Reactions of 4-chloro-2,6-dimethoxypyrimidine and 2-chlorothiazole with carbanion nucleophiles

Reactions of 4-chloro-2,6-dimethoxypyrimidine (1) with enolates of acetone, pinacolone, diisopropyl ketone, and ethyl phenylacetate generated by means of potassium amide in 1 liquid ammonia were found to proceed by the S<sub>RN>1 mechanism upon photostimulation with near-UV light to give good yields of substitution products resulting from displacement of chloride ion. Both photostimulated and dark reactions of 4-chloro-2,6-dimethoxypyrimidine (1) with the carbanions of acetonitrile and propionitrile proceed exclusively by an ionic mechanism in liquid ammonia or THF to give a mixture of monosubstitution products resulting from displacement of chloride or the 6-methoxy substituent. With the acetonitrile carbanion the product resulting from displacement of methoxide was the major substitution product, while reaction of 1 with propionitrile carbanion afforded a preponderance of the product resulting from chloride displacement. Photostimulated reaction of 2-chlorothiazole (2) with the potassium enolate of pinacolone proceeds by a radical-chain mechanism to give the substitution product resulting from chloride displacement. However, when 2 is allowed to react with pinacolone enolate in the dark a completely unexpected product is formed. Under these conditions, the tertiary alcohol, 2-(2-chlorothiazol-4-yl)-3,3-dimethyl-2-hydroxybutane, was formed in which the pinacolone unit had been incorporated in an aldol fashion at the 4-position of 2. Both photostimulated and dark reactions of 2 with the enolate of diisopropyl ketone produced a similar carbinol, 3-(2-chlorothiazol-4-yl)-2,4-dimethyl-3-hydroxypentane, in good yields. Treatment of 2 with potassium amide in liquid ammonia or LDA in THF followed by addition of benzophenone afforded 2-chloro-4-(diphenylhydroxymethyl) thiazole in excellent yield. Trapping experiments with deuterium oxide and iodomethane provide evidence that such aldol-type reactions take place via initial metalation of 2 at position-4, followed by reaction of the resulting carbanion with the appropriate electrophile. This is the first example of direct metalation occurring at the 4-position of a thiazole derivative.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemistry

Department dc:contributor.department

Chemistry

Grantor dc:publisher

Virginia Polytechnic Institute and State University

Year dc:date.issued

1984

Author dc:creator

• Dillender, Samuel C.

Chair dc:contributor.committeechair

• Wolfe, James F.

Committee members dc:contributor.committeemember

• Hudlicky, Milos
• McGrath, James E.
• Ogliaruso, Michael A.
• Mason, John G.

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10919/76069

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/76069