Isopropyl esters

Phosphate triesters (18) are iatermediates ia both the phosphotriester and phosphoramidite methods, and under appropriate conditions for deprotection of the bases and cleavage of the support, can be obtained directiy by usiag these approaches. The ethyl and isopropyl esters have been obtained directiy by usiag the phosphoramidite method because these are stable duting the normal deprotection procedure (62). By changing the oxidizing agent to Sg, both amidate and triester thiolates can be obtained. 

Chemical Designations - Synonyms Butoxyethyl 2,4-Dichlorophenoxyacetate Butyl 2,4-Dichlorophenoxyacetate 2,4-Dichlorophenoxyacetic Acid, Butoxyethyl Ester 2,4-Dichlorophenoxyacetic Acid, Isopropyl Ester Isopropyl 2,4-Dichlorophenoxy Acetate Chemical Formula 2,4-Cl2C H30CH2C00R, where R=C4H9, CjH, or CH2CH2OC4H9. 

Chemical Designations - Synonym Acetic acid, isopropyl ester 2-Propyl acetate Chemical Formula CH3COOCH(CH3)j. 

Hydroxy-l,l-dioxo-l,2-dihydro-lX -benzo [e] [1,2] thiazine-3-carboxylic acid isopropyl ester (55)... 

Butanediol Acetone Isopropyl esters n-Butanol 2-ElJiylhexanDl 2-Butene -i- ethylene... 

D. Mass Spectra of 1V-PFP Isopropyl Esters of D and L Amino Acids The molecular ion is usually not observed but can be deduced by adding 87 (COOC3H7) Daltons to the most abundant, high-mass ion. Masses 69 (CF3) and 119 (C2F5) may also be observed.2... 

Loss of C(0)0C3H7 from A-TFA, isopropyl esters of amino acids... 

Figure 8.41 Separation of the enantiomers of the common protein amino acids (N-perfluoropropionylamide isopropyl esters) on a 20 m X 0.25 mm I.D. open tubular column coated with Chirasil-Val. (Reproduced with permission from ref. 764. Copyright Elsevier Scientific Publishing Co.)...

Amino acid esters act as chelates to Co111 for example, the /3-alanine isopropyl ester is known as both a chelate and as an /V-bonded monodentate,983 and the mechanism of hydrolysis of the ester, which is activated by coordination, to yield chelated /3-alanine has been closely examined. 

In recent years, a variety of aryl boronic acids are commercially available, albeit in some cases they may be expensive for large scale purposes. During our work in the mid-1990 s boronic acid (II) was not commercially available and so two different protocols were used to prepare this acid. The first approach involved the transmetallation with n-butyl lithium of aryl bromide (I) and trapping the lithio species generated with trialkyl borate followed by an acid quench. Aryl bromide (I) is easily prepared by reaction of o-bromobenzenesulfonyl chloride with 2-propanol in the presence of pyridine as a base. The second approach was a directed metallation of isopropyl ester of benzene sulfonic acid (VII), to generate the same lithio species and reaction with trialkyl borate. The sulfonyl ester is prepared by reaction of 2-propanol with benzenesulfonyl chloride. From a long-term strategy the latter approach is... 

Suzuki Coupling Reaction (IV). The coupling of boronic acid (II) with iodooxazole (III) was the first Suzuki reaction done on-scale at Bristol Myers Squibb. Our hope from the beginning was to isolate isopropyl ester of the coupled biaryl, so that issues related to removal of Pd can be separated from other quality issues of the coupling reaction as outlined in Scheme 3. 

All efforts in the laboratory to isolate the coupled product as its isopropyl ester were unsuccessful. The high pH of the reaction required for the coupling reaction renders partial hydrolysis of the coupled isopropyl ester. Thus the reaction mixture on complete consumption of the iodoxazole (III) has a mixture of nearly 1 1 of the coupled isopropyl ester to its hydrolyzed product. Additional water was added to the reaction and the reaction was further heated at 40-50 °C for 4-16 hours when complete hydrolysis to the sodium salt is observed (Scheme 4). 

Ricks, E.E., Estrada-Vades, M.C., McLean, T.L. and Iacobucci, G.A. (1992) Highly enantioselective hydrolysis of (/ ,Sl-phenylalanine isopropyl ester by subtilisin Carlsberg. Continuous synthesis of (Sl-phenylalanine in a hollow fibre/liquid membrane reactor. Biotechnology Progress, 8, 197-203. 

