O- 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. 

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). 

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

A similar strategy can also be applied for the analogous synthesis of naphthyridine derivatives [93]. Here A-allyl derivatives of o-aminobenzaldehyde,... 

The Friedlander quinoline synthesis is particular useful for the preparation of 3-substituted quinolines, which are less accessible by other routes. A drawback however is the fact that the required o-aminobenzaldehydes or o-aminoarylketones are not as easy to prepare as, e.g., the anilines that are required for the Skraup synthesis. 

Benzotriazine (8, R = H), for example, can be isolated as a reasonably stable, colorless crystalline solid, but it reacts rapidly in solution with water to give o-aminobenzaldehyde, presumably by initial covalent hydration to give 98, which decomposes to o-aminobenzaldehyde via the triazene 99. Reaction of 8, R = H, with other nucleophiles also occurs readily, while 4-substituted 1,2,3-benzo-triazines react similarly but more slowly, as expected, owing to a combination of steric and electronic effects. 

The reaction of o-aminobenzaldehyde with DMAD gives rise to dimethyl quinoline-2,3-dicarboxylate (28) [Eq. (11)]. Similarly, the... 

Bismuth(lll) chloride catalyzes the intramolecular hetero-Diels-Alder reaction of aldimines, generated in situ from aromatic amines and the A -allyl derivative of o-aminobenzaldehyde, in acetonitrile at reflux to generate [l,6]naphthyridine derivatives <2002TL1573>. The hetero-Diels-Alder reaction of 3-aryl-2-benzoyl-2-propeneni-triles and enol ethers yields 2-alkoxy, 6-diaryl-3,4-dihydro-2//-pyran-5-carbonitriles (Scheme 29) <1997M1157>. 

There was confusion for many years regarding the identity of the product obtained by reacting o-aminobenzaldehyde with acetic anhydride. It was originally thought to be... 

Self-condensation of suitable aminocarbonyl compounds in various forms is a potential route to symmetrically substituted 1,5-diazocines of many kinds, but the successful applications are largely limited to benzo fused derivatives. o-Aminobenzaldehyde, despite earlier... 

This reaction is particularly useful in the Fricdlander quinoline synthesis, the use of which has been limited hy the inaccessibility of o-aminobenzaldehydes. Thus a one-pot synthesis of quinolines is now possible by reduction of an o-nitrobenz-aldehyde with the reagent in the presence of an a-mcthylene ketone. 

Note Prepn of o-aminobenzaldehyde is described in OSRD Rept 739(1942)... 

Bis(pyrrole-2-aldiminato)nickel(II) complexes (125) are diamagnetic in the solid state when R = H, Pr, Pr and Et, and paramagnetic pseudotetrahedral when R = Bu. 1001-1003 In solution there exists an equilibrium between square planar and tetrahedral species when R = Pr1, Bus and Bu Such equilibria were also investigated for complexes of the type (126) obtained from the condensation reaction in basic media of o-aminobenzaldehyde and a number of diamines in the presence of nickel(II).1004-1007 Square planar complexes (127)1008,1009 and (128)1010 were obtained with deprotonated pyridinecarboxamide ligands. In these complexes the Ni—N (amide) bond distance (184-187 pm) is shorter than the Ni—N (pyridine) distance (192-195 pm). 

Self-condensation of o-aminobenzaldehyde Oh X= Br, I, N03, NCS, C104 with Ni(N03)2 hydrate in EtOH... 

D Self-condensation of o-aminobenzaldehyde SqPl Y = C104, BF4, BPh4 2651,2754... 

Tetrabenzo-l,5,9,13-tetraazacyclohexadeca-l,5,9,13-tetraenepalladium dichloride (47) may be formed by template condensation of o-aminobenzaldehyde. 

Reaction LIV. (c) Condensation of o-Aminobenzaldehydes with Aldehydes, Ketones, Ethyl acetoacetate, etc., under the influence of a trace of Sodium Hydroxide, to give Quinoline Derivatives (B., 16,1835 25,1752). —The first stage is the formation of an o-aminostyryl ketone. 

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