Pyridine N-alkylation

In addition to phosphines and pyridines, N-alkylated imidazoles are also known to act as a nucleophilic catalysts in acylation reactions [1], In the approach by Miller et al. short oligopeptides incorporating N-alkylhistidine derivatives were used as enantioselective acylation catalysts [27]. The design of, e.g., the tripeptide... 

By reaction with covalent organic bases (Et3N, Me2PhN, pyridine) N-alkyl-2-cyanoacrylates can be transformed to zwitterions of the type... 

In the Fujiwara reaction chlorohydrocarbons react with pyridine (N-alkylation) under complete destruction of the ring. But the reaction path will go through a number of Schiff base intermediates, which, depending of the kind of analyte, have different life times and absorbances in the visible range. Thus mixtures of 1,1,1-trichloroethane, trichloroethylene, and chloroform could be resolved, even in the presence of unknown interfering substances. 

Zheng J., Zhan, C., Qin, J., Zhan, R. (2002), Synthesis and fluorescence of pyridine-n-alkyl carbazole copolymer prepared by oxidative-couphng reaction. Chemistry Letters, 12, 1222-3. 

There are several reports that alkylated pyridine N-oxides react with Grignard reagents to give 2-alkylated pyridines (50,51). 

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. 

Phthalimidobutyl)-2,3,4,4u,5,6-hexahydro-l//-pyrazino[l,2-u]quino-line was obtained in the reaction of 2,3,4,4u,5,6-hexahydro-l//-pyrazino[l,2-u]quinoline and A-(4-bromobutyl)phthalimide in boiling MeCN in the presence of K2CO3 (97MIP12). 2,3,4,4u,6,7-He-xahydro-l//-pyrazino[l,2-ujquinolines were N-alkylated with 3-dimethylaminomethyl-l//-pyrrolo[2,3-6]pyridine and a mixture of l//-pyrrolo[2,3-6]pyridine and 37% aqueous H2CO in aqueous AcOH in the presence of NaOAc (96USP5576319). 3-[3-Substituted 2-propen-l-yl]-2,3,4,4u, 5,6-hexahydro-l//-pyrazino[l,2-u]qui-... 

Zur Hydrodimerisierung von N-Alkyl-succinimiden s.S. 580. Zur kathodischen Polymerisation von 4-VinyI-pyridin s. Lit.3. 

When an a-amino acid is treated with an anhydride in the presence of pyridine, the carboxyl group is replaced by an acyl group and the NH2 becomes acylated. This is called the Dakin-West reaction The mechanism involves formation of an oxazolone. The reaction sometimes takes place on carboxylic acids even when an amino group is not present. A number of N-substituted amino acids, RCH-(NHR )COOH, give the corresponding N-alkylated products. 

The encapsulated complex with bulky alkyl groups was more active than the complex without alkyl groups. The catalytic activity increases on the addition of axial ligands as pyridine N-oxide, and the highest enantiomeric excess, 88%, was also achieved in the presence of the pyridine N-oxide. 

Azomethine ylides such as 412 react with triafulvenes again by analogy with cyclopropenones. (3 + 2) Cycloaddition of the 1,3-dipole to the CVC2 bond and subsequent loss of C02 produces l,4-dihydro-4-methylene-N-alkyl pyridines 559, which as merocyanines show marked solvatochromic and thermochromic effects260. ... 

Electrophiles can add to N-3, the azomethine =N-of 1,3-azoles as they can to the pyridine nitrogen. N-Alkylation is complicated in the case of imidazole... 

According to the second way, thieno[3,2-c]pyridine undergoes N-alkylation using 2-chlorobenzylchloride, and the resulting pyridinium salt (24.2.2) is further reduced by sodium borohydride to the desired ticlopidine. 

A majority of routes leading to bicyclic pyridoazepines schematically falls into four categories (Scheme 3) They can be described as 1.2 or 2.1 cyclizations, each of them basing on a pyridine (7a and b, respectively) or an azepine derivative (7c and d, respectively). Among the synthetic methods involved are classical ones (N-alkylation, lactamization, Dieckmann condensation, etc.) and an increasing part of enamine, enamide, and... 

Alkylating agent Salt cation Solvent Overall conversion (%) N-Alkyl (%) O-Alkyl (%) Pyridin-2-one (%)... 

The direct alkylation of dihydropyridines to produce alkyl-substituted dihydropyridines has not proven to be a very successful reaction. Although initial alkylation at the /3-position probably occurs, the intermediate 2,5-dihydropyridinium ions (148) apparently induce polymerization of the unreacted dihydropyridine. To overcome this problem a two-phase system has been developed (74JA7364). The alkylated product (152) is reduced and N-alkylated under the reaction conditions. This method may have application to the synthesis of 3,5-substituted tetrahydropyridine and pyridine derivatives (Scheme 20). 

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