Figure 14.8 Partial m/z 44 and m/z 45/44 traces obtained by GC C IRMS analysis of commonly occurring amino acids (as their triflouroacetyl isopropyl ester derivatives) together with a range ofco injected internal standards...

Heating of isopropanol under conventional reflux conditions, with 2,4,6-trimethyl-benzoic acid and a catalytic amount of sulfuric acid, afforded the corresponding isopropyl ester in only 2% conversion after 28 h. With the MBR, the product was isolated in 56% yield after 1 h at 148°C[26] (Scheme 2.1 - please note that in all schemes herein, the use of a double headed arrow does not imply a balanced equation). 

Sepasolv MPE [Methyl isopropyl ester] A variation on the Selexol process, using the methyl isopropyl ethers of polyethylene glycol as the solvent. Developed by BASF. Four commercial plants were operating in 1985, removing hydrogen sulfide from natural gas. Wolfer, W., Hydrocarbon Process., 1982,61(11), 193. 

Various substituted phenyl and 2-naphthyl groups were introduced to the / -position of isopropyl ester 78 with enantioselectivities ranging from 93% to 97% ee in high yields in the reactions with lithium arylborates (Scheme 34).110... 

The esters differ from each other in stability. To decompose the isopropyl ester, higher temperatures and higher acid strengths are needed than for decomposition of the s-butyl ester. It is claimed that the resulting carbenium ions are stabilized by solvation through the acid (25-27). Branched alkenes do not form esters. It is believed that they are easily protonated and polymerized (28). 

Theoretically, even the direct alkylation of carbenium ions with isobutane is feasible. The reaction of isobutane with a r-butyl cation would lead to 2,2,3,3-tetramethylbutane as the primary product. With liquid superacids under controlled conditions, this has been observed (52), but under typical alkylation conditions 2,2,3,3-TMB is not produced. Kazansky et al. (26,27) proposed the direct alkylation of isopentane with propene in a two-step alkylation process. In this process, the alkene first forms the ester, which in the second step reacts with the isoalkane. Isopentane was found to add directly to the isopropyl ester via intermediate formation of (non-classical) carbonium ions. In this way, the carbenium ions are freed as the corresponding alkanes without hydride transfer (see Section II.D). This conclusion was inferred from the virtual absence of propane in the product mixture. Whether this reaction path is of significance in conventional alkylation processes is unclear at present. HF produces substantial amounts of propane in isobutane/propene alkylation. The lack of 2,2,4-TMP in the product, which is formed in almost all alkylates regardless of the feed (55), implies that the mechanism in the two-step alkylation process is different from that of conventional alkylation. 

By means of nickel-catalyzed couplings of vinyl zirconocenes, Schwaebe et al. succeeded in obtaining fluorinated materials using a-bromo esters as electrophiles (Scheme 4.62) [113]. The yields achieved, albeit modest (24—65%), were far better using Ni(0) than those obtained in experiments based on several palladium(O) sources (no product observed). Isopropyl esters appear to be crucial, as competing 1,2-addition occurs with both ethyl and n-butyl analogues. Curiously, t-butyl esters were found to completely inhibit both modes of reaction of the zirconocene. 

Death took place rapidly (for example, a concentration of 1 10,000 of the di-isopropyl ester killed 6/6 rats, 10/10 mice and 2/3 rabbits within 25 min. from the beginning of exposure of 10 min.). Such rapid effect and quick knock-out action was ihown by few other gases or vapours. 

Whereas diethyl phosphorofluoridate was hydrolysed in aqueous solution in about 4 hr., the di-isopropyl ester required 72 hr. for complete hydrolysis, and small quantities could be steam-distilled. DicycZohexyl phosphorofluoridate was very stable, and vigorous shaking with water did not produce any appreciable hydrolysis. It was hydrolysed by boiling water only after several hours. When stirred vigorously with 2 per cent sodium hydroxide solution at 28-5°, the time taken to bring about hydrolysis according to the equation... 

Results. Both the dimethyl and di-isopropyl ester were found to inhibit the cholinesterase activity of human plasma, and their action was stronger than that of eserine. Of the two esters, the di-isopropyl had a more powerful cholinesterase-inhibiting action than the dimethyl ester. An accurate quantitative comparison was made of the action of the di-isopropyl ester with that of eserine sulphate. Under the conditions of Adrian s experiment, the ester at 1/80 million had about the same cholinesterase-inhibiting action as eserine sulphate at 1/14 million, i.e. the di-isopropyl ester was about 5 times as active as eserine sulphate when compared weight for weight, and about 3 times as active when compared in molar solution. 

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