Azabenzocycloheptenones. Part 20. Synthesis and utilisation of 4-amino-1,2,3,4-tetrahydro-1(1H)-benzazepines

Abstract

1,2,3,4-Tetrahydro-6- and -7-methoxy-4-oxo-1-(p-tolylsulfonyl)quinolines and 1-ethoxycarbonylmethyl-1,2,3,4-tetrahydro-7-methoxy-4-oxoquinoline have been ring-expanded in two steps to 2,3,4,5-tetrahydro-7- and -8-methoxy-4-oxo-1-(p-tolylsulfonyl)-1H-1-benzazepines and 1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-8-methoxy-4-oxo-1H-1-benzazepine. Redn. of the oximes gives 4-amino-2,3,4,5-tetrahydro-7-methoxy-1-(p-tolylsulfonyl)-1H-1-benzazepine, 4-amino-2,3,4,5-tetrahydro-8-methoxy-1H-1-benzazepine, and 4-amino-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-8-methoxy-1H-1-benzazepine. From these, several N-substituted and N,N-disubstituted compds. have been obtained and 3-amino-2,3,4,5-tetrahydro-1-(p-tolylsulfonyl)-1H-1-benzazepine has been made by similar means. Two routes are described to 2,3,4,5-tetrahydro-8-methoxy-5-oxo-1-(p-tolylsulfonyl)-1H-1-benzazepine which is converted to 2,3,4,5-tetrahydro-8-methoxy-4-methoxyimino-5-oxo-1-(p-tolylsulfonyl)-1H-1-benzazepine and thence to 5-[2-(ethoxycarbonyl)ethynyl]-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-4-methoxyimino-1-(p-tolylsulfonyl)-1H-1-benzazepine and 5-[2-(ethoxycarbonyl)ethyl]-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-4-methoxyimino-1-(p-tolylsulfonyl)-1H-benzazepine. Redn. of 2,3,4,5-tetrahydro-8-methoxy-4-oximino-5-oxo-1-(p-tolylsulfonyl)-1H-1-benzazepine in two steps gives both cis- and trans-4-acetamido-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-1-(p-tolylsulfonyl)-1H-1-benzazepines which are sep. deacetylated and cyclised with Et chloroacetate to cis- and trans-2,3,4,4a,5,6,7,11b-octahydro-9-methoxy-3-oxo-7-(p-tolylsulfonyl)[1,4]oxazino[3,2-d][1]benzazepine. By similar methodol. cis- and trans-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-4-propionamido-1-(p-tolylsulfonyl)-1H-1-benzazepines have been obtained, sepd. and the latter reduced to trans-2,3,4,5-tetrahydro-5-hydroxy-8-methoxy-4-(n-propylamino)-1-(p-tolylsulfonyl)-1H-1-benzazepine. In three steps the latter is converted to trans-2,3,4,4a,5,6,7,11b-octahydro-9-methoxy-4-(n-propyl)-7-(p-tolylsulfonyl)[1,4]oxazino[3,2-d][1]benzazepine

The Application of the Schmidt Reaction and Beckmann Rearrangement to the Synthesis of Bicyclic Lactams: Some Mechanistic Considerations

“…[18,23,24] For the Beckmann rearrangement, conversion of the ketones to the ketoximes was achieved by refluxing the ketone with hydroxylamine hydrochloride and sodium acetate in ethanol for 2 h (Table 2). [25][26][27][28][29] Literature procedures on the synthesis of ketoximes are not specific regarding the geometry (syn or anti) of the oxime group and full characterization is seldom performed as they are transitory. Hence, the ketoxime intermediates are reported as either non-specific or are assumed to be in the sterically favoured anti-arrangement.…”

Oximes of Seven-Membered Heterocyclic Compounds Containing One Heteroatom

“…The classical method for the synthesis of azepane oximes is based on the reaction of azepane ketones with hydroxylamine hydrochloride in the presence of different bases [1], aqueous or aqueous methanolic solution of NaHCO 3 [2,3] or pyridine in methanol or ethanol [4][5][6]. Azepane oximes 2 have been obtained in the two-step reaction from the acid 1 in the presence of polyphosphoric acid (PPA) and hydroxylamine hydrochloride [6].…”

“…Azepane oximes have been successfully obtained also by the nitrosation of side chain of azepane derivatives. As nitrosation agents NaNO 2 / H 2 O / AcOH [11], BuONO / KHMDS (potassium bis(trimethylsilyl)amide)/ THF [12], BuONO / KHMDS / PhMe [13], tert-BuONO / tert-AmONa / PhH / PhMe [14], tert-BuONO / tert-BuOK / PhMe [15], tert-BuONO / tert-BuOK / CHCl 3 / PhMe [16], iso-AmONO / HCl [4,17] and iso-AmONO / LiHMDS / THF [18] are used. Interesting is the fact that the reaction of 2,5-dihydrobenzo[f]azepin-2,5-dion-3-ol (9) in the system NaNO 2 / NaOH (then 2М aqueous solution of H 2 SO 4 ) leads to formation of 4-oxime of 1Н-benzo[b]аzepin-2,3,4,5-tetraone (10) [19].…”

“…Similar reaction of oxime 77 with concentrated H 2 SO 4 affords apotacamine 78 in 42% yield [65]. Novel four step method of synthesis of the novel heterocyclic system oxazinoazepines from 4-oximes of azepin-4,5-diones has been described [4]. Thus, the reductive amidation of oxime 79 leads to formation of amide 80.…”

“…Thus, the reaction of azepine oxime 87 in thionyl chloride gives 8-nitro-1,3,4,6-tetrahydrobenzo[b] [1,4]diazocin-2,5-dione (88) in 80% yield [6]. Oxime of 4,5-dihydrobenzo[b]oxepin-3-one (89) and PPA at 90 о С afforded selectively the derivative of 1,4-oxazocine 90 [23].…”