General Esterification Procedure

4 PREPARATION OFACETONIDE PROTECTED [G2J-C00H [12] AND GENERAL PROCEDURE FOR THE REMOVAL OF THE BENZYL ESTER PROTECTING GROUP 

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The reaction of trialkyloxonium salts with carboxylic acids is a mild, general esterification procedure that does not require the use of more hazardous reagents such as Hexamethylphospho-lie Triamide-Thionyl Chloride, lodomethane. Dimethyl Sulfate, 3-Methyl-l-p-tolyltriazene, or Diazomethane. The reaction proceeds smoothly with sterically hindered acids, as well as with acids containing various functional groups such as amides or nitriles (eq 10). ... 

HydrophobicaHy Modified, Ethoxylated Urethane. HEUR associative thickeners are in effect poly(oxyethylene) polymers that contain terminal hydrophobe units (66). They can be synthesized via esterification with monoacids, tosylation reactions, or direct reaction with monoisocyanates. There are problems associated with aH of the methods of synthesis. The general commercial procedure for their synthesis is by a step-growth addition of... 

Since depsipeptides, in contrast to classical peptides, contain units constructed from amino and hydroxy acid residues, the various methods for their preparation are generally pathways involving the formation of ester bonds. The novel achievements in this area discussed (vide infra) are associated with further developments in the mixed anhydride technique, the application of effective catalysts in the carbodiimide procedure, and adaptation of the known Mitsunobu reaction to the depsipeptide case. A number of significant and efficient esterification procedures utilized for the preparation of depsipeptides are considered. 

The following standard esterification procedure was applied to /V-benzoylalanine oxalyl chloride was added to a solution of /V-benzoylalanine in anhydrous THF, the mixture was stirred overnight at room temperature, then the solvent and residual traces of oxalyl chloride were evaporated in vacuo. Triethylamine and then methanol were added to the residue at 0°C. On work-up, none of the expected amino acid ester was obtained. The product, isolated in 51% yield, was found to be methyl 2-phenyl-4-methyloxazole-5-carboxylate, and the process was found to be general for a variety of IV-benzoylated a-amino acids. 

Starch is capable of ester formation with either organic or inorganic acids. Reaction may, in general, be effected by any of the well-known esterification procedures after their adaptation and modification to fit the special requirements of the starch macromolecules. The esters pro-... 

Dealing with the sulphosuccinate diester synthesis, the esterification procedure is performed very similar to that described above for monoesters but the feed of hydroxyl-bearing material (generally Ce-u alcohols) should be twice more with respect to maleic anhydride. The first step is performed under a gradually increasing temperature to 120-150 °C and with continuous vacuum distillation of water from esterification. At that step esterification catalyst may be used, such as /7-toluenesulphonic acid or ABSA. The sulphonation with sodium bisulphite proceeds as described above. A representative example of diesters is sodium bis(2-ethylhexyl) sulphosuccinate known as Aerosol OT of the formula ... 

Polysaccharides are capable of ester formation with either organic or inorganic acids. Reaction may, in general, be effected by any of the well-known esterification procedures after their adaptation and modification to fit the possible special requirements of carbohydrate macromolecules. The esters produced are derivatives of high polymers and as such portray typical macromolecular properties in addition to natural ester behavior. Esterification with organic acids usually alters the properties from hydrophilic to hydrophobic, and, hence, alters the solubility so that the ester is no longer soluble in water but is soluble in organic liquids. 

This procedure is generally applied to the esterification of highly sensitive acids, which might otherwise undergo isomerisation. Thus in the example given, no ethyl crotonate is formed. 

The acid chlorides are generally more reactive than the corresponding acid anhydrides. In fact, the alcoholysis of acid chlorides is probably the best laboratory method for preparing esters. Frequentiy, basic materials are added during the course of the reaction to neutralize by-product hydrochloric acid. When the basic material is aqueous caustic, the procedure is referred to as the Schotten-Baumann procedure (73). Esterification of tertiary alcohols by acid chlorides is described in Reference 74. Esters of tertiary alcohols can also be formed through an intermediate /-butyl thioate group (75) ... 

