Intermediate esters

Linalool can be converted to geranyl acetone (63) by the CarroU reaction (34). By transesterification with ethyl acetoacetate, the intermediate ester thermally rearranges with loss of carbon dioxide. Linalool can also be converted to geranyl acetone by reaction with methyl isopropenyl ether. The linalyl isopropenyl ether rearranges to give the geranyl acetone. 

Alkylation of diethyl acetamidomalonate with the bromomethyl-pyrimidine (88) yielded 6-acetamido-6-ethoxycarbonyl-6,6-dihydro-2-methylthiopyrido[2,3-d]pyrimidin-7(8//)-one (90), via the cyclization of the intermediate ester (89). 

A similar reaction with ethylenechlorhydrin gave intermediate ester 307, which under alkaline conditions cyclized to lactone 308 (64JOC3707). 

Amongst the reported syntheses of phosphonic esters, one of cyclohexylphos-phonic esters depends on treatment of cyclohexanthione with trialkyl phosphites followed by desulphurization of the intermediate esters (47) with Raney nickel.41... 

Although the present procedure illustrates the formation of the diazoacetic ester without isolation of the intermediate ester of glyoxylic acid />-toluenesulfonylhydrazone, the two geometric isomers of this hydrazone can be isolated if only one molar equivalent of triethylamine is used in the reaction of the acid chloride with the alcohol. The extremely mild conditions required for the further conversion of these hydrazones to the diazo esters should be noted. Other methods for decomposing arylsulfonyl-hydrazones to form diazocarbonyl compounds have included aqueous sodium hydroxide, sodium hydride in dimethoxyethane at 60°, and aluminum oxide in methylene chloride or ethyl acetate." Although the latter method competes in mildness and convenience with the procedure described here, it was found not to be applicable to the preparation of aliphatic diazoesters such as ethyl 2-diazopropionate. Hence the conditions used in the present procedure may offer a useful complement to the last-mentioned method when the appropriate arylsulfonylhydrazone is available. 

TETRAHEDRAL INTERMEDIATE ESTER HYDROLYSIS MECHANISM CHYMOTRYPSIN SERPINS (Inhibitory Mechanism)... 

Formation of products of rearrangement may be looked upon as occurring by way of loss of hydrogen from a carbon atom which is not adjacent to the carbon atom holding the phosphate radical. This results in the transitory formation of a cyclopropane or cyclobutane ring which then opens to yield the rearranged olefin. Thus, in the copolymerization of isobutylene with 2-butene, the intermediate ester may react in the following ways ... 

The intermediate ester which was claimed 12S) to melt at 118° and to be insoluble in benzene and chloroform, was found to be very soluble in these solvents and to melt at 96° The preparation has been reinvestigated on the basis of these properties and the yield reached 95 %. 

Guelcher et al. (1) prepared a hydrolyzable polyurethane foam under physiological conditions by condensing a polyester triol with e-caprolactone/glycolide and then postreacting the intermediate ester with the biocompatible diocyanate, lysine methyl ester diisocyanate. 

Anticholinesterases also react with Achase but the intermediate ester formed will not hydrolyze easily. As a result the enzyme is tied up irreversibly with the inhibitor and the Ach can go on working at its receptors with impunity. 

Primary alkyl halides (chlorides, bromides, and iodides) can be oxidized to aldehydes easily and in good yields with dimethyl sulfoxide.311 Tosyl esters of primary alcohols can be similarly converted to aldehydes,312 and epoxides313 give a-hydroxy ketones or aldehydes.314 The reaction with tosyl esters is an indirect way of oxidizing primary alcohols to aldehydes (9-3). This type of oxidation can also be carried out without isolation of an intermediate ester The alcohol is treated with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC),315 and anhydrous phosphoric acid.316 In this way a primary alcohol can be converted to the aldehyde with no carboxylic acid being produced. 

