Saponification ethyl esters

C. Saponification. The ester is saponified by refluxing for 5 hours with 75 ml. of a 10% sodium hydroxide solution containing 3 ml. of ethyl alcohol it is then poured into 150 ml. of water and decolorized with Norite. Upon acidification of the alkaline solution with dilute hydrochloric acid, 18-19 g. (40-43%) (Notes 7 and 8) of acid is obtained, melting at 191-193° (corr.). 

Fig. 3.10. Approximate energy diagram for saponification of ethyl esters of cis- and traKi-4-r-butylcyclohexanecaiboxylic acid.

This concept has also been applied to the acid-base equilibria of indole-2-carboxylic acids (15) and of coumarilic acids (16) and to the rates of saponification of their ethyl esters. The data were excellently... 

Terpinyl acetate in the absence of esters of high molecular weight, or ethyl esters of the fatty acids of coconut oil, is indicated by a difference to be observed in the apparent ester value by different times of saponification. This ester is far more resistant to the action of caustic alkali than is linalyl acetate, and requires two hours at least for complete saponification. Hence, if the oil shows a difference in the saponification value in thirty minutes and in two hours, which amounts to more than from 1 to 2, terpinyl acetate is almost certainly present. The following table shows the effect of this partial-saponrfication on the two esters and on adulterated oils —... 

A dissertation from 1943 [2] describes an interesting investigation concerning synthesis and properties of pure ether carboxylates. With metallic sodium and chloroacetic acid ethyl ester followed by saponification, ether carboxylates were made with the general formula... 

The completion of the synthesis of 1 required installation of the (R)-nipecotic moiety. The original method used (R)-ethyl nipecotate L-tartrate 21, which was commercially available, but the availability of this intermediate on multi-kilogram scale required long lead times and cost was a major factor. In addition, it was also discovered that saponification of the ethyl ester in the final stages of the synthesis, as shown in Scheme 7.3, was accompanied by small amounts of epimerization at the carboxylic acid center of 1, resulting in diastereomeric contamination of the final product. 

Saponification of esters with sodium hydroxide is an important commerical reaction. In general, the reaction involves an ester reacting with sodium hydroxide to form an alcohol and sodium salt of the organic acid for example, ethyl acetate forming ethanol and sodium acetate ... 

In this synthetic sequence, displacement of the benzylic chloride from o-chlorobenzylchloride 100, with ethyl cyanoacetate anion afforded 3-(2-chlorophenyl)-2-carboethoxypropionitrile 101 in 68% yield after distillation. Saponification of the ethyl ester followed by thermal decarboxylation and fractional vacuum distillation, provided 3-(2-chlorophenyl)propionitrile 102 in 92% yield. Intramolecular cyclization was accomplished with sodium amide in liquid ammonia to afford 1-cyanobenzocyclobutene 103 as a colorless liquid in a... 

So far, only a limited use of thiazolidine-2-carboxylic acid (12) in peptide synthesis has been reported. This amino acid has been acylated as the alkyl ester with suitably N-protected amino acids via the HOBt/DCC method. 165 Subsequent saponification of peptidyl-thiazolidine-2-carboxylic acid ethyl ester proceeds smoothly with 1M NaOH in dioxane/water mixtures. 165 ... 

Nitrocyanoacetic Acid, NC-CH(N0Z).C00H m 130.05, N 21.54% prepd by saponification of the ethyl ester of nitrocyanoacetic acid with Ba(OH)2. The Barium salt, BaC3N204 + H20, lt-yel cryets, insol in w org solvs, on treatment with dil HC1 loses C02 and forms nitro-cyanomethane, NC.CH2.N02 Refs l)Beil 2, (258) 2)C.Ulpiani, Gazz 42,... 

