614. Quinolizines. Part II. A synthesis of alkyl- and of aryl-quinolizinium salts

Abstract

The synthesis of a number of substituted 1 : 2 : 3 : 4-tetrahydro-l-0~0quinolizinium bromides is reported. When boiled in acetic anhydride these ketones were converted in high yield into the corresponding substituted quinolizinium salts. From the tricyclic ketones (XXVIII), (XXIX), and (XXX), by similar treatment, the three benzoquinolizinium compounds were obtained.THE simple quinolizinium salts (I; X = I, ClO,, and picrate) were first obtained by Boekelheide and Gall,l by dehydrogenation of the dihydroquinolizinium iodide (11). This method has also been successfully applied to the synthesis of 4-methylquinolizinium saIts (XXIV) but has failed to give 4 : 6-dimethylquinolizinium salts.3 A second synthesis was reported by Richards and Stevens,* who have extended it subsequently to the preparation of a number of alkyl-and aryl-quinolizinium compound^.^ More recently, Nesmeyanov and Rybynskaia have described a synthesis which is specific for the preparation of 2-substituted quinolizinium salts6In a preliminary communication 7 we recorded the conversion of 1 : 2 : 3 : Ptetrahydro-l-oxoquinolizinium bromide 8 (111) into a quinolizinium salt, isolated as quinolizinium picrate (I; X = picrate), by treatment with boiling acetic anhydride containing a drop of sulphuric acid. We now record improvements in this synthesis, together with

Heterocycles Containing a Ring‐Junction Nitrogen

“…Of the three only one of them enabled the isolation of the parent compound 26 while the two other are useful for the synthesis of derivatives. The same strategy used for the synthesis of the ketone 216 (Scheme 22.49) when applied to 1-cyanoisoquinoline, afforded the tricyclic ketone 327, which under the aromatization conditions gave 26 in 66% yield (Scheme 22.90) [168]. The Westphal reaction between 1,2-diketones and the appropriate isoquinolinium salts 328 yields 9,10-disubstituted derivatives 330 [213] while the 8,10-dimethyl derivative is also obtained by reaction between isoquinoline perchlorate (329) and mesityl oxide [214].…”

“…Alternative methods that produce 25 and alkyl-and phenyl-derivatives 333 in poor yields involve cyclization of 2-(2-picolyl)benzonitrile and 2-(2-picolyl)benzaldoxime (Scheme 22.91) [217]. Treatment of the ketone 334, obtained in a similar way to 327, with boiling acetic anhydride also furnished 25 in 62% yield [168] while cyclization of 2-benzylpyridine with acetic acid/sulfuric acid is also a convenient procedure for the preparation of the 6-methyl derivative 337a (Scheme 22.92) [218]. Two more recent methods have also allowed the synthesis of the 6-phenyl-derivative 337b and the parent 25 using different strategies.…”

“…Cleavage of the ether with hydrobromic acid allows the formation of the bromide, which cyclizes to the bicyclic ketone 216 by heating in chloroform. This ketone is the common intermediate to produce 16 by heating under reflux in acetic anhydride [168] and can also give 1-hydroxy-, 2-hydroxy-and 2-bromoquinolizinium derivatives (217-219) using simple reagents [169]. Ketone 216 can be obtained in better yield by reaction of 2-ethoxycarbonylpyridine and c-butyrolactone in the presence of NaH followed by treatment with hydrobromic acid to produce decarboxylation, bromination, and cyclization (Scheme 22.49) [170].…”

“…This method also allows the preparation of the 2-, 3-, and 4-methylquinolizinium salts (223-225) by using 3-ethoxypropylmagnesium bromides with the appropriate substitution [168]. 1-Methylquinolizinium picrate (226) can be obtained by reaction of 3,3-diethoxypropylmagnesium chloride with 2-acetylpyridine [165c] (Scheme 22.51).…”

“…Quinoline derivatives are used as starting materials in the synthesis of the precursor ketone 338 [168] and in the Westphal substrate 339 [174]. From methylpyridine two similar approaches have been developed to construct the cationic tricycle by reaction with 2-chlorobenzaldehyde and 2-chlorobenzonitrile.…”