Alkyl bromides, from alcohols, benzyl

Alkyl bromides, from alcohols, benzyl bromide, and triphenyl phosphite,... 

Akylation, of acids, 50, 61 by oxonium salts, 51,144 Alkyl bromides, from alcohols, benzyl bromide, and triphenyl phosphite,... 

Alkyl Bromides from Aleohols. Alkyl bromides (29) are obtained in high yields by the reaction of the corresponding alcohols (28) with Me6Si2 and p)nidinium hydrobromide perbromide (eq 14). The substitution reaction is very fast for tertiary, allylic, and benzylic alcohols, but very slow for primary and secondary alcohols. Inversion of configuration is observed with secondary alcohols. 

Alkyl bromides. Alcohols are converted into bromides by reaction with bromotrimethylsilane (1.5-4 equiv.) in CHCI3 at 25-50° (equation I). The reaction occurs with inversion. Tertiary and benzylic alcohols react more rapidly than primary or secondary alcohols. Bromides are not formed under the same conditions from Irimethylsilyl ethers of alcohols. However, trimethyl orthoformate is converted into methyl formate, HC(OCH3)3 —s HCOOCH3. Unlike iodotrimethylsUane, the bromosilane does not dealkylate esters, ethers, or carbamates. 

Vanhoye and coworkers [402] synthesized aldehydes by using the electrogenerated radical anion of iron pentacarbonyl to reduce iodoethane and benzyl bromide in the presence of carbon monoxide. Esters can be prepared catalytically from alkyl halides and alcohols in the presence of iron pentacarbonyl [403]. Yoshida and coworkers reduced mixtures of organic halides and iron pentacarbonyl and then introduced an electrophile to obtain carbonyl compounds [404] and converted alkyl halides into aldehydes by using iron pentacarbonyl as a catalyst [405,406]. Finally, a review by Torii [407] provides references to additional papers that deal with catalytic processes involving complexes of nickel, cobalt, iron, palladium, rhodium, platinum, chromium, molybdenum, tungsten, manganese, rhenium, tin, lead, zinc, mercury, and titanium. 

Perimidine has an acidic NH proton and therefore behaves differently from pyrimidine and quinazoline. The product is a neutral molecule. Like imidazoles, perimidines are best A-alkylated in alkaline media (79) in an inert atmosphere. Alkylation with primary alkyl bromides or iodides can be performed in an alcoholic solution. Dimethyl sulfate is recommended for methylation. Yields drop with secondary halides. A-Substitution reactions are sensitive to steric interference from 2-and 4(9)-substituents 2-alkyl or aryl derivatives can be methylated but not alkylated by benzyl chloride or isopropyl, allyl or phenacyl bromides. 4(9)-Substituted perimidines are preferentially alkylated at the remote nitrogen. 

The reaction is particularly advantageous for preparation of alkyl bromides and iodides from sterically hindered or unsaturated alcohols. For preparative purpose it is especially useful when R X is benzyl bromide, methyl iodide, bromine (Br2), or iodine (I2), but use of benzyl chloride and chlorine (Cl2) is also significant R can usefully be H only when R X is HC1. When the alcohol is sensitive to heat, the quasi-phosphonium compound should be prepared first and then allowed to react with the alcohol. Also, for use with unsaturated alcohols in cases when R X is Cl2, Br2, or I2 the crude (C6H50)3PX2 should be prepared as a separate stage. In general, however, the three reactants can be allowed to react together, as in (a). 

Reduce 3,5-dimethoxybenzoic acid with lithium aluminum hydride to 3,5-dimethoxybenzyl alcohol (I), to 10.5 g (I) in 100 ml methylene chloride at 0° C add 15 g PBr3 warm to room temperature and stir for one hour. Add a little ice water and then more methylene chloride. Separate and then dry, evaporate in vacuum the methylene chloride. Add petroleum ether to precipitate about 11.5 g of the benzyl bromide (II). To 9.25 g (II), 15 g Cul, 800 ml ether at 0° C, add butyl (or other alkyl)-Li (16% in hexane), and stir for four hours at 0° C. Add saturated NH4C1 and extract with ether. Dry and evaporate in vacuum the ether (can distill 100/0.001) to get about 4.5 g olivetol dimethyl ether (HI) or analog. Distill water from a mixture of 90 ml pyridine, 100 ml concentrated HC1 until temperature is 210° C. Cool to 140 0 C and add 4.4 g (III) reflux two hours under N2. Cool and pour into water. Extract with ether and wash with NaHC03. Make pH 7 and dry, evaporate in vacuum to get 3.8 g olivetol which can be chromatographed on 200 g silica gel (elute with CHC13) or distill (130/0.001) to purify. 

The at complex from DIB AH and butyllithium is a selective reducing agent.16 It is used tor the 1,2-reduction of acyclic and cyclic enones. Esters and lactones are reduced at room temperature to alcohols, and at -78 C to alcohols and aldehydes. Acid chlorides are rapidly reduced with excess reagent at -78 C to alcohols, but a mixture of alcohols, aldehydes, and acid chlorides results from use of an equimolar amount of reagent at -78 C. Acid anhydrides are reduced at -78 C to alcohols and carboxylic acids. Carboxylic acids and both primary and secondary amides are inert at room temperature, whereas tertiary amides (as in the present case) are reduced between 0 C and room temperature to aldehydes. The at complex rapidly reduces primary alkyl, benzylic, and allylic bromides, while tertiary alkyl and aryl halides are inert. Epoxides are reduced exclusively to the more highly substituted alcohols. Disulfides lead to thiols, but both sulfoxides and sulfones are inert. Moreover, this at complex from DIBAH and butyllithium is able to reduce ketones selectively in the presence of esters. 

The interaction of alkyl halides, preferably iodides or bromides, with hexamine in chloroform or alcohol solution forms quaternary ammonium salts which on heating with hydrochloric acid are readily converted to primary amines. The procedure has been employed successfully in the reaction of primary, but not secondary or tertiary, aliphatic halides, certain benzyl halides, halo ketones, halo acids, and halo esters. The yields range from 40% to 85%. 

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