SUBSTITUTED α-DIALKYLAMINOALKYL-1-NAPHTHALENE-METHANOLS. VII. SYNTHESIS OF SOME PROPANOLAMINES BY MEANS OF GRIGNARD REAGENTS¹

Abstract

In the synthesis of j3-dialkylaminoethyl-l-naphthalenemethanols, I, CH(OH)CX2CH2NR2 Z\Z\ VU Y I the failure of the method involving preparation and reduction of the Mannich ketones (1) in those cases where Y = Cl, X = H or Y = CH30, X = CH3 led to the investigation of other methods. The synthesis of compounds representative of this second case (Y = CH30, X = CH3) was accomplished successfully by treatment of a,a-dimethyl-/3dialkylaminopropionaldehyde with 4-methoxy-l-naphthylmagnesium bromide: MgBr zX/\ + R2NCH2C(CH3)2CHO och3 CH( OH) C (CH3)2 CH2NR2 z\A och3The a ,a-dimethyl-/3-dialkylaminopropionaldehydes were readily prepared according to the method of Mannich, Lesser, and Silten (2). The preparation of several of these compounds has been recorded in the literature: methylamino (3), dimethylamino (2), diethylamino (2), piperidino (2), and morpholino (4). We have extended the series to include those amino aldehydes containing the di-npropyl, di-n-butyl, and di-n-amyl groupings. The properties of these compounds are summarized in Table I.The Grignard reagent prepared from l-bromo-4-methoxynaphthalene (5) re-

SUBSTITUTED α-DIALKYLAMINOALKYL-1-NAPHTHALENE-METHANOLS. IX. α-(2-DIALKYLAMINOETHYL)-α-METHYL ARYLMETHANOLS1

“…The resulting compound was identical with that obtained from l-dibutylamino-3-butanone and 4-methoxy-lnaphthylmagnesium bromide. A few examples of similar syntheses have been reported (7,13,14).…”

The use of [2,3] sigmatropic rearrangements for the specific ortho-substitution of polycyclic aromatic amines. The methylation of naphthylamines and the synthesis of 1H-benz[g]indoles and 3H-benz[e]indoles

“…A hydrochloride was prepared, mp 227-230 °C (lit.18 mp 228-231 °C). l-Methylthio-2-methyl-3H-benz[e]indole (17). To a stirred solution of 3.75 g (26 mmol) of 2-aminonaphthalene (4) in 75 mL of tetrahydrofuran at ca.…”

“…The ether layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure to give crude 17. Chromatography on silica gel (benzene eluent) gave 4.5 g (76%) of 1-methylthio-2-methyl-3//-benz[e]indole (17), mp 112-113 °C. Recrystallization from hexane gave an analytical sample: mp 112.0-112.5 °C; IR (KBr) 2.90, 7.29, 7.52, 8.30, 10.35, 12.35, 13.36, 14.42 Mm; NMR (CDCI3) 2.25 (3 H, s), 2.37 (3 H, s), 7.0-8.0 (6 H, m), 9.60 (1 H, d).…”

“…Treatment of 8 with 1 equiv of tert-butyl hypochlorite followed by 1 equiv of methylthio-2-propanone and then by triethylamine gave a 65% yield of 15. Raney nickel desulfurization of 15 gave a 90% yield of 16. In a similar fashion, /3-naphthylamine was converted into l-methylthio-2-methyl-3H-benz[e]indole (17) in 73% yield. Raney nickel desulfurization of 17 gave 18 in 88% yield.…”