Benzylic alcohols from aromatic aldehydes

Point of view of the chemistry lignin is a natural amorphous cross-linked resin that has an aromatic three-dimensional polymer structure containing a number of functional groups such as phenolic, hydroxyl, carboxyl, benzyl alcohol, methoxyl, and aldehyde as shown in Figure 5.1, which make lignin potentially useful as an adsorbent material for removal of heavy metal ions from water [52]. 

An enantioselective difluoro Reformatsky reaction with imines was disclosed recently by Ando and coworkers. According to this valuable procedure, , -difluoro-P-lactams are obtained directly due to an in situ condensation following the addition of the zinc enolate. For this purpose, ethyl bromodifluoroacetate 324b was allowed to react with Af-benzyl-protected imines 391 that are derived from aromatic aldehydes. Diethyl zinc was used to generate the zinc enolate. When the reaction was mediated by the amino alcohol 323, required in equimolar amounts, P-lactams 392 were obtained in fair chemical yields and remarkably... 

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. 

ALDEHYDES FROM ALLYLIC ALCOHOLS AND PHENYLPALLADIUM ACETATE 2-METHYL- 3-PHENYLPROPIONAL-DEHYDE, 51, 17 ALDEHYDES FROM AROMATIC NITRILES p-FORMYLBENZENE-SULFONAMIDE, 51, 20 ALDEHYDES FROM 2-BENZYL-4,4,6-TRIMETHYL—5,6-DIHYDRO-l, 3-(4H)-OXAZINE 1-PHENYLCYCLO-PENTANECARBOXYALDEHYDE, 51,... 

The three-component synthesis of benzo and naphthofuran-2(3H)-ones from the corresponding aromatic alcohol (phenols or naphthols) with aldehydes and CO (5 bar) can be performed under palladium catalysis (Scheme 16) [59,60]. The mechanism involves consecutive Friedel-Crafts-type aromatic alkylation and carbonylation of an intermediate benzylpalla-dium species. The presence of acidic cocatalysts such as TFA and electron-donating substituents in ortho-position (no reaction with benzyl alcohol ) proved beneficial for both reaction steps. 

In contrast to phenolic hydroxyl, benzylic hydroxyl is replaced by hydrogen very easily. In catalytic hydrogenation of aromatic aldehydes, ketones, acids and esters it is sometimes difficult to prevent the easy hydrogenolysis of the benzylic alcohols which result from the reduction of the above functions. A catalyst suitable for preventing hydrogenolysis of benzylic hydroxyl is platinized charcoal [28], Other catalysts, especially palladium on charcoal [619], palladium hydride [619], nickel [43], Raney nickel [619] and copper chromite [620], promote hydrogenolysis. In the case of chiral alcohols such as 2-phenyl-2-butanol hydrogenolysis took place with inversion over platinum and palladium, and with retention over Raney nickel (optical purities 59-66%) [619]. 

Nevertheless, for the production of the flavour-active aromatic alcohol derivatives, such as the corresponding aldehydes and acids, metabolic engineering approaches have to compete with conventional oxidative biocatalysis starting from the natural alcohol as a substrate. For instance, the whole-cell oxidation system based on Pichia pastor is AOX already described in Sect. 23.4.1.2 can also be used to convert benzyl alcohol to benzaldehyde in aqueous media although product inhibition restricted the final product concentration to about 5 g L h indicating the need for aqueous-organic two-phase reaction media [51]. Phenylacetalde-... 

With nonpersistent nitroxyl radicals (PINO, Scheme 2) benzyl alcohols give, selectively, the aromatic aldehydes, whereas aliphatic alcohols lead to the carboxylic acids [12], even at low conversions [6], This behavior has been explained on the basis of the prevailing polar effect [6, 13] in the abstraction of hydrogen from benzyl alcohols and by the dominant enthalpic effect in the abstraction of hydrogen from aliphatic alcohols [6[. 

Catalysis by TEMPO has the advantage of being general for oxidation of both benzylic or non benzylic alcohols to aldehydes, whereas catalysis by PINO, although limited to the synthesis of aromatic aldehydes, has the advantage that the radical is generated in situ from the less expensive N-hydroxyphthalimide, which can be more easily recovered and recycled. 

The production of hydrocarbons from aromatic alcohols is most readily explained by the hydrogenolysis of the alcohol, but an alternate possibility should be considered. The formation of an aldehyde and its subsequent decarbonylation under reaction conditions could lead to the hydrocarbon. Both toluene and 2-phenylethanol, the mixture of products secured from benzyl alcohol, may be regarded as derived from phenylacetaldehyde as an intermediate ... 

