Monoalkyl chloride, synthesis

Scheme 17 illustrates enantioselective synthesis of a-amino acids by phase-transfer-catalyzed alkylation (46). Reaction of a protected glycine derivative and between 1.2 and 5 equiv of a reactive organic halide in a 50% aqueous sodium hydroxide-dichloromethane mixture containing 1-benzylcinchoninium chloride (BCNC) as catalyst gives the optically active alkylation product. Only monoalkylated products are obtained. Allylic, benzylic, methyl, and primary halides can be used as alkylating agents. Similarly, optically active a-methyl amino acid derivatives can be prepared by this method in up to 50% ee. 

A significant feature in the synthesis of 2,2-disubstituted tetrahydropyrans from diethyl malonate is the selective chlorination by trifluoromethanesulfonyl chloride of carbanions which can be formed using triethylamine or DBU as the base (79TL3645). Monoalkylation of the diester with l-bromo-4-tetrahydropyranyloxybutane leads to the alcohol (237 R = H)... 

The alkylation of intermediates 161 or 162 can be performed with allylic, propargylic and benzylic chlorides, as well as primary alkyl bromides and iodides. Some recent selected examples of monoalkylation of compound 161174 with the bromide 164 and the iodide 166 afforded products 165 and 167, respectively, which are intermediates in the synthesis of the marine natural products, octalactin A185 and leucascandrolide A186, respectively (Scheme 46). 

The acylation of the sodium enolates of esters (prepared by sodium triphenylmethide) with acyl chlorides gives the corresponding a,a-di-substituted /S-keto esters, RCOCR, CO,C,H,. The synthesis is direct, and the product is free from monoalkylation products usually encountered... 

Partial ammonolysis of phosphorus(V) chloride or bromide and of monoalkyl- or -aryl-substituted dichloro- or dibromophos-phines in the presence of chlorine or bromine is a general method for the synthesis, respectively, of the corresponding simple or substituted phosphonitrile halides. " This type of reaction may yield either cyclic or linear poljuners, depending upon the temperature, solvent, reaction time, and/or reagent ratio. 

In contrast to the anion of diethyl phosphoramidate or trifluoromethanesulfonamide, which cannot be cleanly monoalkylated, - the anion of trifluoroacetamide (100) was monoalkylated by alkyl halides or alkyl methanesulfonate. The resulting A -alkylamides (101) were converted into primary amines by alkaline hydrolysis or reduction (NuBHa Scheme 42). Various primary amines were prepared from (100) with primary alkyl iodides or methanesulfonate, benzyl and allyl halides, a-bromocarbonyl compounds and 2,4-dinitrochlorobenzene. However, competitive elimination is a serious side reaction for less reactive primary alkyl chlorides and secondary halides or methanesulfonate. The synthesis of secondary amines from (100) has also been reported. ... 

Treatment of lV-methanesulfonyl-l,4-dihydFopyridine with n-butyllithium, followed by benzyl bromide, leads to the corresponding lV-l-(2-phenylethyl)sulfonyl-l,4-dihydropyridine in low yield. The sulfonamide shown in Scheme 131 (entry c) has proved a valuable c -isoprenoid synthon which allows the two-step C -homologation of allyl halides. This synthon was used for the remarkable two-step stereoselective synthesis of nerol from 3-methyl-2-butenyl chloride (Scheme 131, entry c). Finally, the a-chloro dicarbanion of 4-(a-chlon>methanesulfonyl)morpholine is readily availabl on reaction with 2 equiv. of n-butyllithium in THF, and it leads to the corresponding dimethyl derivative with no detectable monoalkylated product or starting sulfonamide on methylation. Intramolecular versions of these reactions allow the low yield synthesis of neopentyl cyclopropanesulfonate (scheme 131, entry d) and the efficient preparation of cyclopropanesulfomorpholine (scheme 131, entry e). ... 

The lowest cost (di)alkyl benzenes are by-products from linear monoalkylate manufacture used extensively in detergent manufacture. Synthesis is usually by a Friedel-Crafts-type reaction, either by reaction of the alkyl chloride and benzene with anhydrous aluminium chloride as catalyst, or by the catalysed reaction of the appropriate length a-olefin and benzene. 

The unambiguous regioselective synthesis of chiral polysiloxane-containing CyDs as chiral stationary phases, with the mono-octamethylene spacer in either the 02, 03, or 06 position was performed and the products applied to enantio-selective GC separations [99]. Subtle differences in the chemistry of the hydroxyl groups at the 2-, 3-, and 6-positions of CyDs can be exploited to direct an electrophilic reagent to the desired site. Selective monoalkylation at the primary side of a-CyDs involves the reaction of a-CyD with 4-methylamino-3-nitrobenzyl chloride in 2,6-lutidine. Monoalkylation at the 2-position of j8-CyD is accomplished by the reaction of yS-CyD with l -bromo-4-methylamino-3-nitroacetophenone [100]. 

Glymes are synthesized using Williamson synthesis reaction that involves the cleavage of epoxides. In the Williamson synthesis, a monoalkyl polyalkylene glycol is treated with a base or an alkali metal, typically molten sodium, to form an alkoxide ion, which is then reacted with an alkyl halide such as methyl chloride to form the glyme. The by-products from the Williamson synthesis... 

C-Alkylation. A soln. of 5-methyl-l,3-thiazolidine-2,4-dione in anhydrous tetra-hydrofuran added to a soln. of KNHg prepared from K in liq. NH3, stirred 25 min., a soln. of benzyl chloride in anhydrous tetrahydrofuran added rapidly, and stirring continued 1 hr. -> 5-benzyl-5-methyl-l,3-thiazolidine-2,4-dione. Y 76%. F. e., also 5-monoalkyl analogs with LiNHg, s. J. D. Taylor and J. F. Wolfe, Synthesis 1971, 310. 

Methods for the synthesis of hop bitter acids are due to the elegant work of RiedI (78-84). The substrates are phloracylphenones, which are readily available from condensation of phoroglucinol with acid chlorides (Friedel-Crafts synthesis), nitriles (Hoesch synthesis) or carboxylic acids with boron trifluoride as catalyst. Carbon acylation of a phloracylphenone can give one monoalkylated derivative (13, Fig. 13), two dialkylated derivatives (14 and 15) and one tri- or tetra-alkylated derivative (16 and 17, respectively). The possibility of oxygen acylation can not be excluded. 

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