Experiments towards the synthesis of the ergot alkaloids and related structures. Part 6. N-Acyl-N-(1,2,3,4-tetrahydro-1-oxo-2-naphthyl)glycines and a new aromatisation reaction

Abstract

Three methods are reported for the preparation of N-(1,2,3,4-tetrahydro-1-oxo-2-naphthyl)glycine (4; R = H) hydrochloride from which the title compounds may be prepared. In the first, hydrolysis of the oxazolinone ester (3; R = CH₂CO₂Me, n= 1) with concentrated hydrochloric acid in acetic acid furnished a mixture (ca. 4:1) of the hydrochlorides of the required amino-keto-acid (4; R = H) and β-naphthylglycine (5; R¹= R²= H) which were easily separable. In the second, a similar hydrolysis of the homologous oxazinedione (3; R = CH₂CO₂Me, n= 2) furnished it as the sole product in quantitative yield. In the third, 2-aminotetralone hydrochloride (7) was treated in formic acid solution with glyoxylic acid (ca. 3 mol equiv.) in the presence of base to give the N-formyl-keto-acid (10 = 4; R = CHO) in a crude yield of 85% and from which the hydrochloride of (4; R = H) was obtained by hydrolysis. Benzylamine reacted similarly to give N-formyl-N-benzyglycine but secondary amines do not appear to undergo this novel condensation-reduction reaction. Uncatalysed formolysis of the oxazolinone ester (3; R = CH₂CO₂Me, n= 1) furnished, in essentially quantitative yield, methyl N-formyl-2-naphthylglycinate (5; R¹= CHO, R²= Me)—a new aromatisation reaction which may well be of general utility since the parent oxazolinone and its N-methyl derivative behaved similarly.