhere ls a halogen
(usually elLher 8r
2
or Cl
2
) , Lhen beware of a halogenaLlon reacLlon. CLherwlse, lL ls mosL
llkely safe Lo say LhaL lf you have an alkane ln your reacLlon, lL ls a solvenL and does noL
parLlclpaLe as a reacLanL.
1ake nome Message: If your react|on does not have C|
2
or 8r
2
somewhere, your
a|kane |s most ||ke|y [ust a so|vent.
Crgo I, D|ff|cu|ty:
Þ a g e | 32

#1S- In organ|c chem|stry, ||kes d|sso|ve ||kes.
1hls one goes back Lo your days ln freshman general chemlsLry and lL ls a slmple one, buL
lmporLanL Lo organlc chemlsLry. ln our world, llkes dlssolve llkes. 1hls means LhaL polar
molecules are easlly dlssolved ln polar solvenLs and non-polar solvenLs are easlly dlssolved
ln non-polar solvenLs.
now LhaL we have comes Lo Lerms wlLh Lhls facL, Lhe nexL quesLlon ls: whaL consLlLuLes
polar molecules and solvenLs?
Water
DimethyIsuIfoxide
DimethyIformamide
Acetic Acid
AcetonitriIe
EthyIene gIycoI
MethanoI
EthanoI
IsopropanoI
Pyridine
AcetonitriIe
Nitromethane
DiethyIamine
AniIine
Acetone
Dioxane
EthyIacetate
ChIororform
Tetrahydrofuran
DichIoromethane
DichIoromethane
DiethyIether
Benzene
ToIuene
XyIene
CarbontetrachIoride
CycIohexane
Hexane
Pentane
CarboxyIic acid
Amide
AIcohoIs
Amines
Aromatics
AIkyI HaIides
Ethers
AIkanes
Increasing
PoIarity
SoIvent CIass Specific SoIvent

1he charL above very effecLlvely dlsplays where dlfferenL solvenLs rank wlLh respecL Lo
Lhelr polarlLy. WhaL should you Lake away from all of Lhls?
1) 1here ls no need Lo memorlze Lhe charL. !usL generlcally learn whlch groups
are more polar Lhan oLhers.
2) Alkanes and aromaLlcs are very non-polar.
3) WaLer and alcohols are Lhe maln polar solvenLs.
4) ÞCLAk MCLLCULLS AkL LASIL¥ DISSCLVLD IN ÞCLAk SCLVLN1S. NCN-
ÞCLAk MCLLCULLS AkL LASIL¥ DISSCLVLD IN NCN-ÞCLAk SCLVLN1S.
Crgo I, D|ff|cu|ty:
Þ a g e | 33

1he polarlLy of molecules Lo be dlssolved can be esLlmaLed uslng Lhe charL above. lurLher,
wlLhln classes of molecules, polarlLy can also be esLlmaLed.
OH OH
CH
3
OH
OH
increasing poIarity

Above, we have four alcohols. As we move from lefL Lo rlghL, and Lhe non-polar alkyl
subsLlLuenL ls shorLened, Lhe overall polarlLy of Lhe molecule lncreases. 1herefore, lL can
be concluded LhaL addlng non-polar subsLlLuenLs Lo a molecule wlll +&!.&)*& lLs overall
polarlLy.
lurLher, we can conLlnue Lo dlfferenLlaLe beLween polar solvenLs by deslgnaLlng Lhem as
polar proLlc or polar aproLlc. 1hls ls lmporLanL when worklng S
n
1/S
n
2 problems. (See Llp
#22)
Some Þo|ar Aprot|c So|vents (Iavor S
N
2 react|ons)
S
O
H N
O
CH
3
CN CH
3
NO
2
O
DimethyIsuIfoxide DimethyIformamide AcetonitriIe Nitromethane Acetone


Some Þo|ar Þrot|c So|vents (Iavor S
N
1 react|ons)
OH
O
OH
H
O
H
Water Acetic Acid IsopropanoI


1ake nome Message: Þo|ar so|vents d|sso|ve po|ar mo|ecu|es. Non-po|ar so|vents
d|sso|ve non-po|ar mo|ecu|es.

Þ a g e | 34

#16-8eware of the bad ac|d tr|p: Meet your strong ac|ds.
A problem we see sLudenLs consLanLly runnlng lnLo ls LhaL Lhey do noL readlly recognlze
sLrong aclds. 1hls ls a Lerrlble mlsLake and should never happen, you wlll need Lo qulckly
recognlze sLrong aclds and undersLand whlch aLom Lhey wlll be proLonaLlng. As far as
sLrong aclds go, you should lmmedlaLely ldenLlfy Lhe MagnlflcenL Seven:

S1kCNG ACIDS: Pl, PCl, P8r, PnC
3
, P
2
SC
4
, PClC
3
, P
3
ÞC
4

!usL Lhlnk LhaL LhaL lL's Lhe Lhree hydrogen halldes and Lhe four aclds LhaL have n, S, Cl, and
Þ as cenLral aLoms. Many sLudenLs remember Lhe oLher four aclds wlLh Lhe mnemonlc,
someLhlng you would never say Lo a glrlfrlend: ºNever Say 'Þlease C|ean' ".
Cnce you have recognlzed LhaL you have a sLrong acld presenL ln your reacLlon, lL ls
necessary Lo deLermlne whaL lL ls proLonaLlng. 8emember LhaL P
+
ls elecLron-deflclenL
(Lewls acldlc) and wlll look for an elecLron-rlch (Lewls baslc) aLom Lo proLonaLe. 1hls could
be a nlLrogen aLom, such as an amlne, or an oxygen aLom ln a carbonyl or an alcohol. MosL
ofLen, Lhe aLom belng proLonaLed wlll have a lone palr somewhere on lL.

1ake nome Message: know the strong ac|ds, the mnemon|c "Never Say Þ|ease
C|ean" m|ght he|p


Crgo I, D|ff|cu|ty:
Þ a g e | 3S

#17- Meet your strong nuc|eoph||es.
1hls ls lmporLanL LhroughouL organlc chemlsLry, buL wlll be especlally lmporLanL when
Lrylng Lo deLermlne Lhe producLs of ellmlnaLlon and subsLlLuLlon reacLlons. 1here are
generally Lhree Lrends Lo remember when dlscusslng how nucleophlllc a reacLanL ls:
1) Slze - Cenerally, Lhe more llnear and/or smaller Lhe nucleophlle, Lhe #".&
nucleophlllc lL wlll be. 1hls ls because lL can reacL aL more slLes and wlll noL be
sLerlcally hlndered lf lL ls smaller or llnear.
2) LlecLronegaLlvlLy- 1he more elecLronegaLlve an aLom ls, Lhe %&** nucleophlllc lL
wlll be. 1hls ls because more elecLronegaLlve aLoms wanL Lo hold elecLron
denslLy closer, and Lherefore wlll be less llkely Lo leL LhaL elecLron denslLy
parLlclpaLe ln a reacLlon. We see Lhls ln calculaLlons and experlmenLs LhaL
show nucleophlllclLy decreases as you geL closer Lo fluorlne on Lhe perlodlc
Lable (C > n > C > l)
3) ÞolarlzablllLy- 1he more polarlzable an aLom ls, Lhe #".& nucleophlllc lL wlll be.
ÞolarlzablllLy ls deflned as Lhe ablllLy Lo dlsLorL Lhe elecLron cloud of an aLom,
whlch allows lL lnLeracL wlLh a reacLlon slLe more easlly. Cenerally,
polarlzablllLy lncreases as you Lravel down a column of Lhe perlodlc Lable (l > 8r
> Cl > l)
8elow ls a Lable of relaLlve nucleophlllc sLrengLh. 1hls ls relaLlve because nucleophlllc
sLrengLh ls also dependanL on oLher facLors ln Lhe reacLlon, such as solvenL.
VLk¥ Good
nuc|eoph||es
PS
-
, l
-
, 8S
-

Good
nuc|eoph||es
8r
-
, PC
-
, 8C
-
, Cn
-
, n
3
-

Ia|r
nuc|eoph||es
nP
3
, Cl
-
, l
-
, 8CC
2
-

Weak
nuc|eoph||es
P
2
C, 8CP
VLk¥ weak
nuc|eoph||es
8CC
2
P

As shown above, as a general rule, Lhe anlon of a reacLanL wlll be a beLLer nucleophlle Lhan
Lhe neuLral form. (l.e. 8CC
2
-
ls a beLLer nucleophlle Lhan 8CC
2
P)


Crgo I, D|ff|cu|ty:
Þ a g e | 36

#18- 1hey have worn out the|r we|come--know your |eav|ng groups.
Pave you ever meL LhaL person seems Lo always be saylng ºscrew you guys, l'm golng
home." 1haL ls a leavlng group. 1hey don'L even need a good excuse Lo deparL, Lhey [usL
do someLlmes. So whaL ls Lhe one overrldlng slmllarlLy beLween LhaL guy and a good
leavlng group? Slmple, Lhey boLh en[oy belng negaLlve.
Leavlng groups are aLoms and molecular fragmenLs LhaL can easlly supporL a negaLlve
charge Lhrough resonance, elecLronegaLlvlLy, or polarlzablllLy. 8elow ls a Lable of Lhe mosL
common leavlng groups and Lhelr ºnlcknames".
Iorma| name Structure N|ckname
Iod|de l
-
none
Ch|or|de Cl
-
none
8rom|de 8r
-
none
Methanesu|fonate
S
O
O
O C H
3

ºMesylaLe" or º-CMs"
1o|uenesu|fonate
S
O
O
O C H
3

º1osylaLe" or º-C1s"
1r|f|uoromethanesu|fonate
F
3
C S
O
O
O

º1rlflaLe" or º-C1f"

Palldes are generally known Lo be good leavlng groups, buL lesser known are Lhe sulfonaLe
esLers. uslng resonance, Lhese speclal esLers can dlsLrlbuLe Lhe negaLlve charge over a
number of aLoms, Lhus sLablllzlng lL and maklng lL lablle. ln facL, Lhe sulfonaLe esLers are
beLween 10
3
and 10
8
Llmes more lablle leavlng groups Lhan Lhe halldes.
Also, anoLher Lype of good leavlng group ls Lhe poslLlvely charged porLlon of a molecule.
1he classlc example of Lhls ls when a hydroxyl (poor leavlng group), becomes poslLlvely
charged (aka waLer, a very good leavlng group). See below for some examples where
leavlng groups are used ln subsLlLuLlon or ellmlnaLlon reacLlons.

Crgo I, D|ff|cu|ty:
Þ a g e | 37

OMs
NaN
3
N
3
CI
NaN
3
N
3
Br
NaN
3
N
3
OTf
NaN
3
N
3


1ake nome Message: Good |eav|ng groups are ha||des, su|fonate esters, and
water.

Þ a g e | 38

#19- If you don't start w|th ch|ra||ty, you can't end w|th |t.
1hls mlghL be one of Lhe flner polnLs of Lhe course, buL lL ls an lmporLanL one noneLheless.
Some professors are sLlcklers abouL Lhls polnL and frankly we Lhlnk Lhey should be. 1he
rule (and make no mlsLake, lL ls a rule) ls lf you don'L sLarL wlLh chlrallLy somewhere ls your
reacLlon, you cannoL flnlsh wlLh lL. A chlral cenLer cannoL [usL be creaLed maglcally.
AlmosL always when you creaLe a chlral cenLer wlLhouL any sLarLlng chlrallLy, you have also
creaLed an equal amounL of lLs enanLlomer, maklng lL a racemlc mlxLure.
CI
2
hv
CI
CI
CI
+ +

ln Lhe above reacLlon, Lhe free radlcal halogenaLlon of penLane produces Lhree dlfferenL
producLs, none of whlch possess chlrallLy. 1-chloropenLane ls noL a chlral molecule for
obvlous reasons. 3-chloropenLane ls a meso compound and Lherefore also noL chlral. 2-
chloropenLane conLalns a chlral cenLer, buL has lLs enanLlomer presenL ln equal amounLs
and Lherefore does noL conLrlbuLe Lo Lhe overall chlrallLy of Lhe reacLlon mlxLure. 1hls ls
because Lhe chlorlne radlcal has an equal chance of aLLacklng from elLher face of Lhe
molecule, and Lherefore glves an equal mlxLure of each enanLlomer. 8ecause Lhere ls no
chlrallLy ln Lhe sLarLlng maLerlals, Lhe overall producL mlxLure ls also achlral.
1he nexL loglcal quesLlon would be ºhow do you geL chlrallLy ln your sLarLlng maLerlals"?
1here are Lwo meLhods for dolng Lhls: 1) chlral reacLanL, or 2) chlral caLalysL. We wlll deal
wlLh chlral reacLanLs, as chlral caLalysLs are a complex Loplc and wlll be dlscussed aL a laLer
Llme.
CH
3
CH
3
CH
3
CH
3
H
H
H
2
, Pd-c
Major product

ln Lhe above example, a chlral cenLer ls already seL ln Lhe molecule, so when Lhe molecule
aLLaches Lo Lhe Þd-C caLalysL, hydrogen wlll only be added from one face of Lhe molecule,
on Lhe face opposlLe of Lhe lsopropyl group. 1hls means LhaL Lhe chlral cenLer esLabllshed
by hydrogenaLlon wlll have Lhe meLhyl groups polnLlng ln Lhe same dlrecLlon as Lhe
lsopropyl group.
1ake nome Message: "If you don't start w|th ch|ra||ty, you can't f|n|sh w|th ch|ra||ty."
Crgo I, D|ff|cu|ty:
Þ a g e | 39

#20- Markovn|kov was a ||ar. A d|rty, sme||y, ||ar.
lL ls now Llme Lo sLep lnLo Lhe AceCrganlcChem Llme machlne. We Lravel back Lo 8ussla,
Lhe year ls 1869. 1he czars are blg, personal hyglene ls noL, and we flnd a young chemlsL
named vladlmlr Markovnlkov worklng ln hls chemlsLry lab. ur. Markovnlkov has developed
a ºrule" for organlc chemlsLry LhaL says when addlng a hydrogen hallde (Px) Lo an alkene,
Lhe nucleophlle (x
-
) wlll go Lo Lhe more subsLlLuLed carbon. 1he oLher way Lo Lhlnk abouL
Lhls ls Lo say LhaL whlchever carbon has more hydrogens, geLs Lhe P
+
from Px. And Lhus
Markovnlkov's rule was born. Slnce Lhen, Lhere have been a loL of ways Lo remember
Markovnlkov's rule:
- º1hem LhaL has, geLs" (hydrogens)
- º1he rlch [usL geL rlcher" (hydrogens)
- º1he less subsLlLuLed geLs more lovln'" (hydrogens)
1hls was all good unLll Lhe early 1930's, when chemlsL Morrls kharash began Lo furLher
lnvesLlgaLe Markovnlkov's work and found numerous excepLlons, or anLl-Markovnlkov
reacLlons, LhaL Markovnlkov declde Lo lgnore. kharash concluded LhaL Markovnlkov's rule
was baslcally a guess and should be renamed from ºMarkovnlkov's rule" Lo ºMarkovnlkov's
speculaLlon".
noneLheless, we are less concerned wlLh feudlng dead chemlsLs, and more concerned wlLh
how you use Lhls on an exam. lL ls our oplnlon LhaL you should noL memorlze whlch
reacLlons are Markovnlkov and whlch are anLl-Markovnlkov, buL you should learn Lhe
Lheory and mechanlsm behlnd Lhe reacLlons and be able Lo apply Lo any slLuaLlon. 1he
classlc example here ls P8r addlLlon Lo propene, wlLh and wlLhouL peroxldes.
HBr
Br
HBr
Br
HOOH
via
C
+
via
C* Br

ln Lhe Lop reacLlon, we see Markovnlkov addlLlon of P8r across Lhe double bond. 1hls ls
because Lhe flrsL sLep of Lhe reacLlon ls Lhe addlLlon of P
+
Lo Lhe alkene, whlch when added
Lo Lhe carbon wlLh more hydrogens, wlll provlde a more sLable secondary carbocaLlon
lnLermedlaLe.
1hls ls ln conLrasL Lo Lhe second reacLlon, whlch ls called anLl-Markovnlkov addlLlon. Pere,
Lhe flrsL sLep of Lhe reacLlon ls Lhe addlLlon of 8r*. lf added Lo Lhe Lermlnal carbon, Lhe
lnLermedlaLe ls Lhe more sLable secondary radlcal. 1hus, Lhls reacLlon provldes 1-
Crgo I, D|ff|cu|ty:
Þ a g e | 40

8romopropane as Lhe producL, where as Lhe reacLlon wlLhouL peroxldes glves 2-
8romopropane as Lhe producL.
Some oLher examples of Markovnlkov vs. anLl-Markovnlkov reacLlons are:
Hg(OAc)
2
, H
2
O
then NaBH
4
OH
H
HBr
Br
hv
H+ / H
2
O OH
H
2
SO
4
OSO
2
OH
1.
2.
BH
3
-THF
H
2
O
2
, NaOH
OH
H
Anti-Markovnikov
Anti-Markovnikov
Markovnikov
Anti-Markovnikov
Markovnikov


A beLLer way Lo Lhlnk of would be lf addlLlon of P
+
ls Lhe flrsL sLep, lL probably goes Lhrough
Lhe Markovnlkov addlLlon because Lhe more sLable lnLermedlaLe would be a more hlghly
subsLlLuLed carbocaLlon. lf Lhe flrsL sLep of Lhe reacLlon ls addlLlon of a radlcal or addlLlon
of an elecLrophlllc meLal, Lhen Lhlnk anLl-Markovnlkov, because Lhe more sLable
lnLermedlaLe would be a more hlghly subsLlLuLed carbon radlcal or an elecLrophlllc meLal
on a more nucleophlllc carbon. LlLher way, Lhe key ls Lo know whlch lnLermedlaLe ls more
sLable, Lhen creaLe a producL from LhaL.
1ake nome Message: know why a react|on occurs and you w||| never have to
remember wh|ch react|ons fo||ow "Markovn|kov's fabr|cat|on" and wh|ch ones
don't.

Þ a g e | 41

#21- A d|fferent type of chem|stry test. Iunct|ona| Group 1ests.
?ou should aL leasL be aware of Lhe dlfferenL chemlcal LesLs for funcLlonal groups.
SomeLlmes, Lhese are glven as parL of an unknown molecule ldenLlflcaLlon, or Lo
supplemenL a specLral problem. lf your professor ls golng Lo LesL you on Lhem, Lhen Lhey
wlll mosL llkely be dlscussed ln lecLure. Powever, even lf you are noL golng Lo be LesLed on
Lhem, lL ls worLh aL leasL one page ln Lhls book Lo Lalk abouL Lhe maln ones LhaL can be
used.
1esL name 1esLs for ÞoslLlve LesL produces
2,4-DNÞ Aldehydes and keLones A yellow, orange-red, or red
preclplLaLe
Ieh||ng's so|ut|on Aldehydes A red preclplLaLe
1o||en's reagent Aldehydes A sllver mlrror
Iodoform test AceLaldehyde and
meLhyl keLones
A lemon yellow preclplLaLe
8r
2
Alkenes Colored soluLlon Lurns clear

WlLh Lhe excepLlon of Lhe bromlne LesL, all of Lhe above LesLs are Lo chemlcally ldenLlfy lf
your unknown ls a carbonyl and whlch Lype lL ls. Whlle Lhese LesLs can Lell you whaL class
of molecule you are deallng wlLh, lL cannoL dlsLlngulsh beLween dlfferenL reagenLs wlLhln
LhaL class. lor example, a 1ollen's LesL can Lell you wheLher you have an aldehyde or noL,
buL lL cannoL Lell you wheLher or noL you have formaldehyde or aceLaldehyde.

1ake nome Message: Chem|ca| tests can te|| you what c|ass of mo|ecu|e you have,
but not spec|f|ca||y wh|ch compound |t |s.

Crgo I, D|ff|cu|ty:
Þ a g e | 42

#22- Is |t L1, L2, S
N
1, S
N
2?
?ou are now forced Lo face Lhe mosL common dllemma on an organlc l exam. ?ou have
been provlded a sLarLlng maLerlal and a nucleophlle/base and are asked whaL Lhe
producL/mechanlsm ls. Are you looklng aL an L1, L2, S
n
1, or S
n
2 reacLlon? WlLh some of
Lhese Lhe answer can be very clear cuL, llke lf you have a prlmary subsLraLe and a non-baslc
nucleophlle (S
n
2). 8uL whaL happens when lL ls noL so clear cuL?
8elow ls a charL LhaL glves LhaL condlLlons LhaL help Lo promoLe each reacLlon.
S
n
1 L1 S
n
2 L2
8eacLlon
Mechanlsm
2-sLep wlLh
carbocaLlon
2-sLep wlLh
carbocaLlon
ConcerLed ConcerLed
SLrengLh of
nucleophlle
Can be medlocre,
musL be non-baslc
Can be medlocre,
musL be baslc
SLrong, non-baslc,
non-bulky
SLrong and
baslc
Leavlng Croup
AblllLy
MusL be greaL MusL be greaL Can be medlocre Can be
medlocre
SolvenL Þolar proLlc Þolar proLlc Þolar aproLlc Þolar aproLlc
ÞroducL
SLereochemlsLry
8acemlc* Alkene, bulky
groups are Lrans
Lo each oLher
lnverslon of any
chlral cenLer
Alkene
Þrlmary
SubsLraLe
no reacLlon no reacLlon Plghly favored lavored only
wlLh sLrong
base
Secondary
SubsLraLe
Cnly wlLh non-
baslc nucleophlle
or lf carbocaLlon ls
resonance
sLablllzed
Cnly lf
carbocaLlon ls
resonance
sLablllzed
(benzyllc or
allyllc)
need sLrong non-
baslc nucleophlle,
oLherwlse
compeLes wlLh L2
lavored wlLh
sLrong base
1erLlary
SubsLraLe
lavored wlLh non-
baslc nucleophlle
CompeLes wlLh
S
n
1
no reacLlon Can occur ln
sLrong base
*S
n
1 reacLlons do noL compleLely glve racemlc producLs. Whlle lL ls Lrue LhaL Lhe nucleophlle has an equal chance of
aLLacklng elLher face of Lhe carbocaLlon formed, Lhe leavlng group wlll parLlally block one of Lhose faces as lL goes, whlch
allows prevenLed compleLe racemlzaLlon. lor more lnformaLlon, search for ºlon palrlng" ln your favorlLe search englne.
8efore we proceed any furLher, a qulck dlscusslon of Lhe four reacLlon mechanlsms ls ln
order. ln ls lmporLanL Lo undersLand LhaL ln S
n
1 and L1 reacLlons, Lhe raLe-llmlLlng sLep ls
formaLlon of Lhe carbocaLlon and LhaL anyLhlng LhaL faclllLaLes LhaL formaLlon wlll also
faclllLaLe S
n
1/L1. 8y Lhe same Loken, Lhe raLe-llmlLlng sLep ln S
n
2 and L2 reacLlons ls
pushlng off Lhe leavlng group. 1herefore, anyLhlng LhaL helps Lhe nucleophlle dlsplace Lhe
leavlng group wlll speed up Lhe S
n
2/L2.
Cne of Lhe Lrlcks you can use ls Lo wrlLe ºSnL1S" (8emembered by Lhe mnemonlc
ºSaLurday NlghL Llve 1oLally Sucks") near each LesL quesLlon you have. ºSnL1S" ls Lo geL
Crgo I, D|ff|cu|ty:
Þ a g e | 43

you Lo remember Lhe flve facLors of Lhe reacLlon: SubsLraLe, nucleophlle, Leavlng Croup,
1emperaLure, and SolvenL. 1hen under each facLor, wrlLe Lhe Lype of reacLlon LhaL lL
favors. lor example, lf your reacLlon ls on a 1º subsLraLe, wrlLe ºL2/S
n
2" under subsLraLe.
lf your reacLlon has a sLrong base ln lL, wrlLe ºL1/L2" under nucleophlle.
LeL's examlne Lhls a llLLle closer. Pere are Lhe ma[or facLors ln deLermlnlng wheLher lL ls an
L1, L2, S
n
1, or S
n
2:
1) SubsLraLe: Þrlmary subsLraLes wlll a|ways go S
n
2 or L2. 1erLlary subsLraLes wlll
/*/)%%( go L1 or S
n
1. Secondary subsLraLes are ln Lhe mlddle and wlll mosLly go S
n
2
or L2. 1he excepLlon Lo Lhls ls secondary subsLraLes LhaL are Lhe resonance-
sLablllzed carbocaLlons, llke benzyllc and allyllc carbocaLlons.
2) nucleophlle, sLrengLh and baslclLy: ls lL a sLrong nucleophlle? (See Llp #17 for
sLrong nucleophlles). SLrong nucleophlles wlll promoLe S
n
2 because Lhe leavlng
group has Lo be forced off. ln S
n
1, Lhe nucleophlle ls aLLacklng a vacanL
carbocaLlon and Lherefore does noL have Lo be as sLrong. ls lL also a sLrong base?
Cbvlously bases wlll promoLe ellmlnaLlon, buL remember LhaL many nucleophlles
are also sLrong bases.
3) Leavlng Croup: Medlocre leavlng groups, llke Cl, promoLe S
n
2 and L2 because Lhey
are, by deflnlLlon, forced off of Lhe molecule. CreaL leavlng groups, such as l, wlll
promoLe L1 or S
n
1. 1hls ls because removal of LhaL leavlng group and formaLlon of
Lhe caLlon ls Lhe raLe-llmlLlng sLep.
4) 1emperaLure: LllmlnaLlon ls generally favored aL hlgher LemperaLures (>30ºC)
whlle subsLlLuLlon ls favored aL lower LemperaLures.
3) SolvenL: ls Lhe solvenL proLlc or aproLlc? ÞroLlc solvenLs always promoLe S
n
1/L1,
because Lhey sLablllze Lhe caLlon lnLermedlaLe beLLer. Þolar aproLlc solvenLs
promoLe S
n
2/L2 because Lhey do noL hydrogen bond and cannoL lnLerfere as much
wlLh Lhe aLLack of Lhe nucleophlle.
ln our oplnlon, one of Lhe besL clues for deLermlnlng wheLher you have an S
n
1/L1 or
S
n
2/L2 ls Lhe solvenL. Þrofessors are very careful Lo choose Lhe solvenL for LesL quesLlons
and wlll mosL ofLen follow Lhe rule of proLlc solvenL for S
n
1/L1 and aproLlc for S
n
2/L2.
Cne polnL LhaL musL also be sLressed ls LhaL ellmlnaLlons are always compeLlng wlLh
subsLlLuLlons and vlce-versa. As Lhey say on one of my favorlLe cable 1v neLworks, ºyou
can'L sLop lL, you can only hope Lo conLaln lL." Cn paper and on exams, we can polnL Lo
some reacLlons and say LhaL Lhere ls only one producL, buL ln Lhe lab you wlll almosL always
have a mlxLure of producLs ln Lhese reacLlons.
1ake nome Message: Lxam|ne the f|ve ma[or factors to see |f you have an S
N
1,
S
N
2, L1 or L2 react|on.
Þ a g e | 44

#23-Why you shou|d not stay on the stra|ght and narrow (|f you are
count|ng carbon cha|ns).
lor Lhose of us who were 8oy ScouLs, Clrl ScouLs, 8rownles, or [usL spenL a loL of Llme ln
deLenLlon, you have had an auLhorlLy flgure Lell you abouL Lhe vlrLues of sLaylng on Lhe
ºsLralghL and narrow". Crganlc chemlsLry ls one of Lhose places where LhaL advlce should
be avolded-lf you are Lalklng abouL nomenclaLure and carbon chalns you should avold
llmlLlng yourself Lo [usL looklng aL Lhe sLralghL.
We have yeL Lo see an organlc l exam where Lhe professor dld noL dusL off Lhls ageless
Lrlck. 8eally, noL a slngle one.
Q. Name this compound

1he organlc chemlsLry novlce (or Lhe sLudenL who sLayed up way Loo laLe waLchlng
lnfomerclals and eaLlng burrlLos) would &#'"(()'%*+ name ls compound 2-propyl
hepLane, when Lhe correcL name ls 4-methy| nonane. 1he mlsLake made ls ln assumlng
LhaL Lhe carbon backbone ls ln a sLralghL llne across your page. 1lme and Llme agaln, lazy
professors wlll aLLempL Lo caLch even lazler sLudenLs ln Lhls Lrap. lL ls essenLlal Lo know
LhaL you are namlng Lhe longesL carbon chaln, noL necessarlly Lhe sLralghLesL. We suggesL
LhaL you avold Lhls problem by counLlng Lhe carbons, flndlng Lhe longesL conLlguous chaln
of Lhem, and placlng a clrcle around lL (our ºclrcle" ls ln a large penLagon). 1hen, flnlsh Lhe
[ob by placlng boxes around any subsLlLuenLs. now, our molecule looks llke Lhls.
C H
3
Q. Name this coumpound

1he oLher plLfall Lo avold ln Lhe nomenclaLure game ls asslgnlng Lhe wrong numbers Lo
subsLlLuenLs. SubsLlLuenL groups are always glven Lhe lowesL posslble sLarLlng number,
regardless oLhers LhaL may be presenL. lor example, Lhe molecule below would be 2, 3, 3-
LrlmeLhylhepLane and 012 3, 3, 6-LrlmeLhylhepLane. Lven Lhough Lhe second one mlghL
look ok, Lhe flrsL one ls Lhe correcL name.
Crgo I, D|ff|cu|ty:
Þ a g e | 4S

CH
3
C H
3
CH
3
Correct: 2,5,5-trimethyIheptane
Incorrect: 3,3,6-triemethyIheptane


1ake nome Message: Go for the |ongest carbon cha|n, not necessar||y the
stra|ghtest.

