Westphal condensation

Acenaphthene-1,2-dione condensations, 59, 90, 112 in Westphal condensations, 55, 312, 314 Acenaphtho-fused imidazo-[1.2,4]triazines, 59, 89... 

Dioxan. 2,3-dihydroxy-, as glyoxal substitute in Westphal condensations,... 

Fused acenaphthylene derivative was prepared (52%) by Westphal condensation (89H2369). The reaction of l-ethoxycarbonylmethyl-2,6-di-methypyridinium salt and acenaphthenequinone in the presence of dibut-ylamine gave quinolizinium salt 241. Intramolecular Claisen reaction of 241 occurred under the reaction conditions to afford cyclazinone 242, which was treated with HBr to yield 243. 

Two isomers of azoniafluoranthene have been reported. The reaction of 2-methylpyridine ALoxide with a Grignard reagent gave the pyridine 244 which, on treatment with HBr, cyclized to 245. The Westphal condensation between 245 and 2,3-dihydroxy-1,4-dioxane in the presence of triethyl-amine yielded lOc-azoniafluoranthene salt (246) (33%) [89AG(E)588]. 

Westphal condensation of acenaphthenequinone with 1-ethoxycarbon-ylmethyl-2-methylpyridinium salt and 2-ethoxycarbonylmethyl-l-methyl-isoquinolinium salt in the presence of sodium acetate gave 251 (73%) and 252 (44%), respectively (86JHC1151). On heating 251 with HBr, parent compound 253 was obtained (48%) (85JHC681 86JHC1151 89H2369). 

The Westphal condensation was applied to the synthesis of sempervirine (289) (68JOC3985). Quaternary salt 287 reacted with 1,2-cyclohexanedione in the presence of dibutylamine to give quinolizinium salt 288 (48%), which was hydrolyzed (93%) and decarboxylated (85%) to afford 289. 

Triethylamine has also been employed as a base to induce the formation of an oc-anion in 2-methylalkylthiazolium ions. The resulting anionic species have been made to react with 1,2-dicar-bonyls in an extension of the Westphal condensation <86JHC1889, 94J0C8294>. 

The Westphal condensation between the azoniafluorene salt (219) and glyoxal (in its masked form as 2,3-dihydroxy-l,4-dioxane) or dimethylgly-oxal in the presence of triethylamine gave the lOc-azoniafluoranthene salts (220, 221), respectively (89AGE588 91JOC4858). 

Two additional examples of the Westphal synthesis which do not lend themselves to tabular treatment are the condensation of l-ethoxycarbonylmethyl-5,6,7,8-tetrahy-droquinolinium bromide (201 Scheme 107) with diacetyl to yield a quinolizinium ion (202) having a 1,9-trimethylene bridge, and the condensation of l-ethoxycarbonylmethyl-2-methylpyridinium bromide with phenanthroquinone (Scheme 108) to yield phenanthro[9,10-6]quinolizinium bromide. 

Another elegant approach to alkyl- and aryl-substituted quino-lizines involves the condensation of a-picolinium salts carrying an active methylene group on the nitrogen atom with suitable a-diketones. Westphal et al,11 have reacted 1,2-diketones, e.g. diacetyl, benzil, furil, and pyridil, with 2-methyl-A-carbethoxymethylpyridinium halides in the presence of weak bases such as dibutylamine or sodium bicarbonate and obtained the corresponding 2,3-disubstituted quino-lizinium halides [Eq. (3)]. Spontaneous hydrolysis and decarboxylation... 

Some general reactions of the azinium salts (198) produced by reacting a-halogenocarbonyl compounds (197) with a-methylazines (196) are shown in Scheme 46. They cyclize in the presence of base to give pyrroloazines (199) or alternatively condense with a-diketones to give pyridoazinium salts (200) (the Westphal synthesis). 

Lehrbuch der pharmaceutischen Techniky 1847 2 ed., 1853 (Beindorf s apparatus 74 Liebig s condenser 195 sp. gr. balance 348 cork press 431, nest of cork borers 374 etc.) 3 ed., 1866. The sp. gr. balance was an ordinary balance (9iin. beam) with a glass tube sinker, weighted with mercury, suspended by a fine platinum wire. The Westphal balance was described by Oertling, Z. anal. Ghent, y 1868, vii, 294. 

A modification of the Westphal synthesis is based on fS-(2-pyridyl)substituted fS-hydroxyketones 18, which are available from aldol addition of pyridine-2-aldehyde to methylene ketones R -CH2-CO-R. O-Acylation and subsequent N-quaternization with bromoacetate or bromoacetonitrile transform 18 into pyridinium salts 19, which on treatment with BU2NH are cyclized to quinoHzinium salts 20 by intramolecular aldol condensation and HOAc ehmination ... 

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