Figure 12-1 The active site structure of haloalkane dehalogenase from Xanthobacter autotrophicus with a molecule of bound dichloroethane. See Pries et al.13 The arrows illustrate the initial nucleophilic displacement. The D260 - H289 pair is essential for the subsequent hydrolysis of the intermediate ester formed in the initial step.

Another strategy for catalyzing the hydrolysis of an ester or an amide is to replace water by a stronger nucleophilic group that is part of the enzyme s active site. The HOCH2— group of a serine residue is often used in this way. In such cases, the reaction of the serine with the substrate splits the overall reaction into a two-step process. Instead of immediately yielding the free carboxylic acid, the breakdown of the initial tetrahedral intermediate yields an intermediate ester that is attached covalently to the enzyme. 

The addition of allylic (or benzylic) zinc halides to alkylidenemalonates (105),lo2s-c alkylidene-cyanoacetates (106),l02d e alkylidenephosphonoacetates (108),84,1 alkylidene barbiturates102f and their ary-lidene analogs occurs exclusively in a 1,4-addition mode. However, the addition of allylic zinc halides to alkylidenemalonates (105) is temperature dependent at low temperatures (-15 C), the homoallylic ma-lonate (128) is obtained, while at higher temperatures (68 C) the isomeric 2-cyclopentenedicarboxylate esters (129) are obtained by a zinc halide promoted electrocyclic closure of the intermediate ester (127 Scheme 48).102 ... 

The oxidation of homoserine by Cr(VI) has been compared with that of simple alcohols and 4-hydroxybutyric acid (HBA). The formation of CrOj during the oxidation was taken as evidence for the intermediacy of Cr(II). Whilst the rate law for homoserine has a first- and a second-order term, the rate laws for alcohols and HBA display only the second-order term. The second-order rate constants for HBA and homoserine are similar (suggesting that the ammo group of homoserine does not participate in binding to the chromium in this pathway), and about 10 times lower than for the alcohols, accounted for in terms of carboxylate binding to Cr(VI) in the intermediate ester (2), lowering the rate. The additional first-order term seen only for homoserine must arise from involvement of the amino group and this additional pathway is proposed to proceed via a tricyclic intermediate (l).13... 

The oxidant may aid the elimination in a concerted or E2 type of mechanism, as illustrated in Eq. (7) for such examples, the oxidant is not bonded to the substrate, except possibly in the transition state. Other oxidants, for example chromic acid, have been shown to form intermediate esters such as 1 (although other mechanisms have been proposed7), which subsequently decompose by a related, bimolecular elimination [Eq. (2)] here the leaving group is the reduced form of the oxidant, and the C-H bond must necessarily break with the liberation of a proton. As in Eq. (7), the capture of electrons by the oxidant is the driving force of the reaction, so that the breaking of the C-H bond occurs simultaneously in the rate-determining step (Scheme 1). 

The Woodward Reaction (or Woodward c/s-Hydroxylation) allows the synthesis of syn-diols from alkenes by the addition of iodine followed by nucleophilic displacement with acetate in the presence of water. Hydrolysis of the intermediate ester gives the desired diol. The Prevost Reaction gives crn/z -diols. 

The use of bis/zomotris (122) to replace tris (107) in the original alkylation-amidation sequence gave rise to transesterification products. This suggested that the amidation procedure using tris proceeded via a five-membered intermediate ester 126 to give amide 127 via an intramolecular rearrangement (Scheme 4.35). It was therefore postulated11271 that an unfavorable seven-membered transition state (128) precluded amide formation. Treat-... 

The limited space inside the H-Beta pores becomes apparent when 2-methyl and 2,6-dimethylbenzoic acid are applied as the reactants with resorcinol and compared to benzoic acid. With 2-methylbenzoic acid the conversion to the benzophenone is accelerated due to electronic effects, with 2,6-dimethylbenzoic acid the reaction slows down because the intermediate ester is too bulky to be formed inside in the pores. 65 66... 

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