Þ a g e | 46

#24-Arrows w||| po|nt the way.
Whlle lL may seem llke a mlnor polnL, dlfferenL arrows ln organlc chemlsLry mean dlfferenL
Lhlngs:
Straight single-headed arrow
Shows an irreversible reaction
Two arrows
Shows a reaction equilibrium
Double-headed arrow
Shows resonance
Curved full arrow
Shows flow of electrons
Curved half arrow
Shows flow of single electron (radical)
Large single arrow
Used for retrosynthesis

1he mosL lmporLanL Lhlng Lo undersLand wlLh Lhese arrows ls Lhe elecLron flow wlLh curved
arrows. 1hls wlll be an lnLegral parL of any mechanlsm LhaL you wlll draw. As a sLrlcL rule,
elecLron flow ls ,-.,/0 drawn showlng where Lhe elecLrons are #"34-5 '". 1hls means
LhaL elecLrons wlll flow from negaLlve Lo poslLlve, from nucleophlle Lo elecLrophlle, or from
base Lo acld.
CH
3
O
CH
3
Li
O- Li+
CH
3
CH
3
NucIeophiIe
EIectrophiIe


NaOH O H S OH
O
O
+
NaO S OH
O
O
HOH
+


Crgo I, D|ff|cu|ty:
Þ a g e | 47

#2S- 1here are on|y 3 d|fferent mechan|sms to know. 1hat's |t, [ust 3
(k|nda).
SomeLlmes people make Lhlngs far more dlfflculL Lhan Lhey need Lo be. 8elaLlonshlps,
compuLers, and savlng money on your car lnsurance are [usL a few examples of Lhls. A
fourLh example ls organlc chemlsLry mechanlsms. lor Lhe mosL parL, ln lLs mosL baslc form,
you wlll malnly only be exposed Lo Lhree dlfferenL mechanlsms ln undergraduaLe organlc
chemlsLry. lL's hard Lo belleve, buL LhaL ls lL. Cf course, Lhose Lhree ma[or caLegorles of
mechanlsms can be furLher broken down, buL once lL ls recognlzed LhaL Lhere are only
Lhree dlfferenL mechanlsms, organlc chemlsLry geLs much easler.
1ype 1: Subst|tut|on react|ons- ln a subsLlLuLlon reacLlon, you are replaclng one group wlLh
anoLher. 1hls can be done by reacLlng your subsLraLe wlLh a nucleophlle, elecLrophlle, or
radlcal.

1a. nucleophlllc SubsLlLuLlon 8eacLlons
R X Y R Y X
+

Lxample: Sn2 reacLlons Lxample: Sn1 reacLlons
Br
CN-
NC
+
Br

Br
CN-
NC
+
CN-


1b. LlecLrophlllc SubsLlLuLlon 8eacLlons
R X
Y
+
R Y X
+
+

Lxample: LlecLrophlllc AromaLlc SubsLlLuLlon

CH
3
CI
AICI
3
CH
3




Crgo I, D|ff|cu|ty:
Þ a g e | 48

1c. 8adlcal SubsLlLuLlon: noLe Lhe slngle-headed arrows
R X
Y*
R Y X*
+

Lxample: 8adlcal ÞropagaLlon
C H
3
H
+
CI*
CH
3
*
+
HCI



1ype 2: Add|t|on to Doub|e and 1r|p|e 8onds- AddlLlon Lo double and Lrlple bonds occurs
ln several fashlons. 1hls can elLher be vla elecLrophlllc addlLlon, radlcal addlLlon, or a
cycloaddlLlon.

2a. LlecLrophlllc AddlLlon
+
X Y
X Y
C
+
X
Y

Lxample: Acld hallde addlLlon Lxample: PydroboraLlon
Br
HBr

BH
2
H
BH
3







Þ a g e | 49

2b. Cycllc 8eacLlons
+
X
Y
X
Y

Lxample: ulels-Alder
+
O
H
O
H





2c: 8adlcal AddlLlon
Y
X
HOOH
X Y

Lxample: Acld hallde addlLlon wlLh radlcals
Br
HBr
HOOH




Þ a g e | S0


1ype 3: 8eta-L||m|nat|on- 1hese are reacLlons LhaL requlre a base and proceed vla Lwo
Lypes of mechanlsm, L1 or L2 (each of whlch you should be very famlllar wlLh).
X H
R
R
+
H X



Lxample: L1 Lxample: L2
Br
NaOMe

NaOMe
Br




1ake nome Message: 1here are very few actua| mechan|sms to |earn. 1he key |s
to |earn wh|ch mechan|sm type app||es to your spec|f|c react|on.
Þ a g e | S1

#26- "1hey have the |nternet on computers now??"
1he lnLerneL ls a wonderful Lhlng and a greaL source for organlc chemlsLry help. 8elow are
20 very helpful organlc chemlsLry slLes (ln no speclflc order) LhaL wlll geL you Lhe grade you
wanL.



S|te Address
A spectra| database, w|th
1
n,
13
C,
Ik and MS of many many organ|c
compounds

hLLp://rlodb01.lbase.alsL.go.[p/sdbs/cgl-
bln/dlrecL_frame_Lop.cgl
Iunct|ona| Group Chem|stry: An
e-book
hLLp://books.google.com/books?ld=kkgbl0ux
WlgC&prlnLsec=fronLcover&source=gbs_sum
mary_r&cad=0
Comprehens|ve on||ne text hLLp://www.chem.ucalgary.ca/courses/331/Ca
rey3Lh/Carey.hLml
Comprehens|ve on||ne text hLLp://www.cem.msu.edu/•reusch/vlrLual1ex
L/lnLro1.hLm
Crgan|c keact|on Mechan|sms:
An advanced e-book
hLLp://books.google.com/books?ld=w9l1xlaÞC
ClC&prlnLsec=fronLcover
An organ|c chem|stry g|ossary hLLp://www.chemhelper.com/glossary.hLml
Mechan|sm mov|es hLLp://www.[bpub.com/organlc-
onllne/movles/lndex.hLm
Crgan|c chem|stry he|p board hLLp://www.chemlcalforums.com/lndex.php?
ÞPÞSLSSlu=811738b7ebc34ed2c443ef09233b
8abb&board=3.0
Name react|ons
http://www.organic-
chemistry.org/namedreactions/
Crgan|c Chem|stry ne|p hLLp://www.aceorganlcchem.com
Synthes|s database hLLp://www.orgsyn.org
Crgan|c compounds constants
database
hLLp://www.colby.edu/chemlsLry/cmp/cmp.hL
ml
MI1 chem|stry course webcasts hLLp://ocw.mlL.edu/CcwWeb/ChemlsLry/
Þ a g e | S2











Chapter 3: Crgan|c Chem|stry Strategy


Þ a g e | S3

#27- Go to the hardware store and get a chem|stry too|box.
8eallze lL or noL, you are creaLlng a Loolbox of reacLlons LhaL you can use your exams.
Some of Lhese reacLlons are Lrlvlal, llke a 40-LooLh saw blade, and you mlghL never use
Lhem. CLher reacLlons/Lechnlques are essenLlal, llke a hammer or screwdrlver, and you
wlll use Lhem all of Lhe Llme. And [usL llke ln your real Loolbox (does anyone buL me keep a
Loolbox anymore?) you wanL Lo sorL your Lools by usefulness, keeplng Lhe besL ones on Lop
and placlng Lhe resL ouL of Lhe way. Pere, we are golng Lo help you sorL your Loolbox a
llLLle blL.
AceCrganlcChem's Crganlc ChemlsLry 1oolbox
Carbon-Carbon 8ond
Iorm|ng kxns
Carbon-k 8ond Iorm|ng kxns Iunct|ona| Group
Interconvers|on
Crlgnard addlLlon
Br
Mg
MgBr

Palogen addlLlon Lo an alkane
Br
2
hv
Br

CxldaLlon of alcohols
OH
CrO
3
/H
2
SO
4
OH
O

Alkyne addlLlon
O
C H C
C H
OH

All LlecLrophlllc AromaLlc
SubsLlLuLlons
HNO
3
H
2
SO
4
NO
2

8educLlon of carbonyls
OH OH
O
LiAIH
4

LnolaLe AddlLlon*
O
H H
O
1) BuLi
2)
O OH

Crlgnard lormaLlon
CH
3
CI
Mg
CH
3
MgCI

PydrogenaLlon:
H
2
Pd-C

WlLLlg 8eacLlon *
O
CH
2
PH
3
P=CH
2

LpoxldaLlon
mcpba
O

Pydroxyl Lo chlorlde
OH SOCI
2 CI

Aryl 8lng AddlLlons, l.e.
lrledel CrafL alkylaLlons
CH
3
CI
AICI
3
CH
3

PydraLlon of uouble 8ond
H
3
O+
OH

LsLerlflcaLlon
OH
O
CH
3
OH
H
+
O
OMe

ulels-Alder 8eacLlon
CN
+
CN

Czonolysls
O
3
O
H
H
3
CSCH
3

Carboxyllc acld Lo acld
chlorlde
OH
O SOCI
2
O
CI

Cyanlde AddlLlon
Br
NaCN
CN

ulhydroxylaLlon
OsO
4
OH
OH

nlLro group Lo an amlne
NO
2
SnCI
2
NH
2

*2
nd
Semester react|ons
Crgo I, D|ff|cu|ty:
Þ a g e | S4

We have now gone Lo Lhe largesL hardware sLore ln Lhe counLry and sLarLed Lo creaLe your
organlc chemlsLry Loolbox. We have dlvlded your new Loolbox up lnLo Lhree dlfferenL
secLlons: carbon-carbon bond formaLlon, carbon-x bond formaLlon, and funcLlonal group
lnLerconverslon. lurLher, Lhe mosL lmporLanL of Lhese reacLlons are placed aL Lhe Lop of
each column. Whlle each of Lhe secLlons of Lhe Loolbox ls equally lmporLanL, lL ls necessary
Lo segregaLe Lhem ln order Lo be able Lo undersLand whlch reacLlon Lo use ln whlch
clrcumsLances.
1) Carbon-Carbon 8ond lormlng 8eacLlons: 1hese are Lhe mosL lmporLanL of Lhe
reacLlons. MosL of your synLhesls problems wlll force you Lo use a sLarLlng maLerlal
LhaL has fewer carbons Lhan your flnal producL. ?ou wlll need Lo use one (or more)
of Lhese reacLlons Lo geL Lo Lhe rlghL number of carbon aLoms ln your flnal producL.
2) Carbon-x 8ond lormlng 8eacLlons: ln addlLlon Lo havlng Lhe rlghL number of
carbon aLoms, you musL also have Lhe rlghL funcLlonal groups on your molecule ln
a synLhesls problem. 1hese are Lhe handlesL reacLlons Lo use Lo geL Lhose
funcLlonal groups on Lo your molecule.
3) luncLlonal Croup lnLerconverslon: 1hls ls usually Lhe slmplesL sLep. lL ls aL Lhls
polnL LhaL you already a necessary funcLlonallLy on your molecule, and [usL need Lo
change lL around a llLLle.
A very helpful exerclse ls Lo slL down and do Lhls for yourself. Lach professor ls dlfferenL
and wlll emphaslze dlfferenL reacLlons, so your Loolbox may have some reacLlons LhaL ours
does noL. 1ake some Llme and Lhlnk Lhrough whlch reacLlons are Lhe mosL useful for your
class and geL yourself a good Loolbox Lo ace Lhose synLhesls problems.
1ake nome Message: Make a too|box of the react|ons wh|ch w||| be most he|pfu|
for your spec|f|c c|ass.

Þ a g e | SS

#28- It 1akes A|kynes to Make the Wor|d Go Around (and to react
w|th epox|des)
Lpoxldes are elecLrophlllc Lhree-membered rlngs wlLh an oxygen lnslde. Alkynes, once
deproLonaLed, are greaL nucleophlles and are very good aL formlng carbon-carbon bonds.
A generlc example of Lhls ls shown below:
C H CH
NaNH
2
C H C
C H C
O
+
C H
O H
OH
H
2
, Pd-C

ln Lhe above reacLlon sequence, aceLylene ls deproLonaLed wlLh a sLrong base. ln Lhls case,
sodlum amlde ls used. [Warnlng: naCP and alkoxlde bases are noL sLrong enough Lo
deproLonaLe aceLylene] nexL, Lhe aceLylene anlon ls reacLed wlLh Lhe epoxlde. 1he
aceLylene adds Lo Lhe epoxlde and opens Lhe rlng Lo form an alcohol. ln Lhe flnal sLep, Lhe
alkyne ls reduced Lo Lhe alkane by hydrogenaLlon Lo glve Lhe flnal producL, whlch ls Lhe
alcohol shown. 1hus, we have shown a generlc meLhod for addlng a Lwo-carbon anlon Lo a
Lwo-carbon epoxlde Lo obLaln a four-carbon alcohol.
Whlle Lhe reacLlon shown above ls relaLlvely slmple, more complex reacLlons can be used
Lo obLaln more complex producLs. lor example:
C
O
+
OH
CH
3
OH
CH
3
Na, NH
3

ln Lhe case above, we reacLed a longer chalned alkyne wlLh a subsLlLuLed epoxlde. 1he
general rule for epoxlde openlng ls LhaL under baslc condlLlons [alkynes are baslc
nucleophlles] Lhe nucleophlle wlll aLLack aL Lhe %&** subsLlLuLed carbon, as Lhe nucleophlle
wlll go Lo Lhe less hlndered slde. ln Lhls reacLlon, afLer Lhe alkyne aLLacks, we reduce Lhe
resulLlng compound from Lhe alkyne Lo Lhe Lrans-subsLlLuLed alkene wlLh sodlum and
ammonla. 1hus, Lhls carbon-carbon bond formlng reacLlon ls good for creaLlng subsLlLuLed
alcohols and for lncorporaLlng speclflc double bonds lnLo our LargeL molecule.
1ake nome Message: A|kynes are a great way to attack an epox|de and synthes|ze
an a|coho| w|th a doub|e bond |n |t. If you don't need the doub|e bond, then [ust
use the Gr|gnard reagent |nstead of the a|kyne.
Crgo I, D|ff|cu|ty:
Þ a g e | S6

#29- Iour organometa|||cs to ru|e them a||
Crlgnard reagenLs are a wonderful lnvenLlon. Llke showers, deodoranL, and hoL dogs, Lhey
[usL make llfe so pleasanL. 1he problem ls LhaL Crlgnard reagenLs are noL Lhe besL reagenL
for every reacLlon you may run across. WhaL lf you wanL Lo do a subsLlLuLlon reacLlon on a
hallde? 1haL ls noL a [ob for a Crlgnard reagenL. 1he blg secreL ln Lhe organlc chemlsLry
world ls LhaL Lhere are oLher organomeLalllc reagenLs LhaL wlll do [usL flne LhaL are [usL as
easy Lo form. Pere, we wlll dlscuss Lhe four Lypes of organomeLalllc reagenLs as well Lhelr
besL uses.
Crlgnard (8Mgx):
CH
3
CI
Mg
CH
3
MgCI

CrganoLlLhlum (8Ll):
CH
3
CI
Li
CH
3
Li

CrganocupraLe (8
2
CuLl):
CH
3
Li 2
CuCI
[(CH
3
)
2
Cu]- Li+

Crganozlnc (8Znx)
CH
3
CI
Zn
CH
3
ZnCI

8Mgx 8Ll 8
2
CuLl 8Znx
8aslc? ?es ?es no no
S
n
rxn wlLh
8x?
no ?es, wlLh some
ellmlnaLlon by-
producL
?es ?es, on
dlhalldes Lo
form C-C
bonds
8eacLs wlLh
C=C?
?es ?es no no
8eacLs wlLh
esLers?
?es ?es no no
1,4 addlLlon
Lo €,µ
unsaLuraLed
C=C
Wlll do 1,2
addlLlon flrsL,
Lhen 1,4
Wlll do 1,2
addlLlon flrsL,
Lhen 1,4
?es no
Can form
carbene
no no no ?es

l) Crlgnard 8eagenLs: 1hese are Lhe good old sLandby. Llke an old L-shlrL, Lhey
are comforLable, so you know and love Lhem. lormed by mlxlng an alkyl
hallde wlLh Mg, Lhey wlll reacL wlLh almosL any elecLrophlle. 1he mosL
common use ln for aLLacklng aL a carbonyl carbon. 1hey are baslc, and
Crgo II, D|ff|cu|ty:
Þ a g e | S7

relaLlvely sLable, buL wlll noL do subsLlLuLlon reacLlons aL on alkyl halldes.
Sample reacLlons are shown below:
Br
Mg
0
ether
MgBr
H H
O
OH
H H
2) H
3
O
+
Br
Mg
0
ether
MgBr
O
OH
2) H
3
O
+
Br
Mg
0
ether
MgBr
+
O
OH
2) H
3
O
+


ll) CrganollLhlum reagenLs: 1hese are slmllar Lo Crlgnard reagenLs, buL have one
ma[or beneflL: Lhey can dlsplace a hallde ln an S
n
2 reacLlon, where as a
Crlgnard cannoL. lormed by reacLlng an alkyl hallde wlLh llLhlum meLal, Lhese
nucleophlles can also be used as [usL a sLrong base lL needed. 1hls means LhaL
lf Lhey are Lo be used as a nucleophlle ln an S
n
2 reacLlon, Lhere wlll also be
some L
2
producL observed, due Lo Lhe hlgh degree of baslclLy.
Li
+
CI
Li
+
O
OH


lll) CrganocupraLe reagenLs: Whlle noL Lhe flrsL cholce of many organlc
chemlsLry sLudenLs, organocupraLes can be very useful. lormed by reacLlng
an alkyl llLhlum wlLh copper chlorlde, Lhese reagenLs can perform 1,4
addlLlons Lo unsaLuraLed keLones and dlsplace halldes ln an S
n
2 fashlon. 1he
beneflL Lo Lhe S
n
2 reacLlon ls LhaL Lhe organocupraLes are noL baslc, and
Lherefore wlll noL glve any ellmlnaLlon by-producLs.
Þ a g e | S8

+
(CH
3
CH
2
)
2
CuLi
CH
2
Br CH
2
CH
2
CH
3
CH
3
O
(CH
3
CH
2
)
2
CuLi
+
then H+
CH
3
O


lv) Crganozlnc reagenLs: Crganozlncs are llke LhaL welrd second cousln we all
have. nobody really knows abouL Lhem, and whenever Lhey show up, sLrange
Lhlngs happen. Crganozlnc formaLlon ls slmllar Lo Crlgnard formaLlon, where
zlnc ls lnserLed ln beLween Lhe carbon-halogen bond. Powever, organozlncs
really only have one funcLlon, whlch ls Lo couple of Lhe carbons of dlhalldes.
lor example, lf Lhe sLarLlng maLerlal ls a 1,3 dlhallde, Lhen Lhe producL wlll be
a cyclopropane.

Br Br
Zn
Br ZnBr
Not IsoIated



1ake nome Message: 1here are more organometa|||c reagents out there than
[ust Gr|gnards. 8e aware of the others so you can use the r|ght one for the r|ght
[ob.



Þ a g e | S9

#30- D|e|s-A|der keact|on-Þart 1: An |ntroduct|on
Would lL have Lhe same rlng lf lL were called Lhe ºkurL-CLLo" reacLlon? Þrobably noL. 1hls
reacLlon ls one LhaL many professors llke Lo emphaslze because lL ls one of Lhe only
cycloaddlLlon reacLlons LhaL sLudenLs are shown ln undergraduaLe organlc chemlsLry. 1he
reacLlon ln lLs mosL baslc form ls very slmple:
+
Diene DieneophiIe CycIohexene

ln Lhls reacLlon, a dlene (by deflnlLlon havlng Lwo double bonds ln con[ugaLlon) and a
dleneophlle (someLhlng LhaL ºloves" a dlene) are reacLed Lo glve a cyclohexene rlng as Lhe
producL, whlch can be hydrogenaLed Lo glve a cyclohexane rlng. 1he reacLlon ls consldered
a [4+2] cycloaddlLlon, wlLh Lhe generally accepLed mechanlsm shown below:

As a general rule, Lhls reacLlon proceeds besL wlLh cerLaln Lypes of reacLanLs. Speclflcally,
Lhe reacLlon proceeds besL when Lhe dlene has elecLron donaLlng groups aLLached Lo lL and
Lhe dleneophlle has elecLron wlLhdrawlng groups aLLached Lo lL. Some examples of good
dlenes and dleneophlles are shown below:
MeO
Some Good Dienes
Some Good DieneophiIes
O
H
CN COOCH
3
COOCH
3
O
O
O
COOCH
3
COOCH
3

Some examples of ulels-Alder reacLlons are shown here:
Crgo I, D|ff|cu|ty:
Þ a g e | 60

O
H
CN
COOCH
3
COOCH
3
+
+
+
CN
CHO
COOCH
3
COOCH
3

1&#% 1&#%: lf your LesL quesLlon has a cyclohexane or cyclohexene rlng as Lhe producL and
you have Lo use sLarLlng maLerlals wlLh lCu8 CA88CnS or LLSS, lL almosL cerLalnly wlll
lnvolve a ulels-Alder reacLlon. [?ou can synLheslze a cyclohexane rlng by hydrogenaLlng
your producL]. 1hls ls golng Lo be one of your maln carbon-carbon bond formlng Lools for
your Loolbox.
ln 1lps #34 and #33 we wlll furLher explore Lhls reacLlon and go lnLo some of Lhe condlLlons
LhaL wlll make for a successful ulels-Alder reacLlon.


Þ a g e | 61

#31- Let's go retro: ketrosynthet|c ana|ys|s
Ah, remember Lhe 70's? ulscos, a nlce large 'lro, and socks. 8eLrosynLhesls ls klnda llke
Lhe 70's, excepL lL acLually has a purpose. 1he purpose of reLrosynLhesls ls Lo glve us a
vlable paLhway Lo geL from a small molecule Lo a large one. 1he Lheory behlnd lL ls LhaL lL
ls much easler Lo breakdown a large molecule Lo see whlch small molecule lL could come
from Lhan Lhe oLher way around. 1here are really Lwo acLlons LhaL can be Laken ln a
reLrosynLhesls, as shown here:
X Y
NH
2
NO
2
C
NO
2
+
X

X
+
+
+
Y
+
Y

OH
C

C
+
OH
+
Synthons:
FunctionaI Group Interconversion
CAUTION: Synthons are not necessariIy reaI

SynLhons are Lhe fragmenLs LhaL come from breaklng a bond. 1he lmporLanL polnL wlLh
synLhons ls Lo recognlze LhaL Lhey are noL necessarlly real. 1hey [usL represenL Lhe
fragmenLs LhaL mlghL be posslble. lor example:
OH
C C
+
OH
BrMg
O
H
+
Fragment Synthons ReaI MoIecuIes
C C
+
Li
Br
+

Pere, we are cleavlng sLraLeglc bonds. We asslgn a hypoLheLlcal º+" or º-º charge Lo each
end of Lhe broken bond Lo help us declde whlch real molecules our synLhons should come
from.
Cnce your ma[or carbon-carbon bonds have been formed, lL ls Llme Lo change Lhe
funcLlonal groups ln Lhe groups we need for our flnal producL. ln Lhls secLlon, we wlll noL
Lalk a loL abouL lCl.
Crgo I, D|ff|cu|ty:
Þ a g e | 62

Whlle enLlre books have been wrlLLen [usL abouL reLrosynLhesls, here are some slmple Llps
Lo help you compleLe your synLhesls problems more effecLlvely:
" uC: Work backwards Lo an ºaccepLable" sLarLlng maLerlal
" uC: CounL your carbons so Lhey don'L geL losL or forgoLLen
" uC: LocaLe funcLlonal groups, Lhey wlll be Lhe flrsL & besL place Lo look for
dlsconnecLlons
" uC: Þlace mosL reacLlve funcLlonal groups on producL lasL
" uC: Lxamlne more Lhan one paLhway (Llme permlLLlng)
" uC: lf you run lnLo Lrouble, sLarL lnLerconverLlng funcLlonal groups looklng for
ldeas.

! uCn'1: lgnore oLher funcLlonal groups on Lhe molecule.
! uCn'1: Make up chemlsLry LhaL ºlooks llke lL should work".
! uCn'1: use reacLlons LhaL wlll glve mlxLures of producL. (Þrof wlll dock you pLs)

8eLro lAC's:
C. Where should l choose Lo dlsconnecL?
A. More ofLen Lhan noL, dlsconnecLlons Lake place lmmedlaLely ad[acenL Lo funcLlonal
groups because Lhey have elecLronegaLlvlLy dlfferences from carbon and Lherefore can do
chemlsLry.

C. Pow do l recognlze a good dlsconnecLlon?
A. A good dlsconnecLlon wlll make Lhe molecule vlslbly slmpler.

C. Pow do l declde whlch synLhon carrles Lhe charge?
A. Cne Lrlck ls Lo use resonance. lf you draw a synLhon and Lhe resonance sLrucLure looks
slmllar Lo a real reacLlvlLy lnLermedlaLe, you are mosL llkely on Lhe rlghL Lrack.

C. Was dlsco ever cool?
A. no, Lhey [usL dldn'L know any beLLer back Lhen.






Þ a g e | 63

#32- Cvera|| LAS strategy
LlecLrophlllc AromaLlc SubsLlLuLlon (LAS) problems are llke regular synLhesls problems, buL
dlfferenL ln LhaL Lhey focus more on Lhe order LhaL groups are subsLlLuLed on Lhe benzene
rlng raLher Lhan on Lhe LransformaLlons Lhemselves. 1o be sure, chemlsLry done dlrecLly
on an aromaLlc rlng (llke benzene) ls very dlfferenL Lhan Lhe chemlsLry on oLher organlc
molecules.
lor example, you may be asked Lo synLheslze Lhe molecule below:
NO
2
CH
3

Agaln, Lhe order of your reacLlons ls lmporLanL. 8elow, we show Lwo meLhods Lo obLaln
nlLroLoluene. 1he flrsL meLhod ls Lhe one LhaL wlll glve Lhe correcL producL. noLlce ln Lhe
second example LhaL swlLchlng Lhe sLeps geLs us a dlfferenL producL.
NO
2
CH
3
NO
2
Method 1
(correct)
CH
3
CH
3
NO
2
Method 2
(incorrect)
HNO
3
H
2
SO
4
CH
3
CI
AICI
3
HNO
3
H
2
SO
4
CH
3
CI
AICI
3

1he reason for Lhls ls Lhe ºdlrecLlng" effecL of Lhe flrsL group placed on Lhe rlng. ln general,
groups LhaL wlLhdraw elecLron denslLy from Lhe aryl rlng are deacLlvaLlng groups and wlll
Lend Lo dlrecL new groups Lo Lhe meLa poslLlon. AlmosL wlLhouL excepLlon, groups LhaL
donaLe elecLron denslLy Lo Lhe rlng are acLlvaLlng groups and wlll cause lncomlng
subsLlLuenLs Lo go Lo Lhe orLho and/or para poslLlons. 8elow ls a charL of acLlvaLlng and
deacLlvaLlng groups:
Crgo I, D|ff|cu|ty:
Þ a g e | 64

O
NR
2
NH
2
OH
OR
NHC(O)R
OC(O)R
R
Ph
StrongIy
Activating
ModerateIy
Activating
WeakIy
Activating
O,P Directors
O
2
N
R
3
N
H
3
N
HO
3
S
NC
F
3
C
O
CI
StrongIy
deactivating
ModerateIy
deactivating
+
O
O H
O
RO
O
R
O
H
+
Meta Directors

As a general gulde, aLoms LhaL are aLLached dlrecLly Lo Lhe rlng LhaL have free lone palrs
and/or negaLlve charges wlll be o,p dlrecLors. Conversely, meLa dlrecLors are comprlsed of
carbonyl groups, nlLrlles, and sulfaLes and poslLlvely charged aLoms dlrecLly connecLed Lo
Lhe rlng. 1he only excepLlon Lo Lhe acLlvaLor/deacLlvaLor rule ls halogens. Palogens are
sllghLly deacLlvaLlng, buL acL as o,p dlrecLors.
now LhaL we know Lhe general rules of LAS, we can learn some of Lhe Lrlcks LhaL we can
use Lo synLheslze more complex LAS producLs.


