Alkylation Reactions Nucleophilic Substitution

The C1 methyl building unit is supplied from L-methionine and is introduced by a nucleophilic substitution reaction. In nature, the leaving group is enhanced by converting L-methionine into S -adenosylmethionine (SAM) [Figure 2.4(a)]. This gives a positively charged sulphur and facilitates the nucleophilic substitution (SN2) type mechanism [Figure 2.4(b)]. Thus, O -methyl and N -methyl linkages may be obtained using hydroxyl and amino functions as nucleophiles. The generation of C -methyl linkages requires the participation of nucleophilic carbon. Positions ortho or para to a phenol group, or positions adjacent to one or more carbonyl groups, are thus candidates for C-methylation [Figure 2.4(c)].

A C5 isoprene unit in the form of dimethylallyl diphosphate (DMAPP) may also act as an

Alkylation reactions: nucleophilic substitution (a) formation of SAM

CO2H co2h

L-Met S-adenosylmethionine

,CO2H sn2 reaction © NH2

(c) C-alkylation using SAM

Ss neutral molecule is good leaving group



ortho (and para) positions are activated by OH

II nh2


carbonyl groups increase acidity and allow formation of enolate anion


(d) O-alkylation using DMAPP

PTOp dimethylallyl diphosphate diphosphate is (DMAPP)

good leaving or group

PPOp sn1 reaction

© i . mi .. . ©s resonance stabilized allylic carbocation

Figure 2.4

alkylating agent, and a similar SN2 nucleophilic displacement can be proposed, the diphosphate making a good leaving group [Figure 2.4(d)]. In some cases, there is evidence that DMAPP may ionize first to the resonance-stabilized allylic car-bocation and thus an SN1 process operates instead. C -Alkylation at activated positions using DMAPP is analogous to the C -methylation process above.

Was this article helpful?

0 0
Natural Treatments For Psoriasis

Natural Treatments For Psoriasis

Do You Suffer From the Itching and Scaling of Psoriasis? Or the Chronic Agony of Psoriatic Arthritis? If so you are not ALONE! A whopping three percent of the world’s populations suffer from either condition! An incredible 56 million working hours are lost every year by psoriasis sufferers according to the National Psoriasis Foundation.

Get My Free Ebook

Post a comment