Imines, with carboxylic acids compounds

Chorazepate Chorazepate, 7-chloro-2,3-dihydro-2,2-dihydroxy-5-phenyl-1H-1,4-benzo-diazepin-3-carboxylic acid (5.1.34), which is used in the form of a dipotassium salt, is synthesized by yet another interesting synthetic scheme. 2-Amino-5-chlorobenzonitrile is used as the initial compound, which upon reaction with phenyhnagnesiumbromide is transformed into 2-amino-5-chlorbenzophenone imine (5.1.32). Reacting this with amino-malonic ester gives a heterocyclization product, 7-chloro-l,3-dihydro-3-carbethoxy-5-phenyl-2H-benzodiazepin-2-one (5.1.33), which upon hydrolysis using an alcoholic solution of potassium hydroxide forms a dipotassium salt (5.1.34), chlorazepate [30-32]. 

In connection with these results, and as an extension of their studies toward the reactivity of new bicyclic mesoionic compounds and their usefulness in the synthesis of condensed heterocycles, they further reported the stereoselective synthesis of spiro-(3-lactams 153, 154 (Scheme 36) by reactions of imines with mesoionic compounds or ketenes generated from A-acyl-thiozolidine-2-carboxylic acids 152 [110]. 

There are many routes available for the synthesis of aziridine 2-carboxylic acids, however there are few reactions which yield enantiomerically pure products. These compounds (especially those with cis-stereochemistry) are especially useful for the synthesis of bioactive molecules556. There is thus significant effort in this area of synthesis557,558, but most methods are lengthy multistep procedures. Recently, a simple, one-pot procedure, utilizing imines, has been developed for the asymmetric synthesis of c/s-N-substituted aziridine-2-carboxylic acids via a Darzens-type reaction (equation 154)559. 

The hydrocyanation reactions of electrophilic aldehydes, ketones and their corresponding imines gives direct access to synthetic derivatives of several important structures, including a-hydroxy carboxylic acids, / -amino alcohols and a-tertiary and a-quaternary-a-amino acids. The asymmetric hydrocyanation reaction provides access to chiral synthons, which have proven useful for the construction of many structurally complex and biologically active compounds. Catalysis of these reactions is especially attractive with respect to avoiding the cost and relative chemical inefficiency associated with the use of chiral auxiliaries. 

In a similar heterocyclic quinodimethane ring construction strategy, the hexacyclic adducts (64) were isolated in good yield upon condensation of appropriately functionalized indole imines with ( )-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid chloride (Equation (35)) (88JA2242). In a demonstration of the utility of this new method for indole alkaloid synthesis, further transformations conducted on compound (64 R = R2 = H, R3 = Et) were shown to lead to ( —)-16-methoxy-tabersonine. 

The mechanism, illustrated in Mechanism 20.5 with RCONH2 as starting material, is somewhat different than the previous reductions of carboxylic acid derivatives. Amide reduction proceeds with formation of an intermediate imine, a compound containii a C-N double bond, which is then further reduced to an amine. 

The transformation of an active CH compound into the corresponding diazo derivative with -toluenesulfonyl azide has been designated a diazo transfer reaction and possesses a variety of preparative uses. The method has been useful for the syntheses of diazo derivatives of cyclopentadiene, 1,3-dicar-bonyl compounds, 1,3-disulfonyl compounds,1,3-keto-sulfonyl compounds, ketones, " carboxylic acid esters, and /3-keto imines. Further reaction of these diazo intermediates can lead to azo compounds,"- " 1,2,3-triazoles, and pyrazolinones. ... 

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