Þ a g e | 6S

#33- LAS Strategy: 1urn a meta |nto ortho]para and v|ce-versa.
A professor may glve Lhe followlng sLrucLure and requlre you Lo synLheslze lL from
benzene.
NH
2
CI

1he glarlng problem here ls LhaL you have Lwo o,p dlrecLors LhaL are meLa Lo each oLher.
Pow Lhe heck do you do LhaL? 1here ls an easy sLraLegy Lo allevlaLe Lhls lssue, whlch
lnvolves placlng a meLa dlrecLor on Lhe rlng flrsL. 1hls wlll send our second group lnLo Lhe
meLa poslLlon, Lhen we converL Lhe flrsL group Lo achleve our end producL. ln Lhe example
above, we would flrsL nlLraLe benzene, place our chlorlne ln Lhe requlred meLa poslLlon,
Lhen converL Lhe nlLro group Lo an amlne Lo glve Lhe flnal producL, as shown below.
NH
2
CI
NO
2
NO
2
CI
HNO
3
H
2
SO
4
AICI
3
CI
2
LiAIH
4

ln LAS, Lhere are a number of funcLlonal groups whlch are meLa dlrecLors LhaL can be
converLed Lo orLho/para dlrecLors laLer, and vlce versa. Shown below, are a number of
meLa dlrecLors LhaL can be converLed lnLo orLho/para dlrecLors.
Meta D|rector Converted to o,p d|rector Cond|t|ons
NC
2
nP
2
LlAlP
4

CN CP
2
nP
2
LlAlP
4

CCCn CP
2
CP LlAlP
4

C(C)k 8 P
2
, Þd-C
SC
3
CP naCP, PLA1!

Crtho]Þara D|rector Converted to meta d|rector Cond|t|ons
k CCCP kMnC
4

Nn
2
Cn PCnC, Lhen Cu
2
(Cn)
2

Nn
2
nC
2
mcpba

When Lackllng any problem llke Lhls, Lhe flrsL Lhlng LhaL you should Lhlnk Lo use ls an amlne
lf you need an o,p dlrecLor, or a nlLro group lf you need a meLa dlrecLor. 1he advanLage ls
Crgo I, D|ff|cu|ty:
Þ a g e | 66

LhaL nlLro groups can be converLed Lo amlnes and amlnes can be converLed lnLo many
oLher groups Lhrough dlazo compounds. ulazos are hlghly versaLlle and wlll allow you Lo
converL Lhe amlne Lo anoLher group, or [usL remove lL all LogeLher. 8elow ls a summary of
many of Lhese reacLlons.
NH
2
HONO
N
2
+
H
F
CI
Br
I
CN
OH
H
3
PO
4
NaBF
4
HEAT!
Cu
2
CI
2
HCI
Cu
2
Br
2
HCI
KI
Cu
2
(CN)
2
HBr
H
3
O+

?our sLraLegy on Lhese Lypes of problems should be Lo:
1. ldenLlfy whlch groups on your aryl rlng. Whlch are o,p and whlch are meLa?
2. Can you place Lhe subsLlLuenLs on Lhe rlng wlLh Lhe dlrecLors you have rlghL now, lf
you do lL ln Lhe rlghL order?
3. lf noL, ldenLlfy whlch dlrecLors can be converLed lnLo a dlfferenL Lype of dlrecLor.
(meLa Lo o,p or o,p Lo meLa)
4. lf noL, can you place an nP
2
on Lhe rlng somewhere, use lL Lo dlrecL, Lhen remove
lL?
1ake nome Message: If you are not sure how to get the groups on your ary| r|ng |n the
r|ght p|ace, cons|der chang|ng the subst|tuents on the r|ng to he|p you.
Þ a g e | 67

#34- LAS Strategy: Convers|on of a|ky| groups to carboxy||c ac|ds.

We see clrcumsLances for Lhls sLraLegy arlse more frequenLly Lhan one mlghL expecL. 1he
classlc quesLlon LhaL ls seen on exams ls shown below, where you are asked Lo synLhesls
Lhe followlng molecule from benzene:

COOH
COOH


As ln Llp #33, Lhe obvlous lssue ls LhaL CCCP ls a meLa dlrecLor and Lhe Lwo groups are para
Lo each oLher. 1o solve Lhls problem, you wlll use a sLraLegy where you place orLho/para
dlrecLors on Lhe benzene rlng flrsL, Lhen converL Lhem Lo Lhe meLa dlrecLor afLer you have
Lhem ln Lhe proper place on Lhe rlng. lor Lhls example, we would proceed as follows:

COOH
COOH
CH
3
CH
3
CI
AICI
3
CH
3
CI
AICI
3
CH
3
CH
3
KMnO
4


1he flrsL sLep ls a lrledel-CrafL alkylaLlon of benzene Lo glve Loluene. 1hls ls Lhen followed
by anoLher lrledel-CrafL alkylaLlon Lo glve p-meLhyl Loluene, also called p-xylene. 1he Lrlck
here ls Lhe reacLlon LhaL Lurns an alkyl groups Lo a carboxyllc aclds by sub[ecLlng lL Lo
kMnC
4
. 1hls ls referred Lo as a sldechaln oxldaLlon, and can be performed on a number of
dlfferenL alkyl groups. We now have converLed boLh meLhyl groups lnLo carboxyllc aclds
and compleLed Lhe synLhesls.

lurLher examples of Lhls reacLlon are shown below:

Crgo I, D|ff|cu|ty:
Þ a g e | 68

KMnO
4
KMnO
4
KMnO
4
KMnO
4
COOH
COOH
COOH
No Reaction


1he reacLlon ls a very handy one, and can be used on )%#"*' any alkyl slde chaln. 1he key
Lo Lhe reacLlon ls Lhe benzyl proLons on Lhe alkyl slde chaln, whlch are necessary for Lhe
reacLlon Lo proceed. WlLhouL aL leasL one benzyllc proLon Lhe reacLlon wlll fall, as
lllusLraLed ln Lhe example of L-buLyl benzene.

1ake nome Message: A|ky| s|de cha|ns can be converted |nto carboxy||c ac|ds.
keep th|s |n m|nd |f you see a prob|em where you have a carboxy||c ac|d but can
f|nd out how to p|ace |t on the r|ng.
Þ a g e | 69

#3S- LAS strategy: -SC
3
n and -k are our b|ock|ng groups
lL's fourLh down and we need Lo flnd Lhe endzone. WhaL ls Lhe besL way Lo do LhaL? CeL
yourself a faL blocker and run Lhe ball ln. ln LAS, we have Lwo faL blockers. AL fullback, we
have halogens blocklng for us. AL halfback, we have sulfonlc acld. A Lyplcal problem where
Lhese groups can be useful ls shown below:
CH
3
CH
3
CH
3
Synthesize the foIIowing:

Care musL be Laken ln Lhls problem: boLh groups are o,p dlrecLors whlch means LhaL once
one alkyl group ls placed on Lhe chaln, Lhe naLural Lendency wlll be for Lhe second Lo go Lo
Lhe para poslLlon, as shown below:
CH
3
C H
3
C H
3
CH
3
CH
3
CI
AICI
3
AICI
3
CH
3
CI

So how do we keep LhaL second alkyl groups from golng Lo Lhe para poslLlon? use a
blocklng group.
CH
3
C H
3
C H
3
CH
3
CH
3
Br
CI
AICI
3
AICI
3
CH
3
CI
C H
3
CH
3
Br
C H
3
CH
3
CH
3
Mg
Then water
Br
2
Fe

Crgo I, D|ff|cu|ty:
Þ a g e | 70

As shown above, afLer Lhe flrsL alkylaLlon, we can use a halogenaLlon reacLlon whlch wlll
place a halogen group ln Lhe para poslLlon. Cnce Lhe para poslLlon ls successfully blocked,
Lhe second alkyl group wlll have no cholce buL Lo go Lo Lhe orLho poslLlon. uslng slmple
chemlsLry, we alkylaLed Lhe rlng and Lhen halogenaLed, whlch ls selecLlve for Lhe para
poslLlon. now, because Lhe lsopropyl group ls sLlll an o,p dlrecLor, Lhe nexL group wlll have
Lo go Lo Lhe orLho poslLlon. lrledel-CrafL alkylaLlon places Lhe meLhyl group aL Lhe orLho
poslLlon. 1he flnal sLep ls Lo remove Lhe halogen, whlch can be done wlLh Mg and waLer.
SC
3
P can also be used as a blocklng group, lf halogens are noL approprlaLe, as shown
below:
Br
CI

1hls synLhesls can be accompllshed by Lhe followlng meLhod:
Br
CI
Br Br
SO
3
H
Br
CI
SO
3
H
Br
2
FeBr
3
SO
3
H
2
SO
4
CI
2
AICI
3
H
3
O+

1he sLraLegy ls Lhe same, buL uslng a dlfferenL blocklng group. Pere, because we cannoL
use a halogen, Lhe sulfaLe ls used as Lhe para-blocker. 1hls group can be removed uslng
aqueous acld ln Lhe flnal sLep.
1ake nome Message: If you need an ortho subst|tuted ary| r|ng, cons|der a b|ock|ng
group.
Þ a g e | 71

#36- LAS Strategy: Long cha|n a|ky| groups from Wo|ff-k|shner or
reduct|on
Care musL be Laken when aLLempLlng Lo place a long alkyl chaln on benzene. Conslder Lhe
followlng problem:
?

AL flrsL glance, Lhls may appear Lo be a slmple lrledel-CrafL alkylaLlon. Powever, upon
furLher examlnaLlon we remember LhaL Lhose alkylaLlons proceed Lhrough a carbocaLlon
lnLermedlaLe, whlch wlll rearrange Lo glve a dlfferenL producL.
CI
AICI
3

So how do we synLheslze propylbenzene? When you need a long chaln alkyl group on a
benzene rlng, place Lhe chaln on Lhe rlng vla lrledel-CrafL acylaLlon, Lhen remove Lhe
carbonyl ln a laLer sLep.
O
CI
O
AICI
3
H
2
NNH
2
KOH

1he carbonyl ls removed uslng Lhe Wolf-klshner reacLlon, whlch Lhen glves our flnal
producL. (See Llp #38 for more lnformaLlon on Lhe Wolff-klshner 8educLlon)

1ake nome Message: A|ky| cha|ns that are three carbons or |onger need to be
p|ace on the r|ng v|a acy|at|on]carbony| remova|.

Crgo I, D|ff|cu|ty:
Þ a g e | 72

#37- LAS Strategy: Subst|tuted to|uenes came from to|uene. Duh
1he acorn doesn'L fall far from Lhe Lree. Cur ln our case, Lhe subsLlLuLed Loluene doesn'L
fall far from Loluene. AlmosL all subsLlLuLed Loluene molecules orlglnally came from a
subsLlLuLlon reacLlon on bromo-Loluene.
CH
3
CI
AICI
3
CH
3
Br
2
hv
C H
2
Br

As shown above, Lhe creaLlon of bromo-Loluene ls sLarLed wlLh a lrledel-CrafLs alkylaLlon
of benzene Lo obLaln Loluene. 1hls ls Lhen reacLed wlLh bromlne under free radlcal
condlLlons, whlch causes bromlnaLlon aL Lhe alkyl slde chaln and noL on Lhe aromaLlc rlng.
1hls compound ls now useful because lL has a leavlng group on ln Lhe benzyllc poslLlon,
where lL can undergo an S
n
1 C8 S
n
2 reacLlon (See Llp #40 for more lnformaLlon on benzyllc
leavlng groups). now LhaL lL ls suscepLlble Lo nucleophlllc subsLlLuLlon, we can look aL a
number of dlfferenL reacLlons we creaLe dlfferenL molecules based on bromoLoluene:
O
2
N
CH
2
Br
O
O
O
2
N
C
H
2
O
O
Br
CH
2
CH
2
OH
O

1hus, Lhe reLrosynLhesls for almosL every subsLlLuLed Loluene should look llke Lhls:
R
CH
2
Br
+ R
CH
3




Crgo I, D|ff|cu|ty:
Þ a g e | 73









Chapter 4: ne|pfu| n|nts and C|ues


Þ a g e | 74

#38: Want to |mpress your |nstructor? Start dropp|ng names.
ÞlcLure Lhls--lL's SaLurday nlghL, you had a good Llme aL Lhe bars and are aL a preLLy good
afLer-hours parLy now. ?ou are Lalklng Lo Lhls greaL looklng glrl/guy and lL ls golng preLLy
well unLll you hear Lhlngs llke:

ºl was on Lhe phone wlLh Covernor PlbberL lasL nlghL, he ls such a good
frlend, and he offered me an lnLernshlp Lhls summer."
ºl know Lhe whole baskeLball Leam. 1he sLar forward, Wlggum, sLopped
me on campus Lhe oLher day Lo glve me a klss. Pe ls so sweeL"

name dropplng.Cne of Lhe qulckesL ways Lo Lurn off LhaL poLenLlal maLe. Well, leL me Lell
you where lL ls lmpresslve. When you wrlLe a chemlcal reacLlon on one of your exams and
puL Lhe name of LhaL reacLlon nexL Lo Lhe LransformaLlon (see example below), you have
shown a greaLer masLery of Lhe sub[ecL and are more llkely Lo geL LhaL exLra polnL lf you
somehow weren'L perfecL wlLh Lhe reacLlon.
CI
2
hv
CI
Free radicaI haIogenation


Moreover, Lhls can be essenLlal lf you are uslng a reacLlon on an exam LhaL you were noL
LaughL ln class. 1here are Lhousands of organlc chemlsLry reacLlons LhaL are perfecLly valld
chemlcal LransformaLlons LhaL you were noL shown ln lecLure. Cne of Lhe maln problems
wlLh uslng Lhem on your exam ls LhaL your professor (or Lhe 1A gradlng Lhe exam) mlghL
noL lmmedlaLely recognlze Lhls reacLlon and may erroneously dock you polnLs. 8y placlng
Lhe name of Lhe reacLlon nexL Lo lL, you very pollLely say º?es, l know whaL l am dolng. Co
look lL up."

O
O
TiCI
3
McMurry Reaction


1he McMurry reacLlon ls baslcally a ºreverse ozonolysls" (see Llp #62). lL ls a perfecLly
leglLlmaLe reacLlon and can be used ln a number of slLuaLlons, buL ls noL generally LaughL ln
undergraduaLe classes. lf your professor or 1A ls one LhaL does noL recognlze Lhls reacLlon,
Lhey may erroneously deducL polnLs from your overall score. Cne way Lo help avold Lhls ls
Lo puL Lhe name of Lhe reacLlon nexL Lo Lhe LransformaLlon.

Crgo I, D|ff|cu|ty:
Þ a g e | 7S

#39- Lnant|omers are s|b||ngs and d|astereomers are Cous|ns, wh|ch
makes rotomers your d|ngy aunt.
1he polnL we are Lrylng Lo make wlLh Lhls Llp ls LhaL Lhe molecules are relaLed when you
compare Lhem. ?ou can'L [usL walk up Lo someone on Lhe sLreeL and know LhaL Lhey a
slsLer, you have Lo know whose slsLer Lhey are. Molecules are Lhe same way. A molecule
[usL lsn'L an enanLlomer, you have Lo compare lL Lo lLs mlrror lmage Lo know lL's Lhe
enanLlomer. 1hls ls lllusLraLed below:
CI
Br
CI
Br
enantiomers
CI
Br
CI
Br
enantiomers

Pere, we show Lwo dlfferenL ways you can Lurn a compound lnLo lLs dlasLereomer. 1he
flrsL way ls by drawlng lLs mlrror lmage, whlch ls Lhe deflnlLlon of an enanLlomer. ?ou
could keep Lhe molecule's orlenLaLlon Lhe same and [usL reverse all of Lhe sLereocenLers by
Lurnlng Lhe dashes Lo wedges and vlce versa. 8oLh are accepLable ways Lo deLermlne Lhls
compound's enanLlomer. 1hese Lwo meLhods can be applled Lo llscher pro[ecLlons Loo.
enantiomers
CH
3
H Br
H CI
H H
CH
3
CH
3
Br H
CI H
H H
CH
3

ueLermlnlng dlasLereomers ls [usL as easy. WlLh dlasLereomers, Lhe dlfference beLween
Lhe compounds shown would be LhaL only one of Lhe sLereocenLers ln Lhe molecule were
dlfferenL.
Crgo I, D|ff|cu|ty:
Þ a g e | 76

CI
Br
CI
Br
Enantiomers
CI
Br
CI
Br
Enantiomers
Diastereomers
Diastereomers
Diastereomers

keeplng lL sysLemaLlc, as we have above, ellmlnaLes Lhe problem of dupllcaLlon of
molecules. Moreover, we can even use a formula Lo deLermlne Lhe LoLal number of
posslble dlasLereomers wlLhouL acLually drawlng Lhem all ouL
1ota| # of poss|b|e d|astereomers = 2
N
[where N |s the number of ch|ra| centers |n the
mo|ecu|e]
ln our example above, Lhere are Lwo chlral cenLers, so Lherefore we have 2
2
or 4 poLenLlal
dlasLereomers. ln Lhe molecule below, we have far more Lhan LhaL.
O
OH
O
OAc
O
N
OH
Ph
O
Ph O
AcO
H
O H
BzO
H
TaxoI

1axol ls a poLenL anLl-cancer drug derlved from Lhe ?ew Lree. AcLually changlng one
sLereocenLer aL a Llme Lo deLermlne Lhe LoLal number of dlasLereomers ls noL feaslble,
however lL ls feaslble Lo counL LhaL Lhere are 12 sLereocenLers. We can now use our
formula deLermlne LhaL Lhere are 2
12
or 4096 posslble dlasLereomers for 1axol.

1ake nome Message: Use a ||nk chart ||ke above to systemat|ca||y create a|| of the
d|astereomers for a mo|ecu|e. Use the formu|a: 1ota| # of poss|b|e
d|astereomers = 2
N
to [ust determ|ne the tota| number w|thout draw|ng each
one.
Þ a g e | 77

#40- 8enzy||c and a||y||c |eav|ng groups are better than they |ook.
Cverachlevers can really be annoylng someLlmes. l mean, leL's face lL, who wanLs Lo waLch
LhaL all of Lhe Llme. 1hls ls your cousln LhaL graduaLed from ?ale Lo aLLend ÞrlnceLon
Medlcal School and helps homeless veLerlnarlans ln hls spare Llme. 8enzyllc caLlons are
Lhe overachlevers of organlc chemlsLry. upon flrsL glance, Lhe benzyl caLlon looks llke an
average prlmary caLlon. Slnce we know LhaL prlmary caLlons are noL sLable, we would
Lhlnk LhaL Lhe benzyllc caLlon would noL exlsL.
CH
2
+
BenzyI
Cation

Powever, Lhls ls no ordlnary caLlon. 8ecause Lhe poslLlve charge ls locaLed one carbon off
Lhe aryl rlng, Lhls compound has resonance sLrucLures whlch make lL much more sLable
Lhan your average prlmary caLlon.
CH
2
+
C
+
CH
2
C
+
CH
2
C
+
CH
2

As shown above, Lhe poslLlve charge can be delocallzed Lhrough Lhe aryl rlng Lo provlde
furLher sLablllLy. We are now spreadlng LhaL charge over Lhe enLlre aryl rlng, lnsLead of [usL
one carbon aLom. 1he greaLly enhances Lhe sLablllLy of Lhe caLlon, glvlng lL sLablllLy greaLer
Lhan a normal secondary caLlon. We can furLher enhance Lhls sLablllLy be placlng an
elecLron donaLlng group ln Lhe orLho or para poslLlons.
CH
2
+
O
C H
3
C
+
CH
2
O
C H
3
C
+
CH
2
O
C H
3
C
+
CH
2
O
C H
3
CH
2
O
+
C H
3

now, Lhe oxygen aLom can also parLlclpaLe ln Lhe resonance sLrucLures, even furLher
enhanclng Lhe sLablllLy of Lhe caLlon.
Crgo I, D|ff|cu|ty:
Þ a g e | 78

lor Lhe same reasons, we can apply Lhls loglc Lo allyl caLlons Loo. Powever, ln Lhls case,
Lhe charge can only be spread over Lhree aLoms. Whlle Lhls ls sLlll more sLable Lhan an
ordlnary prlmary caLlon, lL does noL enhance lL as much as Lhe aryl rlng example above.
CH
2
+
C
+
H
+

Whlle allyl and benzyllc caLlon are Lhe overachlevers of Lhe caLlon famlly, vlnyl caLlon are
Lhe underachlevers. 8ecause Lhe charge ls dlrecLly on Lhe sp
2
carbon ln a vlnyl caLlon,
Lhere are no sLable resonance sLrucLures LhaL can be drawn. lurLher, Lhe double bond
acLually serves Lo desLablllze Lhe caLlon Lo a small exLenL. So alLhough Lhe caLlon below
looks llke a secondary caLlon, lL acLually has sLablllLy llke lL was prlmary.
C
+
H
VinyI
cation

We can now lncorporaLe our newly found relaLlves lnLo Lhe overall famlly sLrucLure and
compare Lhelr sLablllLles Lo each oLher.
CH
2
+
C
+
H
CH
2
+
VinyI
CH
3
+
CH+
CH
2
+
C
+
MethyI Primary Secondary Tertiary BenzyI AIIyI
!"#$%&'(") +&,(-" .,&/(0(,1


1ake nome Message: 8ecause of resonance, a||y| and benzy||c cat|ons are more
stab|e than they appear. V|ny| carbocat|ons are |ess stab|e than they appear.

Þ a g e | 79

#41- 8efore you d|e, you see the [aromat|c] r|ng
8ack ln Lhe days of Lhe early alchemlsLs, compounds were named by Lhelr Lwo mosL
ldenLlfyable properLles: smell and LasLe. Whlle we would flnd Lhls revolLlng Loday, Lhe
names for some of Lhese compounds have sLuck, whlch ls where we geL Lhe name for
aromaLlc compounds.
1here are Lwo crlLerla for a compound Lo be consldered aromaLlc:
1) 1here musL be 4n+2 pl elecLrons [where n ls any lnLeger, lncludlng 0]. 1herefore,
lf a compound has 2, 6, 10 or 14 pl elecLrons, lL has saLlsfled Lhe flrsL requlremenL
of aromaLlclLy.
2) 1he pl elecLrons musL be con[ugaLed ln a conLlguous rlng. 8y Lhls, we mean LhaL
Lhe rlng needs Lo conLlnuously alLernaLe beLween double and slngles bonds
LhroughouL Lhe enLlre rlng. 1hls ls Lhe Lough one Lo deLermlne someLlmes, buL we
wlll help coach you Lhrough Lhls.

8elow are some of Lhe easler examples of aromaLlc and non-aromaLlc compounds:
6 pi eIectrons,
conjugated and contiguous
therefore is AROMATIC
10 pi eIectrons,
conjugated and contiguous
therefore is AROMATIC
4 pi eIectrons,
NOT contiguous
therefore is NOT AROMATIC
8 pi eIectrons,
conjugated and contiguous
therefore is NOT AROMATIC

Whlle Lhese examples are noL Loo hard Lo navlgaLe, Lhere are oLher problems one may run
lnLo LhaL are dlscussed below:
C
+
C
+
6 pi eIectrons,
conjugated and contiguous
therefore is AROMATIC
2 pi eIectrons,
conjugated and contiguous
therefore is AROMATIC
C

6 pi eIectrons,
conjugated and contiguous
therefore is AROMATIC
C
+
4 pi eIectrons,
conjugated and contiguous
therefore is NOT AROMATIC
4 pi eIectrons,
conjugated and contiguous
therefore is NOT AROMATIC
C

6 pi eIectrons,
NOT contiguous
therefore is NOT AROMATIC


1he Lrlck here ls Lhe poslLlve or negaLlve charge has been lncorporaLed lnLo Lhe rlng. 1hese
charges are llke brldges and connecL Lhe double bonds Lo each oLher. Second, negaLlve
Crgo I, D|ff|cu|ty:
Þ a g e | 80

charges wlll supply Lwo pl elecLrons, whereas poslLlve wlll noL supply any. So lf you have
Lhe rlghL number of elecLrons, !"/-'4-5 '6& &%&!'."-* 7."# '6& !6).5&, and Lhey are
conLlguous LhroughouL Lhe enLlre rlng, Lhen lL wlll be aromaLlc.

1he lasL Lrlck ln aromaLlc compound ls nlLrogen and oxygen-conLalnlng heLerocycllc rlngs.
1he lone palrs of Lhese heLeroaLoms may or may noL parLlclpaLe ln Lhe aromaLlclLy,
dependlng on a couple of facLors. 1he flrsL facLor ls wheLher a bond can be sLralned Lo
place Lhe elecLrons ln a poslLlon Lo bond and parLlclpaLe ln aromaLlclLy. ln Lhe case of
pyrldlne, because of Lhe double bond Lo nlLrogen, Lhe lone palr on nlLrogen can never geL
lnLo Lhe proper geomeLry Lo parLlclpaLe ln Lhe pl elecLron sysLem. 1hls ls noL a problem,
because Lhey are noL needed Lo achleve aromaLlclLy. Powever, ln Lhe cases of pyrole and
furan, Lhe lone palrs are needed Lo achleve aromaLlclLy. 1herefore, Lhe bond angles of Lhe
nlLrogen and oxygen are sLralned a llLLle blL ln order Lo bend Lhe lone palr lnLo Lhe correcL
geomeLry Lo parLlclpaLe as pl elecLrons. lnLeresLlngly enough, slnce Lhere are Lwo lone
palrs on oxygen and only one ls needed Lo geL Lo Lhe requlslLe aromaLlc maglc number of 6,
one lone palrs parLlclpaLes ln aromaLlclLy whlle Lhe oLher does noL. Some say LhaL
aromaLlc molecules are llke a snoLLy sofLball Leam ln LhaL once Lhey geL Lhe rlghL number of
players, Lhey don'L accepL any oLhers.

N
N
H
O
pyridine pyroIe furan
aII are aromatic




O




1ake nome Message: 1here are two cr|ter|a for a mo|ecu|e to be aromat|c: 1) the
r|ght # of p| e|ectrons, and 2) that they are |n a cont|guous and con[ugated.
ÞarLlclpaLes ln aromaLlclLy
uoes noL parLlclpaLe ln
aromaLlclLy
:
.
.
.
.

