2- Aminobenzaldehyde, reaction with

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). 

Authentic N-analogs of spirobenzopyrans, the 1,2-dihydrospiro-2//-quinolines (79) (or their open forms), have never been isolated, despite many attempts during the past 35 years. In reactions with Fischer s base, 5-nitro-2-aminosalicylaldehyde gave no reaction, whereas 2-aminobenzaldehyde gave only a polymer.7 The open form of the desired compound could be considered a quinone monoimine and therefore be expected to have poor stability. 

An alternative method of studying the reaction is by dinitrophenylation of the acid hydrazides (see above). The DNP derivatives are red in alkali and can be determined colorimetrically. Gallop et al. (1959) first used hydrazine to demonstrate ester links, but gave few details except that the fall of molecular weight was similar to that produced by hydroxylamine. The bound hydrazides were demonstrated by the reaction with p-dimethyl-aminobenzaldehyde, by dinitrophenylation, and by reduction of copper salts. 

Heating the aminoacetal (2.1) with ethanolic hydrogen chloride produces a quinoline [2612], but sulphuric acid causes the cyclization to follow another course (see Chapter 3, Section II. 1). n-Aminoaldehydes are cyclized by heating with a reactive methylene-containing ketone, ester or nitrile but in the reaction with the pyrazole aldehyde (2.2), yields seem to depend greatly on the nature of the A -substituent for example, when R = R = CN, the product is obtained in either 3.6% or 83% yields according to whether R is methyl or phenyl [2798]. The chemistry of a-cyanothioacetamide (2.4), which is used in the conversion of 2-aminobenzaldehyde (2.3) to 2-aminoquinoline-3-thiocarboxamide [2926], has been reviewed [3331]. 

Early work involved the use of metal cations as templates in macrocyclization reactions. Seidel [6] reacted 2-aminobenzaldehyde 1 with anhydrous zinc chloride (Scheme 1-1), but did not recognize that he had prepared the macrocycle 2, and it was not until 40 years later that Busch [7] and co-workers elucidated the structure of this type of macrocycle and investigated how metal cations template its formation. 

The reaction between amino group (-NH2) and a carbonyl group (C=0) elsewhere in the same molecule has been used in the synthesis of many heterocyclic compounds. For example as shown in Equation 9.53, substituted quinolines can be produced by acid-catalyzed cyclization of the appropriate aminoketones (formed during the Friedlander synthesis, in this instance between propanone and ortho-aminobenzaldehyde, in an aldol-type reaction with loss of water this chapter, vide infra), and even more than one reaction can be induced to occur. Thus, in Equation 9.54,1,2-benzenediamine (ort/io-aminoaniline) undergoes acid-catalyzed addition to 2,3-butane-dione to produce 2,3-dimethyl-13-benzopyrazine (23-dime thy Iquinoxaline). ... 

The most specific method for sialic acid determination is possible with enzymes. Using acylneuraminate pyruvate-lyase (EC 4.1.3.3), sialic acids are cleaved to acylmannosamines and pyruvate. By coupling this reaction to lactate dehydrogenase the reduction of pyruvate allows monitoring of the pyruvate concentration and drives the lyase reaction, otherwise an equilibrium reaction, to completion (Brunetti et al. 1963). The concentration of sialic acid can be measured by spectrophotometry or fluorimetry of the amount of NADH oxidized on completion of the reaction, or by measurement of the initial rate of NADH oxidation. A less sensitive alternative is determination of N-acylmannosamine using colorimetric methods. Brunetti et al. (1962) utilized the Morgan-Elson reaction with dimethyl-aminobenzaldehyde for this purpose. 

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. 

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