Kinetic and Organic Reaction Mechanism

Kinetic and Organic Reaction Mechanism
Pertemuan ke-6
Reactive Intermediate.
Radical, carbene, nitren, carbocation, carbanion, aryn.
1
Chapter 4
Reactive Intermediate
References
E. V. Anslyn, D. A. Dougherty: Modern Physical Organic Chemistry, University Science Books, 2006.
R. A. Moss et al.: Reactive Intermediate Chemistry, Wiley, 2004.
D. E. Evans: Harvard University; Advanced Problems in Organic Chemistry and Chemical Biology, 2006.
I. Fleming: Molecular Orbitals and Organic Chemical Reactions, Wiley, 2009.
A. Rauk: Orbital Interaction Theory of Organic Chemistry
F.A. Carroll: Perspectives on Structure and Mechanism, Brooks/Cole, 1998.
T. H. Lowry, K. S. Richardson: Mechanisms and Theory in Organic Chemistry, Harper Collin, 1987.
F. A. Carey, R. J. Sundberg: Advanced Organic Chemistry, Kluver Academic, 1990.
R. Bruckner: Advanced Organic Chemistry, Elsvier, 2002.
2
Huckel Molecular Orbital (HMO) and substituents
Note: definition of substitution designation (I. Fleming) ... for further discussion
3
Reaction Intermediates - Intermediates as Local area Minimum
Intermediate vs. transition state
Ref pdf: Dougherty 1989 JACS cyclopentadienyl radical
4
Reaction intermediates - intermediates
The Appearance of reactive (short-lived) intermediates is an endothermic process
... ETS ~ EIntermediate (late TS)
E.g. carbocation:
5
Reaction intermediates - intermediates
Bell(s)–Evans(s)–Polanyi principle:
6
Radical - history
• Radical (= "free") on carbon - unpaired electron and charge 0.
• Gomberg (1900):
• Lankamp et al. (1968) (NMR):
7
Radicals - conjugation = stability
Examples of long-living radicals (hydrazyl is commercially available):
Etc.
8
Radicals - Detection and Identification
EPR ... spin of electron
The energy difference between the two quantum states:
ΔE = h = geH0
... g: spectroscopic resolution factor (magnet torque and electron torque
ratio; 2,002 for e-);
e: is Bohr's magneton (9,27x10-21 erg / gauss); Ho: Magnetic field size
- hyperfine signal splitting in the methyl radical (1: 3: 3: 1) (cleavage due
to electron interaction - 3 equivalent protons)
13
erg (1 erg = 10−7 joule) … ergon (řecky) = práce
Radicals - Detection and Identification
Signal splitting in the ethyl radical:
10
Radicals - Structure
Alkyl radicals: both planar and pyramidal ... inversion (analogy to ammonia)
Pro. chlorination of (S) -1-chloro-2 methylbutane
or
racemáte
11
Spectroscopy: The EPR distinguishes the planar and pyramidal structure
- the methyl radical is almost planar, ie carbon is sp2 (type p-orbital ...  radical);
- the trifluoromethyl radical is pyramidal, ie sp3 (hybrid orbit ...  radical)
... ie EWG substitute: interaction of SOMO (2p) and LUMO )
(Pauling: due to the high electronegativity of F, the C-F bond has more p character
than C-H)
12
• t-Butyl according to EPR is not planar from steric and electron (interaction
with  bonds) reasons:
Ref pdf: Pacansky 1991 JACR Structure of radicals
•Rigid formations such as 1-adamantyl and 7-norbornyl radicals exist but their
stability and rate of formation are low:
13
Radicals - Stabilization
Stabilization SOMO–HOMO (3-elektrons, 2-orbitals), i.e. with partial destabilization

over the cation; if ESOMO is high (e-donor substituent) then SOMO–LUMO
X: … stabilization through the HOMO substituent; the nucleophilicity of the radical is

higher; the radicals are well oxidizable (ESOMO is high)
Z … stabilization thanks to the LUMO substituent; the radical is more electrophilic
(ESOMO is low)
14
C … stabilization thanks to -delocalization; ESOMO does not change
Radicals - Stabilization
Reaction Z- vs. X-substituted C = C with radical: radical polymerization
Different interactions:
15
Radicals - Structure and hyperconjugation
Loss of planarity in radicals with EDG also thanks to:
hyperconjugation of the orbital with an adjacent  bond, e.g., ethyl radical:
16
Radicál - Appearance
17
18
AIBN
(azobis-
isobutyronitril)
19
Photochemistry - Radicals and Biradics
20
Radicáls – radical traps (spin)
- Intramolecular capture
26
2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)
... radar trap; additions to reactive groups; biomolecules
... detection by MS, NMR, etc.
Zdroj: M. A. Hossain, J. Biol. Chem.

