Pyridines under Vilsmeier conditions

Ring closure of (17) under Vilsmeier conditions led to pyridine compound (18) (Scheme 12) <95JHC(32)505>. 

Ring closure under Vilsmeier conditions leads to the pyridine structure (Equation 90) <1995JHC505>. 

Friedlander quinoline synthesis, cyclisations under Vilsmeier conditions, six-membered mesionic heterocycles of the m-quino-methane dianion type,2 the basic properties of 2,6-di-t-butyl-pyridine,2 and isotopic exchange in purines.22... 

Carboxylic acid chlorides. Conventional methods for conversion of an acid into the acid chloride usually require acidic reagents. Lederle chemists have accomplished this transformation under neutral conditions by conversion of the acid into the t-butyldimethylsilyl ester. The esters react with oxalyl chloride in CH2CI2 in the presence of catalytic quantities of DMF to form the acid chloride with evolution of gas. Since DMF is essential, dimethylformiminium chloride (Vilsmeier reagent) is probably the reactive species. The acid chloride is formed in 85-95% yield, as shown by conversion to esters with ethanol-pyridine. 

Compound (8), under Vilsmeier formylation and nitration (nitric acid-acetic anhydride) conditions, proceeded as might have been expected for electrophilic substitution reactions to give the 1-substituted products (142) and (143). Reduction of (143) gave predominantly the imidazopyridine (144) with a small amount of the tetrahydro derivative (145) (81JCS(P1)78). Heating (8) in D2O led to the 1-deutero derivative (78HCA1755) via deuter-ation-deprotonation or via the tautomeric 2-(diazomethyI)pyridine tautomer of (8). 

Reactions with electrophilic reagents take place with substitution at C-3 or by addition at the pyridine nitrogen. All the aza-indoles are much more stable to acid than indole (cf. 20.1.1.9), no doubt due to the diversion of protonation onto the pyridine nitrogen, but the reactivity towards other electrophiles at C-3 is only slightly lower than that of indoles. Bromination and nitration occur cleanly in all four parent systems and are more controllable than in the case of indole. Maniuch and Vilsmeier reactions can be carried out in some cases, but when the latter fails, 3-aldehydes can be prepared by reaction with hexamine, possibly via the anion of the azaindole. Alkylation under neutral conditions results in quatemisation on the pyridine nitrogen and reaction with sodium salts allows A-1-alkylation. Acylation under mild conditions also occurs at N-1. The scheme below summarises these reactions for the most widely studied system - 7-azaindole. Acylation at C-3 in all four systems can be carried out at room temperature in the presence of excess aluminium chloride. ... 

Condensation of p-O-methoxyphenylhydrazine (74S) with 2,5-dimethylcyclohexanone (746) gave mainly the tetrahydrocarbazole 747, which was dehydrogenated with chloranil in refluxing THF. The resulting carbazole 746 was formylated under Vilsmeier-Haack conditions to afford 744. Formation of the pyridine ring can then be achieved by condensation with the diethylacetal of aminoacetaldehyde followed by reduction of the imine, N-tosylation, and cyclization to give 743 as described previously (Scheme 57). When the 4-methyl group is not present in the carbazole 748,... 

Benzo-l,4-thiazines and Related Compounds.— The chemical behaviour of the Vilsmeier product (111), derived from l,4-benzothiazin-3(4H)-one, has been the subject of detailed studies. Hydrolysis under different conditions affords the acid (112), the aldehyde (114), or the chloro-aldehyde (113), depending on the method of hydrolysis. Treatment of the perchlorate of (111) with DMSO leads to the displacement of the chlorine atom to give the dimethylsulphoxonium derivative (115), while reaction with pyridine proceeds with selective attack at the aminomethylene function, yielding the pyridinium salt (116). This latter reacts readily with aniline in acetic acid medium to give, along with 2-formyl-3-anilino-l,4-benzothiazine (117), the anilinomethylene derivative (120), whose formation probably involves an intramolecular rearrangement of the intermediate pyridinium salt (118), as depicted. 

The most useful general method for the C-acylation of pyrroles is the Vilsmeier-Haack procedure in which pyrrole is treated with the phosphoryl chloride complex (55a, b) of an AiA-dialkylamide (54). The intermediate imine salt (56) is hydrolyzed subsequently under mildly alkaline conditions to give the acylated pyrrole (57). On treatment of the imminium salt (56 R =H) with hydroxylamine hydrochloride and one equivalent of pyridine and heating in DMF, 2-cyanopyrrole (58) is formed (80CJC409). 

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