C| CHEM- 334 EXAM | Roview Material Chapter IT: Aoactions of Aromatic | Raockons of sida choins Cempanis *Pregio specific reaction shore Gris a = 7 > Oh Sisto the Boalt eral , HBr t HBr PHO. pubs Brin via we. tee Xt : AN For? Nbr Fee radical fore Prarbocation ue asi 4. Oxidation of Side Chains ors te Otte nef ens of | bunwic evton is ocdized to COOH inless the carton © | 1S already -complately occupied. like ter Bo. | 3.Eleclophilic Aromatic Substitution (EAS) | OneNpeation seit , : 9 ne Br= Br Feb Bt =Febr, 7 GeO Re, Onar O° 7 tg, |. Oe eS > a Q Ren) —s ors Abe, Ow Ones, om ‘in os > sy LQ soy | ‘Ae a : foopraif ne ¥ oper 20 AL NAL Q f— Bee ° | ao a Pe e hb = Gy © GAG) ‘0! NoxoFe/HCI Nh a <> > & Su, of (ais) Oy falter, oes (per 3® ei H aoe Goming) Yeo ONe (RC poas Ore, @ Alkylation (Fietlle~ Crafts) paeci ot Pnole beware of covbomtion | AlCl, re wlin te okey) | op het Ss eancting iS hs | only pls applies. 10-993 cov Pro! Non ae ot work 0 / opt carbons | AN Hite Q | + Rlyalkylotion occurs in reality but ae only nood | to show * EDGE make benzene more nucliophilic + therefore speed up EAS reactions | * ELOG makes benzene less 11 |. Slows down reaction | ® Aaslation # mechanism ‘is Ha some | eta 5, ore as. otlers | Alls | ‘SOC, | A) synthesis of Ada Chlorides * A,, Gray A, b) Acid Anhydrides obo work Orit Me ia. Redaction ag Vai 7m i One Om mg ahede, or. “fre c oS ay :1) CREM- 354 EXAM &) Review Material ony | = eP. |B. Disubstitved, Genzones welt | 9) Meh, > No, (ElLVG.) => EXCEPT FOR HALOGENS | Ortho) Para > cH, (€06s) “ | POP Directing | Sala irectin © Strong Activating 1 © Madarotely Deoctiveting 5 NH, Ata OR. O-R , stig pes seers i 1 aga", . amides, fot. esters FoSe | erly Fam 5 BEEN, a ® Weak Activating a : Faron k alky| groups + Ph = | @ Strongly ,Deactivating t © Weak” deactivating 1 =n, Meee ey G Halegens (Ci, F, Be, ---) ! ~ Re Ro,p directing must be pub in First # maka cannot come first in synpwsis %/ it is deactivating unless other substituents nazdl to be putin make positions 1) ‘anole’ Activating depends on LPE ovcileble ; Deoctiveting Woo Wich pulls asay © dhorge fom ving Fnole! Pide shramper activating group Fist # nole* ow excess, Bees ao or 85 hv< ~|Chapler 18: Aldohysas + Ketones (ont'A) 3. Synthesis of Ketones &) Ozenolysis =~ 0% = =< ons” = | ©) Friedal Craft Acylation : 7 | node St pA 2 OY AlCl ) & Alechol Oxidation ° Ky AK or HCr04 /kerno,, 3) Orgromatellic. Addition to Nitrile Rmx N a eX a~Na’ | © oa Aw Barman AB a) Symmetrical Alkyne Hydroboration ge Oxymarcuretion = Ons —"N @ 4,0, NoOH @) —— OH (OAC), yh @h,50,, H,08) feduction of Acid Chlorides, a I @LAH Net On aon ° Maen QUAM Ces (PN owe torlap In these two mechanisms, | ate © bmds ple | ceogaet Fest ®) Raduction of Esters + Nirils ares mock ‘Abler His bonded, weiereR trove. Nace bond 2, i. @otel-H a , formed by cleaving initial ak , _ 4 + BOK bording “o/ reagint. | | | ‘on’ Igoe | @He Workup | A) Hydreboration (am4a) ObHy mA eH = | @x0,.m0n 4 =e wrt | we (eno wtomerizestion, a Toutomerization: oF 3 ppm A A = a, 4, 7) e) asin of Terminal a CY gute on Cy gue H,0 | | | | #) Gilmart s Reagents (aoe: | A ofaoy ok © Gilman's deesvit react wo) ! | | Oyo e . Aldehydes Anbydrides Ketonss tries >a A FHhis 1S ond season we UR gilmon's to make ketones ahi +4 ctor productsON at + i) Clemmanson or Wolfkishner Reduction Bn! oO HO, reflux AY Comm. — wolfe Neal, ROA ) Nitrogen Agelsghiles.