Substitution elimination reaction in cyclohexyl system for organic aspirants

1. Substitution &
Elimination Reaction in
Cyclohexyl System
BY K.
LOGANATHAN
ORGANIC
CHEMISTRY

2. Dynamic stereochemistry deals with the studies of
effect of stereochemistry on the rate of chemical
reactions. This involves bond making or bond
breaking or conformational transformations.

3. One of the important reactions is the substitution
reactions. Substitution reactions are those reactions in
which an atom or a group of atoms (function group) in a
chemical compound is replaced by another atom or
functional group. It is mainly of three types, i.e.
Electrophilic substitution reactions , Nucleophilic
substitution reaction and Fee radical substitution reactions.
Dynamic Stereochemistry of acyclic and cyclic molecules

4. One of the important reactions is the substitution
reactions. Substitution reactions are those reactions in
which an atom or a group of atoms (function group) in a
chemical compound is replaced by another atom or
functional group. It is mainly of three types, i.e.
Electrophilic substitution reactions , Nucleophilic
substitution reaction and Fee radical substitution reactions.
Dynamic Stereochemistry of acyclic and cyclic molecules

5. Substitution Nucleophilic Unimolecular (SN1)
In a cyclic system, the mechanism is affected by the axial-
equatorial positions of hydrogens. For example, in the
acetolysis of cis- and trans-4-tert-butyl cyclohexyl tosylates
(a) & (b), 1,3-axial interaction leads to a faster SN1
reaction. In case of cis isomer, the tosyl group are at axial
position which have 1,3-non bonded interaction with the
axial hydrogens leading to a faster SN1 reaction than the
trans isomer

9. Substitution Nucleophilic Bimolecular (SN2)
• In case of cyclohexane derivatives, the SN2 reaction involves a
transition state in which a penta-coordinated carbon atom to which the
leaving group (X) and the incoming nucleophile (Nu) are partially
bonded as shown in next slide.
• The main interaction is in between Nu and the two axial hydrogens in
figure 1 and between X and the two axial hydrogens in figure 2 for the
trans and cis isomers respectively.
• If Nu is bulkier than X, transition state in figure 1 is of higher energy
than transition state in figure 2 and the equatorial isomer react at a
slower rate. Thus for the 4-tert-butylcyclohexyl bromide, the cis
isomer reacts approximately 60 times faster than the trans isomer
with sodium thiophenate (PhS-) in aqueous ethanol

13. Most of the substitution reactions proceed either via
racemisation or by inversion of configuration. But there
are nucleophilic substitution reactions which proceed via
100% retention of configuration. This type of reaction
involves two SN2 processes and also known as
neighboring group participation (NGP). The reaction
which proceeds via such type of participations has
enhanced the rate of reaction.
For example, 5-methoxytosylates undergo acetolysis faster
than the n-hexyltosylates due to NGP of O atom of the
methoxy group

15. Also, participation of double bond can help
in removing a leaving group if suitably
oriented through NGP. For example, the
relative rate of acetolysis of the three
norborane derivatives (a), (b) and (c) are
shown in scheme 10. The anti-tosylate (b)
reacts 1011 times faster than the norbornyl
tosylate (a) which proves that the double
bond participates in NGP to form non-
classical carbocation which only react from
the right hand side giving an acetate having
retention of configuration. While in (c) there
is no NGP.

16. On the other hand, the syn isomer (c) dissociates without
anchimeric assistance into homoallylic carbocation which
rearrange to an allylic one and leads to the formation of
different bicyclic product (d) (Scheme 11). The 104 times
reactivity of (c) as compared to (a) is due to the σ bond
electron participation.

17. Radical brominations are normally carried out with a
suspension of N-bromosuccinimide (NBS) in carbon
tetrachloride. During this reaction, NBS serves as a continous
source of very small amounts of bromine, as it is insoluble
in CCl4. Therefore, the conditions of this reaction are ideal for
a bromination in allylic position.
The reaction between cyclohexene and NBS results in 3-
bromocyclohexene in high-yield. This allylic
brominationresembles the halogenation of alkanes - it is a
two-step radical chain reaction.

18. Allylic halogenation of cyclohexene.
Allylic halogenation of cyclohexene.

20. MECHANISM
STEP 1

21. STEP 2

22. STEP 3

24. E2 elimination
The E2 elimination reaction is also known as elimination, bimolecular reaction. In this case,
the rate determining step involves an interaction between two reactants or a reactant and a
reagent. For a reaction between, an alkyl halide and a base, the rate determining step
involves an interaction between the base and the alkyl halide. The reaction takes place in
concerted way . The simultaneous removal of the proton (H+) by the base, loss of the leaving
group (X) and formation of the pi-bond takes place .
The rate of elimination depends on the concentration of both the substrate and the base. This
is kinetically a second order reaction, i.e., first order with respect to substrate and first order
with respect to the base. Thus, in the rate expression both the substrate (generally alkyl
halide) and base are involved.
In E2 elimination reaction, it was observed that the dehydrohalogenation
of the erythro halide gave only the Z alkene and the threo gave only the E alkene .
Rate = k [substrate (RX)] [base (B-)]

25. Elimination reaction
Cis-Elimination
The cis elimination usually takes place by pyrolysis. The pyrolysis of esters like acetate ester,
methyl xanthate ester takes place by cis elimination leading to the formation of olefins. They go
via cyclic transition state formation
In cyclic system, like cyclohexane system, the axial-equatorial alignment plays important role. For
example, the pyrolysis of both cis and trans of cyclohexane derivative gave the same product, 1-
p-tolylsulfonyl-1-cyclohexene. Trans compound undergoes cis elimination and cis compound
undergoes trans elimination to give the same product

26. 1,4
Elimination
This is also known as fragmentation. For example, Grob fragmentation. The Grob
fragmentation has strict bond geometry requirements. This is stereospecific towards double
bond formation. This occur most easily from conformationally locked 1,3-difunctionalized
compounds. Here, the breaking C-X and C-C bonds are aligned anti-periplanar .

28. THE STEREOCHEMICAL RULE FOR ELIMINATON