Elimination, direction carboxylic acid ester

The structural features of organophosphorus esters, which are very similar to those of the carboxylic acid esters, suggest that nucleophilic displacement at the central phosphorus atom will occur by an addition-elimination mechanism. Mechanistic studies, however, have demonstrated that hydrolysis occurs through direct nucleophilic displacement at phosphorus and does not involve formation of a pen-tavalent intermediate with H2O or OH (Hudson, 1965 Kirby and Warren, 1967). Accordingly, hydrolysis rates for phosphorus esters will be sensitive to electronic factors that alter the electrophilicity of the central phosphorus atom and steric interaetions that impede nucleophilic attack. 

Treatment of [2- C]malonic acid with acetone in the presence of acetic anhydride and catalytic amounts of concentrated sulfuric acids provides [5- C]Meldrum s acid (419). one of the most versatile low molecular weight building blocks . As summarized in Figure 6.124, its reactivity at C2 is analogous with that of the malonate diesters already discussed. However, the reactivity of the initial adducts differs. For example, hydrolysis or alcoholysis (including tert-BuOH) of the initial adducts with alkyl halides , aldehydes and acyl chlorides gives directly the [2- C]carboxylic acids/esters, a,/3-unsaturated acids/esters and /3-keto acids/esters, respectively, with simultaneous elimination of acetone and In contrast, the 2-(alkoxymethylene)[2- C]malonate... 

An interesting class ot covalent Inflates are vin l and ar>/ or heteroaryl Inflates Vinyl inflates are used for the direct solvolytic generation of vinyl cations and for the generation of unsaturated carbenes via the a-elimination process [66] A triflate ester of 2-hydroxypyridine can be used as a catalyst for the acylation of aromatic compounds with carboxylic acids [109] (equation 55)... 

From the preceding discussion, it is easily understood that direct polyesterifications between dicarboxylic acids and aliphatic diols (Scheme 2.8, R3 = H) and polymerizations involving aliphatic or aromatic esters, acids, and alcohols (Scheme 2.8, R3 = alkyl group, and Scheme 2.9, R3 = H) are rather slow at room temperature. These reactions must be carried out in the melt at high temperature in the presence of catalysts, usually metal salts, metal oxides, or metal alkoxides. Vacuum is generally applied during the last steps of the reaction in order to eliminate the last traces of reaction by-product (water or low-molar-mass alcohol, diol, or carboxylic acid such as acetic acid) and to shift the reaction toward the... 

Direct elimination of a carboxylic acid to an alkene has been accomplished by heating in the presence of palladium catalysts.Carboxylic esters in which the alkyl group has a P hydrogen can be pyrolyzed, most often in the gas phase, to give the corresponding acid and an alkene. No solvent is required. Since rearrangement and other side reactions are few, the reaction is synthetically very useful and is often carried out as an indirect method of accomplishing 17-1. The yields are excellent and the work up is easy. Many alkenes have been prepared in this manner. 

Carbocarbonylation [216] of alkyl halide with a perfluoro substituent leads directly to the analogous carboxylic acids and esters, provided the ) -hydride elimination is slower than CO insertion. The use of PdCl2(dppf) in the esterification of 68 gives... 

The direction of elimination from esters has been extensively studied (DePuy and King, 1960). In general, where special structural features are absent, olefin with the smallest number of alkyl substituents is most abundant. Thus from s-butyl acetate 60% of butene-1 is produced, while from t-pentyl acetate, 2-methylbutene-l occurs to the extent of 75%. In distinction to the halides, which, as has been seen, give the Saytzeff product, the esters give predominately the Hofmann product. This may in part be due to the fact that the carboxylic acid which is found along with the olefin, is not capable of bringing about isomerization, as can the hydrogen halide in the case of the alkyl halides. 

The presence of electron withdrawing groups at the a position (R3) of the acrylate derivative increases the reactivity of the reagent toward conjugate addition, while substituents in the ( position (R4) tend to provide steric constraints that hinder carbon-carbon bond formation (Scheme 3). Of the various acrylate derivatives employed in these reactions, the most frequently used have electron withdrawing functionality such as a carboxylic acid, amide, ester, or nitrile group or a combination of these. Direct pyridone formation can be achieved primarily through the use of either a,(J acetylenic esters or acrylate derivatives with P substituents (Y = SR, OR, NR2) that eliminate under the reaction conditions. 

Elimination of water and fluoroboric acid from 1073 (Ri = H) afforded the H-pyrrole 1074, directly. However, for 1073 (Ri H), elimination of water and fluoroboric acid produced the 3//-pyrrole-3-carboxylic acid methyl ester 1075 in modest to good yield. In these cases, 1075 (R2 = H) was readily converted to the 17/-pyrrole 1076 in refluxing toluene via a [1,5] sigmatropic rearrangement of the carbomethoxy group. 

The presence of the good leaving group (chloride) attached directly to the carbon-oxygen double bond makes all manner of addition-elimination reactions possible for acid chlorides. The acid chloride can be used to make anhydrides, esters, carboxylic acids, amides, aldehydes, ketones, and alcohols. 

With commercially available boronate esters as aryl coupling partners, the first Pd(ll)-catalyzed P-C(sp )-arylation of simple carboxylic acids was reported (Scheme 1.2) [5]. The reaction presumably relied on the binding of carboxylate directing group to Pd(ll) center, triggering a C-H activation/transmetalation/ reductive elimination sequence. The P-arylated carboxylic acids can be obtained in satisfactory yields. It represents an important step forward in arylation of C(sp )-H bonds. 

The nonhydrolytic M—O—M bond formation via ester elimination between metal alkoxides and carboxylic acids is a well-known approach in sol-gel chemistry. In this direction, titanium -butoxide and acetic acid were used for the nonhydrolytic synthesis of anatase Ti02 nanopartides at 100 °C [92]. Moreover, spindle-shaped nanoporous anatase Ti02 mesocrystals with a single-crystal-like structure and tunable sizes were synthesized in the tetrabutyl titanate and acetic acid system without any additives imder solvothermal conditions [93]. A complex mesoscale assembly process, involving oriented aggregation of tiny anatase nanocrystals and entrapment of in situ produced butyl acetate as a porogen, was proposed for the formation of the mesocrystals. They exhibited a good performance as anode material for lithium ion batteries [93]. 

Although the nature of the general polar effect suggested by Kamernitzsky and Akhrem " to account for axial attack in unhindered ketones is not clear, several groups have reported electrostatic interactions affect the course of borohydride reductions. Thus the keto acid (5a) is not reduced by boro-hydride but its ester (5b) is reduced rapidly further, the reduction of the ester (6b) takes place much more rapidly than that of the acid (6a). Spectroscopic data eliminate the possibility that in (5a) there is an interaction between the acid and ketone groups (e.g. formation of a lactol). The results have been attributed to a direct repulsion by the carboxylate ion as the borohydride ion approaches. " By contrast, House and co-workers observed no electrostatic effect on the stereochemistry of reduction of the keto acid (7). However, in this compound the acid group may occupy conformations in which it does not shield the ketone. Henbest reported that substituting chlorine... 

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