— ae 9 oo Se @ NaBH, Xx a @ Wem” A Alda OP) Ciwine Aowing Kako | it a ANS, Ni Aco : A Baty GO NoOoK Ae A He (2° awiws): 9 sti, “Swe PA ER KR SR ax. GJ oo vy Hot > oF i We Nn Anok that this is halphol for of acebjation of ketonas5] > C h) Avene. Diazoriwn Salt Reactions ey" Ma eNO, Ren ‘ancl Or CO role? tis is explosive + needs 40 be kept cold or Ke or (oy ters “iste < a Gi | 1) Fluronation + Todination Cnckelal in stone factions) i0) Esterification (Fischer Esterification) Be a f + HO | Nom a © Eailibrwm Rasetion j con le pushed fomords. preduct by taking excess olechel - femoving 4,0 from products © Mechanism : @ _ A i a Addi r An BA 5 A= AN =— Ww on Ho = on 5 aN Ce ee ee YR Po Se Rr 6 elk “ee ® Naming Esters —> indicate. tua group aHachad ito Are. af —— Bhoned GP ine emai ail ae Which tht btbix- "ic acid is replaced by. "ae ° ” AAS Baek | ‘O = = ash greep Cs, on Dea rrewa. of carta acid! Ace Atl 5 i Cs Mathyl Cylchaere.corbory ole © Internal, Esterifention Ne HSO, eas Yon — > ° ° AXA, Beis Ho: on | é MA | e |One nog ¥ oS i“ x one Faia > He mo, me ares HN os ao Natt. GMM, INOS 1,90, wer Fdin” oot Sav i doe ork Nat, Ho, (Yo Stes OOS Ces CssCHEM- 234 Lecture Notes sn f 3. Acid Chloride. Reactions (cont'd) ° no HCl gereroteal A, elk — AA no pyridine nance Ag Cypher satin 2 AAs EN Mechanism, 3 = Be Aga = to “$s uo 3 ee cre a (eee) 8; ee atte ie | CHEN 322 Practice Exam ae4 5. Raoctions of Esters 0) SapBonificotion (bose hydrolysis) - ‘min od G ° “@NoOH . Aemachonism iS So ee con ©) Esters > Amidas lass practical + inftident)") it’s eosier ) 5 Nwoted amides foree mene mikes ps - reno C “ io Ri AN pe! ee fg = 0h ran amas Aus + R-OH Machanism’ Ad NH, , bose takes H trom Ally , eliminate . a -OR Frm Of e-), add H to -OR via acid formedly, Add Angydrides Raoctons CHEM- 334, Lechuve Noles oat t oR rn ONa0 oy mole? Sata So KG oo,.- A CHEN CHEM - 334 Lecture Noks a Sheay 2) Tronsesterification (Ester —> different ester) AL Se ORE Lyy RS @4o .: CRERA- 222 Pretice Fv nun st4 | © Paoctions of Amides — Carboxylic Acids § HO ° ae et Sa, ° SOT al NH, al N © Ht Workup ° HT/HL0 ° AL NON ao Non i QNeOH | Pan AO. S Van \ metal lies a) Acid Chloride. 4 Alcohel ROR A, oo, Ag HY workyp @ 8) © i 2S aes Wa St ch . Ri Ly © pr Wedaip on Wee A eeCHEM- 334 Lecture Notes oncey P > orfzi/zo —|Chopter Aa: Condensations + o- Substitvtions of Cacbony|s. (cont'd) |. Thacmodynamic Enolode Formation , 7 2) must “sek up an equillibriom of deprstonation = prokonation until | the most stable cendlate. forms, es | ®) use Pon / Po fnprereed seul HAE ce © ia. Kinglié Enolate Frrmation Hf ee oO | a) ro equilibrivm allowed I | pnd string bulky base. that grabs I a | _prokm thats easiest to get og; a . 4 ef we Be Ba { i to =— | 5 8. Enolote: Reachons @) Halogenotion @ Ha o- corkon oO “ dg a y Ss 5 XK asd of Gree 3 © bose Machonism Rimi ctpyane yy. er Fo @ or be Ce | @ Acid Mochonism oh hose Ge" oe — bc Cosase&@ CHEM-334 Leche Nokes €) Alleylotion of fgtoras OE and 1° allylic halides (Aa Renole? ole! con Use I alla) halides, FP beney| halides (@~), We car), USe enolates for SN reactions, bout ‘con also use in addition reoctons such a addition to carbony!s@ go ae | |.) Adel Action (Curse) A OW A+ Ay, oS By Exolode. tan _ . Bo hydroxy ketone OMechanisin fer Self Aol: Condensodion a g ROOK 2 RO Addition go PRG ES KR ee 4 (2 ee) evmation