A method for synthesizing methyl 2, 3-dihydro-2-benzofurancarboxylates from o-allylphenols is described. The reaction of 6-allyl-2, 3-dichlorophenol (3) with benzenesulfenyl chloride (PhSCl) in acetonitrile gave a mixture of PhSCl-adducts, which was heated in aqueous acetonitrile then with sodium bicarbonate to obtain 6, 7-dichloro-2-(phenylthiomethyl)-2, 3-dihydrobenzofuran (6). α-Dichlorination of the phenylthiomethyl group of 6 and subsequent methanolysis gave the methyl ester 5 in high yield. The generality of this synthetic method was examined by the conversion of o-allylphenols 11 having various substituents on the benzene ring into the corresponding methyl esters 23. Cyclizations of 11 to the sulfides 12 could be achieved similarly to hte case of 3. However, in the subsequent conversions of 12 to 23, selective α-dichlorination followed by methanolysis could be achieved only with 12 substituted with an electron-withdrawing group such as a chloro or nitro group.
The nucleophilic reaction of NaN3 with the chloromethylheteroalicycles, 4-benzyl-3chloromethyl-morpholine 5a, -tetrahydro-4H-1,4-thiazine 5b, -1-methylpiperazine 5c and 1-benzyl-2-chloromethylpiperidine 5d, gave the ring-expanded compounds 6-azido-4-benzylhexahydro-1,4-oxazepine 11a and its analogues 11b–d along with the normally substituted compounds 3-azidomethyl-4-benzylmorpholine 10a and its analogues 10b–d in varying ratios. LUMO frontier electron densities of the reaction centres indicated that the reaction proceeded via the aziridinium intermediate 9 and accounted for the predominance of the reaction product 10 or 11.
Azolium ylides react with dialkyl acylphosphonate to form generally six membered azine derivatives by ring expansion of the azolium heterocycle.This article gives a survey of the reaction with thiazolium, thiadiazolium, oxazolium, oxadiazolium, and imidazolium, and also discusses the relationship of the nature of 4'-suhtituents to the stability and reactivity of thiamine and its analogues in this novel reaction.Many reports have been published on the mechanism of decarboxylation of pyruvate by the enzyme pyruvate decarboxylase, and since the thiazolium ylide hypothesis was proposed by Breslow' interest has especially centred on the formation of 2-suktituted thiazolium compounds by the reaction of thiamine and the related thiazolium salts with various electrophiler.The authors themselves have tried the reaction with aldehyde^,^ a-ketoaldehyde~,~ irocyanate~,~ irothi~cyanates,~ and carbodiimides6 : chemical model experiments for the f i n t step of the decarboxylation reaction.Compared with these electrophiles, dialkyl a~~lphosphonates react with thiamine and related thiazolium salts i n better yields, giving the 3-0x0-2,3-dihydro-4H-thiazine ring system.When applied to other azolium salts,the acylphosphonate reaction proceeds i n almost the same way as with thiazolium, though some differences are observed depending on the character of the azolium salt used.These differences are mostly attributed to the character of heteroatom involved.In this paper we wish to give an outline of our studies on the acylphosphonate reaction with thiazolium, thiadiazolium, oxazolium, oxadiazolium, and imidazolium salk, as the results seem to be interesting for understanding the nature of azolium heterocycles. I. ~hiamine'-IzThis reaction is carried out under basic conditions as i t involves a thiazolium ylide as an intermediate.O u r experimental conditions were as follows: to an ice-cooled suspension o f thiamine hydrochloride i n dry dimethylformamide, three molar amounts of triethylamine and an equimolar amwnt of dialkyl acylphosphonate were added and the mixture was allowed to stand overnight at room temperature under nitrogen atmosphere.Evaporation of the dimethylformamide, extraction with chloroform, washing the chloroform extract with aqueous sodium bicarbonate solution and evaporation of chloroform left yellow crystals of I-phenyl-3(2-hydroxyethyl)-4,9-dimethyl-1,6-dihydropyrimido[4',5'-4,5] pyrimido[2,3-c] [ 1,4] thiazine (Ill) i n 87% yield.W i t h ordinary azolium salts which have no amino group participating i n the reaction center,
An efficient and practical method for the synthesis of (6R)-6-amino-1-methyl-4-(3-methylbenzyl)hexahydro-1H-1,4-diazepine 2, which serves as the amine part of DAT-582, a potent and selective 5-HT3 receptor antagonist, is described. The key intermediates, the chiral 2,3-diaminopropionic esters 20 and 26, are prepared by treatment of the optically active aziridines (R)-13 and (S)-13, obtained from D- and L-serine methyl ester hydrochlorides (R)-9 and (S)-9, with the ethylenediamine 19 and its protected derivative 18, respectively. Intramolecular reductive cyclization of 20 gives the chiral 6-benzyloxycarbonylaminohexahydro-1H-1,4-diazepine 22 with high optical purity via the corresponding iminium salt. Deprotection of 22 affords the desired chiral amine 2. As an alternative method, intramolecular amidation of the 2,3-diaminopropionic acids 23 and 28, which are prepared from 20 and 26, gives the 6-benzyloxycarbonylaminohexahydro-1H-1,4-diazepin-5-one 24 and the 7-oxo analogue 29. After removal of the benzyloxycarbonyl group, the resultant compounds 25 and 30 are reduced with diisobutylaluminium hydride to produce the optically active amine 2.
Abstract An efficient and practical synthesis of N,N-diethyl-7-indolyloxyacetamide (1) from 3-hydroxy-2-nitrotoluene (4) via 7-hydroxyindole (2) is described. Treatment of 3-benzyloxy-2-nitrotoluene (5) obtained from 4 with DMF dimethyl acetal and pyrrolidine afforded the (E)-2-nitro-β-pyrrolidinostyrene 6, which can be readily converted into the 2-nitrophenylacetaldehyde semicarbazone 7 without isolation of 6. Hydrogenation of 7 over Pd/C, followed by reaction of the resulting 2 with 2-chloro-N,N-diethylacetamide produced 1 in good yield.
Abstract An efficient asymmetric synthesis of ( R )‐6‐amino‐1‐methyl‐4‐(3‐rnethylbenzyl)hexahydro‐1 H ‐1,4‐diazepine [( R )‐2] which serves as the amine part of ( R )‐1, a potent and selective 5‐HT 3 receptor antagonist, is described. Formation of the hexahydro‐1 H ‐1,4‐diazepine ring was achieved by the intramolecular ami‐dation of the optically active aminocarboxylic acid 18 or reductive cyclization of the optically active aminoaldehyde 25. Compounds 18 and 25 were prepared from L‐asparagine via the key aziridine derivatives 15 and 22 , respectively, with retention of the configuration. The intramolecular aziridine ring opening reaction of 29 gave the C 2 N bond cleavage product of the aziridine ring, the piperazin‐5‐one 30 , as the main product along with the desired 7‐membered ring, the hexahydro‐1 H ‐1,4‐diazepine product 19 .
