From carboxylic acid derivatives

Hydroxymethylpyrazines may be prepared by reduction of carboxylic acid derivatives. Thus reduction of 2-amino-3-methoxycarbonylpyrazine with lithium aluminum hydride in tetrahydrofuran gave 2-amino-3-hydroxymethylpyrazine (1074, 1075) the imide from 23-dicarboxypyrazine (20) with sodium borohydride in tetrahydrofuran gave 2-carbamoyl-3-hydroxymethylpyrazine (21), and the methylcarbamoyl analogue was prepared similarly (1076). 

2-Methoxy-3-methoxycarbonyl-5-methylpyrazine with methylmagnesium iodide in ether gave 3-(a-hydroxyisopropyl)-2-methoxy-5-methylpyrazine (844). 

From Alkylpyrazine A -Oxides with Acetic Anhydride Followed by 

In an approach to simple Nuphar quinolizidine alkaloids, the piperidine compound 213 was converted to compound 214 that underwent one-pot detosylation, conjugate reduction, and cyclization to produce the quinolizidin-4-one 215 

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A common procedure in C-C-bond formation is the aldol addition of enolates derived from carboxylic acid derivatives with aldehydes to provide the anion of the [5-hydroxy carboxylic acid derivative. If one starts with an activated acid derivative, the formation of a [Mac lone can follow. This procedure has been used by the group of Taylor [137] for the first synthesis of the l-oxo-2-oxa-5-azaspiro[3.4]octane framework. Schick and coworkers have utilized the method for their assembly of key intermediates for the preparation of enzyme inhibitors of the tetrahydrolipstatin and tetrahydroesterastin type [138]. Romo and coworkers used a Mukaiyama aldol/lac-tonization sequence as a concise and direct route to 3-lactones of type 2-253, starting from different aldehydes 2-251 and readily available thiopyridylsilylketenes 2-252 (Scheme 2.60) [139]. 

Fragments S-C-N-N and C Thiohydrazide derivatives with a carbon source 5.10.9.2.2 From carboxylic acid derivatives... 

Table 2.3. Heteroatom-substituted carbene complexes prepared from carboxylic acid derivatives and metallates.

Enolate anions from carboxylic acid derivatives... 

The a-hydrogens of carboxylic acid derivatives show enhanced acidity, as do those of aldehydes and ketones, and for the same reasons, that the carbonyl group stabilizes the conjugate base. Thus, we can generate enolate anions from carboxylic acid derivatives and use these as nucleophiles in much the same way as we have already seen with enolate anions from aldehydes and ketones. 

In this section we give you a quick look at a few additional and potentially useful reactions of Ccirboxylic acids and compounds derived from carboxylic acids (derivatives). 

Formation of amides from carboxylic acid derivatives already has been discussed in some detail (Section 23-9A) ... 

Ketenimines are usually prepared from carboxylic acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl halides under strong basic conditions (21,64). 

Because of the toxicity of cadmium compounds two alternative methods for the preparation of ketones from carboxylic acid derivatives are worthy of attention. The first involves the reaction of organocopper reagents [formed from copper(i) iodide and an alkyllithium] with a carboxylic acid chloride.12 7a,b... 

Synthesis of aromatic ketones from carboxylic acid derivatives (Expts 6.126 and 6.127). 

Equation 6.4 shows the following in strongly basic solutions, SN products can be produced from carboxylic acid derivatives in two steps. An example of such a reaction is the saponification PhC(=0)0Et + KOH —> PhC(=0)0 K + EtOH. However, in approximately neutral solutions the four-step path to the SN product should predominate. An example of this type of reaction is the amino lysis PhC(=0)0Et + HNMe2 —> PhC(=0)NMe2 + EtOH. 

NH3 or RNH2 or R2NH Amide formation from carboxylic acid derivatives (mild) or from carboxylic acids (A technical synthesis of nylon-6,6) transamidation [capro-lactame —> nylon-6 (perlon)] Peptide synthesis (Section 6.4.3)... 

Preparation of Nitriles from Carboxylic Acid(Derivative)s... 

Irradiation of alkoxycarbene complexes in the presence of aUcenes and carbon monoxide produces cyclobutanones. A variety of inter- and intramolecular [2 + 2]cycloadditions have been reported. The regioselectivity is comparable with those obtained in reactions of ketenes generated from carboxylic acid derivatives. Cyclobutanones can be obtained with a high degree of diastereoselectivity upon reaction of alkoxy carbenes with chiral A-vinyloxazolidinones. For example, photolysis of (19) in the presence of (20) gives cyclobutanone (21) (Scheme 31). In addition to aUcoxycarbenes, carbenes having a thioether or pyrrole substituent can also be employed. Related intramolecular cycloadditions of y,5-unsaturated chromimn carbenes afford bicyclo[2.1. IJhexanones (Scheme 32). 

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