Methyl oxalate, reactions hydrolysis

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Treatment of D-glucoascorbic acid (XV) with diazomethane gives a 2,3-dimethyl derivative (LXXIX) and this upon repeated treatment with silver oxide and methyl iodide yields 2,3,5,6,7-pentamethyl-D-glucoascorbic acid (LXXX). Ozonization of the latter followed by hydrolysis gives oxalic acid and 3,4,5-trimethyI-D-arabonic acid (LXXXI). This acid was shown to possess a free hydroxyl group at C2 by reason of the fact that the amide of LXXXI gives a positive Weerman reaction for a-hydroxy amides, i.e., when the amide is treated with sodium hypochlorite, sodium isocyanate is produced, the latter being identified by... 

Fig. 12. First-order rate coefficients for the hydrolysis of weakly basic esters, as a function of acid concentration. Data for phenyl and methyl trifluoroacetates in HCIO, in 70% dioxan-water at 0°C (from refs. 89 and 90). and for o-nitrophenyl hydrogen oxalate in aqueous HCI at 25.5°C (from ref. 171 corrected for the reaction of the anion using pA", = 0.35).

As shown in Scheme 17,180 was available from the common, totally synthetic, intermediate 17. Using reported methodology for the introduction of vinylsilanes,57 17 was reacted smoothly with (methoxy dimethylsilyl) trimethylsilyl methyl-lithium in pentane to afford (EIZ) vinyl silane 220 in 54% yield. The main by-product in this reaction was ketone 17, which could be recycled thus, based on recovered 17, the yield of 220 was 93%. Hydrolysis of ketal 220 occurred without protodesilylation upon exposure to aqueous oxalic acid absorbed onto silica gel to give ketone 221 in 80% yield. Upon low-temperature ozonolysis of 221 in methanol, a remarkably stable dioxetane 223 was produced, as evidenced in the H NMR... 

Base-catalyzed condensation of 2-pentanone and diethyl oxalate gave the diketoester 1. Cycliza-tion of 1 with hydrazine gave the pyrazole 2, which could be methylated with good selectivity to give the pyrazole 3. Subsequent hydrolysis reaction gave the acid 4. Classical nitration and conversion of the acid to the amide via the acid chloride gave the nitropyrazole 5. This intermediate is common to all of the synthetic routes discussed in this chapter. The nitropyrazole 5 was reduced... 

When geraniol reacts with phenols in the presence of acid, the common products are usually cyclized the use of 1 % oxalic acid has now been found to minimize cyclization in the reaction between orcinol and geraniol. Nerol has been labelled with deuterium in various positions [a, b, c, and d in (32)] and then converted into the chloride (33). Kinetic isotope effects on hydrolysis of (33) were measured, and 7r-participation in the cationic intermediate (34) leading to the cyclized terpinyl derivatives is discussed. Schwartz and Dunn proposed to use the complex (35), from geranyl methyl ether, as a model for a farnesol cyclization. They were not able to isolate this complex (although there was some evidence for its formation), the main complex (36%) being a dimeric a-complex (36), together with 39 % of the ketone (37), but no cyclized material. The cyclization of the acid chloride (38) to menthone and the C9 hydrocarbon (39) with tributyltin hydride, and also the optimum conditions for the cyclization of (-i-)-citronellal... 

Displayed below is the reaction route for the Reissert indole synthesis from c>-nitrotoluene and dimethyl oxalate, where the hydrolysis of methyl indole-2-carboxylate could be omitted, depending on the reaction conditions. 

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