CONVERTING ALCOHOLS INTO ESTERS

The reaction scheme is as follows (Fig. 21). It is reasonable to assume that BTMA Br3 can be dissociated by water as shown in Equation 1. The resulting hypobromous acid may act as the major active oxidizing species and may convert alcohols into esters as Equation 2. In the case of ethers, we can show as Equation 4. Generated hydrobromic acid can be removed by Na2HP04 which has been added previously (Eqn. 5). 

Esters are usually prepared from carboxylic acids by the methods already discussed. Thus, carboxylic acids are converted directly into esters by SK2 reaction of a carboxyfate ion with a primary alkyl halide or by Fischer esterification of a carboxylic acid with an alcohol in the presence of a mineral acid catalyst. In addition, acid chlorides are converted into esters by treatment with an alcohol in the presence of base (Section 21.4). 

The structurally simplest silicon reagent that has been used to reduce sulphoxides is the carbene analog, dimethylsilylene (Me2Si )29. This molecule was used as a mechanistic probe and did not appear to be useful synthetically. Other silanes that have been used to reduce sulphoxides include iodotrimethylsilane, which is selective but unstable, and chlorotrimethylsilane in the presence of sodium iodide, which is easy to use, but is unselective since it cleaves esters, lactones and ethers it also converts alcohols into iodides. To circumvent these complications, Olah30 has developed the use of methyltrichlorosilane, again in the presence of sodium iodide, in dry acetonitrile (equation 8). A standard range of sulphoxides was reduced under mild conditions, with yields between 80 and 95% and with a simple workup process. The mechanism for the reaction is probably very similar to that given in equation (6), if the tricoordinate boron atoms in this reaction scheme are replaced... 

The traditional method for transforming carboxylic acids into reactive acylating agents capable of converting alcohols to esters or amines to amides is by formation of the acyl chloride. Molecules devoid of acid-sensitive functional groups can be converted to acyl chlorides with thionyl chloride or phosphorus pentachloride. When milder conditions are necessary, the reaction of the acid or its sodium salt with oxalyl chloride provides the acyl chloride. When a salt is used, the reaction solution remains essentially neutral. 

The salt is used as reagent to convert alcohols into alkyl iodides. This reaction proceeds with inversion of configuration on the C atom bearing the - OH group. N-Methyl-N,N -di-t-butyl-carbodiimide tetrafluoroborate is used as condensation agent in the synthesis of ethers and esters. ... 

Identify the types of reactions nsed to convert alcohols into alkyl halides, esters, and alkenes. 

Reagents such as 1 are coined Mukaiyama reagents and have demonstrated a great deal of synthetic versatility by converting carboxylic acids and alcohols into esters, amides, lactones, lactams, thiol esters, acid fluorides, olefins, allenes, carbodiimides, isocyanates, isothiocyanates, and nitriles.1... 

The alkali salts of oxyacids give, in addition to the above, many other substances, principally aldehydes, and the results are the same even if the attempt is made to weaken the action of the electrolytic oxygen by converting the alcohols into esters. 

Miscellaneous Reactions. The adduct (19) from dimethylformamide and benzoyl chloride converts alcohols into formate esters in generally good yields. 

The structure and nomenclature of sulfonate esters (see 113, 114, or 115) are described in Chapter 20 (Section 20.11.2). It is also true that sulfonate esters are good leaving groups in the substitution reactions described in this chapter (see Section 11.2.4). Sulfonate esters are prepared by the reaction of sulfonic acids with alcohols—much the way that carboxylic acid esters are prepared from carboxylic acids and alcohols (described in Chapter 20, Section 20.11.2). More commonly, sulfonate esters are prepared by the reaction of a sulfonyl chloride (see 112) with an alcohol. This reaction is also described in Chapter 20. This section presents only a simple preview of that chemistry, with the goal of showing that it is easy to convert alcohols into sulfonate esters, which are then useful as leaving groups in substitution reactions. The formal mechanism of these reactions will be discussed in Chapter 20. 

Trialkylboranes transfer an alkyl group to ethyl acrylate or methacrylate in a Michael sense under electrolytic conditions to give saturated esters in 51—94% yields.Simple Grignard reagents can be converted directly into esters in 70—80% yield by sequential treatment with pentacarbonyliron and an alcohol saturated with iodine the presumed intermediates are acyltetracarbonylfer-rates. An aprotic deamination of primary amines with isoamyl nitrite in the presence of a carboxylic acid also leads directly to esters. 