on . AK @ Acid 3 Cotolyzed meen » & tn nod o- hydrogen a) 2) U5 ketene os nucleophile “*/ ketonas ore not oS reactive os cachophilts (°. won't react usaf) ie ° RE ects A, tt oO ° y AS A EBS ucphits: Lg Ja] 4) Introwlecolor Aldel (cont'd) RAS OH, AA, @ Ona ( | way Ck OCF ” No So 4) Clasien Condansation (Esters + Endlolé | Eloctrophites) . * - AS os AA, A. Ow gues ve 40° os the bose inskod of. On” 1 SOH would io lear ley lye ese to corkany acid \ Cif ue ved qnethar allot j would Un —_ idaxrgo transesteri cat D2 } Anos = Jeo = VQ pow 8 ko x0 A> ci =— oy Eg 7 ANN eed ‘Rdprotoration drives eeaction forward ® “note: nooo ester wy] & & hydrogens to do this reachon whon using weak alvenide b boses. i EL0® bl only | echyliagen ada i strong bases «/ preformed enolates also worksfo | reece “pob nok have te worry @. presence i. F at's on electophile when OH ° CHEM-234 Lecture Notes - 04/23/20 Nole? Con Use Strunggr bose and perform ovr enolate (stepuire) Jah OS ier “pn ) eo A\dol Les er making, 5 +6 member rings 0) iF enolate. Toned eT a T member cing wou lh be made So Prone L stable enolate oo ‘ne @5 uu alespilc“Gactrophile wrolade [rap alia ea QR | coAin pei oto, ® Ark, io fh Orokp : : + ') Crossed mbD (a. aiff estes oct) ; ol Ester hos no &-hydegens atom if 7 a \AY 9 OH wap 7 ]H* Wekup: gels —__ ney 5 * tha oy ONAOEt 5 Aw aN Ba Ve Sep AA _ j ADA oN Bae NE 0” ‘o" yp @ Ht wrkue i ' @ »/ _freformad, Enololes go Pee LOA Se ae ee . Etiounation 10% Obrm | aie PPR OW Yow. Overview hole? Tmportont doservtion in Synthesis as ~e : - on fi x - , tee oF (oan REE ee Oeic CREM-334 Lecture Noles ShrayP, 9) Closien Condensation (cont a) out i ome. he Bivins o7 LOS G16 : — Uk oN OS0RES RA on 2 09 0 a ° ) @HO,4 aay Ah On VO @ Bose Effects Ester Raoction | ° © RS ales Ave Aydvalysis Paduch> ° WA Os, SA TransesteriFication 0° h) Taskrawanlocs tor Closen ( Dieckmann Condnsetion)CHEM-234 Lechite Nokes nee 5) Michael Additions (conjugate. Additions) ae OAdditions. to B= unsoturated carbonyls “ps 5 on D+ nucleophile Hacks 6 position all + does w/ specific nucleophiles Attacks 4 position °/ of resomonce. structwres where enclates can be found * S02 im 00 oe feo (= f= pee ey connst_contrl sheng rurlegphiles (Grignords]orgene Lithivws) thay attack both §* “positions ° 5 7 pA (OE ow | ore Os) re * SS o : aI cay wt, we have more corrbol to add @ B-position w/ weaker nucleophiles © 0 °° ° cxampls> AK Jt AL °° oe ° Se B-dikeones oo ed Bhebeskes A UA Nig NHR, NAR, + EA) A- heb iris B- diester Gilman's Raogpxit (dialey| cwprates) Enaming| 3) Michoel Additions (cont'd) @® Common conjugate: addition 8 ° io & | rashes Kdows Esters electrophiles pm Amides, my mM NR @H* Workup ¢ ; Ty : @Mechonism , & o oe Vere Bo oat 5 eto “ Coon Syl ex foe) ee eon oft ra =o ae ==etS 4 { (a epiv.) 5 Y ‘ Maio Ss No ak fr equiv Na o 0 ae ° iin she. OO, or ¢ @® ao, Ht om" o °° > Eto 6 =o fl CANA i i o%me | ~y CANA, SA wr ati N a ey RTCHEM- 224 Lecture Noles shreyP j) Michael Additions, (amt 4) mee ® Additions w/ organocuprotes (Gilman's ) E: Ole coli ole: Enomine ‘acts as an @p* Workeup enolate equivalent 3 Ne wy OPA Cou q | Oar aan Ct Ph I te a $ == te 3 fi S 4 , A _/ oon | k) Enolaes of -dicarbonyl compounds AL BA ( eee ") : age iVzatiem eka 20 éKoe Anil | sinbellion akon Lester © POH +PoR are sheng enough 4 dee products 7can, wie use. © oe = SE + wet Pko= 10 pKa = Mle , oc@&t Sm ef