Sodium alkyl carboxylate transfer

An interesting preparation of alkyl carboxylates in high yield (Table 3.14) from the sodium salt of the carboxylic acids under mild phase-transfer catalytic conditions involves their reaction with alkyl chlorosulphate [50] and has been used with success in the preparation of alkyl esters derived from p-lactam antibiotics. The procedure is also excellent for the production of chloromethyl esters, particularly where the carboxylic acids will not withstand the classical Lewis acid-catalysed procedure using an acid chloride and formaldehyde, or where the use of iodochloromethane [51] results in the formation of the bis(acyloxy)methane. The procedure has been applied with some success to the synthesis of chloromethyl A-protected a-amino carboxylates [52],... 

The ability of quaternary ammonium halides to form weakly H-bonded complex ion-pairs with acids is well established, as illustrated by the stability of quaternary ammonium hydrogen difluoride and dihydrogen trifluorides [e.g. 60] and the extractability of halogen acids [61]. It has also been shown that weaker acids, such as hypochlorous acid, carboxylic acids, phenols, alcohols and hydrogen peroxide [61-64] also form complex ion-pairs. Such ion-pairs can often be beneficial in phase-transfer reactions, but the lipophilic nature of H-bonded complex ion-pairs with oxy acids, e.g. [Q+X HOAr] or [Q+X HO.CO.R], inhibits O-alkylation reactions necessitating the maintenance of the aqueous phase at pH > 7.0 with sodium or potassium carbonate to ensure effective formation of ethers or esterification [49,64]. 

A convenient way of obtaining secondary amines without contamination by primary or tertiary amines involves treatment of alkyl halides with the sodium or calcium salt of cyanamide NH2—CN to give disubstituted cyanamides, which are then hydrolyzed and de-carboxylated to secondary amines. Good yields are obtained when the reaction is carried out under phase-transfer conditions.815 R may be primary, secondary, allylic, or benzylic. l,o>-Dihalides give cyclic secondary amines. 

In the presence of alkyl halides and base, alkyltetracarbonylcobalt complexes are formed with Co2(CO)8 these species [RCo(CO)4] carbonylate a wide range of aryl halides or heterocyclic halides to various products, which depend upon the specific conditions. In the presence of alcohols, carboxylic esters are formed. Under phase transfer conditions and with iodomethane, mixtures of methyl ketone and carboxylic acid formation are realized (equation 207). In the presence of sodium sulfide or NaBH4 in water-Ca(OH)2 (equation 208) good amounts of double carbonylation are realized under very mild conditions412-414. 

Synthesis of Esters and Aldehydes. Monoalkylation of methylthiomethyl p-tolyl sulfone (MT-sulfone) with an alkyl halide is achieved by the action of a phase-transfer catalyst (PTC) in toluene-50% aq NaOH. sodium hydride and butyl-lithium also generate a carbanion of MT-sulfone. Arylmethyl derivatives of MT-sulfone are prepared by sodium borohydride reduction of the Knoevenagel condensation products with aromatic aldehydes. The monoalkylated products are converted into the corresponding methyl esters (eq 1). This functionalization can be utilized for synthesizing a-alkoxy carboxylic esters (eq 2) and Q -amino acids (eq 3). ... 

Many phase transfer processes are conducted in the absence of solvent. The early ester formation reactions, for example, were carried out with solid carboxylate salt in the presence of a mixture of alkyl halide and a small amount of tertiary amine [14a]. (It was not until the efficacy of sodium iodide as a cocatalyst was demonstrated that 2-butanone was added as cosolvent [14b].) In Starks synthesis of alkyl cyanides by direct displacement of halide, no organic cosolvent was present [10]. Numerous other examples are recorded. Nevertheless, it is common to conduct a phase transfer reaction in the presence of an organic solvent or cosolvent, particularly if the substrate is a solid. 

Polymeric amines can be proton acceptors, acyl transfer agents, or ligands for metal ions. The 2- and 4-isomers of poly(vinylpyridine) (11) and (12) and the weakly basic ion exchange resins, p-dimethylaminomethylated PS (2) and poly(2-dimethylaminoethyl acrylate), are commercial. The ion exchange resins are catalysts for aldol condensations, Knoevenagel condensations, Perkin reactions, cyanohydrin formation and redistributions of chlorosilanes. " The poly(vinylpyridine)s have been used in stoichiometric amounts for preparation of esters from acid chlorides and alcohols, and for preparation of trimethylsilyl ethers and trimethylsilylamines from chlorotrimethylsilane and alcohols or amines. Polymer-suppored DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) (52) in stoichiometric amounts promotes dehydrohalogenation of alkyl bromides and esterification of carboxylic acids with alkyl halides. The protonated tertiary amine resins are converted to free base form by treatment with aqueous sodium hydroxide. 

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