Zinc chloride as catalyst for acetylation

Mercaptolysis of /3-D-glucopyranose pentaacetate in ethyl mercaptan at 0°, with zinc chloride as catalyst, gives ethyl tetra-O-acetyl-l-deoxy-1-thio-/S-D-glucopyranoside in 71% yield. Under the same conditions, a-D-glucopyranose pentaacetate reacted only very slowly, but it could be shown that the deoxy-thio-/3-D-glucoside is formed in much greater amount than is the a anomer. Mercaptolysis of the D-mannopyranose pentaacetates under the same conditions for 48 hours resulted in a 70% yield of ethyl tetra-O-acetyl-l-deoxy-l-thio-a-D-mannopyranoside from the /3-D-pentaacetate, and in a 60% yield from the a anomer.103 Inspection, by preparative paper chromatography, of the residual sirups, after deacetylation, led in each case to the isolation of the anomeric ethyl-1-... 

Zinc chloride is a Lewis acid catalyst that promotes cellulose esterification. However, because of the large quantities required, this type of catalyst would be uneconomical for commercial use. Other compounds such as titanium alkoxides, eg, tetrabutoxytitanium (80), sulfate salts containing cadmium, aluminum, and ammonium ions (81), sulfamic acid, and ammonium sulfate (82) have been reported as catalysts for cellulose acetate production. In general, they require reaction temperatures above 50°C for complete esterification. Relatively small amounts (<0.5%) of sulfuric acid combined with phosphoric acid (83), sulfonic acids, eg, methanesulfonic, or alkyl phosphites (84) have been reported as good acetylation catalysts, especially at reaction temperatures above 90°C. 

For complete acetylation of polyhydric compounds, such as glucose (p. 141) and mannitol (p. I42), even undiluted acetic anhydride is insufficient, and a catalyst must also be employed. In such cases, the addition of zinc chloride or anhydrous sodium acetate to the acetic anhydride usually induces complete acetylation. ... 

Mannitol, CH,0H(CH0Hi4CH40H, is a hexahydric alcohol obtained by the reduction of mannose. Since ring formation does not occur in mannitol, the hexacetyl derivative can exist in only one form, and therefore either zinc chloride or sodium acetate can be used as a catalyst for the acetylation. 

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

The exceedingly high reactivity of ferrocene to Friedel-Crafts acylation is exemplified by the fact that mild catalysts such as stannic chloride (63), boron trifluoride (32), zinc chloride (86), and phosphoric acid (29), can be used with considerable success. When ferrocene and anisole were allowed to compete for limited amounts of acetyl chloride and aluminum chloride, acetylferrocene was the sole product isolated, again illustrating the high reactivity of ferrocene toward electrophilic reagents (6). 

The fibrous acetylation process is performed in the presence of a suitable liquid, such as benzene, in which the reaction product is insoluble and which thereby retains the fiber form. For fibrous acetylation vapor-phase treatment with acetic anhydride can also be used. Besides sulfuric acid, perchloric acid and zinc chloride have been used as catalysts. 

Zinc chloride, although commonly used as a catalyst in the acetylation of simple sugars, has not been extensively investigated as a catalytic agent for starch acetylation. Law has reported that he could not acetylate ordinary starch with a mixture of zinc chloride, acetic acid, and acetic anhydride. Starch heated in glycerol at 100-170 , and therefore probably degraded, has been acetylated, however, in a mixture of zinc chloride and acetic anhydride at 50-80 . 

More recently, Eastman Chemical Company published three patents involving the use of ionic liquids containing carboxylate anions for cellulose acetylation [163-165], Ionic liquids with carboxylate anions resulted in faster acetylation of cellulose at lower temperatures relative to the rate in ionic liquids with the same cation and a chloride anion. Transition metals such as zinc were found to be good catalysts for the acetylation of cellulose in ionic liquids [164],... 