..
Þ a g e | 81

#42: "L[ect! L[ect! L[ect!" Carbony|s w|th an e[ectab|e group are
added to tw|ce.
1hese funcLlonal groups remlnd me of 1983 when Maverlck flew Lhrough Lhe [eL wash and
Coose and he had Lo e[ecL from Lhelr l-14 1omcaL. WhaL does Lhls LlLle mean? WhaL we
are Lrylng Lo say ls LhaL carbonyls can be classlfled Lwo dlfferenL ways: e[ecLable or non-
e[ecLable. WhaL Lhls means ls LhaL someLlme when a carbonyl ls aLLacked by a nucleophlle
Lhe carbonyl wlll e[ecL one of lLs subsLlLuenLs 8&7".& lL reduces Lhe carbonyl Lo an alcohol.
AfLer Lhe group has been e[ecLed, Lhen a second equlvalenL of nucleophlle wlll reduce Lhe
carbonyl Lo alcohol.
ln essence, Lhls means lf a carbonyl has an e[ecLable group on lL, a nucleophlle wlll add
Lwlce Lo LhaL carbonyl. Some examples of e[ecLable and non-e[ecLable sysLems are below:
O
R H
O
R R
O
R OR
O
R CI
"Non-ejectabIe" "EjectabIe"

ln Lerms of synLhesls, we wlll Lhen observe Lhe followlng:
O
R H
O
R R
O
R OR
O
R CI
1.0 equiv
CH
3
MgBr
1.0 equiv
CH
3
MgBr
1.0 equiv
CH
3
MgBr
1.0 equiv
CH
3
MgBr
OH
R CH
3
OH
R R
CH
3
O
R CH
3
O
R CH
3
1.0 equiv
CH
3
MgBr
1.0 equiv
CH
3
MgBr
OH
R CH
3
CH
3
OH
R CH
3
CH
3
"Non-ejectabIe"
"EjectabIe"
Grignard adds
once
Grignard adds
twice

As shown above wlLh Lhe keLone and Lhe aldehyde (whlch have non-e[ecLable
subsLlLuenLs), Lhe Crlgnard reagenL can only add once Lo Lhe carbonyl, glvlng an alcohol as
Lhe producL ln boLh lnsLances. Powever, ln Lhe case of Lhe acld hallde and esLer (whlch
have e[ecLable groups aLLached) Lhe flrsL equlvalenL of Crlgnard klcks off Lhe e[ecLable
Crgo II, D|ff|cu|ty:
Þ a g e | 82

group Lo glve a keLone. 1hls keLone can Lhen be reacLed wlLh anoLher equlvalenL of
Crlgnard reagenL Lo glve Lhe flnal producL, whlch ls a LerLlary alcohol. ln Lhe example
above, we have added Lwo equlvalenLs of Crlgnard Lo Lhe sLarLlng maLerlal ln Lwo dlfferenL
sLeps. Powever, lf Lhe alcohol ls your deslred end-producL, you can do Lhls all ln one sLep
by addlng Lwo or more equlvalenLs of Crlgnard reagenL.
O
R OR
O
R CI
2.1 equiv
CH
3
MgBr
2.1 equiv
CH
3
MgBr
OH
R CH
3
CH
3
OH
R CH
3
CH
3


1ake nome Message: Nuc|eoph||es w||| subst|tute tw|ce at the carbony| |f the
start|ng mater|a| |s an ac|d ha||de or an ester.
Þ a g e | 83

#43- n|nt: "h! !! !" means a rad|ca| |s brew|ng.
1hls one ls preLLy slmple. ºh!" ls Creek for ºllghL and heaL" and slgnlfles LhaL your reacLlon
condlLlons conLaln llghL and heaL added Lo Lhe mlxLure. ln nearly every lnsLance ln
sophomore organlc chemlsLry, Lhls ls Lhe lnlLlaLlon of a radlcal reacLlon.
Br
2
hv
Br
CI CI
2
hv

lL ls lmporLanL Lo bear ln mlnd LhaL h! can slgnlflcanLly alLer Lhe reacLlon LhaL occurs:
Br
2
Br
2
hv
dark
Br
Br
Br

ln Lhe above example, Lhe flrsL reacLlon was Lhe reacLlon of an alkene wlLh molecular
bromlne Lo form Lhe vlclnal dlhallde. ln Lhe second reacLlon, uslng Lhe same reagenLs buL
dlfferenL condlLlons, we undergo a radlcal reacLlon Lo provlde Lhe allyllc bromlde producL.
8emember LhaL Lhe only dlfference ln Lhese reacLlons ls LhaL Lhe Lop reacLlon was done ln
Lhe dark and Lhe boLLom one was done wlLh Lhe addlLlon of llghL and heaL.
Powever, you can also have a radlcal reacLlon wlLhouL ºh!" also, as peroxldes are capable
of lnlLlaLlng a radlcal reacLlon.
HBr
HBr
Peroxides
Br
Br


Crgo I, D|ff|cu|ty:
Þ a g e | 84

1he flrsL reacLlon ls an lonlc reacLlon where Lhe producL ls based on Lhe more sLable
carbocaLlon lnLermedlaLe formed. 1he second reacLlon ls performed wlLh peroxldes and
goes Lhrough a radlcal mechanlsm, where Lhe more sLable radlcal lnLermedlaLe glves Lhe
ma[or producL.
8adlcal lnlLlaLlon ls noL llmlLed Lo ºhv" or peroxldes Lhough. 8emember LhaL heaL or
chemlcal lnlLlaLors (such as Al8n) can all be used Lo lnlLlaLe a radlcal reacLlon:
CI CI
2
100C
HBr
HOOH
Br


1ake nome Message: If you see "hv", th|nk rad|ca| mechan|sm

Þ a g e | 8S

#44- 1-buty| groups on cyc|ohexane means no r|ng f||ps..k|nda.
We all know LhaL cyclohexane undergoes rlng fllps beLween chalr conformaLlons. 1haL ls
Lhe easy parL. lL geLs a llLLle harder when Lalklng abouL subsLlLuLed cyclohexanes. 1he
amounL of rlng fllpplng depends on whaL your subsLlLuenL ls.
F CH
3
F C H
3
% EquatoriaI 60% 95% 97% >99.99%
AxiaI
EquatoriaI

Whlle Lhe 1,3 dlaxlal lnLeracLlons make Lhe equaLorlal form more favorable, Lhe amounL of
equaLorlal form ln soluLlon wlll depend on whaL Lhe subsLlLuenL ls. As you can see above,
aL any one lnsLanL, 99.99• of L-buLyl cyclohexane exlsLs ln Lhe equaLorlal form. uoes Lhls
mean LhaL L-buLyl cyclohexane ls ºlocked" ln Lhe equaLorlal form? ?es and no.
Many professors wlll Lell you LhaL L-buLyl cyclohexane ls locked ln Lhe equaLorlal form and
ls never observed ln Lhe axlal form. lf Lhls ls whaL your professor wanLs you Lo know, Lhen
for your purposes, Lhere ls no axlal L-buLyl cyclohexane. Powever, ln reallLy, axlal L-buLyl
cyclohexane does exlsL ln soluLlon ln mlnuLe quanLlLles. We also know LhaL L2 ellmlnaLlon
cannoL proceed unless Lhe leavlng group ls anLl-perlplanar Lo Lhe µ-hydrogen. Powever,
Lrans-L-buLyl bromocyclohexane (where Lhe leavlng group ls ºlocked" ln a poslLlon LhaL ls
noL anLl-perlplanar) wlll undergo L2 ellmlnaLlon, albelL aL a very slow raLe.
Br
Br
H
H
x500 sIower
trans
cis
FAST


Crgo I, D|ff|cu|ty:
Þ a g e | 86

1he facL LhaL Lhe reacLlon wlll proceed aL all means LhaL rlng fllpplng lL musL occurrlng,
even Lhough lL ls ºlocked" wlLh Lhe L-buLyl group. 1herefore, L-buLyl cyclohexane WlLL rlng
fllp, [usL aL a very, very slow raLe. 1hls can also be seen ln nM8 sLudles.
Powever, an even beLLer example of Lhls ls Lrans-decalln. 8ecause of Lhe geomeLry of Lhe
Lwo fused rlngs, Lrans decalln wlll -&3&. rlng fllp. 1herefore, you musL be very careful lf you
see Lrans decalln ln your exam. usually lL ls only Lhere Lo lllusLraLe an L2 problem wlLh no
rlng fllp.
H
H
trans decaIin

1he problem below should lllusLraLe Lhls concepL well. Pow many L2 producLs are
avallable from Lhe reacLlon below?
H
H
Br
H
Br
H
NaOH

AL flrsL glance, one mlghL Lhlnk Lhere are Lhree posslble L2 producLs, buL once Lhe sLrucLure
ls converLed lnLo lLs chalr form, lL becomes clear LhaL Lhere are no anLl-perlplanar
hydrogens and Lherefore no posslble L2 producLs.
H
H
H
H
Br
Br


1ake nome Message: If your professor says t-buty| cyc|ohexane NLVLk r|ng f||ps,
then |t NLVLk r|ng f||ps. Ctherw|se, rea||ze that |t w||| r|ng f||p at a very, very s|ow
rate. 1rans deca||n NLVLk r|ng f||ps.

Þ a g e | 87

#4S- L|ke Ierry Lew|s ask|ng for money, Lew|s ac|ds are a|ways ask|ng
for e|ectron dens|ty.
Lewls aclds are llke llLLle burglars. 1hey are always Lrylng Lo swlpe someone else's elecLron
denslLy because Lhey are lacklng lL Lhemselves. Crganlc chemlsLs use Lhls Lo Lhelr
advanLage, ln LhaL Lewls aclds can be used Lo make elecLrophlles even more elecLrophlllc.
8ecause Lewls aclds are elecLron-deflclenL, Lhey wlll seek ouL elecLron-rlch aLoms. 1he
elecLron-rlch aLom (Lhe oxygen aLom below) wlll Lhen sLeal denslLy from Lhe closesL aLom
Lo lL (Lhe carbon aLom), whlch resulLs ln Lhe carbon becomlng more elecLrophlllc. 1hls ls
very much llke ºrobblng ÞeLer Lo Þay Þaul" and wlll make Lhe carbonyl carbon more prone
Lo aLLack by a nucleophlle.
O
Somewhat eIectrophiIic carbon
O
AICI
3
Much more eIectrophiIic carbon
"# "# "# "#
"# "# "# "#
"$ "$ "$ "$

?ou have seen numerous examples of Lhls ln your organlc chemlsLry class, as shown below:
CI
2
AICI
3
CI
CI CI
AICI
3
"# "# "# "#
"$ "$ "$ "$
AICI
3
O
CI
O
AICI
3
CI
O
"# "# "# "#
"$ "$ "$ "$
Aromatic HaIogenation
FreideI-Craft AcyIation
AICI
3
CH
3
FreideI-Craft AkyIation
CH
3
CI
AICI
3
C H
3
CI
"# "# "# "#
Reaction
LiAIH
4
Reductions
O
H
OH
LiAIH
4
AIH
3
O
H R
"# "# "# "#
H
ExampIe Lewis Acid CompIex

Crgo II, D|ff|cu|ty:
Þ a g e | 88

Cne way Lo Lhlnk abouL Lhls ls ln Lerms of bullles. LeL's Lake Lhe LlAlP
4
example. 1he Lewls
acld ls Lhe blggesL bully and sLeals lunch money from Lhe oxygen. 1he oxygen ls a blL of a
bully hlmself, Lhough. 1he oxygen Lhen sLeals Lhe same amounL of lunch money from Lhe
carbon. Carbon ls noL a bully aL all, buL ls acLually a very sweeL llLLle boy. Carbon doesn'L
sLeal from anyone and ls [usL lefL wlLh no lunch money.

1ake nome Message: Lew|s ac|ds stea| e|ectron dens|ty to make some atoms
more e|ectroph|||c. If you see a Lew|s ac|d |n a m|xture, there |s probab|e and
attack at the e|ectroph||e.
Þ a g e | 89

#46- n
2
SC
4
and nNC
3
: 1he good-cop]bad-cop of n|trat|ons.
1hls one mlghL be a slmple one for mosL of you, buL many of you wlll see Lhls quesLlon on
an exam somewhere, so lL ls worLh dlscusslng one more Llme. P
2
SC
4
and PnC
3
comblne
LogeLher ln Lhe followlng way Lo form ºnC
2
+
", Lhe nlLronlum lon, a hlghly elecLrophlllc
specles capable of nlLraLlng cerLaln nucleophlles.
N
+
O
O OH
+
H
2
SO
4 N
+
O
O OH
2
+
+
HSO
4
-
O N
+
O
+
OH
2 +
HSO
4
-
nitronium ion

8ecause sulfurlc acld ls a sLronger acld Lhan nlLrlc (P
2
SC
4
pk
a
of -4 vs. PnC
3
pk
a
-2), Lhe
sulfurlc wlll proLon Lhe nlLrlc acld. Cnce proLonaLed, Lhe nlLrlc acld has a greaL leavlng
group aLLached Lo lL (P
2
C
+
). 1he waLer ls now capable of leavlng, whlch generaLes Lhe
ºnC
2
+
", whlch wlll be Lhe nlLraLlng agenL.
1he mosL common example of Lhls you wlll see ls ln elecLrophlllc aromaLlc subsLlLuLlon
(LAS) reacLlons:
HNO
3
H
2
SO
4
NO
2

Powever, Lhere are oLher Llmes when Lhls reagenL can be used.
OH
HNO
3
H
2
SO
4
ONO
2

8emember LhaL ulLlmaLely nlLraLlon ls Lhe process of a nucleophlle aLLacklng Lhe nlLronlum
lon and LhaL many non-aromaLlc nucleophlles can also do Lhls.

1ake nome Message: nNC
3
]n
2
SC
4
|s a n|trat|on react|on.

Crgo I, D|ff|cu|ty:
Þ a g e | 90

#47- 1he Incred|b|e 8u|k: 8u|ky bases.
1here are a number of bases LhaL, when speaklng ln a sLerlc sense, are very, very large.
1hese º8aslc 8lg 8oys" are Lhe baddesL bullles on Lhe block. 8ecause of Lhelr slze and bulk,
Lhey cannoL reacL aL mosL elecLrophlllc slLes on anoLher molecule. 1hls means LhaL Lhey
can only acL as a base, because Lhey are Loo large Lo acL as a nucleophlle.
8elow are Lhe four mosL common bulky bases:
O
K
+
Potassium
tert-butoxide
N
Li
+
Lithium Di-isopropyI
amide (LDA)
N
2,6 DimethyI
Pyridine
N
TriethyIamine

ln subsLlLuLlon/ellmlnaLlon problems, ellmlnaLlon wlll always be favored over subsLlLuLlon
when uslng Lhese bases, as lL ls lmposslble for Lhem Lo acL as a nucleophlle.
CI
O- K+
ONLY E2, NO SN2


1ake nome Message: 8u|ky bases cannot act as a nuc|eoph||e, LVLk!


Crgo I, D|ff|cu|ty:
Þ a g e | 91

#48 - noffman vs. 2a|tsev: 1he e||m|nat|on.
lL ls Lhe maLch LhaL we have been walLlng for Lhe ulLlmaLe, exLreme ellmlnaLlon beLween
Poffman and ZalLsev. Pere ls how we break down Lhe flghL:

noffman
8orn: !uly 18, 1937
WelghL: 8ulky
8ule: ÞroLon absLracLlon occurs Lo glve
less subsLlLuLed alkene

2a|tzev
8orn: 1841
WelghL: Slender
8ule: ÞroLon absLracLlon Lo glve
more subsLlLuLed alkene
1here are generally Lwo facLors LhaL wlll favor one flghLer's producL over Lhe oLher. lacLor
one: 8ulklness of Lhe base.
Br
O
+
Br
O
+
Hoffmann
Product
Zaitsev
Product
71% 29%
28% 72%

1lp #47 provlded a summary of whaL ls a bulky base and whaL ls noL. As you can see, Lhe
producL obLalned ls greaLly affecLed by whlch base you use. 1he general rule ls LhaL bulky
bases wlll glve a Poffman producL because Lhe base ls Loo large and cannoL easlly reach
any proLon LhaL ls noL near Lhe edge.
+
X
NaOMe
X = CI
X = I
X = F
X = OTs
19%
33%
69%
83%
81%
67%
21%
17%
Hoffman Zaitzev

Crgo I, D|ff|cu|ty:
Þ a g e | 92

Leavlng group ls Lhe second deLermlnlng facLor ln Lhese ellmlnaLlons. 1he above reacLlons
are all conducLed uslng sodlum meLhoxlde, a very -"-964-+&.&+ base. Whlle lL's no
surprlse LhaL lodldes and chlorldes favor ZalLzev ellmlnaLlon, lL should be somewhaL
surprlslng LhaL LosylaLes favor Poffman ellmlnaLlon and more surprlslng LhaL fluorldes are
leavlng groups aL all. ln facL, LosylaLes are large and bulky and block Lhe place where Lhe
base would reacL Lo glve Lhe ZalLzev producL. lluorldes are noL large, buL are such poor
leavlng groups LhaL Lhey do noL allow Lhe sLandard L2 ellmlnaLlon Lo proceed and are
acLually LhoughL Lo proceed Lhrough anoLher mechanlsm called L1cb. uon'L worry, mosL
professors wlll noL requlre you Lo know Lhe L1cb mechanlsm, whlch ls LhoughL Lo proceed
Lhrough a carbanlon lnLermedlaLe.

1ake nome Message: 8u|ky bases, "crazy" |eav|ng groups, or un|mo|ecu|ar
e||m|nat|ons most|y |ead to noffman products. kegu|ar bases, norma| |eav|ng
groups, and most b|-mo|ecu|ar e||m|nat|ons (|.e. L2) g|ve 2a|tzev products.

Þ a g e | 93

#49- Dude, where's my carbocat|on?
1here are few hard and fasL rules ln organlc chemlsLry, buL here ls one of Lhem: lf a
carbocaLlon can rearrange, lL wlll. CarbocaLlon sLablllLy ls: 3º > 2º > 1º >>meLhyl.
1herefore, lf a 2º caLlon can rearrange Lo a more sLable 3º caLlon, lL wlll.
Br
O
H H
OH

+
+
carbocation rearrangement

A beLLer quesLlon Lo address here Lhough ls how do rearrangemenLs occur. 1here are
Lhree mechanlsms by whlch a carbocaLlon can rearrange from less sLable Lo a more sLable.
1. 1,2 Pydrlde ShlfL: 1hls ls where P
-
shlfLs from an ad[acenL carbon Lo Lhe
carbocaLlon. 1hls leaves a º+" charge on Lhe carbon whlch losL Lhe P
-
and
compleLes Lhe hydrlde shlfL.

a.
H
H
CH
3
H
H
+ rearrangement
H
CH
3
H
H
H
+
H
Less StabIe More StabIe


2. 1,2 MeLhlde shlfL: 1he process ls Lhe same as wlLh hydrlde shlfL, excepL ln Lhls case
lL ls CP
3
-
shlfLlng lnsLead of P. 1hls ls noL as preferred as a hydrlde shlfL, buL can
sLlll occur.

a.
CH
3
CH
3
CH
3
H
C H
3
+ rearrangement
H
CH
3
C H
3
CH
3
C H
3
+
CH
3
-
Less StabIe More StabIe


3. 1,2 Þhenyl shlfL: 8are, buL sLlll posslble are phenyl shlfLs, where an ad[acenL phenyl
group shlfL Lo form a more sLable carbocaLlon. As wlLh all carbocaLlon formaLlon,
buL especlally wlLh phenyl shlfLs, hlghly lonlzlng solvenLs are necessary for
carbocaLlon formaLlon.
Crgo I, D|ff|cu|ty:
Þ a g e | 94

#S0- Iree rad|ca| ha|ogenat|on: 1he mo|ecu|ar hand|e.
LeL's face lL, Lhere ls noL much you can do wlLh alkanes. 1hey are decenL nonpolar
solvenLs, Lhey power our Suvs/hybrlds, and fuel our llghLers. Alkanes are generally very
unreacLlve because Lhey are only composed of C-C and C-P slngle bonds, nelLher of whlch
ls very reacLlve. 1he lssue for you as a sophomore organlc chemlsL ls LhaL many of your
professors wlll asslgn problems where you can only use a sLralghL chaln alkane as Lhe
sLarLlng maLerlal. Slnce Lhe C-P bond ls so unreacLlve, where do you sLarL?

1he besL way Lo sLarL one of Lhese problems ls Lo puL a funcLlonal group on your alkane
LhaL ls reacLlve. Slnce our cholces are llmlLed, we recommend sLarLlng wlLh free radlcal
halogenaLlon. We belleve LhaL Lhe besL way Lo lmplemenL Lhe free radlcal halogenaLlon
reacLlon ls Lo use a sLarLlng maLerlal LhaL ls symmeLrlc. 1hls wlll provlde a slngle producL
and avold mulLlple producLs, whlch many professors wlll dock polnLs over. Pence, Lhe
sLarLlng maLerlals whlch wlll work Lhe besL are meLhane, eLhane and all cycloalkanes.
CH
4
H
3
CCH
3
Br
2
hv
Br
2
hv
Br
2
hv
Br
2
hv
Br
Br
Br
CH
3
Br

8romlnaLlon also provldes you an addlLlon advanLage, as bromlne ls less reacLlve Lhan
chlorlne. 1hls means lL ls more selecLlve for Lhe more subsLlLuLed carbon, whlch can
supporL Lhe radlcal lnLermedlaLe more effecLlvely. 1hls allows Lhe below reacLlons Lo Lake
place ln hlgh yleld.

Br
2
hv
Br
97%
Br
2
hv
Br
98%
Br
2
hv
Br
97%

Crgo I, D|ff|cu|ty:
Þ a g e | 9S


PalogenaLlon provldes a gaLeway lnLo many, many oLher LransformaLlon, lncludlng
subsLlLuLlon, ellmlnaLlon, oxldaLlon, and organomeLalllc formaLlon. lf one of Lhese (or
anoLher) LransformaLlon of Lhe halogen ls planned ln subsequenL sLeps and you don'L need
a speclflc halogen ln Lhe producL, we recommend uslng Lhe bromlnaLlon reacLlon, as lL ls
more selecLlve and can be used wlLh greaLer flexlblllLy Lhan chlorlnaLlon.

1ake nome Message: know the a|kanes wh|ch w||| g|ve you one product v|a free
rad|ca| ha|ogenat|on, espec|a||y brom|nat|ons.


Þ a g e | 96

#S1- My 1hree keduct|ons: keduct|on methods for a|kynes
As we learned above, alkynes are a greaL way Lo form carbon-carbon bonds. Cnce you
have performed your alkyne-carbon coupllng reacLlon, whaL do you do wlLh your Lrlple
bond lf lL ls noL ln your flnal producL? ?ou have Lhree alLernaLlves:

! ÞarLlal reducLlon Lo Lhe Lrans alkene: uslng sodlum and ammonla, you can reduce
an alkyne Lo Lhe Lrans alkene. 1he reacLlon does noL work on alkenes, only
alkynes, whlch ls why Lhe reacLlon does noL conLlnue Lhe reducLlon Lo Lhe alkane.
1he mechanlsm of Lhe reacLlon ls a slngle-elecLron Lransfer.

Na / NH
3


! ÞarLlal reducLlon Lo Lhe cls alkene: uslng ºLlndlar's caLalysL", you can selecLlvely
reduce Lhe alkyne Lo Lhe cls alkene. Llndlar's caLalysL ls Þb-CaCC
3
-ÞbC wlLh P
2
,
however mosL professors wlll leL you geL away wlLh [usL wrlLlng ºLlndlar's caLalysL"
or ºLlndlar PydrogenaLlon"

Pb-CaCO
3
-PbO /H
2
"LindIar"


! lull reducLlon Lo Lhe alkane: 1hls ls Lhe nuclear opLlon. 1hls ls also Lhe
hydrogenaLlon LhaL mosL of you are used Lo seelng. lL ls your sLandard
hydrogenaLlon uslng P
2
/Þd-C. 1hls wlll Lransform Lhe alkyne Lo Lhe fully-reduced
alkane. 1hls ls a greaL way for maklng carbon-carbon bonds when you do noL wanL
Lo have any Lrace of Lhe alkyne ln your flnal producL.
H
2
/ Pd-C



1ake nome Message: A|kynes are a great way to form carbon-carbon bonds.
1hey can then be reduced three d|fferent ways |f you do not need a tr|p|e bond
|ater.


Crgo II, D|ff|cu|ty:
Þ a g e | 97

#S2- Is a ha|ogen squatt|ng on your mo|ecu|e? kemov|ng the
unwanted ha|ogen.

!usL llke ln a laLe nlghL lnfomerclal, where you mlghL wanL Lo remove unwanLed halr ln your
nose or on your upper llp, someLlme you mlghL wanL Lo remove LhaL unwanLed halogen
from your molecule.

ln Lhe lasL secLlon, we dlscussed addlng a halogen Lo your alkane Lo glve a ºmolecular
handle" whlch ls a place for your reacLlons Lo geL sLarLed. 8uL whaL happens lf you geL Lo a
parL of your synLheLlc sequence and have an exLra halogen? Pow would you geL rld of lL?
Can you [usL make Lhem dlsappear? 1he answer ls yes, Lhrough Lhe maglc of Lhe Crlgnard
reacLlon.

Br
1) Mg
2) water
+
MgBrOH


1he reacLlon proceeds by formaLlon of Lhe Crlgnard reagenL, whlch Lhen aLLacks waLer and
absLracLs a proLon, leavlng Mg8rCP salL as a byproducL. 1he reacLlon ls hlghly exoLhermlc,
so care should be Laken when conducLlng Lhls reacLlon ln Lhe laboraLory.

Whlle Lhls ls a very slmple example of halogen removal, Lhls meLhod can be applled Lo a
number of slLuaLlons where lL ls [usL Llme Lo have LhaL halogen go away.

As shown above, Lhls reacLlon ls used Lo lnLenLlonally remove a halogen. lor Lhe same
reason, when you are ln your lab secLlon formlng a Crlgnard reagenL, lL ls lmporLanL Lo
keep Lhe reacLlon mlxLure free of molsLure. Any waLer ln your reacLlon wlll desLroy your
Crlgnard before lL can be used.

1ake nome Message: kemove the unwanted ha|ogen w|th magnes|um and water.



Crgo I, D|ff|cu|ty:
Þ a g e | 98

#S3- ¥ou don't want a "D" on your transcr|pt, but you m|ght want one
on your mo|ecu|e.
Whenever scared organlc chemlsLry sLudenLs hear abouL a ºu", Lhey lmmedlaLely run for
Lhe hllls or curl up ln Lhe feLal poslLlon and hope lL wlll all work lLself ouL on lLs own. 8uL ln
organlc chemlsLry, a ºu" can be a wonderful Lhlng. We look aL ºu's" as helper aLoms
someLlmes. ºu" ls obvlously deuLerlum, whlch ls a hydrogen aLom wlLh one more neuLron
ln lLs nucleus. 1hlnk of deuLerlum as a faL hydrogen. And because lL ls faL wlLh Lhe exLra
neuLron, lL can be deLecLed ln nM8 experlmenLs and can be used Lo deLermlne Lhe
mechanlsm of some reacLlons. Whlle Lhls may noL be fasclnaLlng Lo you, whaL should caLch
your lnLeresL ls how Lo form Lhese.
1he reacLlon lLself ls easy and ls very slmllar Lo 1lp #32. All we are golng Lo do ls place a
halogen where we wanL our deuLerlum Lo go, Lhen reacL lL wlLh Mg/u
2
C. u
2
C ls
deuLerlum oxlde, aka ºheavy waLer", and wlll resulL ln a neL replacemenL of Lhe halogen
wlLh deuLerlum.
CH
4
Br
2
hv
Br
2
hv
Br
CH
3
Br
Br
2
hv
Br
HCI
CI HOOH
D
2
O
Mg
D
2
O
Mg
D
2
O
Mg
D
2
O
Mg
D
CH
3
D
D
D

Warnlng: When conducLlng Lhese reacLlons, be careful of chlral halldes. Chlral halldes do
noL necessarlly form chlral Crlgnard reagenLs and Lherefore can lead Lo racemlzed
producLs. Cenerally, when Lhe reacLlons are performed wlLh powdered Mg, Lhe resulLlng
producL afLer LreaLmenL wlLh u
2
C ls mosLly racemlc. Whlle research has shown LhaL uslng
oLher forms of Mg (l.e. 8leke Magneslum) can glve chlral deuLeraLed producLs, lL ls noL a
glven LhaL your professor wlll recognlze Lhls and lL ls beLLer Lo sLay away from Lhls reacLlon
lf Lhe producL ls a chlral deuLerlde.

1ake nome Message: If you are asked to create a mo|ecu|e w|th a "D" somewhere
|n |t, odds are |t came from the ha|ogen.
Crgo I, D|ff|cu|ty:
Þ a g e | 99

#S4- D|e|s-A|der Þart 2: keg|ochem|stry and stereochem|stry

ln 1lp #30, we had a brlef dlscusslon abouL Lhe ulels-Alder reacLlon. 1he Lake home
message from Lhls was LhaL lf you have a cyclohexane or cyclohexene rlng, lL probably
came from a ulels-Alder reacLlon. 1lp #30 had Lhe baslcs of Lhe reacLlon, now we wlll
expand upon Lhls. llrsL, lf you have a dl-subsLlLuLed dleneophlle, lL ls lmporLanL Lo noLe
wheLher lL ls cls or Lrans, as Lhe producLs from boLh wlll dlffer. 1he rule of Lhumb ls LhaL lf
you have a cls dleneophlle, you wlll have a cls producL aL Lhose subsLlLuenLs. Conversely, a
Lrans dleneophlle wlll glve you a Lrans producL, as shown below.
+
CN
CN CN
CN
+
CN
NC CN
CN

lurLher, lf Lhe dlene ls noL symmeLrlc, Lhere ls Lhe chance for Lwo dlfferenL reglochemlcal
producLs, as shown below:
OMe
+
O
H
O
H
OMe
+
O
H
OMe
Major product

Why ls Lhe ma[or producL Lhe ºorLho" lsomer shown above? [noLe: We are calllng Lhls Lhe
ºorLho" lsomer because Lhe subsLlLuenLs are nexL Lo each oLher. 1o be proper, orLho
should only be used when speaklng abouL aromaLlc rlngs, buL we are golng Lo cheaL a llLLle
on LhaL nomenclaLure here Lo make lL easler Lo undersLand.] 1he answer lles ln resonance
sLrucLures. lf we were Lo draw a resonance sLrucLure we would see LhaL Lhe dlene has an
elecLron donaLlng group aL Lhe Lop, whlch places a parLlal negaLlve charge on Lhe furLhesL
carbon. We can also draw a resonance sLrucLure for Lhe dleneophlle, whlch places a parLlal
poslLlve charge on Lhe furLhesL carbon. 8ecause we are cerLaln LhaL opposlLes aLLracL, lf
we were Lo maLch Lhe poslLlve and negaLlve porLlons of Lhe reacLanLs, we can easlly see
why Lhe ma[or producL ls Lhe ºorLho" producL.
Crgo II, D|ff|cu|ty:
Þ a g e | 100

C
O
+
CH
3
C
+
O
H
Resonance
of diene
Resonance
of dieneophiIe
O
H
OMe
Major product
Match the C+ to C-

8y Lhe same Loken, we can look aL anoLher ulels-Alder reacLlon where Lhe elecLron
donaLlng group on Lhe lnLerlor parL of Lhe dlene. ln Lhls reacLlon, Lhe ma[or producL ls Lhe
ºpara" producL.
MeO
O
H
MeO
MeO
O
H
O
H
+
+
Major product

AfLer drawlng our resonance sLrucLures agaln, we can see LhaL Lhe same loglc hold Lrue for
why we obLaln Lhls reglochemlsLry ln Lhe producL.
C
C
+
O
H
O
+
C H
3
+
Resonance
of diene
Resonance
of dieneophiIe
O
H
MeO
Major product
Match the C+ to C-

llnally, we have Lhe endo-exo lssue. Llke Lhe Þepsl Challenge, boLh Lhe endo and Lhe exo
LranslLlon sLaLes look good, buL only one can be Lhe wlnner. ln almosL every ulels-Alder
reacLlon you wlll see, Lhe endo producL ls Lhe ma[or producL of Lhe reacLlon.
+
CN
CN
+
CN
Endo isomer
Major product
Exo isomer
Minor product

Þ a g e | 101

#SS- D|e|s-A|der Þart 3: What makes a good D|e|s-A|der react|on?

