Aliphatic acid chlorides substitution reactions

Most reactions in two-phase systems occur in a liquid phase following the transfer of a reactant across an interface these are commonly known as extractive reactions. If the transfer is facilitated by a catalyst, it is known as phase-transfer catalysis [2]. Unusually, reactions may actually occur at an interface (interfacial reactions) examples include solvolysis and nucleophilic substitution reactions of aliphatic acid chlorides [3 ] and the extraction of cupric ion from aqueous solution using oxime ligands insoluble in water [4], see Section 5.2.1.3(ii). 

The familiar substitution reactions of derivatives of carboxylic acids with basic reagents illustrate nucleophihc substitution at aliphatic sp carbons. (Substitution reactions of carboxylic acids, and their derivatives, with acidic reagents are covered in Chapter 4.) The mechanisms of these reactions involve two steps (1) addition of the nucleophile to the carbonyl group and (2) elimination of some other group attached to that carbon. Common examples include the basic hydrolysis and aminolysis of acid chlorides, anhydrides, esters, and amides. 

A phenyl-substituted cyclic silyl enolate is synthesized from 1,1-dimethylsilacyclobutane and benzoyl chloride in the presence of a stoichiometric amount of triethylamine and a catalytic amount of PdCl2(PhCN)2 (eq 8). In the case of aliphatic acid chlorides, the use of diisopropylamine instead of triethylamine gives better results. A platinum complex, Pt(CH2=CH2)(PPh3)2, also mediates the reaction although its performance is inferior to that of palladium complexes. Acid anhydrides or combinations of organic halides and carbon monoxide are alternatives to acid chlorides. In the case of acid anhydrides, the amine is not necessary for the reaction. 

Compound 211 and several related compounds are readily accessible by stereospecific deprotonation of the appropriate optically active carbamic esters with 5-BuLi/TMEDA ° . Much of the knowledge about the stereochemical course of substitution in benzyUithium derivatives was obtained from experiments with these compounds. Only the reaction with proton acids, aliphatic aldehydes, ketones or esters as electrophiles proceed with retention for alkyl, silyl and stannyl halides, acid chlorides. 

This acid chloride is prepared from oxalyl chloride and 6-oxodecanoic acid.127d The reaction procedure is applicable to a range of unsubstituted and substituted aliphatic and aromatic acid chlorides. 

Another catalytic application of chiral ketene enolates to [4 + 2]-type cydizations was the discovery of their use in the diastereoselective and enantioselective syntheses of disubstituted thiazinone. Nelson and coworkers described the cyclocondensations of acid chlorides and a-amido sulfones as effective surrogates for asymmetric Mannich addition reactions in the presence of catalytic system composed of O-TM S quinine lc or O-TMS quinidine Id (20mol%), LiC104, and DIPEA. These reactions provided chiral Mannich adducts masked as cis-4,5 -disubstituted thiazinone heterocycles S. It was noteworthy that the in situ formation of enolizable N-thioacyl imine electrophiles, which could be trapped by the nucleophilic ketene enolates, was crucial to the success of this reaction. As summarized in Table 10.2, the cinchona-catalyzed ketene-N-thioacyl-imine cycloadditions were generally effective for a variety of alkyl-substituted ketenes and aliphatic imine electrophiles (>95%ee, >95%cis trans) [12]. 

Hence the larger the n value, the stronger the nucleophile, and the smaller the [nucl]50o/o. As already pointed out earlier, the [nucl]50o/o values given in Table 2 show that in uncontaminated freshwaters, hydrolysis is by far the most important nucleophilic substitution reaction. Furthermore, since the hydrolysis of a carbon-halogen bond is generally not catalyzed by acids, one can assume that the hydrolysis rate of aliphatic halides will be independent of pH at typical ambient conditions (i.e., pH < 10). In this context it is also important to note that no catalysis of the hydrolysis of alkyl halides by solid surfaces has been observed (El-Amamy and Mill, 1984 Haag and Mill, 1988). In salty or contaminated waters, reactions of organic chemicals with nucleophiles other than water or j hydroxide ion may be important. Zafiriou (1975), for example, has demonstrated j that in seawater ([Cl ] 0.5 M), a major sink for naturally produced methyl j iodide is transformation to methyl chloride j... 

Disconnection between C=0 and C=C with the aliphatic Friedel-Crafts reaction in mind would require acylation of the unsymmetrical alkene 76 with the acid chloride 77. The alkene 76 is ideal for acylation as it is tri-substituted and therefore relatively electron-rich and will react at the required (less substituted) end. The P-chloroketone 78, formed when SnCl4 was used as the Lewis acid, was treated with base without isolation to give the enone 74 in 60% overall yield. Lithium chloride may not look very basic, but in dipolar aprotic solvents like DMF (DiMethylFormamide, Me2NCHO), that do not solvate anions, chloride is a good base. 

The application of the aliphatic Friedel-Crafts reaction (chapter 5) to alkynes is a stereoselective approach to vinyl-lithiums that forms a bridge between the Shapiro reaction and the next section-hydrometallation. Acid chlorides 64 react with alkynes under Lewis acid catalysis to give E-P-chloroenones -65 stereoselectively. The chlorine can be replaced by more reactive iodine by conjugate substitution.11... 

Reaction with acid chlorides.2 The adduct reacts with aliphatic and aromatic acid chlorides to give phosphate esters of a-hydroxy /3-diketones (1) in yields of 70-90%. The reaction is considered to involve nucleophilic substitution at the carbonyl group of the acid chloride. The esters are hydrolyzed to a-hydroxy-/3-di-ketones readily by refluxing aqueous benzene (12 hrs.). 

The acylation of cellulose with acid chlorides in DMA/LiCl is most suitable for the homogeneous synthesis of readily soluble partially functionalized long-chain aliphatic esters and substituted acetic acid esters (Table 16.3). In contrast to the anhydrides, the fatty acid chlorides are soluble in the reaction mixture and soluble polysaccharide esters may be formed with a very high efficiency. Even in the case of stearoyl chloride, 79 per cent of the reagent is consumed for the esterification of cellulose. 

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