Esters unsaturated, hydrolysis

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

Scheme 7 comprises the following patterns First, a metallacycle gives rise to ketones by CO insertion and reductive elimination. Next, a nickel hydride inserts an unsaturated substrate L, followed by CO. The acyl intermediate can give rise to reductive elimination with formation of acyl halides or acids and esters by hydrolysis, or it can insert a new ligand with subsequent reductive elimination as before. Alternatively, there may be a new insertion of carbon monoxide with final hydrolysis. Third, an intermediate R—Ni—X is formed by oxidative addition. It can react in several ways It can insert a new ligand L, followed by CO to give an... 

TABLE 7.39. A-ACYL DEHYDROAMINO ACIDS AND ESTERS FROM HYDROLYSIS AND ALCOHOLYSIS OF UNSATURATED 5(4H)-OXAZOLONES... 

Thus, the N,N-dibenzyl-protected aminonitrile 55 was prepared via Swern oxidation of N,N-dibenzylaminoethanol 54 followed by treatment with the enantio-pure amine auxiliary (S,S)-53 and HCN, resulting in the formation of a 3 2 epimeric mixture of the aminonitriles 55 in 55% yield, from which the single dia-stereomers could be isolated by chromatography. After lithiation with LDA, addition to the requisite (E)-a, P-unsaturated esters and hydrolysis of the aminonitrile moiety with silver nitrate, the desired a-amino keto esters R)-S6 were obtained with yields of 65-81% and enantiomeric excesses ee of 78-98%, which could be improved to ee > 98% by a simple recrystallization. Since the amino ketone functionality can be cleaved oxidatively, the 5-amino-4-oxo-esters 56 could be transformed to the corresponding succinic half-esters 57 with hydrogen peroxide in methanol in good to excellent yields (68-90%) (Scheme 1.1.15). 

The controversy centered, on the structure of the free acids which were obtained from the esters by hydrolysie,and the question was not easily settled for apparently the reactions of the compound could be interpreted in two ways. In perfect accord with the unsaturated formula the acid added hydrobromic acid easily1 to give a product wnich was shown to be CKatJr-CHa-CH< ) ) on heating the vlnaconic acid", carbon dioxide was evolved and a monobasic acid and lactone CHa - CH - CHs were obtained. Tne forma-... 

Construction of the triene required for the Diels-Alder cycloaddition began with the chain extension of glycidaldehyde (8) to the a,p-unsaturated ester and hydrolysis to the diol 9 in 66% overall yield. Selective protection of the primary alcohol as the silyl ether and oxidation of the free secondary hydroxyl group gave the unsaturated keto ester 10 (78%). Ester 10 was condensed with ethylidene triphenyphosphorane and reduced to afford a 66% yield of a mixture of dienes 11. Upon NMR analysis, this material was established to be a mixture of the desired and (Z,Z)-isomers (5.7 1). Chromatographic separation led to... 

The first synthesis of vermiculine by Corey, outlined in Scheme 4.14, employed an isopropenyl group as a protected version of the acetone sidechain. Aldehyde 57, the Dibal reduction product of readily available dimethyl 2,2-dimethoxyglutarate, was condensed with dimethallyl cadmium and the resulting alcohol silylated to produce 58 (70%). Reduction of ester 58 to the aldehyde followed by two-carbon homologation afforded a 94% yield of a,P unsaturated ester 59. Hydrolysis of 59 to the to the acid and conversion to the 2-thiopyridyl ester (77%) set the stage for double lactonization. This transformation was accomplished by thermolysis of a diluted solution of the thioester, affording a 30% yield of the diasteromeric diolides 60a and 60b (1 1). The former was then converted by oxidation into the synthetic 56 and the latter into the meso isomer 61, both in 70% yield. 

Fatty acids are GC analysed after their conversion to non-polar derivatives such as methyl or silyl esters (Evershed, 1992a). Often, esters are prepared as derivatives of the fatty acids liberated from wax esters or sterol esters by hydrolysis (Summchen et al., 1995 Szafranek Synak, 2006). The details and other important considerations of fatty add analysis have been well summarized by Christie (1994). Generally speaking, fatty add methyl esters (FAME) can be GC analysed employing non-polar stationary phases like other cuticular wax components. Unsaturated compoimds should be analysed on polar stationary phases (e.g. Carbowax). The determination of FAME often requires high resolution for the separation of positional and configurational isomers. The elution order is as follows (Evershed, 1992a) ... 