260, 12920-12926, 1985.
22
E.g.
- nitrones, nitroso compounds
• antioxidants (vitamin A, C, E) as radical traps
23
Radicáls – reaction
E.g.
- Fragmentation
- addition
- elimination
24
Radicáls – reaction
Chain reactions
25
Carbens – Structure
Neutral particles with a non-bonding electron pair:
Linier Non-linier
- Linear Structure (Sp hybridization): electron structure with unpaired electrons

(ie triplet) in two orbitals perpendicular to the same energy.
- Non-linear structure (~ sp2 hybridization): The orbital in the plane of bonds
has a hybrid character (mixing the waist), ie it becomes a part of the system
(and has a lower energy) and the perpendicular orbital is pure p: triplet and
singlet ).
The bending of a linear triplet does not yet mean a change in multiplicity, since
the pairing of electrons is associated with energy intake.
Triplet is the lowest electron state. Singlet with a filled orbital is higher energy
31
Carbens – Structure
Viz pdf: Goddard 1992 JACS Carbenes S-T gap

Tomioka 1997 ACR Persistent carbenes
27
Carbens – Stabilization
Energy  (spn) orbital is not significantly affected by the substitute.

The substitution quality can change the levels S0 and T1.
X: ... restituent increases the energy of 2p orbitals (increases the separation between
2p and  energy); ie the baseline is S0
Z, C ... reduce the separation between 2p and  energy; ie the multiplicity is usually T1
28
Carbens – Detection and Identification
- reaction
- matrix isolation (spectroscopy)

- EPR (triplet)
- Technic of time resolved spectroscopy
29
Carbens – Formation
The formation of carbenes (in singlet state):
Diazoalkanes or dialkylazirins
or hv
or hv
• N-nitrosoureas  diazoalkanes
base
30
The formation of carbenes (in singlet state):
• Tosylhydrazon
• -Elimination reaction
base base-H
• Carbenoid formation (Simmons-Smith reaction)
(carbenoid)
carbenoid: a singlet carbene stabilized by association with metal 36
Triplet Carben may originate directly by sensitization (spinning law!)
or photochemical route from the triplet excited compound.
... or indirectly (by relaxing the singlet carben to triplet)
Typical reactions of the singlet carben are the polar reactions,

whereas in the triplet reaction the radicals:
37
Carbens – Reaction
Reaction of singlet carbenes (examples)
- dimerization
- cyclopropanation
- reaction with Lewis bases
33
Reaction of triplet carbenes (examples)
- cleavage of hydrogen (tunneling - triplets only)
- reaction with (triplet) oxygen
34
Reaction of triplet carbenes (examples)
- Addition to double bonds
35
Nitrenes
R N
Similar to carbenes: the triplet is a biradical and basic state:
- the energy of the triplet nitrogen (NH) is 36 kcal / mol (151 kJ / mol)
lower than the singlet (Coulomb repulsion decreases, T is less reactive
than the singlet)
Singlet states are (twice) degenerated due to high symmetry

... are generated directly from singlet responses and mostly do not
participate in bimolecular reactions (converts to triplets)
36
Nitrenes
The emergence of,
for example,:
azide
or apparently even in the Hofmann rearrangement (amide + NaOH + Br2)
Reactions, such as insertion into a bond
37
Carbocation
Carbene ions (CH3+), ie formally "carbenic”
Carbonic ions (CH5+), non-classical (hypercoordinated)
Ref pdf: Hehre 1975 ACR carbocations
38
Carbocation-Structure
Hybridization sp2 - planar
Stability: - Hydride ion affinity (HIA)

- It also depends very much on solvation!
ΔH f / kcal/mol (kJ/mol)
kation 0 HIA (R+) / kcal/mol (kJ/mol)
methyl 261 (1094) 312 (1307)

ethyl 219 (918) 273 (1144)
i-propyl 192 (804) 247 (1035)
t-butyl 164 (687) 230 (964)
allyl 226 (687) 256 (1073)
vinyl 266 (1115) 287 (1203)
benzyl 213 (892) 234 (980) 39
X: … strong stabilization; LUMO is high (reduces reactivity with Nu, eg

