Benzyl alcohol, preparation reactions

Heteroarylmethyl p-tolyl sulfones. These compounds can be prepared from the corresponding benzylic alcohols by reaction with 4-MeC6H4S02Na and HCOOH. The method is useful for substrates possessing values between —1.90 to —0.95 in the aryl ring. 

Benzyl saUcylate can be prepared by the reaction of ben2yl chloride with an alkaU salt of saUcyhc acid at 130—140°C or by the transesterification of methyl saUcylate with benzyl alcohol. It is used as a fixative and solvent for nitro musks and as a fragrance for detergents. Benzyl saUcylate was priced at... 

Ben /ben ate [120-51-4] CgH COOCH2CgH, mp, 21°C, cff , 1.118 bp, 323—324°C at 101.3 kPa , 1.5681. This is a colorless, oily liquid with a faiat, pleasant aromatic odor and a sharp, burning taste. It occurs naturally iu Pern and Tolu balsams, is spariugly volatile with steam, and is iusoluble iu water. Benzyl benzoate is prepared commercially by the direct esterification of benzoic acid and benzyl alcohol or by reaction of benzyl chloride and sodium benzoate. The pleasant odor of benzyl benzoate, like other benzoic esters, has long been utilized iu the perfume iadustry, where it is employed as a solvent for synthetic musks and as a fixative. It has also been used iu confectionery and chewing gum flavors. 

Fleischer1 prepared benzylaniline by heating aniline with benzyl chloride at i6o°. This reaction may be very violent and always leads to mixtures. Bernthsen and Trompetter 2 reduced thiobenzanilide with zinc and hydrochloric acid or sodium amalgam, while O. Fischer 3 reduced bcnzalaniline with sodium and alcohol, to benzylaniline. Knoevenagel4 obtained a 32 per cent yield of benzylaniline from benzyl alcohol and aniline in the presence of iodine. Ullmann5 describes the preparation of benzylaniline from benzyl chloride and excess of aniline at low temperatures. 

Finally, reaction of primary, secondary, or tertiary alcohols 11 with Me3SiCl 14 in the presence of equivalent amounts of DMSO leads via 789 and 790 to the chloro compounds 791 [13]. n-Pentanol, benzyl alcohol, yS-phenylefhanol or tert-butanol are readily converted, after 10 min reaction time, into their chloro compounds, in 89-95% yield, yet cyclohexanol affords after reflux for 4 h cyclohexyl chloride 784 in only 6% yield [13] (Scheme 6.5). 1,4-Butanediol is cyclized to tetrahydrofuran (THF) [13a], whereas other primary alcohols are converted in 90-95% yield into formaldehyde acetals on heating with TCS 14 and DMSO in benzene [13b] (cf also the preparation of formaldehyde di(n-butyl)acetal 1280 in Section 8.2.1). 

Benzyl groups are usually introduced by the Williamson reaction (Section 3.2.3). They can also be prepared under nonbasic conditions if necessary. Benzyl alcohols are converted to trichloroacetimidates by reaction with trichloroacetonitrile. These then react with an alcohol to transfer the benzyl group.183... 

The drug candidate 1 was prepared from chiral cyclopentanol 10 as shown in Scheme 7.3. Reaction of 10 with racemic imidate 17, prepared from the corresponding racemic benzylic alcohol, in the presence of catalytic TfOH furnished a 1 1 mixture of diastereomers 18 and 19 which were only separated from one another by careful and tedious chromatography. Reduction of ester 18 with LiBH4 and subsequent Swern oxidation gave aldehyde 20 in 68% yield. Reductive animation of 20 with (R)-ethyl nipecotate L-tartrate salt 21 and NaBH(OAc)3 and subsequent saponification of the ester moiety yielded drug candidate 1. 

Alcohols can be phosphorylated to phosphoric diesters by ionic phosphoric monoimidazolides in acetone at temperatures of about 50-60 °C over the course of several hours. These imidazolides are generally prepared by reaction of the appropriate phosphate with CDI (see Section 2.2). Reactions with ethyl, -butyl, w-pentyl, -octyl benzyl alcohol and various other alcohols have also been described.[1]... 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

Normally, only a small stoichiometric excess (2-30 mol%) of silane is necessary to obtain good preparative yields of hydrocarbon products. However, because the capture of carbocation intermediates by silanes is a bimolecular occurrence, in cases where the intermediate may rearrange or undergo other unwanted side reactions such as cationic polymerization, it is sometimes necessary to use a large excess of silane in order to force the reduction to be competitive with alternative reaction pathways. An extreme case that illustrates this is the need for eight equivalents of triethylsilane in the reduction of benzyl alcohol to produce only a 40% yield of toluene the mass of the remainder of the starting alcohol is found to be consumed in the formation of oligomers by bimolecular Friedel-Crafts-type side reactions that compete with the capture of the carbocations by the silane.129... 

