Carbanions pyridine

Carbon Substituents. Alkyl groups at positions 2 and 4 of a pyridine ring are more reactive than either those at the 3-position of a pyridine ring or those attached to a benzene ring. Carbanions can be formed readily at alkyl carbons attached at the 2- and 4-positions. This increased chemical reactivity has been used to form 2- and 4-(phenylpropyl)pyridines, eg, 4-(3-phenylpropyl)pyridine [2057-49-0] (21) (24). 

Tetraphenyl-3//-azepine (2) is formed by the action of sodium hydride on 1-benzyl-2,4,6-triphenylpyridinium tetrafluoroborate (1) in refluxing toluene.37 The 3//-azepine. which arises by attack of the carbanion, generated at the benzylic carbon, at the 2-position of the pyridine ring, is also formed, unexpectedly, in the reaction of the pyridinium tetrafluoroborate with the enolate of ethyl 2-methyl-3-oxobutanoate. 

Another approach to an oxidative desulphonylation reaction is to oxidize an a-sulphonyl carbanion with an oxidizing agent that is also nucleofugal. An example of this was presented by Little and Sun Ok Myong203 who used a molybdenum peroxide complex (M0O5.Pyridine.HMPA) as the oxidant. However, this reagent is expensive and... 

An efficient procedure for the synthesis of 2,4,6-trisubstituted and 2,3.4,6-tetrasubstituted pyridines 5 and 6 involves the one-pot reaction of in situ generated a,p-unsaturated imines with carbanions <95TL(36)9297>. 

Another example in which the free acid undergoes ready decarboxylation, but this time via a carbanion intermediate (50, actually an ylid), is pyridine-2-carboxylic acid (51), which is decarboxylated very much more readily that its 3- or 4-isomers ... 

Carbonylation at the 3-position of a pyridine is illustrated in Scheme 130.197 In these processes the intermediate carbanion from arylation of pyridine can be trapped by iron pentacarbonyl and the ensuing acyliron... 

The hydrogenations become analogous to those involving HMn(CO)5 (see Section II,D), and to some catalyzed by HCo(CN)53 (see below). Use of bis(dimethylglyoximato)cobalt(II)-base complexes or cobaloximes(II) as catalysts (7, p. 193) has been more thoroughly studied (189, 190). Alkyl intermediates have been isolated with some activated olefinic substrates using the pyridine system, and electronic and steric effects on the catalytic hydrogenation rates have been reported (189). Mechanistic studies have appeared on the use of (pyridine)cobaloxime(II) with H2, and of (pyridine)chlorocobaloxime(III) and vitamin B12 with borohydride, for reduction of a,/3-unsaturated esters (190). Protonation of a carbanion... 

That there is also considerable carbanion character on the carbon adjacent to the sulfonyl group in the rate-determining transition state for sulfene formation from phenylmethanesulfonyl chlorides is shown (King and Lee, 1969) by the fact that p for sulfene formation from ArCH2S02Cl and pyridine is +2.3, with the rates being better correlated by a - rather than o-values. 

A report of a more extensive Hammett smdy has included estimates of values of Pacyi for aminolysis of members of the sulfamate ester series (XC6H4NHSO2ONP) in chloroform and acetonitrile using piperidine and a set of five pyridines variation of the pyridines allowed the determination of Ppyr values for several esters. The Pacyi values become less negative with decrease in amine basicity, apparently as a consequence of diminished H cleavage and a progression from a partial carbanion-like transition state to a more central E2 type mechanism (10). 

In the aqueous pH region the mechanism for hydrogen-deuterium exchange in pyridine involves attack of deuteroxide ion on the pyridin-ium ion to give an ylide intermediate (Scheme 8). The ylide then reacts with D2O to give the deuterated p30 idine. In more basic media the proposed mechanism involves rate-determining deprotonation from the neutral molecule to give a carbanion intermediate which then abstracts a deuteron from the solvent (Scheme 9). 

The formation of jp -carbanions adjacent to pyridine-like nitrogen in 6-membered heteroaromatic rings is complicated by the fact that with alkyl and aryllithiums, 1,2-nucleophilic addition to the azomethine double bond (Scheme 103) normally occurs in preference to metalation [88H2659, 88MI2 88T1 90H(31)1155 91AHC(52)187]. 

The formation of pyridine 3-carbanions is thermodynamically a more favorable process than that for the 2-analogs, and this is exemplified by the exchange reaction between 2-lithio- and 3-bromopyridines (Scheme 107), which occurs readily at -100°C (77JOC257). 

However, by far the most useful route to 3-pyridyl carbanions is via directed metalation [91AHC(52)187], which can be achieved by the lithia-tion of either 2- or 4-heterosubstituted pyridines (Tables IX and X). 

---