2- Aminobenzaldehydes

The alkaloid vasicine was first isolated from Adhatoda vasica in 1925 but the structure (996) was elucidated only after a great amount of work, culminating in two independent syntheses in 1935 (B-53MI21301). It was made subsequently by a simple route from 2-aminobenzaldehyde and 4-amino-2-hydroxybutyraldehyde (994) followed by dehydration of the tricyclic intermediate (995) (60TL(25)44>. Vasicine has bronchodilatory activity of a low order. Two related unnamed alkaloids (997) and (998) were obtained in 1965 from members of the Araliaceae family, viz. Mackinlaya subulata and M. macrosciadia both had been synthesized earlier (66AJC151). 

Aminobenzaldehyde phenylhydrazone (Nitrin) [63363-93-9] M 211.3, rn 227-229 . Crystd from acetone. [Kndpfer Monatsh Chem 31 97 1910.]... 

Aminobenzaldehyde [29159-23-7] M 121.1, m 28-30 , pKEst-2.0. Crystd from ethyl acetate. 

In a recent paper, Schopf and Steuer ° describe the synthesis under physiological conditions of rutaecarpine from 4 5-dihydro-3-carboline perchlorate and a-aminobenzaldehyde. 

Condensation of A -pyrroline with o-aminobenzaldehyde leads to dihydroquinazolinium salt 202 on acidification, which in turn can be reduced to desoxyvasicine (203). 

The synthesis of alkaloids from dihydronorharmane, condensation of which with o-aminobenzaldehyde gives rutaecarpine (204) 321-323), is of a particular interest. 

Friedlander reported the condensation of 2-aminobenzaldehyde (4) with acetaldehyde (5) to provide quinoline (6) in 1882. ... 

The Friedlander reaction is quite versatile. The primary limitation on the o-aminobenzaldehyde component is preparation of the starting material as one might expect, these compounds are prone to self-condensation. Both electron rich and electron poor o-aminobenzocarbonyl compounds undergo the Friedlander reaction. When ketone partner 2 has only one available reactive methyl or methylene or is symmetrical, only one product is obtained. Even when two products can be formed, it is possible to choose reaction conditions such that only one product is isolated vide infra). The reaction can be promoted by acid catalysis, sometimes with improved results. 

The Henegar modification of the Friedlander reaction has been recently reported. The A-Boc protected derivative of o-aminobenzaldehyde (25, in this case prepared via directed ortho metallation of 24) is a stable, crystalline compound that can be stored for extended periods (in contrast with 4, which typically is freshly prepared). Treatment of 25 with ketone 26 in acetic acid results in deprotection of the aniline in situ and subsequent formation of 27, an intermediate in the synthesis of mappicine. 

Methylation of hydroxyquinazolines invariably produces a mixture of 0- and A -methylated derivatives. The A -methyl derivatives are, therefore, best prepared by unequivocal syntheses. 1-Methyl-2(1H)-quinazolinone (16) is not known. When o-aminobenzaldehyde is treated with methylisocyanate, 3-methyl-2(3i7)quinazolinone (17) is obtained. If this is heated in ethanol it dissolves and an alcoholate, presumably (18), crystallizes out, and this can be converted back to (17) by vacuum sublimation. Methylation of l-methyl-4(lH)Quinaz-... 

Unsubstituted quinazoline 3-oxide was prepared in an attempt to react quinazoline with hydroxylamine. This reaction gave a product of variable composition, but when an acetone solution was heated in a sealed tube it gave quinazoline 3-oxide. The oxide is more conveniently prepared, in excellent yield, from o-aminobenzaldehyde oxime and ethyl orthoformate. This method appears to be of general use and has been used for the preparation of 4-methylquinazoline... 

Peganine has two nitrogen atoms and its monoacidity is due to the formation of a cyclic amidinium cation. The Schopf-Oechler scheme for the synthesis of peganine from o-aminobenzaldehyde and... 

Like peganine a laboratory synthesis of rutaecarpine (51a) under physiological conditions has been realized by condensation of o-aminobenzaldehyde with a -carboline (Scheme 16). 

The same pathway is traced in the reaction of o-aminobenzaldehyde, which with 4-methoxybut-3-en-2-one forms 2-methylquinoline-3-carbaldehyde dimethylac-etal (231) (80MI1). With 3-aminocyclohex-2-enone it gives tetrahydroquinolinone 232 in 72% yield (76BRP1432579). 

Depending upon the structure of the substrates 49, 52, and 56 hexahydropyrido[l,2-n]-[3,l]benzoxazines 50, 54, 2-aminobenzaldehyde 53, 1-substituted piperidones 51, 55, 57, 3,4,5,6-tetrahydropyridinium salt 58, or their mixture was obtained during the oxidation of 1-(2-hydroxymethyl-, 2-formyl- and 2-acetylphenyl)piperazines (49, 52, 56) with Hg(II)-EDTA complex (Schemes 6-8) (79AP219, 98ZN(B)37, 98ZN(B)1369). 

Condensation of o-aminobenzaldehydes with a-methylene carbonyl compounds... 

Quinolines 3 can be obtained from reaction of orr/zo-aminobenzaldehydes or o-aminoarylketones 1 with a-methylene carbonyl compounds.Various modified procedures are known a related reaction is the Skraup quinoline synthesis. 

It is found in civet and in the wood of Celtis reticulosa. It forms crystals melting at 95° and boiling at 265° to 266°. It yields a hydrochloride, 2(C9HgN). HCl, melting at 167° 10 168°, and a picric acid compound melting at 172° to 173°. Skatol yields a blue colour with a solution of dimethyl-aminobenzaldehyde. 

Amines, preparation from isothiocyanates, 18, 5 from ketones, 17, 76 m-Aminobenzaldehyde, 13, 28... 

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