Premium
Synthese und Reaktionen 8‐gliedriger Heterocyclen aus 3‐Dimethylamino‐2,2‐dimethyl‐2 H ‐azirin und Saccharin bzw. Phthalimid
Author(s) -
Chaloupka Stanislav,
Vittorelli Piero,
Heimgartner Heinz,
Schmid Hans,
Link Helmut,
Bernauer Karl,
Oberhänsli Willi E.
Publication year - 1977
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19770600734
Subject(s) - chemistry , dimethylamine , medicinal chemistry , methylamine , phthalimide , sodium borohydride , decarbonylation , ring (chemistry) , derivative (finance) , stereochemistry , organic chemistry , catalysis , financial economics , economics
Synthesis and Reactions of 8‐membered Heterocycles from 3‐Dimethylamino‐2,2‐dimethyl‐2 H ‐azirine and Saccharin or Phthalimide 3‐Dimethylamino‐2,2‐dimethyl‐2 H ‐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‐4 H ‐1,2,5‐benzothiadiazocin‐6‐one‐1,1‐dioxide ( 3a ) and 4‐dimethylamino‐3,3‐dimethyl‐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 4 H ‐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)benzyl alcohol ( 15 , Scheme 6 ) which is easily converted to the O ‐acetate 16 . Hydrolysis of 15 with 3 N HCl at 50° leads to an imidazolinone derivative 17a or 17b , whereas hydrolysis with 1 N 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′‐methylethyl)phthalimide ( 21 , Scheme 7) whose structure has been established by an independent synthesis starting with phthalic anhydride and 2‐amino‐isobutyric acid. However, the reaction mechanism is not clear at this stage.