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Synthese und Reaktionen 8-gliedriger Heterocyclen aus 3-Dimethylamino-2,2-dimethyl-2H-azirin und Saccharin bzw. Phthalimid


Chaloupka, Stanislav; Vitorelli, Piero; Heimgartner, Heinz; Schmid, Hans; Bernauer, Karl; Link, Helmut; Oberhänsli, Willi E (1977). Synthese und Reaktionen 8-gliedriger Heterocyclen aus 3-Dimethylamino-2,2-dimethyl-2H-azirin und Saccharin bzw. Phthalimid. Helvetica Chimica Acta, 60(7):2476-2495.

Abstract

3-Dimethylamino-2,2-dimethyl-2H-azirine (1) reacts at 0-20° with the NH- acidic compounds saccharin (2) and phthalimide (8) to give the 8-membered heterocycles 3-dimethylamino-4,4-dimethyl-5,6-dihydro-4H-1,2,5-benzothiadiazocin-6- one-1,1-dioxide (3a) and 4-dimethylamino-3,3-dimethy1-1,2,3,6-tetrahydro-2,5-benzodiazocin-1,6-dione (9), respectively. The structure of 3a has been established by X-ray (chap. 2). A possible mechanism for the formation of 3a and 9 is given in Schemes 1 and 4. Reduction of 3a with sodium borohydride yields the 2-sulfamoylbenzamide derivative 4 (Scheme 2); in methanolic solution 3a undergoes a rearrangement to give the methyl 2-sulfamoyl-benzoate 5. The mechanism for this reaction as suggested in Scheme 2 involves a ring contraction/ring opening sequence. Again a ring contraction is postulated to explain the formation of the 4H-imidazole derivative 7 during thermolysis of 3a at 180° (Scheme 3). The 2,5-benzodiazocine derivative 9 rearranges in alcoholic solvents to 2-(5’- dimethylamino-4’,4’-dimethyl-4’H-imidazol-2’-yl)benzoates (10, 11), in water to the corresponding benzoic acid 12, and in alcoholic solutions containing dimethylamine or pyrrolidine to the benzamides 13 and 14, respectively (Scheme 5). The reaction with amines takes place only in very polar solvents like alcohols or formamide, but not in acetonitrile. Possible mechanisms of these rearrangements are given in Scheme 5. Sodium borohydride reduction of 9 in 2-propanol yields 2-(5’-dimethylamino- 4’,4’-dimethyl-4’H-imidazol-2’-yl)benzyalcohol (15, Scheme 6) which is easily converted to the O-acetate 16. Hydrolysis of 15 with 3N HC1 at 50° leads to an imidazolinone derivative 17a or 17b, whereas hydrolysis with 1N NaOH yields a mixture of phthalide (18) and 2-hydroxymethyl-benzoic acid (19, Scheme 6). The zwitterionic compound 20 (Scheme 7) results from the hydrolysis of the phthalimide adduct 9 or the esters 11 and 12. Interestingly, compound 9 is thermally converted to the amide 13 and N-(1'-carbamoyl-1'-methylethy1)phthalimide (21, Scheme 7) whose structure has been established by an independent synthesis starting with phthalic anhydride and 2-aminoisobutyric acid. However, the reaction mechanism is not clear at this stage.

3-Dimethylamino-2,2-dimethyl-2H-azirine (1) reacts at 0-20° with the NH- acidic compounds saccharin (2) and phthalimide (8) to give the 8-membered heterocycles 3-dimethylamino-4,4-dimethyl-5,6-dihydro-4H-1,2,5-benzothiadiazocin-6- one-1,1-dioxide (3a) and 4-dimethylamino-3,3-dimethy1-1,2,3,6-tetrahydro-2,5-benzodiazocin-1,6-dione (9), respectively. The structure of 3a has been established by X-ray (chap. 2). A possible mechanism for the formation of 3a and 9 is given in Schemes 1 and 4. Reduction of 3a with sodium borohydride yields the 2-sulfamoylbenzamide derivative 4 (Scheme 2); in methanolic solution 3a undergoes a rearrangement to give the methyl 2-sulfamoyl-benzoate 5. The mechanism for this reaction as suggested in Scheme 2 involves a ring contraction/ring opening sequence. Again a ring contraction is postulated to explain the formation of the 4H-imidazole derivative 7 during thermolysis of 3a at 180° (Scheme 3). The 2,5-benzodiazocine derivative 9 rearranges in alcoholic solvents to 2-(5’- dimethylamino-4’,4’-dimethyl-4’H-imidazol-2’-yl)benzoates (10, 11), in water to the corresponding benzoic acid 12, and in alcoholic solutions containing dimethylamine or pyrrolidine to the benzamides 13 and 14, respectively (Scheme 5). The reaction with amines takes place only in very polar solvents like alcohols or formamide, but not in acetonitrile. Possible mechanisms of these rearrangements are given in Scheme 5. Sodium borohydride reduction of 9 in 2-propanol yields 2-(5’-dimethylamino- 4’,4’-dimethyl-4’H-imidazol-2’-yl)benzyalcohol (15, Scheme 6) which is easily converted to the O-acetate 16. Hydrolysis of 15 with 3N HC1 at 50° leads to an imidazolinone derivative 17a or 17b, whereas hydrolysis with 1N NaOH yields a mixture of phthalide (18) and 2-hydroxymethyl-benzoic acid (19, Scheme 6). The zwitterionic compound 20 (Scheme 7) results from the hydrolysis of the phthalimide adduct 9 or the esters 11 and 12. Interestingly, compound 9 is thermally converted to the amide 13 and N-(1'-carbamoyl-1'-methylethy1)phthalimide (21, Scheme 7) whose structure has been established by an independent synthesis starting with phthalic anhydride and 2-aminoisobutyric acid. However, the reaction mechanism is not clear at this stage.

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Additional indexing

Other titles:Synthesis and Reactions of 8-membered Heterocycles from 3-Dimethylamino-2,2-dimethyl-2H-azirine and Saccharin or Phthalimide
Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:German
Date:1977
Deposited On:29 Oct 2014 12:50
Last Modified:05 Apr 2016 18:26
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0018-019X
Funders:Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung
Publisher DOI:https://doi.org/10.1002/hlca.19770600734
Permanent URL: https://doi.org/10.5167/uzh-99739

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