Pyridine, substituted, alkylation

A monolayer of the pyridine-substituted alkyl merocyanine (12) was prepared in the 1970s (67), and a noncentro symmetric multilayer stmcture of merocyanine amphiphiles was later prepared (68) using derivatives, but introducing long-chain amines as the counter layer in an ABABAB system (69,70). 

Few other reactions of series of substituted pyridines have been investigated extensively. Dondoni, Modena, and Todesco have measured the rate of N-oxidation of a limited series of pyridines and found a good correlation with normal u-values with a p-value of — 2.23. The A-alkylation of pyridines with alkyl iodides in nitrobenzene has been studied by Brown and Cahn and by Clarke and Rothwell. Unfortunately, the only data available are for the parent compound and for alkyl derivatives, and, since the a-values for the various alkyl groups in a given position are substantially constant, this leaves a correlation of only three independent points. However, the rates of A-alkylation of the j8- and y-alkyl derivatives are so nearly equal that it appears as if no correlation existed. Clarke and Rothwell have also studied the alkylation with allyl bromide in nitromethane at various temperatures, and in this case a more extensive series is available. The authors state that no overall Hammett correlation is obtained however, the j8-substituted derivatives fall on one straight line and the y-derivatives on another one with a different slope. The data are shown in Fig. 2. The line for the j8-compounds, p = — 2.53 0.31, r = 0.95, is seen not to be very good the line for the y-derivatives, p = — 1.42 0.06, r = 0.99, is much more satisfactory. It does not seem likely that the discrepancy is due to the intervention of resonance effects, since in this case one would expect the correlation for the y-derivatives to be poorer than that for the j8-analogs. More extensive studies with a wider variety of substituents would seem very desirable. 

A munber of organic compounds are suitable for use as tracers in a process for monitoring the flow of subterranean fluids. The following traces have been proposed benzene tetracarboxylic acid, methylbenzoic acid, naphthalenesulfonic acid, naphthalenedisulfonic acid, naphthalene-trisulfonic acid, alkyl benzene sulfonic acid, alkyl toluene sulfonic acid, alkyl xylene sulfonic acid, a-olefin sulfonic acid, salts of the foregoing acids, naphthalenediol, aniline, substituted aniline, pyridine, substituted pyridines [883]. 

R = CHj, R = and adenocarpine(16 R = CH=CHPh, R = H) ° are likewise dehydrogenated to 2,3 -bipyridine, and related dehydrogenation reactions afford substituted 2,3 -bipyridines. Ullmann and Grignard reactions have been used to synthesise 2,3 -bipyridine, whereas the Gomberg reaction of 3-pyridinediazonium chloride with pyridine and alkyl pyridines affords 2,3 -bipyridine, along with other isomeric bipyridines, and alkyl substituted 2,3 -bipyridines, respectively. " Photolysis of 3-... 

Alkyl radicals for such reactions are available from many sources such as acyl peroxides, alkyl hydroperoxides, particularly by the oxidative decarboxylation of carboxylic acids using peroxy-disulfate catalyzed by silver. Pyridine and various substituted pyridines have been alkylated in the 2-position in high yield by these methods. Quinoline similarly reacts in the 2-, isoquinoline in the 1-, and acridine in the 9-position. Pyrazine and quinoxaline also give high yields of 2-substituted alkyl derivatives <74AHC(16)123). 

Some light on this question can be shed by considering the reaction of a substituted pyridine with alkylating agent and hydroxide. The reaction sequence Is given below. 

The second catalytic method involves reaction of pyridine with alkyl alcohols at both atmospheric (65) and elevated pressures (66-68) over alumina or alumino-silicate catalysts. The atmospheric pressure reaction afforded a mixture of all three picoline Isomers in approximately equal amounts with multi-substitution also reported. At elevated pressures, the substitution is claimed to be primarily in the 3- position with low conversions. 

Reduction of pyridine and benzene-substituted -alkyl esters (Webster et al., 1996). For further examples refer to texts such as Pombeiro and McCleverty (1993)... 

Long-chain halides undergo this reaction at 100°, no C-dialkylated products being formed. In alkylations with aryl-substituted alkyl halides, Ar(CH,) X, n= 1 to 3, yields are improved by performing the reaction rapidly in liquid ammonia (56-9S>%). Also, quinoline methylated in the 2-or 4-position reacts in the same way. A methyl group in the 3-position of pyridine or quinoline is unreactive. 

R = H, aikyi, substituted aikyi R = H, alkyl, substituted alkyl, aryl, heteroaryl R = Me, Et, n-Pr base pyridine, alkylpyridine,... 

HC(44/3)l>. The two most important methods are (i) conversion of thienyllithium to a thienyl-boronic acid by reaction with alkyl borate, followed by oxidation with H2O2, and (ii) reaction of thienylmagnesium derivatives with t-butylperbenzoate, followed by dealkylation of the /-butyl ethers with acid. The boronic acid method has been used for the synthesis of several pyridine-substituted hydroxy thiophenes <92ACS654>. 

---