Halides, acyl reaction with alcohols

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

Allylic silanes react with aldehydes, in the presence of Lewis acids, to give an allyl-substituted alcohol. In the case of benzylic silanes, this addition reaction has been induced with Mg(C104)2 under photochemical conditions. The addition of chiral additives leads to the alcohol with good asymmetric induction. In a related reaction, allylic silanes react with acyl halides to produce the corresponding carbonyl derivative. The reaction of phenyl chloroformate, trimethylallylsilane, and AICI3, for example, gave phenyl but-3-enoate. ... 

For a review, see Talbot, Ref. 197, pp. 226-257. For a review of the mechanisms of reactions of acyl halides with water, alcohols, and amines, see Kivinen, in Patai The Chemistry of Acyl Halides, Wiley New York, 1972, pp. 177-230. 

Because of the special structural requirements of the resin-bound substrate, this type of cleavage reaction lacks general applicability. Some of the few examples that have been reported are listed in Table 3.19. Lactones have also been obtained by acid-catalyzed lactonization of resin-bound 4-hydroxy or 3-oxiranyl carboxylic acids [399]. Treatment of polystyrene-bound cyclic acetals with Jones reagent also leads to the release of lactones into solution (Entry 5, Table 3.19). Resin-bound benzylic aryl or alkyl carbonates have been converted into esters by treatment with acyl halides and Lewis acids (Entry 6, Table 3.19). Similarly, alcohols bound to insoluble supports as benzyl ethers can be cleaved from the support and simultaneously converted into esters by treatment with acyl halides [400]. Esters have also been prepared by treatment of carboxylic acids with an excess of polystyrene-bound triazenes here, diazo-nium salts are released into solution, which serve to O-alkylate the acid (Entry 7, Table 3.19). This strategy can also be used to prepare sulfonates [401]. 

Silyl ethers of aliphatic alcohols are inert towards strong bases, oxidants (ozone [81], Dess-Martin periodinane [605], iodonium salts [610,611], sulfur trioxide-pyridine complex [398]), and weak acids (e.g., 1 mol/L HC02H in DCM [605]), but can be selectively cleaved by treatment with HF in pyridine or with TBAF (Table 3.32). Phenols can also be linked to insoluble supports as silyl ethers, but these are less stable than alkyl silyl ethers and can even be cleaved by treatment with acyl halides under basic reaction conditions [595], Silyl ether attachment has been successfully used for the solid-phase synthesis of oligosaccharides [600,601,612,613] and peptides [614]. 

Because many more alcohols than alkyl halides are commercially available, the Mitsu-nobu reaction enables the synthesis of larger and more diverse compound arrays than alkylation with alkyl halides. A -AcyIsuIfonamides are strongly acidic and can be alkylated with diazomethane (Entry 6, Table 8.9) or trimethylsilyldiazomethane [137]. Resin-bound sulfonamides have been N-acylated by treatment with acyl halides, and N-carbamoylated by treatment with isocyanates [138]. 

SCHOTTEN-BAUMANN REACTION. Acylation of alcohols with acyl halides in aqueous alkaline solution. 

If the reaction is quenched with an alcohol, only the acyl halide reacts and this is a simple way to make a-bromoesters 38. The alternative product 39 is not formed. Water and alcohols are poor nucleophiles in the Sn2 reaction but better with carbonyl groups. 

The alcoholysis of anhydrides (Reaction XVI) is similar in scope to the reaction of alcohols with acyl halides. The reaction is catalyzed by general esterification catalysts, but usually they are not needed unless the anhydride is unreactive or the di-ester (such as a phthalate) is the product sought. 

Similarly, acetals were converted to ethers (113,114), ketones to tertiary alcohols (111), and acyl halides to ketones (113). The reaction of Me3SiPl with 1-hexanal has been used as a key step in the total synthesis of the sperimidine alkaloid anhydrocannabisativine (115). 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a Sn2 mechanism.As with 16-57, the mechanism can be S l or tetrahedral. ° Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 16-58). Lewis acids such as lithium perchlorate can be used. 

Various complex and low yield procedures for the preparation of acetylallene have been described oxidation of homopropargytic alcohol with chromium trioxide in sulfuric acid,11 mild acid hydrolysis of conjugated ethoxyenyne,12 reaction of propargyltrimethylsilane with acyl halide,13 flash vacuum thermolysis of 0-keto trimathylsilyl enol ether14 and cydoelimination of p-silylethyl sulfoxide.15... 

Some reactions of alcohols 104 with isocyanates (93T6849) have been reported, as have reactions of acyl halides with 104 (R = SMe), 105 (93T6849), and 106 (93CC417). In turn, alcohols of type 104 and 105 have been prepared by lithium aluminium hydride reduction of the corresponding ketones or through deprotection of their O-rm-butyldiphenylsilyl derivatives (91TL6033 93T6849). 

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