Benzyl reaction

The Pd-catalyzed coupling of an acyl chloride with benzyl chloride to form the benzyl ketone 854 proceeds in the presence of an excess of Zn. In this reaction, benzyl chloride reacts with Zn to form benzylzinc, which undergoes transmetallation with acylpaliadium complex[729]. The reaction has been applied to the synthesis of riccardin B (855)[730]. 

Na(Hg), 2-propanol, 84-98% yield. The use of methanol or ethanol gives veiy slow reactions. Benzyl ethers are not affected by these conditions. 

CF3CO2H, PhSCH3, 25°, 3 h. ° The use of dimethyl sulfide or anisole as a cation scavenger was not as effective because of side reactions. Benzyl ethers of serine and threonine were slowly cleaved (30% in 3 h complete cleavage in 30 h). The use of pentamethylbenzene had been shown to increase the rate of deprotection of 0-Bn-tyrosine. ... 

For the cydative cleavage step, it turned out that aprotic conditions were definitely superior to the use of protic media. Thus, employing N,N-dimethylformamide as solvent at somewhat elevated temperatures furnished the desired compounds in high yields and excellent purities. Having established the optimized conditions, various phthalic acids and amines were employed to prepare a set of phthalimides (Scheme 7.51). However, the nature of the amine was seen to have an effect on the outcome of the reaction. Benzyl derivatives furnished somewhat lower yields, probably due to the reduced activities of these amines. Aromatic amines could not be included in the study as auto-induced ring-closure occurred during the conversion of the polymer-bound phthalic acid. 

Some 30 benzyl bromides, allyl bromide, and different esters of bro-moacetic acid were found to work well in the /V(4)-alkylation reaction. Benzyl chlorides, a-bromo acetophenones, as well as unactivated alkyl bromides, however, did not give satisfactory results. 

Due to the extremely low nucleophilicity of the imino group, 187,188 acylation of thiazolidine-4-carboxylic acid (11) is not a trivial procedure. In fact, N-protected Thz derivatives can be prepared by standard procedures, but strong acylating conditions are required. The related N-Boc derivative is obtained only by prolonged reaction times with Boc-N3 U2,189 or with Boc20. 113 For preparation of the N-Z derivative, silylation of Thz with, for example, chlorotrimethylsilane is recommended prior to the reaction benzyl chloroformate. 200 Due to the stability of thiazolidine-4-carboxylic acid to acids its methyl ester is obtained by HC1 catalyzed reaction with methanol, 190 whereas the amide is formed by reacting Thz N-carboxyanhydride with ammonia.1 89 Derivatives of thiazolidine-4-carboxylic acid are listed in Table 8. 

Like most photochemical reactions, benzylic fragmentation has been known from the beginning of the twentieth century. The photoinduced cleavage of triphenylmethylcarbinol has been noted by Gomberg in Ann Arbor in 1913 [1] and the generation of triarylmethyl cationic dyes from their leuco form by Lifschitz in Zurich in 1919 [2]. A solution of the colorless derivative obtained from p-rosaniline and cyanide became colored in a few seconds when exposed to an iron arc lamp (Sch. 1, old and new notation). 

Besides the direct application in a synthetically useful reaction, benzylic derivatives can also be useful in an indirect way. As an example, at several instances in this section it has been mentioned that photocleavage of benzylic derivatives generates acids or bases. Such a fragmentation has been applied e.g., in promoting polymerization. 

In Chapter 15, we saw that allylic halides are more reactive than most alkyl halides in both SN1 and SN 2 reactions. Benzylic halides are also more reactive in these substitutions, for reasons similar to those for allylic halides. 

One exception to the amorphous structure has been reported [30]. Crystalline polybenzyl was obtained from the low temperature (- 125° C) polymerization of benzyl chloride. However, the reaction was difficult to reproduce [31,32]. Consequently this procedure is not an effective method for the synthesis of linear polybenzyls. The usual amorphous, highly branched structure is formed as a result of a lack of positional selectivity and multiple substitution of the arene rings. Similar polymeric structures are obtained upon the polymerization of other nonsubstituted benzyl halides and benzyl alcohol [29]. The highly branched structure is a consequence of the involvement of benzyl carbenium ions in the Friedel-Crafts reaction. Benzyl substituents activate the monosubstituted phenyl groups toward further benzylation reaction. However, monomers containing alkyl substituents that sterically hinder substitution at the ortho position have been polymerized to linear polybenzyls. For example, the following... 

