Acylation with oxalate

Oxalic acid is another dicarboxylic acid with restricted occurrence as an acyl moiety of anthocyanins. In addition to some European orchids flowers (Section 10.5.10), cyanidin 3-dioxalylglucoside has been isolated from fruits of Rubus laciniatus. Altogether six different anthocyanins acylated with oxalic acid have been reported. With the exception of cyanidin 3-[6-(oxalyl)glucoside], evidences for proper determination of the linkage position of this acyl moiety are absent. 

Ketones are converted to (3-ketoesters by acylation with diethyl carbonate or diethyl oxalate, as illustrated by Entries 4 and 5 in Scheme 2.16. Alkyl cyanoformate can be used as the acylating reagent under conditions where a ketone enolate has been formed under kinetic control.227... 

The N(4) atom of the side-chain piperazino group of 187 (R = Et, R = piperazino) was acylated with di-/cr/-butyl oxalate. 3-Decarboxylated products (187) were prepared from 186 under different reaction conditions in 44-81% yield (see Scheme 4) [95T11125]. The ester group of 187(R = Et) was hydrolyzed in boiling acetic acid in the presence of concentrated hydrochloric acid to give 3-carboxylic acids (187, R = H). 

In some cases, the product depends on the nature of the acylating agent. Acylation of 182 with 2,2-difluoro-4-pentenoic acid anhydride leads to acylation at C, whereas acylation with 2,2-difluoro-4-pentenoic acid choride yields the 5-acyloxyoxazole 185 as the major compound. The 5-acyloxyoxazole can be rearranged to the 5(47/)-oxazolone 183 upon treatment with 4-(dimethylamino)pyridme. Treatement of 183 with anhydrous oxalic acid promotes decarbonylation to give fluorinated a-amino ketones 184 (Scheme 7.55). Selected examples of 4-acyl-5(4//)-oxazolones are shown in Table 7.20 (Fig. 7.22). 

Amino-l,2,4-triazine-5,6-diones (534), 4-amino-4,5-dihydro-1,2,4-triazines (535), 4-amino-5-imino-l,2,4-triazines (536) and 4,6-diamino-1,2,4-triazin-5-ones (537) were prepared by reaction of hydrazidines (526) with oxalates, a-bromo ketones, acyl cyanides (485) and thioxamidates, respectively (80UP21900). 

COOEt R1 = H, Me) were acylated with diethyl oxalate in diethyl ether in the presence of sodium ethylate at 0-20°C [89JCS(P2)1613]. After the acidification of the reaction mixture, 9-(ethoxycarbonyl)carbonyl derivatives 577 were obtained from the sodium salts. The 9-(ethoxycarbonyl)car-bonyl derivatives 577 exist as 1,6,7,8-tetrahydro tautomers. 

Monoacylation of diols.1 Monoacylation of unsymmetrical 1,2-, 1,3-, and 1,4-diols can be effected by acylation of the dibutylstannylene derivatives, followed by quenching with oxalic acid or ClSi(CH3)2C6H5. This process effects monoacylation of the more-substituted hydroxyl group, even a tertiary one. This method also is... 

Wock-Hardt Ltd.54 reported a manufacturing process for the preparation of 2 (Scheme 8). In their approach, reductive amination of ketone 41 with dimethylamine hydrochloride using NaCNBH3 afforded amine 42 in 69% yield. The phenol was acylated with iV-ethyl-/V-methyl carbamoyl chloride (40) using KO/-Bu as the base instead of NaH to provide racemic carbamate 2 in 88% yield (98% pure by HPLC). Racemic 2 was further purified by making the oxalate salt, which provided 2 as a colorless crystalline oxalate salt in 100% purity. Resolution with DTTA followed by salt formation with tartaric acid afforded chiral tartrate salt 2. The overall yield of this process was 20%. 

Other indirect diazo transfer routes to a-diazo ketones have been reported involving initial activation of the ketone by benzoylation and acylation with diethyl oxalate (a) Metcalf, B. W. Jund, K. Burkhart, J. P. Tetrahedron Lett. 1980, 21. 15 (b) Harmon, R. E. Sood, V. K. Gupta, S. K. Synthesis 1974, 577. 

Appropriate 5-substituted 2-nitrophenols have been transformed by acylation with chloroformylformate into (substituted) ethyl 2-nitrophenyl oxalates as extremely reactive building blocks for the synthesis of the 2,3-dioxo-l,4-benzoxazine skeleton [115]. Due to their extreme sensitivity towards hydrolysis water has to be excluded on reductive cyclisation of these nitrophenyl esters. 

Ketones are acylated with esters in a similar manner. The product is a 1,3-diketone. Again, with intermolecular condensations, the reaction is especially important with nonenolizable esters such as diethyl carbonate, diethyl oxalate, and ethyl formate. And again, the reaction is driven to completion by deprotonation of the very acidic 1,3-dicarbonyl product. 