Whlle lL's easler Lo geL Lhe ulels-Alder reacLlon Lo work Lhan lL ls a 1eamsLer, Lhere are
condlLlons LhaL are necessary or can be opLlmlzed ln order Lo achleve Lhe besL resulLs. 1he
flrsL of Lhese condlLlons ls LhaL Lhe dlene #/*' be able Lo adopL an ºs-cls" conformaLlon
easlly. 1he s-cls conformaLlon ls where Lhe alkenes are on Lhe same slde of Lhe cenLral
*4-5%& bond ln Lhe dlene. lf Lhe dlene ls ln Lhe s-Lrans poslLlon, Lhe ulels-Alder reacLlon wlll
noL work.
CH
3
CH
3
CH
3
C H
3
s-cis conformation
high steric strain
between methyIs
s-trans conformation
no steric strain
however cannot undergo
DieIs-AIder reaction
a rigid diene that
cannot adopt s-cis
conformation = NO DieIs AIder

Second ls a rule LhaL ls more common. 1he dlene should have elecLron donaLlng groups on
lL and Lhe dleneophlle should have elecLron wlLhdrawlng groups on lL. lor a llsL of
common donaLlng and wlLhdrawlng groups, see Llp #32.
1o expand upon Lhls, remember LhaL dlenes and dleneophlles can come ln all shapes and
slzes. uo noL forgeL LhaL you can have a ulels-Alder reacLlon wlLh someLhlng oLher Lhan
Lhe bland, plaln dlene/dleneophlles LhaL you may be used Lo. 8elow ls a charL of some of
Lhe oLher ones LhaL can work:
COOMe
COOMe
O
O
O
O
O
Dienes
DieneophiIes

Crgo II, D|ff|cu|ty:
Þ a g e | 102


LasL, Lhe dlene musL noL be Loo sLerlcally hlndered. Þlaclng bulky alkyl groups on Lhe ends
of Lhe dlene are a sure way Lo sLop a ulels-Alder reacLlon from worklng.
+
CN
CN
CN
CN
Poor YieId


Þ a g e | 103

#S6- It's an urban |egend that S
N
1 react|ons g|ve 3456-787-/ racem|c
products.
We have all heard Lhe sLorles ln our day:
ºAfLer sLumbllng ln drunk Lhe lasL nlghL, Lhe sLarLled co-ed awoke Lhe nexL mornlng Lo flnd
a dead roommaLe and wrlLlng on Lhe mlrror LhaL sald '?ou are lucky you dld noL Lurn on Lhe
llghLs'."
º..Lhe pollce called back Lo say 'We have Lraced Lhe call and lL ls comlng from lnslde Lhe
house. CeL ouL now!' 8uL lL was Loo laLe for Lhe porLly babyslLLer and her sLruggllng arLlsL
hlpple boyfrlend, Lhe klller had already found Lhem."
º..Lhe young, soclally-consclous professlonal sLopped drlvlng hls Suv, buL lL was Loo laLe.
Clobal warmlng had already kllled everyone he knew and loved."
And whlle we know beLLer deep down lnslde, you sLlll wonder someLlmes abouL Lhese
urban legends. Well, Loday we wlll de-bunk one of Lhese myLhs: S
n
1 reacLlons glve
compleLely racemlc producLs.
S
n
1 reacLlons sLarL harmlessly enough. We all know LhaL Lhe leavlng group breaks off of
Lhe sLarlng maLerlal, glvlng a carbocaLlon lnLermedlaLe whlch ls Lhen aLLacked by Lhe
nucleophlle Lo glve Lhe flnal producL.

Br
OH
OCH
2
CH
3
C
+
Intermediate

upon furLher examlnaLlon of Lhe mechanlsm, we see LhaL Lhe carbocaLlon lnLermedlaLe
has a Lrlgonal planar geomeLry. 1hls allows Lhe nucleophlle Lo aLLack from elLher face and
glve whaL we would belleve ls a compleLely racemlc producL. 1hls ls noL Lhe enLlre sLory.
C
+
C H
3
C H
3
CH
3
Top Attack
Bottom Attack

Crgo I, D|ff|cu|ty:
Þ a g e | 104

We know LhaL Lhe formaLlon of Lhe carbocaLlon ls a reverslble sLep ln S
n
1 reacLlons, whlch
means LhaL Lhe leavlng group can come on and off of Lhe sLarLlng maLerlal. 8uL whaL
happens when Lhe leavlng group ls off, buL noL very far away? Could Lhe leavlng group
parLlally block one face of Lhe sLarLlng maLerlal? 1he answer Lo LhaL quesLlon ls yes. 1o
demonsLraLe Lhls, we wlll use a chlral sLarLlng maLerlal Lo form our caLlon.

C
+
CH
3
CH
2
CH
2
CH
3
CH
2
CH
3
Top Attack
Bottom Attack
Br
PartiaIIy bIocked by Br

1he leavlng group usually remalns close Lo Lhe sLarLlng maLerlal, only flnally deparLlng once
Lhe reacLlon ls compleLed. 1hls parLlally/Lemporarlly blocks one of Lhe faces of Lhe
carbocaLlon, Lhe boLLom face ln Lhls example. 1hls leads Lo a sllghL preference for Lhe
producL wlLh lnverLed sLereochemlsLry over Lhe producL wlLh reLenLlon of sLereochemlsLry.
ChemlsLs refer Lo Lhls phenomenon as solvenL-separaLed lon palrs. Whlle lL ls very
lmporLanL Lo recognlze Lhe racemlzaLlon of Lhe sLarLlng maLerlal :1;< occur ln S
n
1
reacLlons, ln reallLy lL ls noL full and compleLe racemlzaLlon. 1yplcally, Lhere ls a 3-10•
preference for Lhe lnverLed producL, meanlng LhaL Lhe sLarLlng maLerlal ls approxlmaLely
83-90• racemlzed. 8elow are some examples:
CH
3
(CH
2
)
5
Br
H
C H
3 water
ethanoI
CH
3
(CH
2
)
5
O H
H
CH
3
CH
3
(CH
2
)
5
OH
H
C H
3
+
55% 45%


1ake nome Message: S
N
1 react|ons |eave you w|th a MCS1L¥ racem|zed product.


Þ a g e | 10S

#S7- "What do you 'Am|ne' you're gett|ng r|d of me?"--now to
e||m|nate an am|ne.
1hroughouL organlc chemlsLry you have been Lold LhaL some aLoms/groups are good
leavlng groups (See Llp #18) and some are noL. normally, you would noL conslder an amlne
Lo be a good leavlng group. Powever, Lhls ls noL mosL clrcumsLances. LnLer Lhe Cope
LllmlnaLlon. ln Lhls reacLlon, Lhe amlne ls oxldlzed uslng hydrogen peroxlde, Lhen
ellmlnaLed Lo Lhe alkene wlLh heaL.
C H
3
CH
3
H N
Ph Ph
C H
3
CH
3
H N
+
Ph Ph
-O
CH
3
C H
3
Ph Ph
HOOH
HEAT!

C H
3
H N
Ph CH
3
Ph
C H
3
H N
+
Ph CH
3
-O
Ph
C H
3
CH
3
Ph
Ph HOOH
HEAT!

lL ls lmporLanL Lo noLe LhaL Lhe sLereochemlsLry of Lhe alkene ls deLermlned by Lhe
sLereochemlsLry aL Lhe chlral cenLers of Lhe sLarLlng maLerlal. lurLher, Lhere also musL be a
free 34!4-)% hydrogen whlch can parLlclpaLe ln Lhe ellmlnaLlon.
AnoLher example of where amlnes can be ellmlnaLed ls seen ln Lhe Poffman ellmlnaLlon,
shown below:
NH
2
3 CH
3
I
NaOH
N
+
C H
3
CH
3
CH
3
I
1) AgOH
2) Heat!

1he reacLlon beglns wlLh exhausLlve meLhylaLlon Lo glve Lhe quaLernary amlne. 1hls can
Lhen be ellmlnaLed uslng AgCP (used Lo replace l
-
wlLh CP
-
), and heaL Lo glve Lhe alkene.
1hls dlsplays Lwo very lmporLanL feaLures of boLh of Lhese reacLlons. llrsL, because amlnes
are so nucleophlllc, meLhylaLlng four Llmes Lo geL Lhe quaLernary amlne ls an easy reacLlon
Lo accompllsh. Second, because Lhe Poffman ellmlnaLlon operaLes under Poffman's rule
(see 1lp #48), whlch sLaLes LhaL sLerlcs have Lhe greaLesL lnfluence on Lhe reacLlon,
hydrogen loss wlll come from Lhe leasL subsLlLuLed carbon. 1hls resulLs ln Lhe less
subsLlLuLed alkene as Lhe ma[or producL.
1ake nome Message: Am|nes can be turned |nto |eav|ng groups, and e||m|nated
us|ng the noffman or Cope e||m|nat|on
Crgo II, D|ff|cu|ty:
Þ a g e | 106

#S8- "Why D|dn't ¥ou Say Were Send|n' the Wo|f?"¬1he Wo|ff-
k|shner reduct|on

1he mosL llkely place for Lhls reacLlon ls under Lhe ºmaklng an unwanLed funcLlonal group
dlsappear" secLlon. 1he Wolff-klshner 8educLlon, [usL llke Lhe Clemmensen 8educLlon,
removes carbonyl groups and converLs Lhem Lo Lhe correspondlng CP
2
. 1he slmllarlLy
beLween Lhe Lwo of Lhese reacLlons ls LhaL boLh wlll only work on a keLone and aldehyde,
noL carboxyllc aclds. 1he dlfference ls LhaL Wolff-klshner ls performed under baslc
condlLlons, whlle Lhe Clemmensen ls performed under acldlc condlLlons. Some examples of
boLh are shown below:

O
H
2
NNH
2
KOH
O
Zn(Hg)
HCI
O
H
H
2
NNH
2
KOH
WoIf-Kishner
CIemmensen
WoIf-Kishner


1he Wolff-klshner 8educLlon (Lhe flrsL and Lhlrd reacLlons above) ls accompllshed uslng
hydrazlne, P
2
nnP
2
, and a sLrong aqueous base, whlch ls usually kCP. [WAkNING:
Pydrazlne ls Lhe chlef componenL of space shuLLle fuel and ls 6456%( Loxlc.] 1he
Clemmensen 8educLlon ls conducLed uslng a zlnc-mercury amalgam, and a sLrong acld,
usually PCl. ln mosL cases, Lhe Lwo reacLlons can be subsLlLuLed for each oLher. Powever,
be careful noL Lo sub[ecL a base-senslLlve molecule Lo Wolff-klshner or an acld-senslLlve
sLarLlng maLerlal Lo Lhe Clemmensen, or slde reacLlons wlll occur.

Whlle Lhe mechanlsm of Lhe Clemmensen 8educLlon ls ouLslde of Lhe scope of an
undergraduaLe organlc chemlsLry class, Lhe mechanlsm of Lhe Wolff-klshner 8educLlon ls
noL. lf we were Lo examlne Lhe componenLs of Lhe reacLlon, we would qulckly recognlze
LhaL carbonyls are elecLrophlllc. lurLher, hydrazlne ls a very sLrong nucleophlle. 1hls
means LhaL Lhe hydrazlne wlll aLLack Lhe carbonyl and provlde a hydrazone as Lhe
lnLermedlaLe of Lhe reacLlon. 1he hydrazone ls Lhen degraded uslng kCP Lo glve Lhe flnal
producL. 1o be more speclflc, Lhe base absLracLs a proLon from Lhe free amlne of Lhe
hydrazone, whlch ls Lhen passed Lo Lhe carbon Lo be reduced. 1he drlvlng force behlnd Lhls
degradaLlon ls Lhe loss of n
2
.
Crgo II, D|ff|cu|ty:
Þ a g e | 107

O
H
2
NNH
2
KOH
N
NH
2
HO-
N
NH-
C
N
NH
O
H H
N
NH
H
HO-
N
N
H
resonance
C
H
Ioss of
N
2
O
H H


Whlle Lhls mechanlsm may look complex, lL can be broken down lnLo Lwo separaLe
porLlons: aLLack of hydrazlne on Lhe carbonyl and degradaLlon ln order Lo release n
2
.
Pydrazlne ls a very sLrong nucleophlle, and Lhus wlll qulckly aLLack Lhe carbonyl. We know
from prevlous examples LhaL carbonyls and amlnes reacLed LogeLher form lmlnes. nexL,
our base lnduces several proLon Lransfers whlch resulL ln Lhe ulLlmaLe loss of nlLrogen,
whlch glves us our flnal producL.


1ake nome Message: Wo|ff-k|shner and C|emmensen keduct|ons are both
react|ons that w||| convert a carbony| |nto a Cn
2
.

Þ a g e | 108

#S9- It takes a 8aeyer-V||||ger to ra|se a ch||d

LsLers can come from a number of reacLlons. Some examples of ways Lo form Lhem from
alcohols are shown below:
CI
O
+
ROH
OR
O
OH
O
+
ROH
OR
O
H
+
O
O O
+
ROH
OR
O
2
From acid chIorides
Fischer esterification
From carboxyIic anhydrides

Cne of Lhe very easy ways Lo form an esLer ls by uslng Lhe 8aeyer-vllllger reacLlon. 1hls
reacLlon Lakes a keLone and converLs lL dlrecLly Lo Lhe esLer Lhrough reacLlon wlLh a
peroxyacld.
C H
3
CH
3
O
C H
3
O
O
CH
3
O
OH
O
O
OH
O
O
Ph Ph
O
O Ph
Ph

1he examples shown above are symmeLrlc keLones LhaL would provlde Lhe same producL
regardless of whlch slde Lhe oxygen was added Lo. When Lhe keLone ls noL symmeLrlc, Lhe
oxygen wlll add Lo Lhe more subsLlLuenL slde of Lhe keLone. 1hls means LhaL Lhe order of
subsLlLuLlon wlll be LerLlary before secondary before prlmary.

Crgo II, D|ff|cu|ty:
Þ a g e | 109

C H
3
O
C H
3
O
O
O
OH
O
C H
3
O
O
OH
O
C H
3
O
O

Powever, Lhe maln use of Lhe 8aeyer-vllllger reacLlon ls ln Lhe formaLlon of lacLones (aka
cycllc esLers). 1hese are noL easlly formed uslng Lhe meLhods above (acld chlorlde,
anhydrlde or llscher meLhods) and are well-sulLed for Lhe 8aeyer-vllllger reacLlon. As
above, Lhe oxygen aLom wlll sLlll add Lo Lhe more subsLlLuLed slde of Lhe cycllc keLone.
O
O
O
O
O
O
O
O
O
O
O
O


8aeyer-vllllger ls generally regarded as Lhe besL way Lo creaLe a lacLone on an
undergraduaLe exam.

1ake nome Message: Cyc||c esters (aka |actones) most ||ke|y came from the
8aeyer-V||||ger react|on.
Þ a g e | 110

#60- Symmetr|c d|o|s came from the Þ|naco| react|on
Some of your professors wlll Lry Lo sneak Lhls one ln on you durlng an exam: ?our
professor wlll ask you Lo synLheslze Lhe symmeLrlc dlol shown below and you wlll elLher
noL know how or you wlll come up wlLh a convoluLed, dlfflculL or wrong answer.
OH O H
CH
3
C H
3
Synthesize this moIecuIe using any organic
moIecuIe of TWO carbons or Iess

Whlle noL obvlous, Lhere ls a very slmple way Lo creaLe a symmeLrlc dlol uslng Lhe Þlnacol
reacLlon. uslng a number of reduclng agenLs, keLones and aldehydes can be coupled wlLh
Lhemselves Lo form a symmeLrlc dlol, as shown below:
Mg
H
O
Ph
OH O H
Ph Ph
Na-Hg
H
O
Ph
OH O H
Ph Ph
Mg
CH
3
O
C H
3
OH O H
CH
3
C H
3

1he reacLlon ls also called Lhe Þlnacol Coupllng 8eacLlon and can be used on mosL
aldehydes and keLones, buL noL on acld halldes or carboxyllc aclds. now Lo address Lhe
orlglnal synLheLlc problem above:
OH O H
CH
3
C H
3
O
H
CH
3
CH
2
Li
OH
K
2
Cr
2
O
7
H
2
SO
4
O
Mg

1he flrsL sLep ls reacLlon of Lhe reacLlon of eLhyl llLhlum wlLh eLhanal Lo form 2-buLanol.
1hls ls Lhen oxldlzed Lo 2-buLanone uslng !ones' oxldaLlon. now, under Þlnacol Coupllng
condlLlons, 2-buLanone ls Lhen reacLed wlLh lLself uslng magneslum Lo form Lhe flnal
producL.

1ake nome Message: Symmetr|c 1,2 d|o|s came from the Þ|naco| react|on.
Crgo II, D|ff|cu|ty:
Þ a g e | 111

#61- Convert a n|tro group |nto the a|dehyde or ketone.

MosL of you are aware LhaL nlLro groups can be converLed lnLo amlnes vla reducLlon. 1hls
reacLlon ls mosL useful when performlng elecLrophlllc aromaLlc subsLlLuLlon reacLlons.
Powever, nlLro groups can also be converLed lnLo keLones and aldehydes under relaLlvely
slmple condlLlons. Whlle Lhls reacLlon may noL ever geL used on a sophomore organlc
exam, lL ls good Lo know LhaL lL exlsLs. 1he llLLle-known organlc reacLlon ls Lhe converslon
of a nlLro group dlrecLly lnLo an aldehyde or keLone uslng alkallne kMnC
4
. 1he reacLlon wlll
converL a prlmary nlLro group lnLo Lhe aldehyde and a secondary nlLro group lnLo a keLone.

NO
2
NO
2
KMnO
4
, NaOH
KMnO
4
, NaOH
O
O
H


1he reacLlon mechanlsm lnvolves absLracLlon of Lhe proLon ad[acenL Lo Lhe nlLro group,
followed by complexaLlon of Mn Lo Lhe oxygens of Lhe nlLro group, and rearrangemenL Lo
Lhe carbonyl compound. lL ls lmporLanL Lo remember LhaL kMnC
4
ls a poLenL oxldlzlng
agenL, so Lhls reacLlon should only be used on molecules where Lhe kMnC
4
cannoL
unlnLenLlonally oxldlze anoLher funcLlonal group, such as ‚CP somewhere else on Lhe
molecule.

1o go a sLep furLher, now lf you wanLed Lo compleLely remove Lhe carbonyl, you could do
LhaL wlLh Lhe Wolff-klshner reacLlon. (See Llp #38) 1hls now becomes a very effecLlve way
Lo compleLely remove a nlLro group from your molecule lf you so deslre.

1ake nome Message: When |n a b|nd, you can convert an a||phat|c n|tro group
|nto a carbony|.




Crgo II, D|ff|cu|ty:
Þ a g e | 112

#62- 1he McMurry react|on: A "reverse" ozono|ys|s.
A handy reacLlon for Lhe full oxldaLlon of a double bond Lo a carbonyl ls an ozonolysls
reacLlon. Pere, molecular ozone ls used and goes Lhrough Lwo lnLermedlaLes, called
prlmary ozonldes and secondary ozonldes. When flnal cleavage of Lhe secondary ozonlde
occurs, lL can proceed ln Lwo dlfferenL paLhs, based on whlch Lype of workup ls used. lf a
reducLlve workup ls used (Zn, or CP
3
SCP
3
) Lhen Lhe resulLlng producL wlll be an aldehyde.
lf an oxldaLlve workup ls performed (P
2
C
2
), Lhe resulLlng producL wlll be a carboxyllc acld.
Lesser known ls LhaL lf a fully reducLlve workup ls performed (na8P
4
or LlAlP
4
), Lhe
resulLlng producL wlll be an alcohol.
1) O
3
2)
1) O
3
2)
1) O
3
2)
Zn, AcOH
H
2
O
2
LiAIH
4
H
O O
+
OH
O O
+
OH
OH
+

A qulck Lrlck Lo flnd all producLs of an ozonolysls reacLlon ls Lo draw a dashed llne Lhrough
all of Lhe double and Lrlple bonds ln your molecule and add an oxygen aLom Lo Lhe end of
each bond you [usL cleaved. 1he Lype of funcLlonal group you creaLe wlll be based on Lhe
Lype of workup. ln our example below, we used a reducLlve workup wlLh zlnc, whlch wlll
glve aldehydes and keLones as your producLs.
O
3
O O
O
O O
O
Zn, AcOH
1)
2)

Much less known, however, ls Lhe McMurry reacLlon. AL lLs essence, Lhe McMurry reacLlon
can be LhoughL of as a ºreverse ozonolysls" reacLlon. 1he reacLlon ls performed uslng
LlLanlum Lrlchlorlde, 1lCl
3
, (someLlmes called º1lckle Chlorlde" or º1lckle Me Chlorlde") and
wlll proceed ln hlgh yleld under Lhe rlghL condlLlons. 1hose condlLlons are based on Lhe
Crgo II, D|ff|cu|ty:
Þ a g e | 113

sLarLlng maLerlal used, noL Lhe reacLlon condlLlons Lhemselves. 1hls means LhaL only Lhe
rlghL compounds wlll glve good McMurry reacLlons.
1here are Lwo ways LhaL Lhe McMurry reacLlon can be successfully employed. llrsL, ls lf
Lhe sLarLlng maLerlal ls symmeLrlc and ls reacLed wlLh lLself. ln Lhe McMurry reacLlon, all
comblnaLlons of alkenes wlll be generaLed, based on Lhe sLarLlng maLerlal. 1herefore, lf a
symmeLrlc sLarLlng maLerlal ls used, only one producL wlll resulL and a mlxLure of producLs
can be avolded.
O
TiCI
3
O
TiCI
3
potassium
Zn

1hls reacLlon ls noL as effecLlve when symmeLrlc sLarLlng maLerlals are noL used, as cross-
reacLlons are as plenLlful as nerds aL a Scl-ll convenLlon. See below for an example of a
McMurry reacLlon wlLh unsymmeLrlcal sLarLlng maLerlals.
O
TiCI
3
Zn
O
+
1 2
"cis" 2 + 2 "trans" 2 + 2
"cis" 1 + 2 "trans" 1 + 2
"cis" 1 + 1 "trans" 1 + 1

ln Lhe unsuccessful example above, Lhere are slx posslble producLs. 1hey are: sLarLlng
maLerlal 1 reacLlng wlLh lLself, sLarLlng maLerlal 2 reacLlng wlLh lLself, and a cross reacLlon
beLween 1 and 2, =>2? a cls and Lrans verslon for each. 1hls should be avolded llke lL was
namedrop here
See 1lp #38
Þ a g e | 114

a Scl-ll convenLlon. (unsure why l am so down on sclence flcLlon Loday. Apologles Lo all
1rekkles, 1rekkers, and u&u klds.)
1he oLher Lype of successful McMurry reacLlon ls performed lnLramolecularly. 1he facL
LhaL Lhe carbonyls are so close Lo each oLher ln space allows for Lhe reacLlon Lo proceed
smooLhly. lurLher, 4-'&.molecular coupllng can be avolded lf Lhe reacLlon ls performed
under hlgh dlluLlon condlLlons. 1hls can Lhen be uLlllzed as a very effecLlve way of closlng
rlngs, especlally large ones.
O
O
H
H
TiCI
3
Zn
O
O
TiCI
3
Zn

Pelp yourself ouL: As dlscussed ln Llp #38, lL ls a good ldea Lo ºdrop some names", when
uslng a reacLlon noL LaughL by your professor. 1hls wlll keep LhaL snoLLy graduaLe sLudenL
grader from marklng you down for uslng perfecLly valld chemlsLry.

1ake nome Message: 1he McMurry react|on |s a "reverse ozono|ys|s".

namedrop here
See 1lp #38
Þ a g e | 11S

#63- ko|e reversa|: N|tr||e hydrat|on and the Letts N|tr||e synthes|s
ln Lhe nexL lnsLallmenL of our serles on converLlng Lwo funcLlonal groups beLween each
oLher, we now scruLlnlze nlLrlles. 1o do Lhls, we wlll Lravel back ln Llme and re-examlne Lhe
forgoLLen arL of elecLrophlllc aromaLlc subsLlLuLlon (LAS). nlLrlles can be easlly converLed
lnLo carboxyllc aclds by acld-caLalyzed hydraLlon, as shown below:
OH
O
N
H
3
O+
HEAT!

lurLher, lf you were so lncllned, you could go back Lo Lhe nlLrlle from Lhe carboxyllc acld
uslng a procedure called Lhe LeLLs nlLrlle SynLhesls.
OH
O
N
KSCN
HEAT!

uslng poLasslum LhlocyanaLe, aromaLlc carboxyllc aclds can be converLed back lnLo Lhe
nlLrlle. 1hls reacLlon ls only valld for )."#)'4! carboxyllc aclds, n oL for alkyl carboxyllc
aclds.
1he nlce feaLure of Lhls reacLlon, from an LAS perspecLlve, ls LhaL Lhe carboxyllc acld and
Lhe nlLrlle are boLh meLa-dlrecLors. 1herefore, you can lnLer-converL beLween Lhe Lwo and
wlLhouL worrylng abouL messlng wlLh your overall LAS sLraLegy for lnsLalllng dlfferenL
funcLlonal groups on your molecule.

1ake nome Message: N|tr||es can be converted |nto carboxy||c ac|ds v|a hydrat|on
and back to the n|tr||e us|ng the Letts N|tr||e Synthes|s.

