Esterification with isobutene

Preparative Methods prepared by esterification of f-leucine with Isobutene and cone Sulfuric Acid (under pressure). Typical yields are 62-64% and 12-14% of recovered amino acid, t-Leucine itself is commercially available in racemic and optically pure forms. It can also be prepared by oxidation of pina-colone to trimethylpyruvic acid, followed by oxime formation and zinc reduction. Resolution of the iV-formyl derivative of t-leucine has been carried out using brucine. ... 

The classical method for tert-butyl esterification involves nnineral add catalyzed addition of the amino acid to isobutene. Both, N-protected, e.g. Z-Xaa-OH, and unprotected amino acids form tert-butyl esters with isobutene in the presence of catalytic amounts of sulfuric acid or TosOH. " Another efficient method is the transesterification of an acetic acid tert-bvXy ester catalyzed by perchloric acid. " Amide tert-butylation was recognized as a side reaction in the presence of perchloric acid, but could be completely suppressed by using sulfuric acid. Both methods, acid-catalyzed addition to isobutene and the transesterification of acetic add terf-butyl esters, result in simultaneous terf-butyl-ation of hydroxy and sulfanyl groups. A synthetic route to Z-Thr-OtBu, Z-Ser-OtBu, and Z-Hyp-OtBu without conconnitant O-alkylation involves the hydroxy protection by the acetoacetyl group, which is readily cleaved by treatment with 2 equivalents of hydrazine in EtOH for 30 minutes. ... 

H-Pro-OtBu Typical Procedure for Esterification of N -Protected Amino Acids with Isobutene - ... 

Substituted oxazolidin-5-one derivatives, which are prepared from N -protected a-annino dicarboxyhc acids and paraformaldehyde, are employed for dual protection of the a-annino and a-carboxy groups in the synthesis of P-aspartyl and y-glutamyl esters (Scheme 4).Py For this purpose the oxazolidinone derivatives are synthesized by treatment of the Z amino acids with paraformaldehyde in a nnixture of acetic anhydride, acetic acid, and traces of thionyl chloride or by azeotropic distillation of the Z amino acids with paraformaldehyde and 4-toluenesulfonic acid in benzene. The resulting heterocychc compounds are readily converted into the tert-butyl esters with isobutene under acid catalysis. Esterification is achieved with tert-butyl bromidet or with Boc-F.P l Finally, the oxazolidinone ring is opened by alkaline hydrolysis or catalytic hydrogenolysis to yield the tert-butyl esters. 

Butenes are usually derived from Crack-C4 from naphtha steam cracking [27]. After the removal of butadiene (by extraction) and isobutene (by conversion into methyl t-butylether) from the crude stream, the so-called Raffinate II contains 1-butene (50-65%), cis/trons-2-butene, and the isomeric butanes. Raffinate II is the cheapest source of butenes, and their most valuable hydroformylation product is n-pentanal, whereas the isomers 2-methylbutyraldehyde and 3-methylbutyraldehyde are less in demand and lower in value. The main application for -valeraldehyde is its transformation into 2-propylheptanol (2-PH) by aldolcondensation and subsequent hydrogenation of the product (Scheme 14.4) [28, 29]. like 2-EH, 2-PH is also an important plasticizer alcohol. n-Valeraldehyde is also used as an ingredient in flavoring mixtures. w-Valeraldehyde can be converted into -valercarboxylic ester by subsequent oxidation and esterification with tertiary valeric alcohol, providing a useful lubricant and a substitute for Freon. 

Praill, having discovered the efficiency of acylium perchlorates as acylating agents, decided to examine the esterification of /err-butanol as opposed to its dehydration to isobutene. Using acetic anhydride and perchloric acid mixtures, both tert-h xty acetate and isobutene were rapidly produced and in accordance with the known alkyl oxygen fission of tertiary esters, the proportion of isobutene increased with time. In these reactions where acetic anhydride was in excess, crystalline material was deposited in the mixture. Later this was shown to be 2,4,6-trimethylpyrylium perchlorate, identified by its conversion to 2,4,6-trimethyl pyridine and its picrate. When isobutene itself was acylated using acetic anhydride and perchloric... 

Preparation.—Synthesis of acid-labile esters can be achieved by treatment of the corresponding lithium alkoxide, from the alcohol and n-butyl-lithium, with an acid chloride t-butyl pivalate can be obtained in 64% yield by this procedure. Hindered acids are esterified by triethyloxonium fluoroborate in the presence of ethyl di-isopropylamine. The use of boron trifluoride etherate-alcohol is recommended as a mild, efficient esterification method, as is the employment of alkyl t-butyl ethers, which react with carboxylic acids under acid catalysis to give the alkyl ester, isobutene, and water, no free alcohol being ever present. 

Hellmuth (1953) developed the first commercial process, for esterification and ester hydrolysis over Wofatit, phenolsulphonic acid-formaldehyde condensation polymers, in the 1940s in the context of the German war effort. Kemp (1972) describe an approach to reduce the amount of byproduct produced in an esterification reaction, in which isobutene was esterified with a carboxylic acid in the presence of a macroporous, acidic cation-exchange resin having a limited cation-exchange capacity (0.4-0.5 meq/g, compared with the usual 4-6 meq/g for fully functionalized microporous cation-exchange resins). 

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