{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/76069"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/76069","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Reactions of 4-chloro-2,6-dimethoxypyrimidine and 2-chlorothiazole with carbanion nucleophiles","abstract":"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.","abstract_html":"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&lt;sub&gt;RN&gt;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.","abstract_has_math":false,"creators":["Dillender, Samuel C."],"institution":"Virginia Polytechnic Institute and State University","degree_name":"Ph. D.","degree_level":"doctoral","degree_discipline":"Chemistry","degree_department":"Chemistry","school":null,"contributors":[],"advisors":[],"committee_chairs":["Wolfe, James F."],"committee_members":["Hudlicky, Milos","McGrath, James E.","Ogliaruso, Michael A.","Mason, John G."],"year":1984,"date_issued":"1984","date_published":"1984","updated_at":"2026-07-22T22:18:52Z","subjects":[],"languages":["en_US"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10919/76069","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Wolfe, James F."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Hudlicky, Milos","McGrath, James E.","Ogliaruso, Michael A.","Mason, John G."]},{"key":"dc:contributor.department","label":"Department","values":["Chemistry"]},{"key":"dc:creator","label":"Author","values":["Dillender, Samuel C."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2017-03-10T15:15:03Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2017-03-10T15:15:03Z"]},{"key":"dc:date.issued","label":"Date","values":["1984"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Polytechnic Institute and State University"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"dc:type.dcmitype","label":"Dc Type Dcmitype","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10919/76069"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. D."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Reactions of 4-chloro-2,6-dimethoxypyrimidine and 2-chlorothiazole with carbanion nucleophiles"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Wolfe, James F."],"dc:contributor.committeemember":["Hudlicky, Milos","McGrath, James E.","Ogliaruso, Michael A.","Mason, John G."],"dc:contributor.department":["Chemistry"],"dc:creator":["Dillender, Samuel C."],"dc:date.accessioned":["2017-03-10T15:15:03Z"],"dc:date.available":["2017-03-10T15:15:03Z"],"dc:date.issued":["1984"],"dc:description.abstract":["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."],"dc:description.degree":["Ph. D."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/10919/76069"],"dc:language.iso":["en_US"],"dc:publisher":["Virginia Polytechnic Institute and State University"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:title":["Reactions of 4-chloro-2,6-dimethoxypyrimidine and 2-chlorothiazole with carbanion nucleophiles"],"dc:type":["Dissertation"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:18:52Z"}