Diethyl 2-pyrrolidinoalkenyIphosphonates, available from pyrrolidine and diethyl 1-formylalkylphosphonates, on low-temperature treatment with i-BuLi in THF, undergo metallation under kinetic control in the P-position to phosphorus. Acylation of the resulting oc-pyrrolidino anions with methyl or allyl chloroformate proceeds uneventfully to produce diethyl phosphonopyruvates in moderate to good yields after mild acid hydrolysis with oxalic acid on... 

Acylation with methoxalic anhydride (the anhydride of the monmethyl ester of oxalic acid) in pyridine produced starch monomethoxalate.1907... 

For acylations with reactive esters, such as formate or oxalate (see Section 3.6.4.5), sodium alkoxides are still the bases of choice, but sodium hydride, dimsyl sodium, sodium or potassium amide or sodium metal have all been used for the in situ generation of the enolate anion. A typical example is shown in Scheme 47. Acylation by esters results in the production of 1 equiv. of the alkoxide ion, along with the p-dicarbonyl compound proton transfer then results in the production of the conjugate base of the dicarbonyl compound. This process normally leads to the more stable anion in the acylation of an unsymme-trical ketone. The acyl group thus becomes attached to the less-substituted a-position of the ketone. The less stable 0-acylated products are normally not observed in such reversible base-catalyzed reactions. Methyl alkyl ketones are normally acylated on the methyl group where both a-carbons are substituted to the same extent, acylation occurs at the less-hindered site. Acylation is observed only rarely at a methine carbon as the more stable p-diketone enolate cannot be formed. 

Methyl- and 2,3-dimethylquinoxalines have been acylated with benzoate, trifluoroacetate, oxalate, and phthalate esters using sodium hydride as the condensing agent. Both mono- and diacyl derivatives are obtained from 2,3-dimethylquinoxaline with excess of methyl benzoate and diethyl oxalate the products 55 and 56 are obtained, respectively. Compound 57 is produced by condensation of the dimethyl compound with diethyl phthalate. ... 

Acylation of anisole with carboxylic acids, in particular with octanoic acid, is described to be carried out over variously activated HBEA zeolites [51, 52]. Activation of the zeolite by treatment with oxalic acid after steaming results in a significant decrease of the surface area (from 670 to 500mVg) and an increase of the bulk SAR (from 13 to 51). This provides an increase in activity and selectivity in fact, HBEA itself exhibits an activity, defined as the initial apparent first-order constant k, of 0.031/g j h and a selectivity toward compound 17 (R = C. Hjj) of 80% at 50% conversion, whereas a great activity increase ( =0.121/g -h) and a selectivity improvement... 

Picoline 1-oxide can be satisfactorily acylated by esters in the presence of sodamide and is more reactive than 2-picoline598. In line with this, 2- and 4-picoline 1-oxide react satisfactorily with oxalic ester in presence of potassium ethoxide sec,... 

Ketones are converted to )8-ketoesters by acylation with diethyl carbonate or diethyl oxalate. The products are readily alkylated by the procedures discussed in Chapter 1. A convenient procedure for introduction of an ester group alpha to a ketone uses an alkyl cyanoformate as the acylating reagent. These reactions can... 

Depending on the respective reaction partner, acetic acid esters can react either as C-H acidic compounds or as acylating agents. Both are illustrated by the self-condensation of ethyl [ 1 acetate in the presence of 0.5 equivalent of sodium ethoxide or triphenymethyl sodium to give ethyl [1,3- C2]acetoacetate (Claisen condensation). In the first case, however, because of the relatively low radiochemical yields (40-45%) obtained by this procedure, it is of minor importance for the preparation of labeled ethyl acetoacetate. The deprotonation of alkyl acetates with LiHMDS followed by acylation with unlabeled or labeled acyl halides to labeled give /3-keto esters is discussed in Section 6.4. Claisen condensation of alkyl [ CJacetates with esters lacking a-hydrogens (i.e. ethyl formate, diethyl oxalate, aromatic/heteroaromatic carboxylic acid esters) proceed unidirectionally and are valuable pathways in the synthesis of ethyl [ C]formyl acetate (521. diethyl [ C]-oxaloacetate (53) and ethyl 3-oxo-3-pyrid-3-yl[2- C]acetate (54). The last example... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

The reduction of o-nitrophenyl acetic acids or esters leads to cyclization to oxindoles. Several routes to o-nitrophenylacetic acid derivatives arc available, including nitroarylation of carbanions with o-nitroaryl halides[2l,22] or trif-late[23] and acylation of o-nitrotoluenes with diethyl oxalate followed by oxidation of the resulting 3-(u-nitrophenyl)pyruvate[24 26]. 

Reaction with esters of strong acids, such as formates or oxalates, yields the acyl derivatives of ethyleneimine dimer (238,239). 

---