Crgo II, D|ff|cu|ty:
namedrop here
See 1lp #38
Þ a g e | 116

#64- ko|e reversa|: D|hydroxy|at|on and Corey-W|nter C|ef|nat|on
1he more common reacLlon of Lhls Llp ls Lhe dlhydroxylaLlon, where a double bond can be
reacLed Lo form a dlol, as shown below.
OH
OH
OsO
4

ln Lhls reacLlon, CsC
4
ls used as Lhe dlhydroxylaLlng agenL, and glves Lhe cls dlol as Lhe
producL. 1hls reacLlon ls very useful and ls one of Lhe ma[or ways Lo form a cls 1,2 dlol. ln
conLrasL, Lhe Lrans 1,2 dlol can be formed by epoxldlzlng a double bond, Lhen openlng lL
wlLh hydroxlde lon.
OH
OH
mcpba
O
OH-

?eL Lhere ls a much lesser known way Lo go from a 1,2 dlol back Lo Lhe double bond. 1he
reacLlon ls called Lhe Corey-WlnLer CleflnaLlon and ls a slmple meLhod for obLalnlng double
bonds.
OH
OH
1)
2)
CI CI
S
(MeO)
3
P

1he mechanlsm of Lhe reacLlon ls a llLLle more complex. lL lnvolves reacLlon of Lhe dlol
wlLh Lhlophosgene, Lo form Lhe cycllc Lhlo-carbonaLe. 1hls ls Lhen degraded Lo Lhe double
bond uslng LrlmeLhyl phosphlLe. Slnce Lhe reacLlon proceeds Lhrough a cycllc lnLermedlaLe,
4' !)- "-%( 8& $&.7".#&+ */!!&**7/%%( "- !4* +4"%*. 1herefore, we could nC1 perform Lhls
reacLlon on Lhe Lrans dlol shown above.
OH
OH
1)
2)
CI CI
S
(MeO)
3
P
OH
OH
1)
2)
CI CI
S
(MeO)
3
P
No Reaction

Crgo II, D|ff|cu|ty:
namedrop here
See 1lp #38
Þ a g e | 117

8emember LhaL lf Lhe dlol ls a sLralghL chaln alkane, Lhen lL may be roLaLed Lo place Lhe
hydroxyls ln a cls conformaLlon, so LhaL even Lhough lL appears Lo be a Lrans dlol, Lhe
reacLlon can sLlll be performed.
CH
3
OH
OH
Ph
same as
OH
Ph OH
CH
3
1)
2)
CI CI
S
(MeO)
3
P
Ph
CH
3

1he conflguraLlon of Lhe alkene obLalned depends on Lhe orlglnal conflguraLlon of Lhe dlol.
Wherever Lhe dlol subsLlLuenLs are locaLed ln Lhe orlglnal sLarLlng maLerlal ls how Lhe
alkene wlll be formed.
CH
3
OH
OH
Ph
same as
OH
Ph OH
CH
3
1)
2)
CI CI
S
(MeO)
3
P
Ph
CH
3
CH
3
OH
OH
Ph
1)
2)
CI CI
S
(MeO)
3
P
Ph CH
3


1ake nome Message: CsC
4
can convert an o|ef|n |nto the c|s 1,2 d|o|.
1h|ophosgene]tr|methy| phosph|te w||| convert the c|s d|o| back |nto the o|ef|n.

Þ a g e | 118

#6S- ko|e reversa|: na|ogens and carboxy||c ac|ds
As dlscussed ln prevlous secLlons halogens are Lhe mosL versaLlle funcLlonal group ln
organlc chemlsLry. 1hey are Lhe Lddle Murphy of funcLlonal groups. 1hey can be Lurned
lnLo any one of a number of zany characLers, llke double bonds, eLhers, or carboxyllc aclds.
1he converslon Lo a carboxyllc acld ls whaL we wlll dlscuss here. 1he reacLlon ls relaLlvely
slmple, and conslsLs of reacLlon of Lhe halogen wlLh magneslum meLal followed by reacLlon
wlLh excess carbon dloxlde. 1he magneslum ls responslble for converLlng Lhe halogen Lo a
Crlgnard reagenL, whlch ls Lhe reacLed wlLh carbon dloxlde, an excellenL elecLrophlle.
Br
Mg
MgBr
CO
2
COOH
Mg CO
2
Br MgBr COOH
CI
2
CCI
4
CI
CI
Mg
CO
2
COOH
COOH
1)
2)

1he mechanlsm of Lhe Crlgnard aLLack ls worLh brlefly dlscusslng. Crlgnard reagenLs are
excellenL nucleophlles. 1hls wlll aLLack carbon dloxlde, whlch ls a very good elecLrophlle.
Cnce Lhls reacLlon has occurred, Lhe producL ls Lhe magneslum bromlde salL of Lhe
carboxyllc acld, whlch musL be converLed Lo Lhe free carboxyllc acld. 1hls can be
accompllshed uslng by acld workup.
MgBr COOH
O
C
O
O
OMgBr
H
3
O+

1he reverse of Lhls reacLlon, whlch can Lurn a carboxyllc back lnLo a halogen, ls Lhe
Punsdlecker reacLlon. ln Lhls reacLlon, Lhe carboxyllc acld ls converLed Lo Lhe sllver salL
uslng AgCP, whlch ls a sLrong base. 1hls ls Lhen reacLed wlLh molecular bromlne, Lo
converL Lhe compound Lo Lhe bromlde.
COOH
AgOH
COO-Ag+
Br
2
Br

Crgo II, D|ff|cu|ty:
Þ a g e | 119

Above Lhe reacLlon ls shown ln Lwo separaLe sLeps, however on an exam you wlll be able Lo
comblne Lhe Lwo sLeps as shown below.
AgOH
Br
2
Br COOH 1)
2)

AgCP ls a sLrong base, so be careful when performlng Lhls reacLlon ln Lhe presence of
anoLher funcLlonal group whlch lL mlghL reacL wlLh. 1he obvlous aLom you don'L wanL
somewhere else on your moelcule ls a halogen, whlch could posslbly ellmlnaLe Lo Lhe
double bond. ?ou should also avold any double bonds ln your sLarLlng maLerlals, as Lhls
wlll glve poor ylelds ln real llfe and may cause your professor Lo dock you polnLs.
1he reacLlon ls besL sulLed for alkyl carboxyllc aclds, buL can also be used on aryl carboxyllc
aclds. lurLher, Lhe reacLlon ls noL solely llmlLed Lo formaLlon of Lhe bromlde, as Lhe lodlde
and chlorlde have also been formed.
AgOH
CI
2
CI COOH 1)
2)
COOH
AgOH
Br
2
1)
2)
Br

llnally, Lhe reacLlon wlll only Lransform carboxyllc aclds, lL wlll noL affecL any oLher Lype of
carbonyl wlLhln your molecule, as shown below.
O
O
OH
MeO
1) AgOH
2) Br
2
O
MeO Br

1ake nome Message: Mg]CC
2
can convert a ha|ogen to the carboxy||c ac|d.
AgCn]k
2
w||| convert |t back to the ha|ogen.

namedrop here
See 1lp #38
Þ a g e | 120

#66: Mus|ca| doub|e bonds: Us|ng cata|yt|c I
2
.
Cnce agaln, lodlne [usL can'L play llke lLs oLher halogen slbllngs. ?ou would expecL Lhls
reacLlon Lo occur llke dl-bromlnaLlon or dl-chlorlnaLlon, where Lhe halogen adds across Lhe
double bond ln an anLl-fashlon, buL lodlne doesn'L play llke LhaL.
When caLalyLlc lodlne ls sub[ecLed Lo an alkene, lsomerlzaLlon (noL addlLlon) occurs. 1he
reacLlon sLarLs ouL Lhe same as bromlnaLlon or chlorlnaLlon, as Lhe halogen reacLs Lo form
Lhe lodonlum lon (Lhe flrsL lnLermedlaLe). Powever, lnsLead of l
-
openlng up Lhe Lhree-
membered rlng Lo glve Lhe dl-lodlnaLlon, Lhe rlng opens on lLs own, placlng a poslLlve
charge ad[acenL Lo Lhe halogen. 1hls ls referred Lo as Lhe eplhalonlum lon. l
-
Lhen acLs as a
base and removes Lhe lodlne and creaLes Lhe new double bond. 1he reacLlon works
because Lhe lodonlum lnLermedlaLe does noL sLay a Lhree-membered rlng, buL opens up
and allows free roLaLlon abouL Lhe newly-formed carbocaLlon, whlch allows Lhe newly-
formed double bond Lo assume Lhe more Lhermodynamlcally-favored Lrans conflguraLlon.
cat. I
2
I
+
I
+
I
+
Ì
2

As you can see above, aL Lhe end of Lhe reacLlon, we have regeneraLed molecular lodlne,
whlch ls Lhe reason we can use caLalyLlc amounLs of lodlne.
1hls caLalyLlc lsomerlzaLlon reacLlon ls noL conflned Lo small molecules, buL has also been
used on large ones Loo. 8elow ls Lhe LransformaLlon from 11-cls-reLlnal Lo all-Lrans reLlnal.
ln Lhe human reLlna, a phoLon of llghL may sLrlke 11-cls-reLlnal and converL lL lnLo all-Lrans-
reLlnal. Powever, we can lnduce Lhls LransformaLlon ln a flask ln Lhe dark by addlng
caLalyLlc lodlne, as shown below.
O
H
C H
3
C H
3
CH
3
CH
3
CH
3
CH
3
C H
3
CH
3
O
H CH
3
CH
3
cat. I
2

1ake nome Message: Cata|yt|c I
2
does not behave ||ke other ha|ogens |n the
presence of a|kenes, as |t w||| transform c|s doub|e bonds |nto trans doub|e
bonds.
Crgo II, D|ff|cu|ty:
Þ a g e | 121

#67- Iust L|ke the Secret Serv|ce, Þrotect|ng Groups Are Chem|ca|
8odyguards
luncLlonal groups are Lhe vlÞs of Lhe chemlcal world. 1hey have all of Lhe lnfluence ln a
glven reacLlon and wleld all of Lhe power. ConsequenLly, Lhere are a number of bad
characLers ouL Lhere LhaL wanL Lo assasslnaLe Lhe funcLlonal groups. 1hese are reagenLs
LhaL are meanL Lo reacL wlLh one funcLlonal group, buL could ºklll" anoLher funcLlonal
group. 8elow ls a classlc example of Lhls:

1he lnLended reacLlon ls Lhe deproLonaLlon and alkylaLlon of Lhe alkyne above. Powever,
Lhls reacLlon wlll noL occur ln hlgh yleld. 1hls ls because once Lhe nucleophlle ls creaLed, lL
wlll reacL wlLh Lhe closesL elecLrophlle (Lhe carbonyl) and noL Lhe lnLended one (Lhe CP
3
8r).
Cnce agaln, our vlÞ has been assasslnaLed. nexL Llme, leL's geL a bodyguard.
8elow ls anoLher reacLlon sequence LhaL may show Lhls concepL a llLLle more clearly. lf we
[usL reacLed Lhe sLarLlng maLerlal wlLh LlAlP
4
, we would reduce boLh Lhe keLone and Lhe
carboxyllc acld. Powever, we can selecLlvely reduce Lhe carboxyllc acld lf we wanLed by
proLecLlng Lhe keLone. 1he sequence ls Lhe same as above. We wlll proLecL Lhe keLone as
Lhe 1,3-uloxane. We can Lhen selecLlvely reduce Lhe carboxyllc acld wlLh LlAlP
4
, and Lhen
remove Lhe proLecLlng group wlLh sLrong acld. 1hls example should clearly show LhaL Lhe
resulLs are qulLe dlfferenL when we use a proLecLlng group.
O
O O H
OH
O H
O
O
O O H
O
O
O H
O
O H
O H OH
LiAIH
4
LiAIH
4
HCI
pH < 1

1o speak more speclflcally abouL proLecLlng groups, Lhere are Lhree generlc sLeps Lo uslng a
proLecLlng group on your funcLlonal group. 1he flrsL sLep ls proLecLlon of Lhe funcLlonal
Crgo II, D|ff|cu|ty:
Þ a g e | 122

group (hlre a bodyguard). 1he second sLep ls Lo perform Lhe deslred reacLlon (bodyguard
proLecLs Lhe vlÞ agalnsL aLLack). 1he Lhlrd sLep ls Lo deproLecL Lhe funcLlonal group Lo glve
Lhe end producL you wanL (pay Lhe bodyguard and send hlm home). Armed wlLh Lhls
knowledge, we can perform Lhe flrsL reacLlon Lhe rlghL way.
O
H
O
CH
3
O H OH
Tosic acid
O
O
H
O
O
H
1)
2)
NaNH
2
CH
3
Br
O
O
CH
3
O
O
CH
3
H
3
O+
Protect
React
Deprotect


ln Lhe reacLlon sequence above, Lhe carbonyl ls proLecLed uslng eLhylene glycol and Loslc
acld as a caLalysL. 1hls lnsLalls Lhe proLecLlng group on Lhe carbonyl so lL cannoL reacL. ln
Lhls case, Lhe carbonyl ls proLecLed as Lhe aceLal, whlch ls a gemlnal dl-eLher. We know
from prevlous secLlons LhaL eLhers are very unreacLlve, and Lherefore make a good
proLecLlng group. We are Lhen free Lo perform our reacLlon, whlch ls now selecLlve for Lhe
alkyne. llnally, we wlll deproLecL Lhe carbonyl wlLh acldlc waLer. 1hls reLurns Lhe orlglnal
carbonyl Lo us and provldes our flnal producL. AlLhough Lhls seems llke an overly lengLhy
sequence, lL ls Lhe besL way Lo synLheslze Lhe flnal producL.
So whaL makes a good proLecLlng group? 1he same Lhlngs LhaL make a good bodyguard.
1) lL should be easy Lo lnsLall. 1hlnk of Lhls ln Lerms of Lhe bodyguard analogy,
meanlng LhaL our bodyguard has Lo be efforLless Lo hlre.
2) lL should be reslsLanL Lo a number of reagenLs LhaL mlghL normally affecL our
funcLlonal group. 1hls means our bodyguard has Lo be Lough and proLecL agalnsL a
number of LhreaLs. lL can'L [usL proLecL agalnsL Al-Caeda, buL musL also be able Lo
proLecL agalnsL PAMAS, Lhe mafla, and hlpple proLesLors.
Þ a g e | 123

3) lL should be easy Lo remove. AfLer proLecLlng agalnsL Lhe LhreaL, Lhe bodyguard
musL be able Lo go home LhaL nlghL when Lhe [ob ls done, leavlng Lhe vlÞ llke he
was before Lhe bodyguard was hlred.
Iunct|ona| Group to
protect
Þrotected as Þrotect|on react|on
cond|t|ons
Deprotect|on react|on
cond|t|ons
Alcohol [8CP] 1rlalkyl Sllyl eLher
O
Si
R
R
R

8
3
SlCl, Þyrldlne P
3
C
+
(pP ƒ 1) or Pl
Alcohol [8CP] 8enzyl eLher
O Ph

ÞhCP
2
Cl, Þyrldlne P
2
/nl, or na/nP
3

Carbonyl [8C(C)8] 1,3-uloxane
O
O

LLhylene Clycol,
Loslc acld
P
3
C
+
(pP ƒ 1) or
Zn/PCl
Amlne [8
2
nP] AceLaLe
N CH
3
O

CP
3
CCCl, Þyrldlne na/nP
3


LnLlre books have been wrlLLen on proLecLlng groups, buL we have summarlzed a few of
Lhe ma[or ones above. We <2@10ABC encourage you Lo read up on Lhese much more
before you Lry Lo use Lhls chemlsLry on your exam, as Lhls ls only meanL Lo be an
lnLroducLlon Lo Lhe Loplc. lor more lnformaLlon on proLecLlng groups, a good webslLe Lo
look aL ls hLLp://www.organlc-chemlsLry.org/proLecLlvegroups/proLecLlnggroups.hLm. 1hls
slLe has charLs for a number of proLecLlng groups and Lhelr sLablllLles relaLlve Lo dlfferenL
reacLlon condlLlons.
Cn your example, you wlll llkely see a very slmple problem uslng proLecLlng groups. lL wlll
mosL llkely only lnvolve proLecLlon, followed by one reacLlon and lmmedlaLe deproLecLlon.
8ecause of Lhls, lL ls probably noL a good ldea Lo wasLe a loL of Llme learnlng proLecLlng
group chemlsLry. We suggesL LhaL you learn [usL a few slmple proLecLlng groups and spend
more Llme learnlng oLher organlc reacLlons.
1ake nome Message: If you have two s|tes that a react|on cou|d potent|a||y occur
at, protect one, react at the other, and deprotect the f|rst.

Þ a g e | 124

#68- Don't hydrogenate that ary| r|ng! ¥ou'|| k||| us a||!
ln Llp #30, we sLaLed LhaL Lhe maln meLhod for obLalnlng a subsLlLuLed cyclohexane was
Lhe ulels-Alder reacLlon. [?our professors love LhaL reacLlon] Powever, ln an efforL Lo
expand your realm of Lhlnklng, we are now golng Lo lnLroduce Lo you a second way Lo
make hlghly subsLlLuLed cyclohexane rlngs. Suppose you are glven Lhls problem:
Synthesize the foIIowing moIecuIe from organic
compounds of six carbons or Iess

AL flrsL blush, you mlghL Lhlnk LhaL Lhe followlng synLhesls would be valld:
+
DieIs-AIder
H
2
/ Pd-C

Powever, Lhere are Lwo problems wlLh Lhls synLhesls: 1) ?our sLarLlng maLerlal has more
Lhan 6 carbons, and 2) ulels-Alder reacLlons uslng dlenes LhaL have a L-buLyl group can be
dlfflculL. Pence, we should have a second rouLe ln mlnd for slLuaLlons llke Lhls.
An alLernaLlve meLhod ls Lo perform elecLrophlllc aromaLlc subsLlLuLlon reacLlons on
benzene, Lhen reduce benzene Lo cyclohexane vla a harsh hydrogenaLlon. 1hls meLhod
would be vlable because Lhe followlng reacLlon can be done ln Lhe lab:
H
2
/ Ni
HEAT AND
PRESSURE!

Crgo II, D|ff|cu|ty:
Þ a g e | 12S

When dolng Lhls reacLlon on an exam, be sure Lo noLe Lwo Lhlngs Lo geL full credlL. llrsL,
use nl as your caLalysL, noL Þd-C. Second, be sure Lo somehow emphaslze Lhe facL LhaL Lhe
reacLlon ls performed uslng hlgh heaL and pressure. (We have chosen Lo hlghllghL LhaL
here uslng all caplLal leLLer and placlng an exclamaLlon polnL aL Lhe end. 1hls ls also why
we are worrled LhaL you wlll klll us all-hlgh pressure hydrogen ls llke a small bomb walLlng
Lo go ºboom".)
uslng Lhls meLhod, our synLhesls wlll look llke Lhls:
CI
AICI
3
CI
AICI
3
H
2
/ Ni
HEAT AND
PRESSURE!

As sLaLed above, Lhe key ls Lo do Lhe LAS chemlsLry flrsL, Lhen reduce Lhe aryl rlng Lo Lhe
cyclohexane. 1he vasL ma[orlLy of professors wlll glve you full credlL for Lhls reacLlon
sequence provlded LhaL you emphaslze Lhe condlLlons under whlch Lhe aryl rlng ls belng
reduced.
As you saw ln your course, Lhere are a number of dlfferenL LAS reacLlons LhaL can be
performed on benzene. Some of Lhese, llke Lhe L-buLyl group above, wlll be lnerL Lo
hydrogenaLlon. Powever oLhers wlll be reduced Lo oLher funcLlonal groups under Lhese
reacLlon condlLlons. Some of Lhese are shown below:
luncLlon Croup on Lhe rlng (Ar = C
6
P
3
) uurlng P
2
/nl reacLlon, converLed Lo :
(C
6
P
11
= cyclohexane rlng)
Ar-CN C
6
n
11
-Cn
2
Nn
2

Ar-NC
2
C
6
n
11
-Nn
2

Ar-C(C)Cn
3
C
6
n
11
-Cn
2
Cn
3

Ar-k C
6
n
11
-k (|nert to n
2
]N|)
Ar-Ck C
6
n
11
-Ck (|nert to n
2
]N|)
Ar-Cn C
6
n
11
-Cn (|nert to n
2
]N|)
Ar-Nn
2
C
6
n
11
-Nn
2
(|nert to n
2
]N|)
Ar-k W||| stop the react|on, no reduct|on of
r|ng

Þlease noLe LhaL Lhls reacLlon cannoL be conducLed lf Lhere ls a halogen on Lhe aryl rlng, as
lL could polson Lhe caLalysL and halL Lhe reacLlon.
Þ a g e | 126

1he Lable above shows Lhe reacLlon LhaL occurs when Ar rlngs are sub[ecLed Lo Lhese harsh
hydrogenaLlon condlLlons and sLaLes LhaL abouL half of your average LAS subsLlLuenLs wlll
noL be changed by Lhe P
2
/nl reacLlon. ln Lhese reacLlons where Lhe subsLlLuenL ls noL
affecLed, only Lhe rlng wlll be hydrogenaLed. Some of Lhe subsLlLuenLs wlll be affecLed
Lhough. lor example, nlLrobenzene wlll be Lransformed Lo cyclohexylamlne under Lhese
condlLlons. Pere, noL only ls Lhe rlng belng reduced, buL Lhe nlLro group ls belng
converLed lnLo an amlne, as shown below:
H
2
/ Ni
HEAT AND
PRESSURE!
NO
2
NH
2

Whlle hydrogenaLlon may affecL some of Lhese groups ln ways you dld noL Lhlnk of, we can
sLlll use Lhls Lo our advanLage. !usL keep ln mlnd LhaL durlng Lhe lasL sLep of Lhe reacLlon,
you are golng Lo Lransform some of Lhese. lor example:
Synthesize the foIIowing moIecuIe from organic
compounds of six carbons or Iess
NH
2

As shown below ln Lhe answer Lo Lhls problem, we obLaln Lhe producL by performlng
sLandard LAS chemlsLry, Lhen reduclng Lhe compound ln Lhe flnal sLep. noLlce LhaL we
needed nC
2
as a meLa dlrecLor ln Lhe second sLep, Lhen reduced lL Lo Lhe amlne ln Lhe flnal
sLep.
H
2
/ Ni
HEAT AND
PRESSURE!
NO
2
NH
2
HNO
3
H
2
SO
4
CH
3
CH
2
CI
AICI
3
NO
2


1ake nome Message: D|e|s-A|der |s the pr|mary method for mak|ng cyc|ohexane
r|ng on exams. nowever, |f you get |n a b|nd, cons|der do|ng LAS chem|stry then
reduc|ng the ary| r|ng to a cyc|ohexane w|th n
2
]N| under h|gh heat and pressure
Þ a g e | 127

#69- It's as Lasy as 1,2 Add|t|on. Cr Is It 1,4 Add|t|on?

LveryLhlng goes back Lo resonance. And here we are agaln, back examlnlng resonance
sLrucLures. ln Lhls lnsLance, we are looklng aL €,µ-unsaLuraLed keLones. lf we sLudy Lhe
resonance sLrucLures, we see LhaL Lhere are Lwo dlfferenL elecLrophlllc slLes: Lhe boLLom of
Lhe keLone and Lhe back of Lhe alkene.
O
C
+
O
C
+
O
1,2 addition site
1,4 addition site
1
2
3
4

lf we sLarL counLlng from Lhe oxygen aLom, we can label all of Lhe aLoms from 1 Lo 4.
8esonance sLrucLures of Lhe unsaLuraLed keLone above show LhaL we do have Lwo slLes
LhaL a nucleophlle could add Lo. 1he burnlng quesLlon now ls whlch nucleophlles wlll add
Lo whlch slLes and why.

Addlng Lo Lhe carbonyl carbon ls referred Lo as 1,2-addlLlon. 1hls ls also called ºdlrecL
addlLlon". 1he 1,2-addlLlon producL ls formed fasLer and ls Lherefore Lhe klneLlc producL.
ln general, sLrongly baslc nucleophlles wlll undergo 1,2 addlLlon. Some examples of Lhese
sLrongly baslc nucleophlles are Crlgnards, organollLhlums, and alkyne anlons, as shown
below:

O
CH
3
O
H
O
CH
3
CH
3
CH
2
MgBr
CH
3
Li
C H
3
C
CH
3
O H
H
O H CH
3
CH
3
CH
3
O H


AddlLlon Lo Lhe alkene carbon ls called 1,4-addlLlon. 1hls ls also called ºcon[ugaLe addlLlon"
or ºMlchael addlLlon". 1he 1,4 producL ls formed slower, buL ls more sLable and ls
Lherefore Lhe Lhermodynamlc producL. ln general, weakly baslc nucleophlles wlll undergo
1,4 addlLlon. Some examples of weakly baslc nucleophlles are organocupraLes, alkyl Lhlols,
Cn
-
, mosL enolaLes, and amlnes, as shown below:

Crgo II, D|ff|cu|ty:
Þ a g e | 128

O
CH
3
O
H
O
CH
3
O
CH
3
NH
3
NaCN
(CH
3
CH
2
)CuLi
CH
3
SH
O
CH
3
NH
2
O
H
CN
O
CH
3
O
CH
3
S

1he Lrlck here ls Lo recognlze LhaL you can add Lhe same group Lo Lwo dlfferenL spoLs on a
molecule dependlng on whlch reagenL you use. lor example, lf you wanLed Lo add a
meLhyl group vla 1,2-addlLlon, you would use meLhyl Crlgnard. Conversely, lf you wanLed
Lo add Lhe meLhyl group vla 1,4-addlLlon, you would use meLhyl cupraLe.
O
CH
3
O
CH
3
(CH
3
)CuLi
CH
3
CH
3
O H
O
CH
3
CH
3
CH
3
MgCI
Direct Addition
Conjugate Addition


1ake nome Message: 1here are two types of add|t|on, 1,2 and 1,4 add|t|on.
Strong|y bas|c nuc|eoph||es part|c|pate |n d|rect add|t|on. Weak|y bas|c
nuc|eoph||es part|c|pate |n con[ugate add|t|on.

Þ a g e | 129

#70- nere's to your annu|at|on, Mrs. kob|nson: Mus|ngs on the
kob|nson Annu|at|on.

As we [usL learned ln Lhe lasL Llp (hopefully you haven'L forgoLLen already) Lhere are Lwo
Lypes of addlLlon Lo €,µ-unsaLuraLed keLones: dlrecL and con[ugaLe. ln Lhls Llp, we are
golng Lo focus on a very speclal Lype of con[ugaLe addlLlon called Lhe 8oblnson AnnulaLlon.
1hls ls a favorlLe of many professors and Lhe mosL llkely meLhod you would see on an exam
for synLheslzlng a compound LhaL has Lwo fused cycloalkanes, llke Lhe one shown below:
O
O


1he 8oblnson AnnulaLlon has Lwo maln sLeps. 1he flrsL sLeps ls a Mlchael (aka con[ugaLe)
addlLlon beLween an enolaLe and an €,µ-unsaLuraLed keLone or aldehyde. 8ecause
enolaLes are weakly baslc, Lhey wlll add ln a 1,4 fashlon Lo Lhe unsaLuraLed keLone Lo glve
Lhe producL shown below. kCP ls used as Lhe base Lo form Lhe enolaLe on Lhe sLarLlng
maLerlal.
O
O
O
1) KOH
2)
O
O
O


1he second sLep ls Lhe cycllzaLlon sLep. Cnce agaln, we sub[ecL Lhe sLarLlng maLerlal Lo
base Lo form an enolaLe whlch wlll aLLack a carbonyl. 1here ls a 1,2 addlLlon Lo a carbonyl
because Lhere ls no double bond for a 1,4 reacLlon. 1herefore Lhe nucleophlle defaulLs Lo a
1,2 reacLlon.
O
O
OH
O
O
O
AI(OtBu)
3

upon closer examlnaLlon, we can see LhaL Lhere are Lhree dlfferenL €-proLons (nexL Lo Lhe
carbonyls) whlch could be deproLonaLed Lo glve enolaLes whlch wlll aLLack a carbonyl.
Moreover, Lhere are Lwo dlfferenL carbonyls whlch could be aLLacked by Lhe enolaLe. So
why do we only geL one producL ouL?
Crgo II, D|ff|cu|ty:
Þ a g e | 130

O
O
O
enoIate formed here gives
6-membered ring = GOOD
enoIate formed here gives
4-membered ring = BAD
enoIate formed here gives
bridged compound = not so good

Cnce we dlssecL Lhe Lhree dlfferenL places where an enolaLe could be formed, we see LhaL
Lhere ls really only one LhaL would glve a Lhermodynamlcally favorable producL, Lhe 6-
membered fused rlng.
O
O
OH
O
O
O
O
O
O
Base
EnoIate Not IsoIated

lf we add a llLLle heaL Lo Lhe flnal producL, lL wlll dehydraLe Lo Lhe unsaLuraLed keLone.
now we can puL Lhe whole Lhlng LogeLher, where lL wlll look llke Lhls:
O
O
O
O
O
1) KOH
2)
O
O
O
Heat
AI(Ot-Bu)
3

1hls ls also noL llmlLed Lo fused 6-membered rlngs, buL can also be used Lo form smaller
fused rlng sysLems.
O
1) KOH
2)
Heat
AI(Ot-Bu)
3
O
O
O O
O
O
O

llnally, we can also use Lhls meLhod Lo make regular slx-membered rlngs. 1hls meLhod ls
very useful for cyclohexane rlngs where Lhe ulels-Alder reacLlon [usL won'L work rlghL.
Þ a g e | 131

O
1) KOH
2)
O
O
EtO
O
O
EtO
O
Heat
AI(Ot-Bu)
3
O
O
EtO

Þlease noLe LhaL lf we were Lo Lry Lo creaLe Lhls molecule vla ulels-Alder, we would have Lo
place a keLone and esLer on our dlene. 1hls ls hlghly unfavorable as Lhe dlene should have
elecLron donaLlng groups on lL. 1herefore, ulels-Alder ls noL Lhe besL meLhod for maklng
Lhls compound.