The choice of which reactions to include is not an easy one. First there are the well known "Name Reactions", that have appeared in various monographs or in the old Merck index. Some of these are so obvious mechanistically to the modern organic chemistry practitioner that we have in fact omitted them for instance esterification of alcohols with acid chlorides - the Schotten-Baumann procedure. Others are so important and so well entrenched by name, like the Baeyer-Villiger ketone oxidation, that it is impossible to ignore them. In general we have kept older name reactions that are not obvious at first glance. 

A more elaborate but general procedure for esterification involves reaction of the A-alkoxycarbonylamino acid with the alkyl chloroformate of the alcohol to be esterified in the presence of triethylamine and a catalytic amount of 4-dimethylami-nopyridine (see Section 4.19) (Figure 3.21). The product probably arises by acylation of the alcohol by the acylpyridinum ion, both originating from decomposition of the mixed anhydride. The method can be used also to prepare activated esters (see Section 2.09), though the latter are usually obtained using the common coupling techniques (see Section 7.7).47 57... 

General Procedure A (esterification of amine) 1 A 50 wt% methanol solution of methyl acrylate (17 g, 0.2 mol) was added to the methanolic solution of Jeffamine T-3000 (100 g, 0.033 mol). This reaction was allowed to stir at room temperature under a nitrogen atmosphere for 48 h. The reaction was then heated to 50°C for 1 h. methanol and excess methyl aerylate were removed by rotary evaporator. After the dialysis using membrane filter with a MWCO of 3 D in methanol, the product was obtained as a yellow viscous oil (6 g, 98%). H NMR (CDCl, 5),... 

The modification of carboxyl groups has been carried out (1) by esterification with dry methanol and HC1, (2) by esterification with aliphatic diazo compounds, (3) by the formation of adducts with carbodi-imides, or (4) by the formation of amides through activation with carbodiimides. Both complete and, apparently specific, partial modification of the 11 free carboxyl groups have been obtained. In general, the first method suffers from the denaturing medium, the second from incomplete reaction, and the third from the uncertain nature of the products. The fourth procedure is perhaps subject to the least question. There are a total of 11 free carboxyl groups in native RNase-A l (Val), 5/ (Asp), 5y(Glu). A summary of the derivatives is given in Table V. 

Medium Boiling Esters. Esterification of ethyl and propyl alcohols, ethylene glycol, and glycerol with various acids, eg, chloro- or bromoacetic, or pyruvic, by the use of a third component such as benzene, toluene, hexane, cyclohexane, or carbon tetrachloride to remove the water produced is quite common. Benzene has been used as a co-solvent in the preparation of methyl pyruvate from pyruvic acid (101). The preparation of ethyl lactate is described as an example of the general procedure (102). A mixture of 1 mol 80% lactic acid and 2.3 mol 95% ethyl alcohol is added to a volume of benzene equal to half that of the alcohol (ca 43 mL), and the resulting mixture is refluxed for several hours. When distilled, the overhead condensate separates into layers. The lower layer is extracted to recover the benzene and alcohol, and the water is discarded. The upper layer is returned to the column for reflux. After all the water is removed from the reaction mixture, the excess of alcohol and benzene is removed by distillation, and the ester is fractionated to isolate the pure ester. 

Since the initial work of Fraenkel-Conrat and Olcott (1945), protein esterification has been described in a number of studies (Mattarella et al., 1983 Chobert et al., 1990, 1995 Bertrand-Harb et al., 1991 Briand et al., 1994, 1995). The conventional procedure involves three steps. The first step is the mixing of reactants (protein, alcohol and acid). The second step is the esterification reaction itself, which generally ranges in length from one to several days, at 4°C. The last step is reaction termination and product recovery. 

These conditions are patterned after a general procedure for esterification reported by Clinton and Laskowski.4... 

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