In our earlier publication (15) the synthesis of the southern part was described. This is shown in Scheme 2, including some improvements. The diene ester prepared from methacrolein and trimethyl-phosphonoacetate >3 underwent a Diels Alder cyclization with methyl vinyl ketone to give only one regio isomer, which after equilibration with base gave the all trans keto ester 9, in an overall yield of 75%. Linder Wadsworth Emmons conditions, 9 reacted smoothly with the t-butyl dimethylphosphonoacetate 10 to give the a, p unsaturated ester 11. Hydrolysis, followed by acid chloride formation and reduction with n-tributyltin hydride gave the aldehyde 12 the yield over 4 steps was 70%. 

This intramolecular nucleophilic acyl substitution reaction of acetylenic carbonates proceeds similarly to afford lactones or a,/3-unsaturated esters after hydrolysis of the resulting titanium complexes (Scheme 12.62) [81]. This sp organotitanium species 94 can also be trapped with an aldehyde, which easily undergoes recycliza-tion to give a substituted butenolide after acidic workup. 

The most common situation studied is that of a film reacting with some species in solution in the substrate, such as in the case of the hydrolysis of ester monolayers and of the oxidation of an unsaturated long-chain acid by aqueous permanganate. As a result of the reaction, the film species may be altered to the extent that its area per molecule is different or may be fragmented so that the products are soluble. One may thus follow the change in area at constant film pressure or the change in film pressure at constant area (much as with homogeneous gas reactions) in either case concomitant measurements may be made of the surface potential. 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

Allylalion of the alkoxymalonitrile 231 followed by hydrolysis affords acyl cyanide, which is converted into the amide 232. Hence the reagent 231 can be used as an acyl anion equivalent[144]. Methoxy(phenylthio)acetonitrile is allylated with allylic carbonates or vinyloxiranes. After allylation. they are converted into esters or lactones. The intramolecular version using 233 has been applied to the synthesis of the macrolide 234[37]. The /i,7-unsaturated nitrile 235 is prepared by the reaction of allylic carbonate with trimethylsilyl cyanide[145]. 

After isolation the Michael adduct may be subjected to ester hydrolysis and decar boxylation When a p unsaturated ketones are carried through this sequence the final products are 5 keto acids (8 keto acids)... 

Acidic Cation-Exchange Resins. Brmnsted acid catalytic activity is responsible for the successful use of acidic cation-exchange resins, which are also soHd acids. Cation-exchange catalysts are used in esterification, acetal synthesis, ester alcoholysis, acetal alcoholysis, alcohol dehydration, ester hydrolysis, and sucrose inversion. The soHd acid type permits simplified procedures when high boiling and viscous compounds are involved because the catalyst can be separated from the products by simple filtration. Unsaturated acids and alcohols that can polymerise in the presence of proton acids can thus be esterified directiy and without polymerisation. 

Also, Michael addition reactions occur between Ai-acylaminomalonic acid esters and unsaturated compounds, ie, acrolein [107-02-8] acrylonitrile [107-13-1y, acryhc acid esters, and amino acids result from hydrolysis of the addition products. 

Composition. Shellac is primarily a mixture of aUphatic polyhydroxy acids in the form of lactones and esters. It has an acid number of ca 70, a saponification number of ca 230, a hydroxyl number of ca 260, and an iodine number of ca 15. Its average molecular weight is ca 1000. Shellac is a complex mixture, but some of its constituents have been identified. Aleuritic acid, an optically inactive 9,10,16-trihydroxypalmitic acid, has been isolated by saponification. Related carboxyflc acids such as 16-hydroxy- and 9,10-dihydroxypalmitic acids, also have been identified after saponification. These acids may not be primary products of hydrolysis, but may have been produced by the treatment. Studies show that shellac contains carboxyflc acids with long methylene chains, unsaturated esters, probably an aliphatic aldehyde, a saturated aliphatic ester, a primary alcohol, and isolated or unconjugated double bonds. 

Two important widely used sulfonic acids are known as TwitcheU s reagents, or as in Russia, the Petrov catalysts. These reagents are based on benzene or naphthalene ( ) and (12), [3055-92-3] and [82415-39-2] respectively. The materials are typically made by the coupling of an unsaturated fatty acid with benzene or naphthalene in the presence of concentrated sulfuric acid (128). These sulfonic acids have been used extensively in the hydrolysis of fats and oils, such as beef tallow (129), coconut oil (130,131), fatty methyl esters (132), and various other fats and oils (133—135). TwitcheU reagents have also found use as acidic esterification catalysts (136) and dispersing agents (137). 

