Pivalate

The reaction of trivalent carbocations with carbon monoxide giving acyl cations is the key step in the well-known and industrially used Koch-Haaf reaction of preparing branched carboxylic acids from al-kenes or alcohols. For example, in this way, isobutylene or tert-hutyi alcohol is converted into pivalic acid. In contrast, based on the superacidic activation of electrophiles leading the superelectrophiles (see Chapter 12), we found it possible to formylate isoalkanes to aldehydes, which subsequently rearrange to their corresponding branched ketones. 

Another synthesis avoids the isolation of 6-APA and starts directly with penidllin G. Reaction with chloromethyl pivalate gives its pivaloyloxymethyl ester. This reacts with PCI5 to an imidoyl chloride which may be solvolyzed with propanol. The add chloride of (R)-... 

Chloro-21-(2,2-dimethyl-l-oxopropoxy)-6a-fluoro-llb-hydroxy-16a-methylpregna-l,4-diene-3,20-dione. See Clocortolone pivalate. 

Pivalates. The selective pivaloylation of sucrose with pivaloyl (2,2-dimethylpropionyl) chloride has been thoroughly investigated (56). The reactivity of sucrose toward pivaloylation was shown to be significantly different from other sulfonic or carboxyflc acid chlorides. For example, reaction of sucrose with four molar equivalent of toluene-/)-sulfonyl chloride in pyridine revealed, based on product isolation, the reactivity order ofO-6 0-6 > 0-1 > 0-2 (57). In contrast, a reactivity order for the pivaloylation reaction, under similar reaction conditions, was observed to be 0-6 0-6 > 0-1 > 0-4. 

I eopentanoic (Pivalic) Acid. Neopentanoic acid [75-98-9] is prepared using the Koch technology in which isobutylene reacts with carbon monoxide in the presence of strong acids such as H2SO4, HF, and BF H20 (119—122). General reaction conditions are 2—10 MPa (about 20—100 atm) of CO and 40-150°C. 

Pha.rma.ceutica.ls. Neopentanoic acid derivatives are widely used in the preparation of pharmaceuticals, eg, as a means of introducing the tert-huty group into a molecule. More frequendy, however, derivatives have been prepared that exploit the enhanced hydrolytic stabiUty of the neopentanoate group. Eor example, when salmon calcitonin is treated with N-hydroxysuccinimide pivalate [42014-50-6], the resulting derivative retains the biological activity of the precursor, but gives an extended duration of activity (51). 

Fuels, Lubricants, and Transmission Fluids. Polyol esters of neopentanoic acid have been used as high vacuum pumping hquids that are stable in chemically aggressive environments (70). Esters such as 6- -ani1inophenoxy)hexy1 pivalate are used as antioxidants for synthetic ester lubricants (71). PivaUc anhydride [1538-75-6] has been claimed as an antiknock additive for gasoline (72). 

The reaction is not suitable for hindered carboxylic acids, since considerable symmetrical anhydride formation (52% with pivalic acid) results. Symmetrical anhydride formation can sometimes be suppressed by the use of stoichiometric quantities of DMAP. 

Pivalic acid (trimethylacetic acid) [75-98-9] M 102.1, m 35.4", b 71-73"/0.1mm, pK 5.03. Fractionally distd under reduced pressure, then fractionally crystd from its melt. Recrystd from benzene. 

Reaction of the cyclopropyl-substituted pivalate (25) with dimethyl benzylidenema-lonate in the presence of a palladium catalyst gave a mixture of alkylidenecyclo-propane (26) and vinylcyclopropane (27). The ratio of these two adducts is found to be quite sensitive to the choice of ligand and solvent. While triisopropyl phosphite favors the formation of the methylenecyclopropane (26), this selectivity is completely reversed with the use of the bidentate phosphite ligand dptp (12). Interestingly there was no evidence for any products that would have derived from the ring opening of the cyclopropyl-TMM intermediate (Scheme 2.8) [18]. 

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