B) Benzyl Carbamate.—A measured aliquot (suitably 10 cc.) of the solution of benzyl chloroformate, prepared as described above, is added slowly and with vigorous stirring to five volumes of cold concentrated ammonium hydroxide (sp. gr. 0.90), and the reaction mixture is allowed to stand at room temperature for thirty minutes. The precipitate is filtered with suction, washed with cold water, and dried in a vacuum desiccator. The yield of practically pure benzyl carbamate, melting at 85-86°, is 7.0-7.2 g. (91-94 per cent of the theoretical amount based on the benzyl alcohol used in. 4). Pure benzyl carbamate melting at 87° is obtained by recrystallizing the slightly impure material from two volumes of toluene. 

Enantioselective addition of R2Zn to aldehydes. Corey and Hannon2 have prepared the diamino benzylic alcohol 1 from (S)-proline and (lS,2R)-( + )-ephed-rine and report that the chelated lithium salt of 1 is an effective catalyst for enantioselective addition of diethylzinc to aromatic aldehydes. Thus benzaldehyde can be converted into (S)-( - )-3 with 95% ee, via an intermediate tridentate lithium complex such as 2 formed from 1. Similar reactions, but catalyzed by diastereomers of 1, show that the chirality of addition of dialkylzincs to aldehydes is controlled by the chirality of the benzylic alcohol center of 1. 

The causes of variations in yield by the use of the okler methods can now be explained. When benzaldehyde is added to the alcoholate, and especially when the latter is still warm, local overheating results in fact, the temperature may rise far above xoo° with the result that benzyl ether is formed. Simultaneously, the sodium benzylate is converted into sodium benzoate, which is of no value for inducing the desired reaction, and consequently very little benzyl benzoate is obtained. The same side reactions explain the failure of this experiment when the benzyl alcohol used in preparing the catalyst (sodium benzylate) is contaminated with benzaldehyde. 

Benzyl benzoate has been identified in certain natural plant products.1 In the laboratory it has been prepared by the action of (a) benzoyl chloride upon benzyl alcohol,2 (b) benzyl chloride upon sodium benzoate, and (c) alcoholates upon benzaldehyde.3 Recently, Gomberg and Buchler 4 have shown that reaction (b) may be conducted even with aqueous solutions of sodium benzoate. 

Phosphonium salts, e.g. (124), derived from polynuclear hydrocarbons and used as intermediates in helicine synthesis, have been prepared by the reaction of the appropriate benzylic alcohol with triphenylphosphine hydrobromide.120 Similarly, the salt (125), of value as an intermediate in carotenoid synthesis, has been prepared by the reaction of a precursor allylic alcohol with triphenylphosphine hydrobromide.121 Bromomethyl a-diketones react with triphenylphosphine to form... 

As, for the most part, the corresponding ester derivatives are a more important synthetic target, recent literature has demonstrated methods to prepare the esters directly. Examples include the use of nickel carbonyl in a methanol/dimethylformamide solvent system(37) the direct conversion of benzyl alcohol to methylphenyl-acetate using cobalt carbonyl(38) and a reaction system which utilizes an ammonium salt bound to an organic polymer(39). 

The reaction conditions were mild (room temperature, 1 atm CO) and a two-fold excess of base was used along with a catalytic amount of cobalt carbonyl. The product distribution was quantified by VPC. The mixtures contained starting material, ester product, and various amounts of methyl benzyl ether. No detectable amounts of benzyl alcohol, ketones, or hydrocarbons were seen. Potassium methoxide alone afforded mostly the ether. A mixture of potassium methoxide and alumina gave a slight improvement in ester yield but the predominant product was again the ether. In contrast, when potassium methoxide on alumina was used, the carboxyalkylated product, methyl phenylacetate, was prepared in 70 yield with little ether detected. Benzyl chloride reacted in a similar fashion under these mild reaction conditions. Other alkoxide and carbonate bases could be used as... 

A series of asym DAMs were synthesized by the condensation reaction of arenes with benzyl alcohols. Benzene, p-xylene, mesitylene, durene, and isodurene were used as arenes because they give only one condensation product. For example, pure 2,5,3 -TrMeDPM is easily prepared by a distillation of the crude product obtained by the following reaction ... 

---