The principal constituents of rosin (qv) are abietic and related acids. Tall oil (qv) is a mixture of unsaturated fatty and aHcycHc acids of the abietic family. Refined tall oil may be high in rosin acids or unsaturated acids, depending on the refining process. Ethoxylates of rosin acids, eg, dehydro abietic acid, are similar to fatty acid ethoxylates in surfactant properties and manufacture, except for thek stabiHty to hydrolysis. No noticeable decomposition is observed when a rosin ester of this type is boiled for 15 min in 10% sulfuric acid or 25% sodium hydroxide (90). Steric hindrance of the carboxylate group associated with the aHcycHc moiety has been suggested as the cause of this unexpectedly great hydrolytic stabiHty. 

Both saturated (50) and unsaturated derivatives (51) are easily accepted by lipases and esterases. Lipase P from Amano resolves azide (52) or naphthyl (53) derivatives with good yields and excellent selectivity. PPL-catalyzed resolution of glycidyl esters (54) is of great synthetic utiUty because it provides an alternative to the Sharpless epoxidation route for the synthesis of P-blockers. The optical purity of glycidyl esters strongly depends on the stmcture of the acyl moiety the hydrolysis of propyl and butyl derivatives of epoxy alcohols results ia esters with ee > 95% (30). 

Hydroxy-20-cyanohydrins can be oxidized to 3-ketones in good yield with chromic acid, and the osmate ester of the unsaturated nitrile is also stable to this oxidant. " After hydrolysis of the osmate ester, the new 17-hydroxy-20-cyanohydrin which is presumably formed cannot be isolated, but loses hydrogen cyanide during the hydrolysis, and only the 17a-hydroxy-20-ketone is obtained. 

When a cold (-78 °C) solution of the lithium enolate derived from amide 6 is treated successively with a,/ -unsaturated ester 7 and homogeranyl iodide 8, intermediate 9 is produced in 87% yield (see Scheme 2). All of the carbon atoms that will constitute the complex pentacyclic framework of 1 are introduced in this one-pot operation. After some careful experimentation, a three-step reaction sequence was found to be necessary to accomplish the conversion of both the amide and methyl ester functions to aldehyde groups. Thus, a complete reduction of the methyl ester with diisobutylalu-minum hydride (Dibal-H) furnishes hydroxy amide 10 which is then hydrolyzed with potassium hydroxide in aqueous ethanol. After acidification of the saponification mixture, a 1 1 mixture of diastereomeric 5-lactones 11 is obtained in quantitative yield. Under the harsh conditions required to achieve the hydrolysis of the amide in 10, the stereogenic center bearing the benzyloxypropyl side chain epimerized. Nevertheless, this seemingly unfortunate circumstance is ultimately of no consequence because this carbon will eventually become part of the planar azadiene. 

A proline derived chiral nickel complex 1 may be used instead of oe,/J-unsaturated esters of lactones modified with a chiral alcohol as the Michael acceptor. The a,(9-unsaturated acid moiety in 1 reacts with various enolates to afford complexes 2 with diastereomcric ratios of 85 15 to 95 5. Hydrolysis of the imine moiety yields the optically active /(-substituted r-alanines. A typical example is shown296. 

The amount of residual sulfonate ester remaining after hydrolysis can be determined by a procedure proposed by Martinsson and Nilsson [129], similar to that used to determine total residual saponifiables in neutral oils. Neutrals, including alkanes, alkenes, secondary alcohols, and sultones, as well as the sulfonate esters in the AOS, are isolated by extraction from an aqueous alcoholic solution with petroleum ether. The sulfonate esters are separated from the sultones by chromatography on a silica gel column. Each eluent fraction is subjected to saponification and measured as active matter by MBAS determination measuring the extinction of the trichloromethane solution at 642 nra. (a) Sultones. Connor et al. [130] first reported, in 1975, a very small amount of skin sensitizer, l-unsaturated-l,3-sultone, and 2-chloroalkane-l,3-sultone in the anionic surfactant produced by the sulfation of ethoxylated fatty alcohol. These compounds can also be found in some AOS products consequently, methods of detection are essential. 

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