Acetic anhydride and aluminum chloride in caibon disulfide gives a high yield of the para-acylated product with thioanisole, and in dichloromethane the same reagents give an almost quantitative yield of 3-acetyl-1-benzenesulfonylindole. Acylation of more nucleophilic heterocycles can be achieved using milder catalysts, such as zinc chloride. It has been known for some time that furan can be acylated very efficiently using acetic anhydride and zinc chloride. The Paal-Knorr furan synthesis (1,4-diketone, acetic anhydride and zinc chloride) can sometimes result in acylation as well as cyclization (equation 40). - Equations (41) and (42) further exemplify the acylation of furan derivatives that have been used in the synthesis of cytotoxic furanonaphthoquinones. 

Reactions of an alcohol with acetic anhydride are greatly accelerated by acid catalysts, such as sulfuric acid, zinc chloride, phosphorus pentoxide, ferric chloride, etc. However, such catalysts cannot be used with sensitive alcohols, such as linalool, which are isomerized or otherwise affected by them. The effective acid strength of a catalyst in an anhydrous medium is the predominant factor in determining its activity. The acidities of mineral acids in glacial acetic acid correspond remarkably well with their activities as acetylation catalysts. Sulfuric and perchloric acids in acetic acid solution have been termed superacid solutions because of thdr exceptional strength as compared with the strength of other acids. Most anhydrides react more rapidly with an alcohol in the presence of a base. The base can be sodium hydroxide, the sodium salt of the acid, or a tertiary amine, which can also be the solvent for the reaction. ... 

A much more environmentally sound procedure was advocated by Paul et al. [164], who used Zn powder as a catalyst for Friedel-Crafts acylation of aromatic compounds. Zinc is a nontoxic, safe, and inexpensive metal which can be used in solvent-free conditions. It was shown to have a remarkably high activity in the acylation of a series of aromatic compounds with acetyl and benzoyl chlorides when performed under microwave irradiation. Yields were much more better than when using conventional thermal heating (Eq. (80), Table 4.28). The Zn powder could also be re-used up to six times after simple washing with diethyl ether and dilute HCl. 

PANIC at 250 MHz, has shown that it is the 1 3 2 6-triacetal and not the 1,2 3,5 A 6-trlacetal as previously claimed. The three products from acetalatlon of D-mannitol with 2-methoxypropene in DMF with tosic acid catalyst have been shown to be 1,2 5,6- 1 2 4 6- and 1,2 3,6-di-0-isopropylidene-D-mannitol. The preparation of 1 2 5,6-di-O-isopropylidene-D-mannitol by three alternative procedures for acetonation of D-mannitol has been investigated using acetylation and capillary g.l.c. to monitor the products. The highest yield was obtained by propanone-zinc chloride, whereas 2 2-dlmethoxypropane -tin(II) chloride and 2-methoxypropene - tosic acid gave more complex mixtures contrary to claims in the literature. A new trlacetal 1 2 3,6 4,5-trl-O-lsopropylidene-D-mannltol vas Isolated and its graded hydrolysis compared with that of 1 2 3 4 5 6-trlacetal. Acetal-... 

In contrast to the aromatic counterpart, very few works have been devoted to the mechanism of the aliphatic Friedel-Crafts acylation. Several mechanisms have been proposed to explain the reaction of 1-methylcyclohexene in acetic acid with zinc chloride catalyst that exclusively gives the 6-acetyl-l-methylcyclohexene. Early discussions by Deno suggest a carbo-cation intermediate. Finally, the observations by Beak of a product isotope effect in the absence of a corresponding kinetic isotope effect in the series of deuterated cyclenes is compelling evidence for a reaction intermediate, such as carbocation species. In the meantime, H.M.R. Hoffmann observed that the acylation of various olefins with acetyl hexachloroantimonate in methylene chloride in the presence of hindered amines affords 8,T-unsaturated ketones. He suggested that the non-conjugated enone is formed via an ene reaction. 

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