Preparation of esters

Esters can be produced synthetically for use in perfumes and synthetic flavourings. 

The following types of reactions are found in this section  

Esters from the reaction of alcohols with carboxylic acids, acid halides and anhydrides. 

Esters from carboxylic acids and halides, sulfoxides and miscellaneous compounds 

20% TiCl4 + 2 AgC104 (ArC0)20, MS3A At = 3,5-trifluoromethylphenyl Shiina, L Miyoshi, So. Miyashita, M. Mukaiyama, T. Chem. Lett., 1994, 515 

Takeda. IC Akiyama, A. Konda, Y. Takayanagi, H. Harigaya, Y. Tetrahedron Lett., 1995, 36, 113 

Esters from the reaction of Alcohols with Carboxylic acids, Acid Halides, and Anhydrides. 

Esters from Carboxylic Acids and Halides, Sulfoxides, and Miscellaneous compounds. 

Further examples of the reaction RCOOH + ROH RCOOR are included in Section 108 (Esters from Alcohols and Phenols) and Section 10A (Protection of Carboxylic Acids). 

Further examples of the reaction ROH - R COOR are included in Section 107 (Esters from Carboxylic Acids and Acid Halides) and Section 45A (Protection of Alcohols and Phenols). 

Kawabata T. Mizugaki, T. Ebitani, K. Kaneda. K. Tetrahedron Lett. 2003,44,9205 

Jenkins. ID. Loughlin, W.A. Tetrahedron Lett. 2004,45,2491. hv, MeOH, CC14, 12h 

Fukuota. S. Takimoto. S. Kalsuki. T. Yamaguchi, M. Tetrahedron Lett, 1987,28, 4711. 

Majdoub, M. Gutierrez, E. Ruiz-Hitzky, E. Tetrahedron, 1990, 46, 5167. 

PIFA = phenyliodonium bis-trifluoroacetate Casev. M, Manage, A.C. Muiphy, P.J. Tetrahedron Lett., 1992, 33, 965. 

16h GooBen.LJ. Dohring, A. Synlett2004,263. PhCH2COOH silica chloride, MeOH, heat 

Show the steps in the mechanism for the reaction of frrans-2-chlorocyclohexanol with sodium hydroxide shown in the previous equation. Explain why m-2-chlorocyclohexanol does not give a similar reaction. 

Show the product, including stereochemistry, for this reaction  

Because of the acidic conditions, this reaction proceeds by an SN1 mechanism. Which hydroxy group acts as the leaving group in the reaction Show all the steps in the mechanism for this reaction  

Esters can be prepared by employing carboxylate salts as nucleophiles, as shown in the following equation  

Because carboxylate salts are only weakly basic, elimination is not a problem when the leaving group is attached to a primary or secondary carbon. Several examples are provided in the following equations  

Ramaseshan, M. MaGee. D.I. Tetrahedron, 1993, 49, 2159 SECTION 107 ESTERS FROM ACID DERIVATIVES 

As mentioned in the preceding section one of the most general methods of synthesis of esters is by reaction of alcohols with an acid chloride or other activated carboxylic acid derivative. Section 3.2.5 included a discussion of two other important methods, namely, reactions with diazoalkanes and reactions of carboxylate salts with alkyl halides or sulfonate esters. There remains to be mentioned the acid-catalyzed reaction of carboxylic acids with alcohols, which is frequently referred to as Fischer esterification  

CHAPTER 3 FUNCTIONAL GROUP INTERCON VERSION BY NUCLEOPHILIC SUBSTITUTION 

Gahriele. B. Salerno. G. Costa, M. Chiusoli, G.P. Chein. Commun., 1999, 1381. 

Vignola, N. Dahinen, S. Enders, D. Briise. S. Tetrahedron Lett., 2001, 42, 7833. 

Py-CH20H,toluene, lOO C pyHjCOjC 830/, C02CH2Py Inoue, S. Yokota, K. Tatamidani, H. Fukumoto, Y. Chatani, N. Org. Lett. 2006, 8, 2519. 

Komeyama, K. Mieno, Y. Yukawa, S. Morimoto, T. Takaki, K. Chem. Lett. 2007, 36, 752. 

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CH3CH2OHCH3. B.p. 82 C. Manufactured by hydrolysis of propene. Used in the production of acetone (propanone) by oxidation, for the preparation of esters (e.g. the ethanoate used as a solvent), amines (diisopropylamines, etc.), glycerol, hydrogen peroxide. The alcohol is used as an important solvent for many resins, aerosols, anti-freezes. U.S. production 1978 775 000 tonnes. 