Sulfanylalkanoyl amino acids and peptides are prepared by reaction of the (acetyl-sulfanyl)- or (benzoylsulfanyl)alkanoic acids or acid chlorides with a-amino esters or peptide esters, followed by deprotection of the sulfanyl and carboxy groups. 8 101114 16 27 29 For example, the 3-(acetylsulfanyl)alkanoic acids 7 are prepared from the condensation of ethyl (diethoxyphosphoryl) acetate 5 with various aldehydes according to the Horner-Emmons reaction, providing the a, 3-unsaturated ethyl esters 6 (a mixture of Z- and E-isomers, 50 50), followed by saponification of the ethyl esters and Michael addition of thiolacetic acid. The 3-(acetylsulfanyl)alkanoic acids 7 can be coupled with a-amino esters or peptide esters and subsequent hydrolysis of the 3-(acetylsulfanyl) derivatives provides the desired products 8 (Scheme 2). 14 ... 

While esters are much more easily hydrolyzed than amides, traditional saponification suffers from the fact that most esters are not soluble in aqueous base and so the rate of the hydrolysis is limited by the solubility, not by the reactivity. This limitation is overcome by the use of lithium hydroxide in aqueous THF, the reagent of choice for basic hydrolysis of esters. Methyl and ethyl esters are cleaved readily by this combination as most esters are soluble in this solvent mixture. 

Step 1 Intramolecular condensation of two esters (Dieckmann condensation). Step 2 Saponification of the ethyl ester provides the P-keto carboxylic acid. 

Reaction of (2-aminophenyl)-(4-bromophenyl)-methanone with methylsulfanylacetic acid ethyl ester and tert-butyl hypochlorite gives a corresponding sulfonium salt. This salt was transformed to initially to the betaine. Electrocyclic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid. Internal ester-amine interchange leads then to 4-bromophenyl-(3-(methylthio)indolin-7-yl)methanone. The thiomethyl group is then removed with Raney nickel to give 4-bromophenyl-(indolin-7-yl)methanone. Saponification of this intermediate affords the (2-amino-3-(4-bromobenzoyl)-phenyl)-acetic acid (Bromfenac). 

Dipropyl acetic acid or valproic acid may be prepared the next way. Propylbromide is mixed with cyanacetic acid in the presence of sodium ethylate, made from absolute ethanol and sodium. By that prepared a,a-dipropylcyanacetic acid ethyl ester is saponified with equimolecular amounts of NaOH to give dipropylacetonitril. The desired dipropylacetic acid is produced by saponification of dipropylacetonitryl with aquatic NaOH. It is colorless liquid. BP 219°-220°C. 

The reaction between ethyl acetate and alkali also known as saponification of ester occurs as follows ... 

Tab. 6.5 Substituent Effects on the Rate of the BA[2 Saponification of Different Ethyl Esters...

The ethyl ester leads to the same conmarin—eif her by saponification of tlu- nitron s rr before the reduction, or by the splitting off of alcohol from the intermediately formal anudooxycinnamic < nt... 

Acetyl-n-valeric acid has been prepared by the oxidation of 1-methylcyclohexene with potassium permanganate 5 by the oxidation of 2-methylcyclohexanone with chromic oxide and sulfuric acid 6 by the reaction of methylzinc iodide on the ethyl ester of adipic acid chloride and saponification of the ethyl ester of 5-acetyl-w-valeric acid so obtained 7 by the saponification of the ethyl ester of diacetylvaleric acid 2 and through the hydrolysis of ethyl a-acetyl-6-cyanovalerate with boiling 20% hydrochloric acid.3... 

Indanyl)-phenol 16 was obtained by reacting p-methoxy-phenyl-acetic acid ethyl ester with benzylchloride to form a-benzyl-p-methoxyphenyl ethyl acetate, saponification into the acid, conversion of the acid with thionylchloride into the chloride, cyclization to 2-p-methoxy-phenyl-l-indanone, NaBH4 reduction to 2-p-methoxyphenyl-l-indanole, dehydration with p-toluene-sulphonic acid in toluene to 2-p-methoxyphenyl-indene, catalytic hydrogenation to 2-p-methoxyphenyl-indene, and treating the ether with HBr [Eq. (5)]. 

The COX-2 inhibitor 76 has been prepared in an efficient manner from the aniline derivative 77 and 2 -bromo-4-chloroacetophenone under basic conditions in N,N-dimethylacetamide (DMA), followed by a saponification of the intermediate ethyl ester 78 <03JOC4104>. Similar results were obtained starting from phenylsulfonyl-protected ( )-2-aminocinnamates similar to 77 <03TL7269>. 

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