1ake nome Message: 1he kob|nson Annu|at|on can be used to create 6-
membered r|ngs, whether they are fused to another cyc|oa|kane or a|one as a
cyc|ohexane.

Þ a g e | 132

#71- k|net|c vs. 1hermodynam|c Lno|ates: ¥ou Choose the W|nner of
1h|s I|ght.
An enolaLe lon can be formed when Lhe €-proLon of a carbonyl ls sub[ecL Lo base. 1hls
removes Lhe proLon and creaLes an enolaLe anlon, whlch ls nucleophlllc and can parLlclpaLe
ln S
n
2 reacLlons. Powever, when deallng wlLh asymmeLrlc keLones, we see LhaL Lhere
could be Lwo dlfferenL €-proLons whlch could reacL wlLh Lhe base. Whlch one wlll reacL
flrsL?
O
H
H
C H
3
H
Two different sets of aIpha protons


When examlnlng Lhe keLone above, we see LhaL Lhe proLons Lo Lhe rlghL and lefL of Lhe
carbonyl are noL equlvalenL and Lherefore may reacL aL dlfferenL raLes. When dlscusslng
enolaLes, Lhere are Lwo dlfferenL Lypes of enolaLe lons LhaL can form: Lhe Lhermodynamlc
enolaLe and Lhe klneLlc enolaLe. 1he charL below summarlzes Lhe dlfferences beLween Lhe
Lwo.

k|net|c Lno|ate 1hermodynam|c Lno|ate
C=C subst|tut|on Less SubsLlLuLed Slde More SubsLlLuLed Slde
1emp formed at Low LemperaLures (le -78ºC) Plgher 1emperaLures (> 0ºC)
8ase used SLrong, hlndered base Weaker, unhlndered base
kevers|b|e? lrreverslble reacLlon 8everslble reacLlon
Speed of format|on lorms qulckly lorms more slowly
8ase counter|on Þrefers llLhlum Þrefers sodlum or poLasslum

1he mosL lmporLanL dlfferences Lo Lake away from Lhe Lable above ls LhaL Lhe klneLlc
enolaLe form qulckly and needs a sLrong, hlndered base aL lower LemperaLures whlle Lhe
Lhermodynamlc enolaLe ls more sLable and needs a weaker unhlndered base aL hlgher
LemperaLures.
C H
3
CH
3
O
CH
3
H
C H
3
CH
3
O
CH
3
C H
2
CH
3
O
CH
3
H
Kinetic enoIate-
Forms faster
Thermodynamic enoIate-
More stabIe
Starting
materiaI


Crgo II, D|ff|cu|ty:
Þ a g e | 133

1he flgure below ls a good example of klneLlc conLrol ln enolaLe formaLlon. noLlce all of
Lhe condlLlons used favor Lhe klneLlc producL (sLrong hlndered base, low Lemps, llLhlum
counLerlon).
O
CH
3
LDA, THF
-78C
O- Li+
CH
3


8elow are several more examples of how changlng Lhe condlLlon under whlch Lhe enolaLe
ls formed wlll affecL whlch producL ls obLalned.
O
CH
3
LDA, THF
-78C
O- Li+
CH
3
O
CH
3
C H
3
Kinetic enoIate-
Not isoIated
O
CH
3
heat
O- Li+
CH
3
O
CH
3
CH
3
Thermodynamic enoIate-
not isoIated
CH
3
Br
CH
3
Br
KOtBu, tBuOH


ln Lhe above example, Lhe alkylaLlon slLe ls changed by preferenLlally formlng one enolaLe
over Lhe oLher. ln Lhe example below, an enLlrely dlfferenL rlng sysLem ls obLalned by
uslng a dlfferenL base and dlfferenL LemperaLures. 8elow, lnsLead of uslng CP
3
8r Lo
alkylaLe lnLermolecularly, we have Lhe alkylhallde aLLached Lo our enolaLe maklng lL an
lnLramolecular alkylaLlon.
Þ a g e | 134

Br
CH
3
O
Br
CH
3
O
Br
CH
2
O
O
O
LDA, THF
-78C
Heat
tBuOK
tBuOH
Heat
Kinetic EnoIate
Thermodynamic EnoIate


1ake nome Message: k|net|c eno|ates are formed qu|ck|y and are formed w|th
bu|ky bases at |ow temperatures. 1hermodynam|c eno|ates are more stab|e and
are formed w|th weaker bases and h|gher temperatures.
Þ a g e | 13S

#72- "Where's A|do|?" Mak|ng an A|do| keact|on Work for ¥ou.

Aldol reacLlons are noL Loo hard Lo geL a grasp on. Aldols producLs come from Lhe
enolaLes of aldehydes. ln Lhls reacLlon, we Lake advanLage of Lwo facLors. llrsL, because of
Lhe elecLron wlLhdrawlng effecL of Lhe carbonyl, Lhe €-proLons ad[acenL Lo Lhe carbonyl are
acldlc. 1he resulLlng carbanlon can Lhen be used as a nucleophlle. Second, Lhe carbonyl
lLself ls elecLrophlllc, and can accepL Lhe elecLron denslLy possessed by Lhe nucleophlllc
carbanlon. 1he lnLeresLlng parL of Lhls reacLlon ls LhaL boLh Lhe elecLrophlle and
nucleophlle are on Lhe same molecule. 1herefore, lf we Lake Lwo of Lhem LogeLher, Lhey
can reacL wlLh each oLher Lo form a new producL as shown below.

H CH
3
O
2
NaOH
5C
H
OH O


1he mechanlsm of Lhls reacLlon ls relaLlvely sLralghL-forward. 1he base deproLonaLes Lhe
€-proLons Lo glve Lhe carbanlon, whlch ls ln resonance wlLh Lhe enolaLe lon. 1he enolaLe
lon Lhen aLLacks Lhe carbonyl of Lhe oLher aldehyde, whlch afLer proLonaLlon wlLh acldlc
waLer, glves Lhe flnal producL.

H CH
3
O
HO-
H CH
2
-
O
H CH
2
O
+
H CH
3
O
H CH
3
O O
H
H CH
3
O OH
H
3
O+


1he above example was performed aL 3ºC and gave Lhe saLuraLed producL, where Lhe
hydroxyl was sLlll presenL. ln Lhe example below, Lhe reacLlon was performed aL 90ºC and
provlded Lhe €,µ-unsaLuraLed producL. uehydraLlon occurs sponLaneously aL Lhls
LemperaLure, and does noL requlre a separaLe sLep.

H CH
3
O
2
NaOH
90C
H
OH O
Not IsoIated
H
O


Crgo II, D|ff|cu|ty:
Þ a g e | 136

ln all of Lhe examples shown Lhus far, we have been reacLlng one aldehyde wlLh lLself. 8uL
could we reacL Lwo dlfferenL carbonyl compounds Lo geL a ºmlxed aldol" producL? 1he
answer ls yes, buL we need Lo be careful whlch carbonyl compounds we use. 8elow, we
have a mlxed aldol reacLlon whlch would be a dlsasLer.
O
+
O
Ph
4 different types of acidic protons
+ 2 different carbonyIs
= one big mess


1here are some ways however Lo sLop mlxed aldol producLs from runnlng wlld on us:

1) LlmlL Lhe number of €-proLons on your molecules. ln Lhe below mlxed aldol
reacLlon, Lhere ls only one acldlc proLon LhaL can reacL. AlLhough Lhere are Lwo
carbonyls, as we wlll see nexL, Lhe aldehyde ls more reacLlve.

CH
3
O
Ph
+
H
O
Ph
O
Ph Ph
OnIy acidic protons


2) use a more reacLlve carbonyl. Aldehydes are more reacLlve Lhan keLones and
formaldehyde ls more reacLlve Lhan oLher aldehydes. 1he nucleophlle wlll
preferenLlally aLLack Lhe more reacLlve carbonyl.

+
H
O
H H
O
H
O
OH A more reactive carbonyI



1ake nome Message: An a|do| react|on |s the react|on of an a|dehyde w|th |tse|f.
M|xed a|do|s are poss|b|e, but to avo|d mu|t|p|e products you shou|d ||m|t the
number of ac|d|c protons and use a more react|ve a|dehyde.

Þ a g e | 137

#73- Acetoacet|c Lster Synthes|s: What you need to know |n one page
or |ess.

Whlle Lhls may look lnLlmldaLlng, Lhe aceLoaceLlc esLer synLhesls ls Lhe mosL effecLlve
meLhod for creaLed subsLlLuLed meLhyl keLones. 1he basls of Lhe meLhod ls Lo alkylaLe a µ-
dlkeLone, Laklng advanLage of Lhe facL LhaL Lhe €-proLons beLween Lhe Lwo carbonyls are
exLra acldlc. A generlc synLhesls ls shown below:
CH
3
O O
EtO
H H
NaOEt
C CH
3
O O
EtO
H
RX
CH
3
O O
EtO
H R
NaOEt
C CH
3
O O
EtO
R
RX
CH
3
O O
EtO
R R
H
3
O+
H
CH
3
O
R R
Heat


1he essence of Lhe reacLlon sequence ls deproLonaLlon/alkylaLlon. ln Lhe above example,
deproLonaLlon ls achleved wlLh sodlum eLhoxlde, whlle alkylaLlon ls accompllshed wlLh an
alkyl hallde on Lhe resulLlng carbonlon. 1he sequence ls repeaLed Lwlce Lo glve dl-
alkylaLlon. llnally, Lhe esLer ls hydrolyzed and decarboxylaLed Lo glve Lhe subsLlLuLed
meLhyl keLone (aka subsLlLuLed aceLone).

SomeLlmes, Lhe reacLlon wlll be shown wlLh Lhe aceLoaceLlc esLer and alkyl hallde on one
slde of Lhe arrow:
CH
3
O O
EtO
H H
Br
+
1) NaOEt
2) H
3
O+ / Heat
CH
3
O
H H

1he mosL common verslon of Lhls problem uses Lhe aceLoaceLlc esLer above. Powever, any
alkyl group can replace Lhe meLhyl group so long as Lhere ls a µ-esLer on Lhe oLher end LhaL
can be hydrolyzed and decarboxylaLed. ln Lhe below example, Lhe meLhyl group ls
replaced by a cyclopenLyl group.

Br
+
1) NaOEt
2) H
3
O+ / Heat
O
O
OEt
O


1ake nome Message: If you see the acetoacet|c ester |n a prob|em, th|nk
deprotonat|on]a|ky|at|on and a decarboxy|at|on when |t |s f|n|shed.
Crgo II, D|ff|cu|ty:
Þ a g e | 138

#74- µ-keto Lsters Came Irom a C|a|sen Condensat|on (NC1 the
C|a|sen kearrangement)

1he Clalsen condensaLlon ls an aldol-Lype reacLlon, excepL lL ls beLween Lwo esLers. 1he
oLher noLable dlfference beLween Lhe Lwo ls LhaL whlle Lhe aldol reacLlon has Lhe
nucleophlle aLLack Lhe carbonyl reduclng lL Lo an alcohol, Lhe Clalsen condensaLlon ºe[ecLs"
one of Lhe esLers (see Llp #42 Lo Lalk abouL ºe[ecLable" groups")
H C H
3
O
NaOH
5C
C H
3
H
OH O
C H
3
O
OEt
NaOH
5C
H C H
3
O
C H
3
O
OEt
+
+
C H
3
O O
OEt
AIdoI Reaction
CIaisen Condensation

1o resLaLe Lhls, ln Lhe aldol reacLlon, Lhe enolaLe creaLed aLLacks Lhe oLher aldehyde
carbonyl and converLs lL Lo Lhe hydroxyl ln Lhe flnal producL. ln Lhe Clalsen CondensaLlon
however, Lhe aLLacklng enolaLe e[ecLs Lhe esLer porLlon, formlng a µ-dlkeLone producL.
1hese problems can become more complex when deallng wlLh longer chalned esLers, as
shown below:
O
OEt
NaOH
5C
O
OEt
+
O O
OEt

lL ls mosL lmporLanL here Lo remember Lo counL your carbons ln your flnal producL Lo make
sure LhaL you have noL forgoLLen any of Lhem. 1he key mechanlsLlc sLep of Lhls reacLlon ls
very slmllar Lo LhaL of Lhe aldol reacLlon. AfLer deproLonaLlon Lo form Lhe enolaLe, Lhe
enolaLe lon aLLacks Lhe oLher esLer and klcks off Lhe esLer porLlon Lo form Lhe flnal producL.
O
OEt
O
OEt
+
O O
OEt
enoIate ion
finaI product

Crgo II, D|ff|cu|ty:
Þ a g e | 139

!usL llke Lwo couslns LhaL grew up LogeLher, Lhe aldol and Clalsen reacLlons have even
more ln common. !usL llke wlLh Lhe aldol reacLlon, you can also perform a mlxed Clalsen
reacLlon. Agaln, Lhe key ls Lo llmlL Lhe number of €-proLons LhaL can lead Lo enolaLes and
have a more reacLlve carbonyl. ln Lhe reacLlon below we have boLh, as Lhere ls only one €-
hydrogen LhaL can be deproLonaLed and Lhe carbonyl accepLor ls a formlc esLer (aka
aldehyde on one slde, esLer on Lhe oLher).
O
Ph H
O
OEt
+
H
O O
Ph
finaI product
NaOH

lurLher, boLh reacLanLs do noL have Lo be esLers. 1he deflnlng characLerlsLlc of Lhe Clalsen
condensaLlon ls LhaL an esLer ls e[ecLed. 1he reacLlon works [usL as well when a keLone ls
Lhe source of Lhe enolaLe nucleophlle.
1ake nome Message: 1he C|a|sen condensat|on |s s|m||ar to the a|do| react|on,
except there |s an ester that gets e[ected.


Þ a g e | 140

#7S - Convert ketones to epox|des fast
1he general school of LhoughL for mosL sophomore organlc chemlsLry sLudenLs ls LhaL
epoxldes came from double bonds as shown below:
mcpba
O
mcpba
O

Powever, [usL llke 1he MaLrlx dld Lo neo, we wanL Lo expand your Lhlnklng. We wanL you
Lo Lhlnk abouL all of Lhe places LhaL funcLlonal groups could come from so LhaL lf you geL
lnLo a blnd you can pull a dlfferenL Lool ouL of your Loolbox. Cne more Lool for LhaL box ls
Lhe Corey-Chaykovsky reacLlon. uon'L worry abouL rememberlng LhaL name, [usL
remember LhaL you can converL keLones and aldehydes Lo epoxldes uslng Lhls reacLlon.
8elow ls a more deLalled descrlpLlon of where Lhe ºCP
2
" ln Lhe new epoxlde comes from:
O
CH
2
S
O
C H
2
same as
O

Pere are several qulck examples of Lhe reacLlon:
O
CH
2
S
O
C H
2
same as
O
O
H
CH
2
S
O
C H
2
same as
O
O
CH
2
S
O
CH
2
O
same as
O
H
CH
2
S
O
C
H
2
same as
O

Crgo II, D|ff|cu|ty:
Þ a g e | 141

1he reagenL shown Lo perform Lhese reacLlons ls a sulfur yllde. 1he mechanlsm for Lhe
reacLlon ls beyond Lhe scope of Lhls LexL, buL sufflce lL Lo say LhaL lL ls very effecLlve aL
lnsLalllng Lermlnal epoxldes ln molecules. 1he CP
2
aL Lhe end of Lhe sulfur yllde ls
effecLlvely lnsLalled ln beLween Lhe C=C bond Lo glve an epoxlde. 1hls means now LhaL you
would have Lwo ways LhaL you could creaLe Lhe epoxlde producL shown below:
O
Synthesize the foIIowing epoxide from
any aIkane or aIcohoI

8ased on whaL we have learned Lo Lhls polnL, Lhere are Lwo meLhods you could use Lo geL
full credlL on Lhls problem:
CH
2
CH
3
Br
O
O
HBr
hv
KOH mcpba
O H O
PCC
S
Method 1:
Method 2:

MeLhod 1 ls Lhe more sLandard sophomore organlc chemlsLry meLhod, uslng halogenaLlon,
ellmlnaLlon, and epoxldaLlon under sLandard mcpba condlLlons. MeLhod 2 uses Lhe Corey-
Chaykovsky meLhod, as shown above. 8oLh of Lhese synLheLlc meLhods are valld and
should geL you full credlL. 8ecomlng comforLable wlLh more Lhan one way Lo synLheslze a
molecule wlll help you Lo be beLLer prepared for problems you have never seen before.

1ake nome Message: Lpox|des are usua||y created us|ng mcpba. 1he Corey-
Chayovsky method |s an a|ternat|ve method for creat|ng epox|des.


Þ a g e | 142

#76- 1wo ways to open one epox|de
Lpoxldes are elecLrophlllc because of resonance. 1hls means LhaL Lhey can be aLLacked by
nucleophlles and opened Lo glve subsLlLuLed alcohols as shown below.
O CH
3
Li
O H
CH
3

1he example above ls of a symmeLrlc epoxlde. WhaL happens when Lhe epoxlde ls noL
symmeLrlc? Whlch slde of Lhe epoxlde wlll our nucleophlle aLLack? 1he answer ls LhaL lL
depends on whaL Lype of nucleophlle ls aLLacklng. llrsL, we wlll look aL whaL happens
when a baslc or non-acldlc nucleophlle aLLacks an epoxlde.
O
CH
3
Li
O H
CH
3
CH
3
-
Key Mechanism Step
O

ln Lhls example, lL ls sLerlcs LhaL deLermlnes Lhe ouLcome. Pence, Lhe nucleophlle wlll go
Lo Lhe LLSS hlndered slde. now, leL's look aL whaL happens under acldlc condlLlons.
O
+
H
CH
3
OH
O
C H
3
OH
HOCH
3
Key Mechanism Step
O
H
+

As we know, Lhe flrsL Lhlng LhaL happens ln an acld-base reacLlon ls Lhe proLon Lransfer.
When we Lransfer Lhe proLon Lo Lhe epoxlde oxygen here, we have Lhe chance Lo see some
sLable resonance sLrucLures. 1he mosL sLable resonance sLrucLure here ls golng Lo be Lhe
one where Lhe carbocaLlon ls on Lhe mosL subsLlLuLed carbon. 1hls makes Lhe subsLlLuLed
carbon Lhe more elecLrophlllc of Lhe Lwo and Lhus drlves Lhe nucleophlle Lo Lhe MC8L
subsLlLuLed carbon under acldlc condlLlons.
O
+
H
O
H
+
C
+
OH
Now is most
nucIeophiIic
carbon via
resonance

Crgo II, D|ff|cu|ty:
Þ a g e | 143

We can use Lhls Lo our advanLage and can deLermlne whlch slde cerLaln nucleophlles
aLLack by uslng Lhe rlghL reagenLs as shown below.
O
H
+
CH
3
CH
2
OH
O
NaOCH
2
CH
3
CH
3
CH
2
OH
OCH
2
CH
3
OH
OH
OCH
2
CH
3

ln Lhls flrsL reacLlon, we used baslc sodlum eLhoxlde Lo geL Lhe subsLlLuLlon aL Lhe less
subsLlLuLed carbon (sLerlc conLrol). ln Lhe second reacLlon, we used acldlc eLhanol Lo geL
subsLlLuLlon aL Lhe more subsLlLuLed carbon (elecLronlc conLrol).

1ake nome Message: Under ac|d|c cond|t|ons, a nuc|eoph||e w||| attack an
epox|de at the more subst|tuted s|de as the react|on |s under e|ectron|c contro|.
Under non-ac|d|c or bas|c cond|t|ons, a nuc|eoph||e w||| attack an epox|de at the
|ess subst|tuted s|de as the react|on |s under ster|c contro|.
Þ a g e | 144











Chapter S: Spectroscopy

Þ a g e | 14S

#77- SCDAk |s not [ust a dr|nk m|xer anymore
8elleve lL or noL, you can deLermlne much more from a compound's molecular formula
Lhan [usL whaL aLoms are ln lL. We can flgure ouL how many rlngs and/or double bonds are
conLalned ln lL Loo. 1hls can be called Lhe degree of unsaLuraLlon, or Lhe Sum of uouble
8onds and 8lngs (SCuA8). ln many of your specLroscopy problems, you wlll be glven a
molecule formula, and can calculaLe your LoLal number of double bonds and rlngs ln Lhe
molecule uslng Lhe formula (2#C + 2 - #P - #x + #n)/2 where:

#C = Lhe number of Carbons
#P = Lhe number of Pydrogens
#x = Lhe number of Palogens
#n = Lhe number of nlLrogens

ln uslng Lhls formula, you lgnore Lhe oxygen or sulfur aLoms. lor example, Lhe molecular
formula C
6
P
6
nCCl would be (2*6 + 2 ‚ 6 ‚1 +1)/2 = 4, meanlng LhaL Lhere are 4 double
bonds and/or rlngs. A double bond ln Lhls case can be an alkene or a carbonyl. lurLher, an
alkyne counLs as 2 double bonds. lL ls helpful Lo remember LhaL benzene rlngs equal Lo 4
on Lhe SCuA8 scale, (3 double bonds and one rlng), so lf you have a SCuA8 LhaL ls 4 or
larger, Lhlnk benzene rlng somewhere ln your molecule.
CH
3
C
7
H
8
SODAR = 4
C
10
H
8
SODAR = 7
O
C
4
H
10
SODAR = 0
C
5
H
4
O
SODAR = 4
CI NH
2
C
6
H
12
NCI
SODAR = 1

Cnce you have calculaLed Lhe SCuA8 for Lhe compound, you can sLarL on Lhe oLher sLeps
for examlnlng Lhe specLra you have been glven Lo deLermlne Lhe sLrucLure of Lhe unknown
compound.
SLep 2: Look for arene proLons ln Lhe
1
P nM8. 1he number of proLons beLween 6.3ppm-
8ppm, known as Lhe A8 reglon, can glve many clues Lo your molecule. We wlll dlscuss Lhls
aspecL more ln Lhe nexL Llp.
SLep 3: Look for Lhe 2 A's, aldehydes and alcohols ln your
1
P nM8. 1hls ls acLually slmpler
Lhan lL sounds, and can glve you some nlce clues. Aldehydes are sharp slngleL peaks LhaL
show up pasL 9ppm. Alcohols are broad slngleLs LhaL can show up anywhere ln Lhe
specLrum, buL wlll ºexchange" wlLh u
2
C, meanlng LhaL Lhey wlll dlsappear lf u
2
C ls added.
MosL organlc chemlsLry professors wlll slgnlfy Lhls by wrlLlng ºexchange" over your
specLrum.
Crgo I, D|ff|cu|ty:
Þ a g e | 146

SLep 4: Add up Lhe lnLegraLlons ln your specLrum and make sure lL equals Lhe number of
proLons LhaL you have. lor example, lf you have 10 P's ln your formula, buL can only have
an lnLegraLlon equal Lo 3 on your specLrum, you need Lo reallze LhaL each lnLegraLlon ls
equal Lo 2 proLons.
SLep 3: SLarL Lo make fragmenLs and Lhen add up Lhe fragmenLs. uslng Lhe lnLegraLlon and
spllLLlng of each peak, you can sLarL Lo wrlLe down fragmenLs of Lhe molecule. lor
example, lf you have a slngleL wlLh an lnLegraLlon of 3, you know LhaL you have a meLhyl
group (3 P's) nexL Lo someLhlng wlLh no proLons. lf you have a doubleL wlLh an lnLegraLlon
of 2, you have a CP
2
LhaL ls nexL Lo a CP. Cnce you have all of your fragmenLs, sLarL Lo
plece Lhem LogeLher and you wlll be flgure ouL whaL your molecule ls.

Cn Lhe whole, undergraduaLe nM8
dlscussed ln Lhe prevlous Llp, you glve yourself a headsLarL by deLermlnlng Lhe LoLal
number of rlngs and double bonds ln a molecule. ln Lhls secL
common spllLLlng paLLerns for alkyl groups ln an nM8. lf you recognlze Lhese spllLLlng
paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well
on your way Lo solvlng Lhe problem qulckly.
#7
Cn Lhe whole, undergraduaLe nM8
dlscussed ln Lhe prevlous Llp, you glve yourself a headsLarL by deLermlnlng Lhe LoLal
number of rlngs and double bonds ln a molecule. ln Lhls secL
common spllLLlng paLLerns for alkyl groups ln an nM8. lf you recognlze Lhese spllLLlng
paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well
on your way Lo solvlng Lhe problem qulckly.
1he eLhyl group (CP
78- Sp||tt|ng shou|d be automat|c, at |east w|th NM
Cn Lhe whole, undergraduaLe nM8
dlscussed ln Lhe prevlous Llp, you glve yourself a headsLarL by deLermlnlng Lhe LoLal
number of rlngs and double bonds ln a molecule. ln Lhls secL
common spllLLlng paLLerns for alkyl groups ln an nM8. lf you recognlze Lhese spllLLlng
paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well
on your way Lo solvlng Lhe problem qulckly.
1he eLhyl group (CP
Sp||tt|ng shou|d be automat|c, at |east w|th NM
Cn Lhe whole, undergraduaLe nM8 problems are usually noL Loo Loo dlfflculL. As we
dlscussed ln Lhe prevlous Llp, you glve yourself a headsLarL by deLermlnlng Lhe LoLal
number of rlngs and double bonds ln a molecule. ln Lhls secL
common spllLLlng paLLerns for alkyl groups ln an nM8. lf you recognlze Lhese spllLLlng
paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well
on your way Lo solvlng Lhe problem qulckly.
1he eLhyl group (CP
2
CP
3
): a quadrup|et w|th 2n and a tr|p|et w|th 3n
Sp||tt|ng shou|d be automat|c, at |east w|th NM
problems are usually noL Loo Loo dlfflculL. As we
dlscussed ln Lhe prevlous Llp, you glve yourself a headsLarL by deLermlnlng Lhe LoLal
number of rlngs and double bonds ln a molecule. ln Lhls secL
common spllLLlng paLLerns for alkyl groups ln an nM8. lf you recognlze Lhese spllLLlng
paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well
on your way Lo solvlng Lhe problem qulckly.
a quadrup|et w|th 2n and a tr|p|et w|th 3n

CH
2
C
Sp||tt|ng shou|d be automat|c, at |east w|th NM
problems are usually noL Loo Loo dlfflculL. As we
dlscussed ln Lhe prevlous Llp, you glve yourself a headsLarL by deLermlnlng Lhe LoLal
number of rlngs and double bonds ln a molecule. ln Lhls secLlon, we wlll show you some
common spllLLlng paLLerns for alkyl groups ln an nM8. lf you recognlze Lhese spllLLlng
paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well
a quadrup|et w|th 2n and a tr|p|et w|th 3n
CH
3
2P
Sp||tt|ng shou|d be automat|c, at |east w|th NM
problems are usually noL Loo Loo dlfflculL. As we
dlscussed ln Lhe prevlous Llp, you glve yourself a headsLarL by deLermlnlng Lhe LoLal
lon, we wlll show you some
common spllLLlng paLLerns for alkyl groups ln an nM8. lf you recognlze Lhese spllLLlng
paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well
a quadrup|et w|th 2n and a tr|p|et w|th 3n
3P
Þ a g e | 147
Sp||tt|ng shou|d be automat|c, at |east w|th NMk
problems are usually noL Loo Loo dlfflculL. As we
dlscussed ln Lhe prevlous Llp, you glve yourself a headsLarL by deLermlnlng Lhe LoLal
lon, we wlll show you some
common spllLLlng paLLerns for alkyl groups ln an nM8. lf you recognlze Lhese spllLLlng
paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well

a quadrup|et w|th 2n and a tr|p|et w|th 3n

147

paLLerns qulckly, and can deLermlne whlch alkyl fragmenL Lhey came from, you wlll be well
1he lsopropyl group [CP(CP 1he lsopropyl group [CP(CP 1he lsopropyl group [CP(CP
3
)
2
]:
1he L-buLyl group:
]: a quadrup|et w|th 1n and s|ng|et w|th 6n

buLyl group: a s|ng|et w|th 9n

CH
CH
C
H
C
CH
3
a quadrup|et w|th 1n and s|ng|et w|th 6n
a s|ng|et w|th 9n
CH
3
H
3
H
3
CH
3
1P
a quadrup|et w|th 1n and s|ng|et w|th 6n

9P
6P
Þ a g e | 148

a quadrup|et w|th 1n and s|ng|et w|th 6n


148

Þ a g e | 149

Above are Lhree sample proLon nM8 specLra deslgned Lo show a polnL. Lach one of Lhose
Lhree groups has a speclflc spllLLlng paLLern and should be able Lo be recognlzed very
qulckly. Lach eLhyl subsLlLuenL wlll always be represenLed by a quadrupleL and a LrlpleL,
havlng Lwo and Lhree proLons, respecLlvely. An lsporopyl subsLlLuLenL wlll always have a
quadrupleL/mullLple represenLlng Lhe CP, and a slngleL represenLlng Lhe Lwo meLhyl
groups. Cne noLe here ls LhaL someLlmes Lhere wlll be Lwo slngleLs ln Lhe specLra, as
shown above. 1hls wlll happen lf Lhe molecule cannoL roLaLe qulckly ln soluLlon, whlch
causes Lhe Lwo meLhyls Lo show up as dlsLlncL. 1herefore, wlLh Lhe lsporopyl group, you
could elLher have one slngleL wlLh 6P or Lwo slngleLs wlLh 3P each. 1he L-buLyl ls group ls
much more slmple Lhough, as lL [usL has one slngleL wlLh 9P, represenLlng all Lhree meLhyl
groups.