Fluorinated Acids. This class of compounds is characterized by the strength of the fluorocarbon acids, eg, CF COOH, approaching that of mineral acids. This property results from the strong inductive effect of fluorine and is markedly less when the fluorocarbon group is moved away from the carbonyl group. Generally, their reactions are similar to organic acids and they find apphcations, particularly trifluoroacetic acid [76-05-1] and its anhydride [407-25-0] as promotors in the preparation of esters and ketones and in nitration reactions. 

Ch1orocarhony1trime11itic acid 1,2-anhydride [1204-28-0] (9), is used in the preparation of esters and amide—imide polymers. TriaHyl trimellitate [2694-54-4] (10) is used as a cross-linking or co-curing agent for ethylene-derived mbbers and plastics. 

See also Chapter 5, on the preparation of esters as protective groups for carboxylic acids. 

General Preparation of Esters, 227 General Cleavage of Esters, 229... 

The preparation of esters can be classified into two main categories (1) carboxy-late activation with a good leaving group and (2) nucleophilic displacement of a caiboxylate on an alkyl halide or sulfonate. The latter approach is generally not suitable for the preparation of esters if the halide or tosylate is sterically hindered, but there has been some success with simple secondaiy halides and tosylates (ROTs, DMF, K2CO3, 69-93% yield). ... 

RCO2H, R OH, BOP-Cl, Et3N, CH2CI2, 23°, 2 h, 71-99% yield. This is an excellent general method for the preparation of esters. 

The section on general preparation of esters should also be consulted. 

Mercury(II) trifluoroacetate is a good electrophile that is highly reactive toward carbon-carbon double bonds [52, 53, 54] When reacting with olefins in nucleophilic solvents, it usually gives exclusively mercurated solvoadducts, but never products of skeletal rearrangement Solvomercuration-demercuratton of alkenes with mercury(II) trifluoroacetate is a remarkably effective procedure for the preparation of esters and alcohols with Markovnikov s regiochemistry [52, 5J] (equation 24)... 

Acyl transfer from an acid anhydride to an alcohol is a standard method for the preparation of esters. The reaction is subject to catalysis by either acids (H2SO4) or bases (pyridine). 

Other methods for the preparation of esters are the action of alcohol on the acid chloride or anhydride (see Reactions, p. 75), or by boiling up the dry powdered silver salt of the acid with the alkyl iodide,... 

Ethyl Benzoate.—The method of Fischer and Speler foi the preparation of esters, by boiling together the acid with the alcohol containing about 3 per cent, of either hydroclaloric acid... 

General Preparations of Esters General Cleavage of Esters Transesterification Enzymatically Cleavable Esters Heptyl, 381... 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information on this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful list, with references, of many protected amino acids (e.g., -NH2, COOH, and side-chain-protected compounds) has been compiled/ Some general methods for the preparation of esters are provided at the beginning of this chapter conditions that are unique to a protective group are described with that group/ Some esters that have been used as protective groups are included in Reactivity Chart 6. 

Preparation of Esters by Use of a Polymer-Supported Carboxylic Acid Imidazolide... 

Preparation of Esters Using Azolides Other than Imidazolides... 

As has been mentioned, preparation of esters of the C-17 hydroxyl group of selected progestins affords compounds with prolonged action. Similar chemical treatment of a corticoid would almost certainly lead to an ester of the sterically more accessible primary alcohol at C-21. In an interesting method for achieving esterification of the more hindered and less reactive tertiary 17-hydroxyl, prednisolone... 

Procedures for the preparation of several compounds of considerable utility are described. These include 1,1 -carbonyl-diimidazole, which has been used in the preparation of esters, amides, and anhydrides, the hydrochloride and methiodide of l-ethyl-3-(3-dimethylamino)-propylcarbodiimide, which can be used for similar purposes and are especially useful in the preparation of peptides, and (+)- and (— )-< -(2,4,5,7-tetranitro-9-fluorenylideneaminooxy) propionic acid (TAPA), which is used for the resolution of polycyclic aromatic compounds. 

DIVERGENT SYNTHESIS OF PAMAM DENDRIMERS VIA EXCESS REAGENT METHOD PREPARATION OF ESTER TERMINATED PAMAM STAR-BRANCHED PRECURSOR [NH2-(CH2)2 6-NH21 (G = -0.5) STAR-PAMAMICO E) [1]... 

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