In a clearly related reaction, benzylic bromides are oxidized to aryl carboxylic acids by photolysis in acetone in the presence of mesoporous silica. ... 

Mitchell has reported that benzyl a-chlorobenzyl sulfides are cleanly converted into stilbenes on successive treatment with PPhs and Bu OK (Scheme 13). Desulfurization of an intermediate thiirane by PPh3 is a likely pathway for this reaction. Benzyl a,a-dichlorobenzyl sulfides are converted into diphe-nylacetylenes under the same conditions." Viehe has reported that pyrolysis of ot-halo-a-alkylthio esters, ketones and nitriles under reduced pressure furnishes a,p-unsaturated esters, ketones and nitriles respectively it is probable that these reactions also take place via intermediate thiiranes. a-Chlorophenacyl phenacyl sulfide is converted into ( )-dibenzoylethylene on treatment with EtsN. ... 

Keywords solid-gas reaction, liquid-gas reaction, benzylic alcohols, benzalde-... 

Keywords gas-solid reaction, benzyl halides, benzyl amines... 

Acidic hydrogens can be protected by alkylation, preferentially by an alkyl group that can be removed after the reaction. Benzyl, t-Bu and tetrahydropyranyl groups are most frequently used for OH and NH groups. The trimethylsilyl group is both stable and easily introduced and removed it can even serve to protect C—H bonds, e.g. ° ... 

R = CH2C6H5, Ci4Hi202, Mt 212.25, Z>p2.okPa 170-171 °C, df 1.1121, ng 1.5680, is the main component of Peru balsam oil. It occurs in fairly large amounts in a number of blossom concretes and absolutes (e.g., tuberose and hyacinth). It forms either a viscous liquid or solid flakes (mp 21-22°C) and has a weak, sweet-balsamic odor. It is prepared either by transesterification of technical methyl benzoate with benzyl alcohol, or from benzyl chloride and sodium benzoate. A third process starts with benzaldehyde, which is converted in high yield into benzyl benzoate in the presence of sodium or aluminum benzylate (Tishchenko reaction). Benzyl benzoate is used in perfumery as a fixative and as a modifier in heavy blossom fragrances. 

Substitution reactions. Benzylation of phenols by benzyl methyl carbonates with Pd catalysis proceeds via transesterification and decarbonylation. Triarylmethanes are obtained from a reaction of benzhydryl carbonates with arylboronic acids. ... 

Substitution reactions. Benzylic and allylic acetates are replaced on reaction with sulfonamides, no matter by what mechanism it proceeds, with the presence of Cu(OTf)2 and r-BuOOAc. ... 

Friedel- Crafts reactions. Benzyl ethers are activated by FeCls to react with arenes to provide diarylmethanes. A-Tosyhmines and aziridines also become electrophilic toward electron-rich arenes. ... 

Coupling reactions. Benzyl ketones and arylacetic acid derivatives of the type ArCH(R)COY are prepared from RCH(X)COY by coupling with ArB(OH)2 using (Ph3P)4Ni as catalyst. ... 

We explained in Chapter 15 that Sn2 reactions adjacent to carbonyl groups are very fast. The regioselectivity of the ring opening of a cyclic sulfate, like that of an epoxide, is directed by the competition between relative rates of two nucleophilic substitution reactions. Benzylic and carbonyl-substituted positions usually open faster. There is more discussion of the regioselectivity of epoxide opening on p. 351. 

Researchers van der Broeke and coworkers[" created perfluoro-functionalized poly(propyleneimine) dendrimers (23 Fig. 4) and demonstrated their potential as phase-transfer catalysts in supercritical carbon-dioxide-water mixtures and as anionic species extractants. The dendrimers were accessed via reaction of perfluorinated, linear alkyl acid chlorides with the terminal amines. Extraction of perinanganate or dichromate from aqueous to CO2 solution was described as rather low, whereas their use as phase-transfer catalysts in a halogen exchange reaction [benzyl chloride to benzyi bromide (24)] resulted in high rates of conversion. 

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