Esterification synthetic utility

S. Hanessian and E. Moralioglu, Chemistry of l-(dimethylamiiio)ethylklcne and a-(dimethyl-amino)benzylidene acetals. Utility as blocking groups for diols and for selective esterification. Tetrahedron Lett. 813 (1971) S. Hanessian and E. Moralioglu, Chemistry and synthetic utility of a-(dimethylamino)benzylidene and 1 -(dimethy lamino)ethylidene acetals. Con. J. Chem. 

Class 2 RCM reactions, involving the use of homoallyhc acrylate esters to form unsaturated lactones, have also found synthetic utility in the context of THP-containing natural products. These acrylate substrates are rapidly accessed from the straightforward esterification of a homoaUylic alcohol. While the second class does not formally yield a THP, the lactone affords the appropriate handles for a reductive acetylation/alkylation protocol, which is a powerful method for THP functionalization (Sect. 6.2). 

Ben /ben ate [120-51-4] CgH COOCH2CgH, mp, 21°C, cff , 1.118 bp, 323—324°C at 101.3 kPa , 1.5681. This is a colorless, oily liquid with a faiat, pleasant aromatic odor and a sharp, burning taste. It occurs naturally iu Pern and Tolu balsams, is spariugly volatile with steam, and is iusoluble iu water. Benzyl benzoate is prepared commercially by the direct esterification of benzoic acid and benzyl alcohol or by reaction of benzyl chloride and sodium benzoate. The pleasant odor of benzyl benzoate, like other benzoic esters, has long been utilized iu the perfume iadustry, where it is employed as a solvent for synthetic musks and as a fixative. It has also been used iu confectionery and chewing gum flavors. 

A broad spectrum of chemical reactions can be catalyzed by enzymes Hydrolysis, esterification, isomerization, addition and elimination, alkylation and dealkylation, halogenation and dehalogenation, and oxidation and reduction. The last reactions are catalyzed by redox enzymes, which are classified as oxidoreductases and divided into four categories according to the oxidant they utilize and the reactions they catalyze 1) dehydrogenases (reductases), 2) oxidases, 3) oxygenases (mono- and dioxygenases), and 4) peroxidases. The latter enzymes have received extensive attention in the last years as bio catalysts for synthetic applications. Peroxidases catalyze the oxidation of aromatic compounds, oxidation of heteroatom compounds, epoxidation, and the enantio-selective reduction of racemic hydroperoxides. In this article, a short overview... 

In addition to the more or less popular methods of depsipeptide synthesis discussed vide supra, there are also a limited number of complementary and effective synthetic procedures that have been described for this purpose. Among these, the well-known method of symmetric anhydrides from N-protected amino acids has to be considered. This method has found successful use in the esterification of hydroxy acids in the presence of some catalyst additives. Initially, the addition of pyridine11091 or 1-hydroxybenzotriazole in pyridine1 101 to a symmetric anhydride was utilized for ester bond formation. As an example, Katakai has prepared a number of didepsipeptides in 85-96% yield by means of a 2-nitrophenylsulfenyl /V-carboxy anhydride with lactic acid derivatives in the presence of pyridine.1 09 ... 

The alkylation products are synthetically useful because simple subsequent transformations furnishes precursors of important natural products as illustrated in Scheme 8E.23. Simple oxidative cleavage of allylic phthalimide 45 generates protected (5)-2-aminopimelic acid, whose dipeptide derivatives have shown antibiotic activity. The esterification via deracemization protocol is not limited to the use of bulky pivalic acid. The alkylation with sterically less hindered propionic acid also occurs with high enantioselectivity to give allylic ester 116, which has been utilized as an intermediate towards the antitumor agent phyllanthocin and the insect sex excitant periplanone. Dihydroxylation of the enantiopure allylic sulfone gives diol 117 with complete diastereoselectivity. Upon further transformation, the structurally versatile y-hydroxy-a,(f-un-saturated sulfone 118 is readily obtained enantiomerically pure. 

Utilization of enzymes in organic synthesis to prepare chiral compounds of synthetic value is well documented.For instance, porcine pancreatic hpase (PPL, E.C. 3.1.1.3.) which is an inexpensive commercially available enzyme, specifically catalyzes the hydrolysis of esters of racemic alcohols and wc50-diols. Thus, on a preparative scale (0.25 mol) dimethyl 2-methyl-butanedioate, on treatment with PPL in buffered water at pH 7.2, underwent regio- and en-antioselective hydrolysis. Extraction with diethyl ether gave the unhydrolyzed dimethyl (/ )-2-methylbutanedioate (93%), while acidification of the aqueous phase provided the (5)-half ester,which on esterification with methanol (acidified by thionyl chloride) gave the dimethyl (5 )-2-methylbutanedioate (76%). 

Of the numerous possibilities arising from the esterification of polycarboxylic acids by polyhydroxylic alcohols, fortunately only a few need be considered seriously from the viewpoint of utility as synthetic ester lubricants. Most of the esters that find application as lubricant fluids are products of the reaction of monohydroxylic alcohols and dicar-boxylic acids for example, the simple type structure shown below ... 

For the preparation of synthetic hydroxy polymers, hydroxyl groups can be introduced by copolymerization of the base monomer with a hydroxy monomer. These groups can then be used for esterification or etherification (Jarowenko, 1965), but the relatively high cost of hydroxy monomers detracts from the widespread use of direct copolymerization. Instead, one introduces the groups required by the complete or partial hydrolysis of the ester groups in an appropriately hydrolyzable polymer, such as poly(vinyl acetate). Complete hydrolysis yields poly(vinyl alcohol) (PVA), a water-soluble polymer with considerable utility as a stabilizer and viscosity modifier for aqueous systems ... 

Additionally, cellulose sulfonates can also function as a protecting group to prevent reaction of the C6 hydroxyl during esterification reactions (Fig. 8). Cellulose tosylates with degrees of substitution from 0.38 to 2.30 have been reported. Although an effective synthetic tool, the expense of organic solvents utilized and the cost and corrosive nature of tosyl chloride have limited the use of this methodology on a commercial scale. 

Carhodiimidazole-Catalyzed Chemical Synthesis of Arylazido Adenine Nucleotide Analogs. The utilization of carbodiimidazole to facilitate the formation of activated carboxylic acids was elegantly applied by Gottikh and his group to the synthesis of a wide spectrum of aminoacyl nucleosides, nucleotides, nucleoside di- and triphosphates, and tRNA derivatives. The formation of an imidazolide intermediate has been used in our work in the synthetic schemes leading to the esterification of adenosine and diphosphopyridine nucleotides. 

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