Westphal synthesis

Westphal synthesis, 2, 566 Woodward synthesis, 2, 551, 552 Quinolizinium salts, l-acetylamino-2,3-dimethyl-oxidation, 2, 540 Quinolizinium salts, 1-amino-synthesis, 2, 541 Quinolizinium salts, 2-amino-applications, 2, 569 diazotization, 2, 542 N-substituted... 

A patent (67MIP21000) has described a general method for the preparation of 2,3-disubstituted quinolizinium ions (149 Scheme 88), a method closely related to the Westphal synthesis viz. [4 + 2] cyclizations). In the example given, 2-picolinaldehyde is allowed to react with deoxybenzoin and the resulting aldol acetylated and quaternized with phenacyl bromide to yield a salt which can be cyclized and cleaved by action of dibutylamine to afford 2,3-diphenylquinolizinium bromide (149) in 68-74% yield. It is claimed that quaternary salts analogous to (148), but formed by reaction of XCH2R (R = alkoxycarbonyl or cyano, X = halogen) may be used likewise. 

Table 12 Quinolizinium Derivatives by the Westphal Synthesis (Scheme 106)...

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. 

Pyridinium salts 15, that possess an alkyl group at the 2-position and an acylmethyl-, alkoxycarbonylmethyl- or cyanomethyl group at the 1-position, cyclocondense with 1,2-dicarbonyl compounds under base catalysis giving quinolizinium ions 16 Westphal synthesis)-. 

A modification of the Westphal synthesis is based on 2-substituted pyridines 18. They are obtained by (9-acylation of the aldol adducts 17 obtained from pyridine-2-carbaldehyde and methylene ketones. The pyridines 18 are quatemized with bromoacetic ester or bromoacetonitrile to 19, followed by base-catalysed cyclization giving 2,3,4-trisubstituted quinolizinium ions 20 ... 

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). 

U. Hammerling and O. Westphal, Synthesis and Use of (7-Stearoyl Polysaccharides in Passive Hemagglutination and Hemolysis,... 

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 ... 

Westphal synthesis (quinolizinium ion) Wesseley-Moser rearrangement 338 Widmann-Stoermer synthesis (cinnoline) Willgerodt-Kindler reaction 98 Wittig reaction 329, 335... 

G. Siewert and O. Westphal, Substitution of secondary p-tolylsulfonyloxy groups by iodine. Synthesis of 4-deoxy- and 4,6-dideoxy-D-xylo-hexose, Liebigs Atmalen der Chemie 720 161... 

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. 

An examination of the scope and limitations of the synthesis due to Westphal et al.H (Eq. 2) was made by Hough and Jones9 in their attempts to prepare aminoquinolizinium salts. A possible steric inhibition was noted... 

R23. Rude, E., Westphal, 0., Hurwitz, E., Fuchs, S., and Sela, M., Synthesis and antigenic properties of sugar-polypeptide conjugates. Immunochemistry 3,137-151 (1966). 

Faix, J., Dittrich, W., Brassier, J., Westphal, M., and Gerisch, G. (1995) pDcsA vectors for strictly regulated synthesis during early development of Dictyostelium discoideum. Plasmid 34,148-151... 

As the proof for the structure of thiamine had depended so largely upon the synthesis of certain breakdown products, the complete synthesis of the vitamin was accomplished very soon afterwards. The first publication came from Williams and Clinei in the U.S. hard on their heels followed Todd and Bergelii jjj England and Andersag and Westphal in Germany. 

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