Selenolates prepared from diphenyl or dimethyl diselenide by reduction with NaBH4 smoothly transform various benzylic alcohols 24 into the corresponding selenides 25 in the presence of aluminum chloride (Scheme 30 a) [41]. AICI3 is considered to activate the alcohol substrate by coordinating to the oxygen. Similar transformations are possible by the reaction of alcohols with phenyl selenocyanate in the presence of tributyl phosphine [52]. When the selenolate is reacted with aromatic aldehydes or ketones 26 in the presence of AICI3, the corresponding benzylic selenides 27 are obtained in moderate yields (Scheme 30b) [41]. 

Aldehydes have been formed from alcohols by the use of other oxidizing agents. Dihydroxyacetone has been oxidized with excess cupric acetate to hydroxypyruvic aldehyde in 87% yield. p-Cyanobenzyl alcohol treated at 0° with a chloroform solution of nitrogen tetroxide gives practically pure p-cyanobenzaldehyde (90%). Aromatic alcohols containing nitro groups have been oxidized to the corresponding nitro aldehydes with concentrated nitric acid, e.g., o- and p-nitrobenzaldehydes (80-85%). m-Nitrobenzenesulfonic acid in basic media has been used for the oxidation of substituted benzyl alcohols, most satisfactorily for the water-soluble phenolic benzyl alcohols. Selenium dioxide, or less effectively tellurium dioxide, oxidizes benzyl alcohol slowly to benzaldehyde. ... 

Benzyl Alcohol.—The simplest aromatic alcohol is the hydroxyl derivative of toluene and is known as benzyl alcohol, CeHs—CH2—OH. The radical, (CeHs—CH2—), is termed benzyl as in the alcohol and chloride above. The alcohol occurs as an ester in Peru balsam, in storax, a resin obtained from a plant sty rax, and in Tolu balsam from which the mother hydrocarbon toluene derives its name. On hydrolysis of the balsam benzyl alcohol is obtained. It is a liquid, b.p. 206.5°, slightly soluble in water and soluble in alcohol or ether. It may be prepared by those syntheses just given which yield primary alcohols. It may also be prepared by the reduction of the corresponding aldehyde, known as benzoic aldehyde or benzaldehyde (p. 655). On oxidation it yields the aldehyde and then an acid, benzoic acid. 

Nickel peroxide, an undefined black oxide of nickel, is prepared from nickel sulfate hexahydrate by oxidation in alkaline medium with an ozone-oxygen mixture [929] or with sodium hypochlorite [930, 931, 932, 933]. Its main applications are the oxidation of aromatic side chains to carboxyls [933], of allylic and benzylic alcohols to aldehydes in organic solvents [929, 932] or to acids in aqueous alkaline solutions [929, 930, 932], and of aldehydes to acids [934, the conversion of aldehyde or ketone hydrazones into diazo compounds [935] the dehydrogenative coupling of ketones in the a positions with respect to carbonyl groups [931] and the dehydrogenation of primary amines to nitriles or azo compounds [936]. 

Instead of pyridine, 4-dimethylaminopyridine can be converted into a chlorochromate, and the complex can be used to oxidize benzylic alcohols to aldehydes [530]. Also, tetrabutylammonium chlorochromate gives good yields of unsaturated and aromatic aldehydes from the respective alcohols [619]. 

Oxidations. Aromatic aldehydes are obtained by oxidation catalyzed with a Mn(IV) complex. A procedure for oxidation of alcohols which is organic solvent free and halide free employs 30% H Oj, Na2W04 dihydrate, and a quaternary ammonium hydrogensulfate. Under such conditions secondary alcohols are oxidized 4-5 times faster than primary alcohols. In toluene the conversion of benzylic alcohols to aldehydes or acids (depending on quantities of HjOj) is accomplished. A similar system is also effective for epoxidation of alkenes. Terminal epoxides are obtained in reactions mediated by a Mn(II) complex or Mg-Al-O-t-Bu hydrotalcite. The last catalyst is capable of inducing epoxide formation from other alkenes and enones. 

Oxidation. Oxidation of aromatic alcohols to corresponding aldehydes Penicillium. Pseudomonas and enzymes from Caldariomyces sp(57). have the ability to convert benzyl, cinnamyl and other alcohols to the corresponding aldehydes. 

The reagent formed by reaction of Znij with NaCNBH3 in CHjClj allows the reduction of aromatic aldehydes and ketones as well as benzylic, allylic, and tertiary alcohols to hydrocarbons, probably by a radical process [LDl] (Section 2.4). Some comparable reductions are carried out in ether media starting from tertiary, benzylic, or allylic halides (Section 2.1). 

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