Synthesis of aryloxyacetaldehydes and N-(aryloxyethyl)cyclohexanamine hydrochloroides

Abstract

Oxidation of 2-(aryloxymethyl)oxiranes with periodic acid gave a series of aryloxyacetaldehydes which reacted with cyclohexylamine in THF, and subsequent reduction of Schiff bases thus obtained with sodium tetrahydridoborate resulted in the formation of the corresponding secondary amines which were isolated and characterized as hydrochlorides.Aryloxyethanamines are known to exhibit biological activity. In particular, compounds acting as local anesthetics, adrenergic neuron blocking agents [1, 2], and dopamine D 2 -receptor inhibitors [3] were found among aryloxyethanamine derivatives. These compounds are commonly synthesized by alkylation of phenols with 2-halo amines [1,4] or of amines with 2-aryloxyethyl halides [4]. Also, reductive amination of aryloxyacetaldehydes with the use of sodium tetrahydridoborate [2, 3, 5] or hydrogen over Pd/C [6] was reported. However, the yields are not high, and they rarely exceed 50%. For example, Sakurai et al. [3] described the reaction of substituted phenoxyacetaldehydes with primary and secondary amine hydrochlorides in methanol in the presence of triethylamine, followed by reduction with NaBH 4 , which afforded 11-31% of the corresponding 2-phenoxyethanamines.Aryloxyacetaldehydes necessary for the synthesis of aryloxyethanamines according to [3] can also be prepared in several ways: by catalytic oxidation of 2-phenoxyethanol [7], by alkylation of phenols with bromoacetaldehyde acetals and subsequent hydrolysis [2,8], by ozonolysis of allyl phenyl ethers [9], and by oxidation of glycerol monophenyl ether with lead tetraacetate [10]. The most appropriate procedure seems to be oxidation of 2-(aryloxymethyl)oxiranes with periodic acid in aqueous medium or aqueous dioxane, which was proposed in [11] for the synthesis of phenoxyacetaldehyde.In the present article we report on the synthesis of 2-(aryloxymethyl)oxiranes and their oxidation with periodic acid to obtain aryloxyacetaldehydes. The latter were converted into the corresponding N-cyclohexyl imines which were reduced to amines with sodium tetrahydridoborate. N-(Aryloxyethyl)cyclohexanamines were isolated and characterized as hydrochlorides.By heating substituted phenols with excess 2-(chloromethyl)oxirane in aqueous sodium hydroxide we obtained the corresponding 2-(aryloxymethyl)-

New method of preparation of alkoxyacetic acids

“…After evaporation, ether Ib produced 1.64 g of a mix ture of compounds IIb and IVb in 25 : 75 ratio (accord ing to GLC and NMR data), column chromatography IR and 13 C NMR spectra were the most informa tive methods to establish the structure of the obtained compounds (IIa, IIb-IVa, IVb) isolated by column chromatography ( Table 2). The obtained spectral and physicochemical characteristics of esters IIa, IIb and aldehydes IIIa, IIIb agree well with the literature data [5][6][7][8][9].…”