Þ a g e | 1S0

#79- C, M, Þ from the aromat|c reg|on of an NMk
When lnLerpreLlng a proLon nM8, Lhere are few Lhlngs LhaL happen norLh of 6.3ppm.
Powever, Lhose peaks LhaL are observed aL shlfLs greaLer Lhan 7ppm are slgnlflcanL and
should be addressed. llrsL, and mosL lmporLanLly, all aromaLlc proLons wlll shown up aL
6.3ppm or greaLer. 1hus, we can easlly Lell how subsLlLuLed our aryl rlng ls by Lhe number
of proLons ln Lhe aromaLlc reglon. 1he complex formula for deLermlnlng Lhe # of
subsLlLuenLs on Lhe rlng ls:
# of ary| subst|tuents = 6 - [# of aromat|c protons]
Popefully Lhls formula dld noL blow your mlnd. 1hus, lf Lhere are flve aromaLlc proLons ln
your specLra, you have a mono-subsLlLuLed aryl rlng. lf Lhere are Lhree aromaLlc proLons,
you have a Lrl-subsLlLuLed aryl rlng.
More lnLeresLlngly, lf Lhere are four aromaLlc proLons, lL means LhaL you have a dl-
subsLlLuLed aryl rlng. 8uL where are Lhe subsLlLuenLs locaLed ln reference Lo each oLher? lf
you have a para subsLlLuLed rlng, lL ls a llLLle easler Lo see Lhan lf lL ls Lhe oLher Lwo. As you
can see below, para subsLlLuLed rlngs glve very clean aromaLlc reglons, wlLh Lwo doubleLs
beLween 6.3-8ppm. 1hls ls because Lhere are only Lwo unlCuL aryl proLons: Lhe Lwo
closer Lo x and Lhe Lwo closer Lo ?.

X
Y
H
H
H
H
Þ a g e | 1S1


lL ls a llLLle more dlfflculL Lo Lell when you have an orLho or meLa subsLlLuLed rlng however.
1heoreLlcally, a meLa subsLlLuLed rlng should have a slngleL ln Lhe aromaLlc reglon, for Lhe
orLho proLon whlch ls noL ad[acenL Lo any oLher proLons. Powever, ln reallLy, Lhls slngleL ls
usually obscured wlLh Lhe oLher aromaLlc proLons and cannoL be dlsLlngulshed. 1herefore,
lL ls noL prudenL Lo rule ouL a meLa-subsLlLuLed rlng [usL because you can'L see Lhe
aromaLlc slngleL.
CLher Lhan Lhe aromaLlc proLons, Lhe only peaks LhaL should show up aL shlfL greaLer Lhan
8ppm are aldehyde and alcohols (someLlmes). Aldehydes wlll have peaks LhaL are very
sharp slngleLs, represenLlng Lhe proLon aLLached Lo Lhe carbonyl, locaLed aL shlfLs greaLer
Lhan 9ppm, dependlng on Lhe molecule. 1he CP proLon of an alcohol can appear ln a
varleLy of places, dependlng on Lhe concenLraLlon of Lhe soluLlon. Many Llmes, Lhe CP
proLon ls a broad slngleL and can appear aL shlfLs greaLer Lhan 8ppm on occaslon.
1ake nome Message: 1he aromat|c reg|on (6.S-8ppm) can te|| us a |ot about a
mo|ecu|e.

Þ a g e | 1S2

#80- Lveryth|ng you ever wanted to know about a
13
C NMk, but were
afra|d to ask
l guess
13
C nM8 ls klnda llke Lhe yln Lo
1
P nM8's yang. 1he Lwo complemenL each oLher
and glve lnformaLlon whlch ls dlfferenL, buL equally lmporLanL. 1ruLh be Lold,
13
C nM8 ls
much easler Lo lnLerpreL Lhan a proLon. 1here are really Lwo Lhlngs you wanL Lo look aL ln
each
13
C nM8 LhaL you run across:
1) Pow many peaks are Lhere? Lach peak ln a
13
C represenLs a unlque carbon aLom ln
your molecule. 1herefore, lf you have 8 peaks, you probably have an 8-carbon molecule. l
say probably because symmeLry needs Lo be Laken lnLo accounL. 1here ls a very good
chance LhaL equlvalenL carbons, such as Lhe meLhyl groups on a L-buLyl group, wlll glve one
slgnal and Lherefore be lndlsLlngulshable. So, remember LhaL Lhe number of peaks
represenLs Lhe number of 9:;<97 carbons, noL necessarlly Lo LoLal number of carbons.

2) Where on Lhe specLra are Lhe peaks?
13
C, more Lhan
1
P nM8, has cerLaln carbon
aLoms' slgnals fall lnLo very speclflc ranges. 8elow ls a generlc charL of Lhese. 1he mosL
lmporLanL peaks Lo qulckly recognlze are Lhe alkyl carbons (generally 0-60ppm), aromaLlc
carbons (130-160ppm) and Lhe carbonyl carbons (180-220ppm). unllke ln
1
P nM8, you
wlll see 6 aromaLlc carbon peaks 7=7>/ 8;57 you have an aryl rlng because
13
C nM8 doesn'L
care lf Lhere are proLons bound Lo Lhe carbons or noL, lL shows all 6 aryl carbons
regardless.
220 200 180 160 140 120 100 80 60 40 20 00
ppm
C C
C C
C O
C C
C O
C O
X


WhaL wlll a carbon nM8 noL Lell you? unllke proLon nM8, carbon nM8 cannoL Lell you
whaL Lhe carbon ls nexL Lo, as Lhere ls noL spllLLlng ln a decoupled carbon nM8. Also, a
decoupled carbon nM8 cannoL Lell you how many proLons are on Lhe carbon, as Lhere ls
noL lnLegraLlon llke ln a proLon nM8. 1hus, care musL be Laken noL Lo over-lnLerpreL Lhe
carbon nM8.
1ake nome Message: kemember the two th|ngs that are |mportant from carbon
NMk: how many carbons there are and what type of carbon they m|ght be.


Crgo I, D|ff|cu|ty:
Þ a g e | 1S3

#81- 1here are on|y four |mportant Ik peaks.
Amazlngly enough, l8 ls noL used much by professlonal organlc chemlsLs. 1hls ls because
all l8 can show ls dlfferenL funcLlonal groups. 1hus, l8 cannoL Lell Lhe dlfference beLween
any of Lhe molecules shown below:
CH
3
CH
3
CH
3
O H OH
OH

All of Lhe molecules above wlll show an CP peak and varlous C-P sLreLches, buL each
specLra wlll look sLrlklng slmllar. Pence, we should recognlze Lhe llmlLs of Lhe lnsLrumenL
and noL Lry Lo use lL for more Lhan lL ls lnLended. lurLher, Lhere are really only four peaks
ln an l8 LhaL we look for Lo Lell us someLhlng abouL our unknown molecule. Pere, we show
Lhem ln order of lmporLance.
1) Carbonyl peak (1730-1630cm
-1
): 1hls wlll be a very sharp, promlnenL peak and
shows LhaL a carbonyl ls presenL ln somewhere ln your unknown molecule. WhaL
ls less obvlous ls whlch Lype of carbonyl lL ls. lL ls noL as easy Lo dlsLlngulsh
beLween keLones, esLers, aldehydes, ecL.
2) CP peak (3300-3200cm
-1
): 1hls ls a large, broad sLreLch whlch cannoL be mlsLaken
for any oLher funcLlonallLy. Cne problem Lo be aware of ls LhaL Lhe CP of waLer
wlll also show up here, ln Lhe evenL LhaL your unknown ls noL LoLally dry.
8emember, LhaL Lhls can be from an alcohol CP or a carboxyllc acld CP.
3) C-C peak (1300-1040cm
-1
): usually a large, sharp peak, Lhls can be from an
alcohol, carboxyllc acld, eLher, or an esLer.
4) C%n (2230-2230cm
-1
) and C%C (2100-2280cm
-1
) peaks: usually raLher small peaks,
buL easy Lo spoL as Lhey are Lhe only peaks ln LhaL area.



1he blggesL deal here ls Lo recognlze LhaL Lhe l8 has lLs llmlLaLlons and Lo noL Lry Lo geL
more lnformaLlon ouL of lL Lhan lL acLually has. lL would be a mlsLake Lo over-lnLerpreL Lhe
l8 and draw mlsleadlng concluslons from lL.
1ake nome Message: know the four peaks to |ook for |n an Ik and don't over
|nterpret |t.
CP
C=C
C-C
Þ a g e | 1S4

#82- Check out the c|eavage on that mo|ecu|e
As we all know, mass specLromeLry (commonly referred Lo as ºmass spec") ls a meLhod for
molecular ldenLlflcaLlon whlch lnvolves breaklng up a molecule and Lhen deLecLlng Lhe
welghL of lLs fragmenLs. More speclflcally, a molecule ls sub[ecLed Lo a hlgh-energy
elecLron bursL, whlch can cause Lhe molecule Lo become a radlcal caLlon, also known as a
molecular lon (M
+
*). 1hls can Lhen fragmenL ln several dlfferenL ways:

1) Slmple Cleavage: 1he molecular lon loses a heLeroaLom, or oLher Lype of
funcLlonal group. ln Lhls cleavage, boLh elecLrons from Lhe cleaved bond are Laken
by Lhe heLeroaLom x.

R C
R
R
X
+
*
R C
+
R
R
+
X
*
R = aIkyI, aryI or H
X = heteroatom


2) €-cleavage: ln Lhls cleavage, Lhe heLeroaLom remalns on Lhe molecular lon, and
forms a double bond. (1hls mechanlsm ls favored when x= C, S, or n). 1hls
cleavage proceeds vla hemolyLlc bond cleavage.

R = aIkyI, aryI or H
X = S, N, or O
R C
R
R
X
+
*
R
R
X
+
R*
+


3) LllmlnaLlon: 1hls process ls very slmllar Lo L2 ellmlnaLlon, and requlres a free µ-
proLon.

R C
C
R
X
+
H H
H
R = aIkyI, aryI or H
X = heteroatom
*
R R
H H
+
+
* HX


lurLher, Lhere ls one Lype of rearrangemenL LhaL ls also a favorlLe of many organlc
chemlsLry professors. 1hls ls Lhe McLafferLy 8earrangemenL.

Þ a g e | 1SS

O
H
+*
O
H
+*


Whlle Lhls may look dlfflculL, Lhe rearrangemenL can be broken down lnLo slmpler parLs.
1he flrsL requlremenL for Lhe rearrangemenL ls a carbonyl somewhere ln your molecular
lon. Second, you musL have a proLon on Lhe „-carbon (Lhe Lhlrd carbon from Lhe carbonyl).
Cnce you have esLabllshed LhaL you have boLh of Lhese, place your molecular lon ln a benL
conflguraLlon as shown above. 1hls ls Lhe slx-membered LranslLlon sLaLe LhaL makes Lhls a
Lhermodynamlcally preferred LransformaLlon. now LhaL you have all of Lhe parLs ln Lhelr
proper place, draw your arrows and cleave Lhe bonds so LhaL you end up wlLh a charged
enol and a double bond. CongraLulaLlons, you have done your flrsL McLafferLy. 1hls
rearrangemenL ls very common ln mass spec and ls seen on a number of subsLraLes, as
shown below.

O
H
+*
O
H
+*
H
O
H
+*
H
O
H
+*
O
+*
No McLafferty rearrangement
(there is no gamma proton)



1ake nome Message: 1here are three ma[or mass spec c|eavages. ¥ou need a
carbony| and a y-proton to have a McLafferty rearrangement.



Þ a g e | 1S6

#83- 1he n|trogen h|nt (not a ru|e)

!usL llke wlLh some of Lhe oLher ºrules" we have heard of, Lhe nlLrogen rule ls noL a real
rule elLher. 1hls ls merely a gulde, or a suggesLlon, Lo help us ouL wlLh Lhe number of
nlLrogen aLoms LhaL MA? be ln a molecule.
1he ºrule" sLaLes LhaL lf you have a normal organlc molecule, and Lhe molecular welghL ls
an even number Lhen you have an even number of nlLrogen aLoms ln LhaL molecule.
Conversely, lf you have a normal organlc molecule and Lhe molecular welghL ls an odd
number Lhen you have an odd number of nlLrogen aLoms ln LhaL molecule. So whaL ls a
normal organlc molecule? lL ls a compound LhaL conLalns only C, P, n, C, Sl, n, S, and Þ.
Some examples are shown below:
NO
2
MoIecuIar Weight =123.11
C
6
H
5
NO
2
NH
2
NH
2
MoIecuIar Weight =102.18
C
5
H
14
N
2
MoIecuIar Weight =86.18
C
6
H
14
N OH O H
MoIecuIar Weight =111.10
C
5
H
5
NO
2
PO
3
NH
2
O
2
S
MoIecuIar Weight =195.20
C
7
H
18
NO
3
P

Where can you use Lhls Lo your advanLage? 1he rule ls mosL helpful when deallng wlLh a
mass spec problem. 1hus, lf a parenL lon ln a mass spec problem ls an odd number, Lhen
you mosL llkely have a nlLrogen aLom somewhere ln your unknown molecule. l say ºone"
nlLrogen aLom because lL ls unllkely LhaL you wlll run across a molecule ln your
undergraduaLe courses LhaL has Lhree or more nlLrogen aLoms, Lherefore lL ls mosL llkely
LhaL lL wlll only be one lf you have an odd mass.
Þ a g e | 1S7

Cne flnal polnL on Lhe ºnlLrogen hlnL": lL only applles Lo organlc molecules, noL lnorganlc
ones. 1herefore your compound musL have carbon and hydrogen ln lL somewhere. As an
example, Lhe nlLrogen rule does noL work for nC and nC
2
.

1ake nome Message: In a mass spec prob|em, the best app||cat|on for the
n|trogen ru|e |s that |f the parent |on's mass |s odd, you most ||ke|y have one
n|trogen atom |n the mo|ecu|e.

Þ a g e | 1S8












Chapter 6: Study 1|ps and Suggest|ons

Þ a g e | 1S9

#84- Are ¥ou a Learner L|ke Socrates or a Memor|zer L|ke a Super
Computer?
lL has been sLudled, mused over, and conLemplaLed for cenLurles. Whlch sLyle of learnlng
ls beLLer? ls someone who learned Lhe ºwhy" more educaLed or knowledgeable Lhan
someone who [usL memorlzes Lhe ºwhaL"?
lL may be surprlslng Lo you LhaL we are noL golng Lo say whlch ls beLLer. 8oLh have Lhelr
merlLs, and boLh can geL you an ºA" ln undergraduaLe organlc chemlsLry. WhaL we are
golng Lo Lry Lo do ls help you deLermlne whlch one you are. ulfferenL slLuaLlons, dlfferenL
clrcumsLances, and dlfferenL professors wlll lend Lhemselves Lo one Lechnlque over Lhe
oLher.
lrom a LheoreLlcal sLandpolnL, lf you had an lnflnlLe amounL of sLudylng Llme, we would
recommend LhaL you do boLh learn and memorlze as much maLerlal as posslble. 1hls way
you can splL ouL an answer qulckly when necessary and aL Lhe same Llme be able Lo reason
your way Lhrough a new problem LhaL you mlghL never have seen before. Powever, wlLh
blochemlsLry courses, physlcs classes, and uanclng wlLh Lhe SLars, who has Llme Lo do
boLh? Pere, we hope Lo help you declde whlch you would llke Lo do. 1herefore, ask
yourself Lhese Lhree quesLlons:
1) Whlch do you feel more comforLable wlLh? We have all been ln school long
enough by Lhls polnL Lo know whlch we have a preference for. Some people [usL
crave knowledge and cannoL [usL accepL LhaL Lhey need Lo memorlze someLhlng.
CLhers [usL wanL Lo know LhaL facL and move on Lo memorlze Lhe nexL facL.
uecldlng on your personal preference wlll go a long way Lo decldlng wheLher you
should memorlze or learn Lhe maLerlal for Lhls class.
2) Are you golng Lo conLlnue ln organlc chemlsLry or ls Lhls Lhe only Llme you wlll use
Lhls maLerlal? lf you are noL ever golng Lo use organlc chemlsLry agaln, Lhen lL ls
much easler Lo [usLlfy memorlzlng Lhe maLerlal. lf you are plannlng Lo go Lo
medlcal school or Lake more chemlsLry courses Lhen lL may be a dlsservlce Lo noL
learn Lhe maLerlal, as laLer on you may need Lo have a good grasp on Lhls maLerlal
before venLurlng lnLo Lougher Lasks.
3) uoes your professor use Lhe same exam quesLlons over and over agaln? lf so, Lhen
memorlzlng mlghL noL hurL you Loo much. lf your professor Lhlnks of new
problems each exam, or makes you reason your way Lhrough a problem you have
never seen before, Lhen you probably wanL Lo be learnlng Lhe maLerlals.


?ou are golng Lo be Lhe only person who can deLermlne whlch meLhod ls besL for you.
now LhaL you have deLermlned LhaL meLhod, whaL ls Lhe besL way Lo sLudy based on your
preference. 1lme and Llme agaln, we have seen LhaL Lhere ls a slmple answer Lo Lhls: lf
you are a memorlzer, flash cards are your besL sLudy alde. lf you are a learner, Lry Lo learn
as many reacLlon mechanlsms you can.
Þ a g e | 160

#8S- What a tang|ed web we weave.
Well websllngers, we are almosL Lo Lhe end. We have found LhaL Lhls ls a wonderful sLudy
alde for sLudenLs aL almosL any Llme ln Lhe semesLer. All lL enLalls ls creaLlng a ºllnk charL"
beLween funcLlonal groups. SLarL wlLh a slmple alkane and Lhlnk of all of Lhe reacLlons you
know on alkanes. 1hen Lake alkyl halldes and flgure ouL all of Lhe reacLlons you know for
Lhose. ÞreLLy soon you wlll see LhaL you are flndlng mulLlple meLhods Lo geL Lo Lhe same
funcLlonal group and mulLlple reacLlons you can do sLarLlng wlLh a cerLaln funcLlonal group.
?our llnes wlll sLarL Lo cross a loL and you wlll see LhaL all of Lhe funcLlonal groups are
lnLerrelaLed. 1hls ls Lhe essence of funcLlonal group lnLerconverslon (lCl), and ls a very
useful Lool Lo masLer. 8elow, we have placed a sample one for you Lo geL sLarLed on. 8e
sure Lo place condlLlons for each reacLlon somewhere ln Lhe web whlle you are dolng lL.
?our web should be dlfferenL from ours based on Lhe dlfferenL reacLlons whlch are
lmporLanL Lo your class. 1he wonderful Lhlng abouL Lhls exerclse lL ls wlll help you sLudy
and slmpllfy synLhesls problems when Lhe Llme comes.
R
O
H
R
O
Cl
R
O
OR'
RCN
R
O
NH
2
RCl
RNH
2
R
R
O
RLi
RMgCl
R H RCH
2
OH
R O
O O
R-H
R
O
OH
RCH
2
OCH
2
R
RSH
R
OH
O H
1
2
3
3
4
4
5
6
7
8
9
9
10
11
12
13
14
15
15
16
17
18
19
20
21
23
23
2
24
25
26
27
28
1
10
17
29
30
31
3
32 33
34
35
30
36
2
R
OH 37
37
23

1. naCP
2. nP
3
, P
2
C
3. P
+
, P
2
C
4. PeaL, loss of P
2
C
3. 2 Ll
6. naCn
7. P
2
S
8. Cl
2
, hv
9. P
2
, Þd-C
10. P
2
C
11. 8r
2
, Lhen nanP
2

12. P
2
, ºLlndlar's" caL
13. mcpba


14. CsC
4

13. LlAlP
4

16. 8CP


17. k
2
Cr
2
C
7
/P
2
SC
4

18. CC
2

19. ul8Al-P
20. CP
3
CCCna
21. Mg, LL
2
C
22. naCP, Lhen
LlAlP
4

23. SCCl
2

24. P
3
ÞC
4
, heaL
23. naCMe, MeCP
26. 8CP, P
+

27. ÞCC or ÞuC
28. na8P
4
or
naCn8P
4

29. C
3
, uMS
30. 8P
3
,1Pl Lhen
P
2
C
2

31. PCl
32. nan
3
, Lhen
naCP/P
2
C/heaL
33. 8r
2
, 2 naCP
34. nP
3
, naCn8P
4

33. Þh
3
Þ=CP
2

36. LlAlP(C-L8u)
3

37. excess CP
3
Mg8r
Crgo II, D|ff|cu|ty:
Þ a g e | 161

#86- 8e a Chatty Þatty and 1a|k Cut ¥our keact|ons.
We all know abouL Lhose people who [usL won'L shuL up. WheLher lL be ln class, aL a bar,
or ln a llbrary, some folks [usL won'L shuL Lhelr ple hole. lf you are one of Lhese people, use
lL Lo your advanLage. We have found LhaL Lalklng ouL organlc chemlsLry reacLlons can
make Lhem easler Lo learn. When you do Lhls, lL ls very helpful Lo use all Lhe llngo you have
learned ln class. lor example:
keact|on:
CI
+
O-Na+

Spoken as: º1hls ls a reacLlon beLween 1-chlorobuLane, a prlmary alkyl hallde and sodlum
LerL-buLoxlde, a sLrong and hlndered base. 1hls reacLlon wlll proceed vla an L2 mechanlsm
Lo glve 1-buLene as Lhe ma[or producL."

keact|on:
OH
O
K
2
Cr
2
O
7
H
2
SO
4
OH

Shouted out |oud as: º1hls ls a sLrong oxldaLlon of eLhanol Lo aceLlc acld uslng Lhe !ones
reagenL."

keact|on:
OsO
4
OH
OH

Þreached to the peop|e as: º1hls ls a dlhydroxylaLlon reacLlon beLween cyclohexene and
osmlum LeLroxlde. 1hls glves Lhe cls dlol producL."
1ake nome Message: 1a|k|ng out your react|ons, [ust ||ke ta|k|ng out your
prob|ems, w||| make you fee| much better and he|p you to |earn organ|c
chem|stry that much qu|cker.
Þ a g e | 162


Þ a g e | 163

1,2-addlLlon. +4.&!' )++4'4"-
1,4-addlLlon, 136
13
C nM8, 3, 161
AceLoaceLlc LsLer SynLhesls, 4, 146
aldol reacLlon, 4, 144, 147, 148
A|do| keact|on, 143
a|kanes, 2, 31, 101, 102, 170
A|kyne, 33
A|kynes, 4, 37, 103
anLl-Markovnlkov, 40, 41, 42
anLl-perlplanar, 90, 91
aromaLlc, 3, 3, 29, 66, 76, 83, 84, 83, 93,
106, 119, 123, 132, 139, 160, 161
aromaLlclLy, 30, 83, 84
Arrows, 3, 48
8aeyer-vllllger, 4, 116, 117
bases
bulky, 3, 97, 99
b|ock|ng groups, 3, 72
bond |engths, 2, 29
Cahn/lngold/Þrelog, 21
carbocat|on, 4, 19, 41, 44, 43, 73, 89,
100, 110, 111, 128, 131
carbocat|ons, 43, 82
Carbony|s, 3, 86
carboxy||c ac|ds, 3, 70, 71, 114, 118, 123,
126, 127
ch|ra||ty, 2, 39, 40
Clalsen CondensaLlon, 3, 147
Clemmensen 8educLlon, 114
con[ugaLe addlLlon, 136, 137
Cope LllmlnaLlon, 113
Corey-WlnLer CleflnaLlon, 4, 124
cycloaddlLlon, 30, 62
cyclohexane, 3, 62, 63, 90, 91, 92, 106,
132, 133, 133, 138, 139
decarboxylaLed, 146
deuLerlum, 23, 103
dlasLereomers, 3, 79, 80
dlazo compounds, 69
ulels-Alder, 3, 4, 31, 33, 62, 63, 106, 107,
108, 109, 132, 133, 138, 139
dleneophlle, 62, 106, 108
dlenes, 62, 108, 132
ulhydroxylaLlon, 4, 33, 124
dlol, 118, 124, 123, 172
d|o|s, 4, 118, 119, 124
dlrecL addlLlon, 133, 136
L1, 2, 44, 43, 46, 32
L2, 2, 44, 43, 46, 32, 60, 90, 91, 99, 164,
172
LAS sLraLegy, 3, 66, 72, 123
elecLron flow, 48
LlecLronegaLlvlLy, 33
LnanLlomers, 3, 79
enolaLe, 137, 138, 140, 141, 143, 147,
148
enolaLes, 4, 136, 137, 140, 142, 143, 148
Lno|ates, 140
LpoxldaLlon, 33
LsLerlflcaLlon, 33
I|scher pro[ect|ons, 2, 20, 79
free radlcal halogenaLlon, 39, 101, 102
lree 8adlcal PalogenaLlon, 4
lrledel-CrafL acylaLlon, 73
lrledel-CrafL alkylaLlon, 70, 73, 73
luncLlonal Croup lnLerconverslon, 33, 36
Iunct|ona| Group 1ests, 42
geometry, 2, 21, 84, 91, 110
Gr|gnard, 33, 38, 39, 60, 61, 86, 104, 103,
126, 136
Poffman
ellmlnaLlon, 4, 98, 99, 113, 114
Puckel's rule, 29
hydrazlne, 114, 113
hydrogenaLlon, 40, 37, 103, 132, 133,
134
l8, 3, 33, 163, 164
lsomerlzaLlon, 128
IUÞAC, 18
|ab sect|on, 13
|eav|ng groups, 2, 3, 37, 38, 43, 76, 81,
99, 113, 114
LeLLs nlLrlle SynLhesls, 4, 123
Lew|s ac|ds, 3, 93, 94
Markovn|kov, 2, 40, 41, 42
mass specLromeLry, 164
McLafferLy 8earrangemenL, 163
Þ a g e | 164

McMurry reacLlon, 4, 78, 120, 121, 122
medlcal school, 11
meLa dlrecLor, 68, 69, 70, 134
MeLhanesulfonaLe, 37
n|trat|on, 93, 96
n|trat|ons, 3, 93
nlLrogen rule, 166, 167
nM8, 3, 91, 103, 134, 136, 138, 139, 161
nomenc|ature, 17
nucleophlle, 17, 44, 43
nuc|eoph||es, 2, 33, 36, 43, 37, 60, 93,
126, 133, 136, 131, 132
o,p dlrecLors, 67, 68, 72
ocLeL rule, 19, 23
CrganocupraLe, 39, 60
CrganoLlLhlum, 39
organomeLalllcs, 3, 39
Crganozlnc, 39, 61
CxldaLlon, 33
Þlnacol reacLlon, 4, 118, 119
Þo|ar Aprot|c So|vents, 33
Þo|ar Þrot|c So|vents, 33
ÞolarlzablllLy, 33
Þre-Meds, 14
professor, 11
proLecLlng groups, 4, 129, 131
Þrotect|ng Groups, 129
rad|ca|, 3, 31, 39, 41, 42, 49, 30, 76, 88,
89, 101, 102, 164
8educLlon, 4, 33, 73, 103, 114
resonance, 19, 23, 26, 29, 37, 44, 43, 63,
81, 82, 106, 107, 133, 143, 131
kesonance, 2, 23, 26, 29, 133
8eLrosynLheLlc analysls, 3, 64
8oblnson AnnulaLlon, 4, 137, 139
S
N
1, 2, 4, 33, 44, 43, 46, 49, 76, 110, 111,
112
S
N
2, 2, 33, 44, 43, 46, 49, 60, 76, 140
SCuA8, 3, 134
solvenLs, 17, 31, 32, 33, 46, 100, 101
strong ac|ds, 2, 34
Subst|tut|on react|ons, 49
SynLhons, 64
1-buLyl groups, 3, 90
1oluenesulfonaLe, 37
1rekkles, 122
1rlfluoromeLhanesulfonaLe, 37
WlLLlg, 19, 33
Wolff-klshner, 3, 4, 73, 114, 113, 119
ZalLsev, 4, 98