C+ (NH2)3 is stable in water.
Z … poor stabilization (HOMO substituent Z is too low); increases Lewis acidity of the
cation
40
C … excellent stabilization of delocalization (e.g., allyl or benzyl cation)
Stabilization by hyperconjugation (alkyl may be considered an X
substituent)
41
Carbocation
Electronic effects
Reactions - rearrangements
42
Group migration is very fast: NMR
1,2-migration
43
Carbocation-Rearranggement
44
Carbocation-Emmergence
1960 (Oláh): alkyl carbene is formed in the presence of superacids
or
Pro. emmergence of tropilium
45
Carbocation-Reactivity
Reaction in water
Lifetime in water
46
You do a lot of work before you really convince yourself that you have
observed something, particularly in a field where for decades and
decades people have tried and failed.
George Andrew Oláh
47
Carbocation-Non-classical ion
"Classic" example: 2-norbornyl cation:
C NMR (-70 oC):

13
1 peak at +101,8 ppm (J = 53 Hz) (atom 1, 2, 6)

1 peak +162,5 ppm (J = 140 Hz) (atomy 3, 5, 7)
1 peak +156,1 ppm (J = 153 Hz) (atom 4)
Ref pdf: Olah 1983 ACR 2-Norbornyl cation
48
Carbanions
-
sp3 hybridized carbon: H3C:
The negative charge on carbon is often simplification:

For example, t-BuLi has a polar C-Li bond and a small neg. charge on C
(13 C NMR)
Formation: organometallic compounds; addition of a nucleophile to an

aromatic compound..
Reaction: SN2; etc.

Carbanions are easily oxidizable! 57
Carbanions-Stabilization
X: ... destabilization; increase nucleophilicity and Lewis basicity

Z ... excellent stabilization due to LUMO substituent Z (including -CF3);
-R3P + i -R2S + stabilize anion (ylides) due to the inductive effect and  * (3d
orbital) enolate anion: overall oxygen carries the largest (-) charge but in HOMO it
is carbon:
C … HOMO does not change; but the reactivity with respect to the 58
electrophile is lower due to the lower carbon coefficient
Carbanions-Stabilization
Carbon acid acidity - delocalization
The mixture of negative charge orbitals with the methyl orbital denies
the logical reduction of acidity by increasing the number of alkyls due
to their electron donor effect.
Acidity (exp.) Increases: ethane <propane (2o hydrogen) <methane

<isobutane (3o hydrogen) in the gas phase; In addition to electron
effects, the steric effect also plays a role.
But: stabilization by a good electron acceptor (I, M) 59
Anion radicals
neutral cationradical anionradical

molecule
52
Anion radicals
Examples of Formation
anion anionradicál
anionradicál
53
Aryne
o-benzyn
p-benzyn (Bergman Cyclization)
Ref pdf: Sander 1999 ACR Benzynes 62

Kinetic and Organic Reaction Mechanism

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Kinetic and Organic Reaction Mechanism

Ref pdf: Dougherty 1989 JACS cyclopentadienyl radical

• Lankamp et al. (1968) (NMR):

Ref pdf: Pacansky 1991 JACR Structure of radicals

Stabilization SOMO–HOMO (3-elektrons, 2-orbitals), i.e. with partial destabilization

X: … stabilization through the HOMO substituent; the nucleophilicity of the radical is

Zdroj: M. A. Hossain, J. Biol. Chem.

• antioxidants (vitamin A, C, E) as radical traps

- Linear Structure (Sp hybridization): electron structure with unpaired electrons

Viz pdf: Goddard 1992 JACS Carbenes S-T gap

Energy  (spn) orbital is not significantly affected by the substitute.

- matrix isolation (spectroscopy)

• Carbenoid formation (Simmons-Smith reaction)

or photochemical route from the triplet excited compound.

... or indirectly (by relaxing the singlet carben to triplet)

Typical reactions of the singlet carben are the polar reactions,

- reaction with Lewis bases

- reaction with (triplet) oxygen

Singlet states are (twice) degenerated due to high symmetry

Reactions, such as insertion into a bond

Carbonic ions (CH5+), non-classical (hypercoordinated)

Ref pdf: Hehre 1975 ACR carbocations

Stability: - Hydride ion affinity (HIA)

methyl 261 (1094) 312 (1307)

X: … strong stabilization; LUMO is high (reduces reactivity with Nu, eg

Pro. emmergence of tropilium

George Andrew Oláh

C NMR (-70 oC):

1 peak at +101,8 ppm (J = 53 Hz) (atom 1, 2, 6)

Ref pdf: Olah 1983 ACR 2-Norbornyl cation

The negative charge on carbon is often simplification:

Formation: organometallic compounds; addition of a nucleophile to an

Reaction: SN2; etc.

X: ... destabilization; increase nucleophilicity and Lewis basicity

Acidity (exp.) Increases: ethane <propane (2o hydrogen) <methane

neutral cationradical anionradical

p-benzyn (Bergman Cyclization)

Ref pdf: Sander 1999 ACR Benzynes 62

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