Preparation of Mixed Carbonates. The reaction of (Me2N)3P with alcohols and dialkyl azodicarboxylates proceeds smoothly at rt to provide mixed dialkyl carbonate esters in moderate to good yields (eq 17). An advantage of the method over the chloroformate method is the neutrality of the conditions employed. It should be noted that the related system Triphenylphosphine-Diethyl AzodicarboxyUite converts alcohols into amines. 

In general the method is more satisfactory with esters of aromatic acids than with esters of aliphatic acids. Esters of alcohols other than methyl and ethyl are best treated by first converting them into methyl esters thus Heat together under reflux i ml. of the higher ester, 5 ml. of methanol and 0-2 g. of sodium methoxide. [In place of the sodium methoxide, it suffices to add o i g. of metallic sodium to the methanol.] After refluxing, distil off the excess of methanol (b.p, 65 ). The residue is then heated under reflux with benzylamine as described above. 

Drop 1 g. of sodium into 10 ml. of ethyl alcohol in a small flask provided with a small water condenser heat the mixture until all the sodium has dissolved. Cool, and add 1 g. of the ester and 0-5 ml. of water. Frequently the sodium salt of the acid will be deposited either at once or after boiling for a few minutes. If this occurs, filter oflF the solid at once, wash it with a little absolute ethyl alcohol (or absolute methylated spirit), and convert it into the p-bromophenacyl ester, p-nitro-benzyl ester or S-benzyl-tso-thiuronium salt (for experimental details, see Section 111,85). If no solid separates, continue the boiling for 30-60 minutes, boil oflF the alcohol, allow to cool, render the product just neutral to phenolphthalein with dilute sulphuric or hydrochloric acid, convert the sodium salt present in solution into a crystalline derivative (Section 111,85), and determine its melting point. 

Properly substituted isoxazolecarboxylic acids can be converted into esters, acid halides, amides and hydrazides, and reduced by lithium aluminum hydride to alcohols. For example, 3-methoxyisoxazole-5-carboxylic acid (212) reacted with thionyl chloride in DMF to give the acid chloride (213) (74ACS(B)636). Ethyl 3-ethyl-5-methylisoxazole-4-carboxylate (214) was reduced with LAH to give 3-ethyl-4-hydroxymethyl-5-methylisoxazole (215) (7308(53)70). 

Replacement of a primary or secondary hydroxyl function with deuterium is usually carried out by first converting the alcohol into a mesylate or tosylate ester, which can then be displaced by treatment with lithium aluminum deuteride. The... 

A terpene yielding isofenchyl alcohol on hydration, which Wallach considers to be one of the fenchenes, was artificially prepared by converting nopinone into a hydroxy ester by means of bromoacetic ester and zinc-dust. The hydroxy ester is dehydrated by potassium bisulphate, and so yields an unsaturated ester, which on saponification yields an acid from which the terpene results by distillation. This fenchene has the following characters —... 

The most reliable work on the isomeric menthols is that of Pickard and Littlebury.2 Starting from the mixture of alcohols which Brunei had obtained by the reduction of thymol, and which he had described under the name of thymomenthol, they isolated from it about 60 per cent, of isomeric menthols, 30 per cent, of menthones, and several other compounds. They prepared the phthalic acid esters and converted them into their magnesium and zinc salts, which were then fractionally crystallised. 

Semmler and Liao have examined the solid body isolated from Manila elemi oil by Schimmel Co. This was found to be a sesquiterpene alcohol, CjgHjgO, which has been named elemol. It was purified by converting it into its benzoic acid ester, from which the cohol was prepared in a pure state by hydrolysis. It has the following characters —... 

Alcohols react with carboxylic acids to give esters, a reaction that is common in both the laboratory and living organisms. In the laboratory, the reaction can be carried out in a single step if a strong acid is used as catalyst. More frequently, though, the reactivity of the carboxylic acid is enhanced by first converting it into a carboxylic acid chloride, which then reacts with the alcohol. We ll look in detail at the mechanisms of these reactions in Chapter 21. 

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