P-Nitrobenzyl acetate

For a series of methylbenzenes, the rates decreased in the order toluene > xylenes > mesitylene > durene > hexamethylbenzene. This order of reactivity is the reverse of that expected for a mechanism involving electrophilic substitution or electron transfer. However, Bushweller598 found that electron-releasing groups facilitate the benzylic oxidation of substituted toluenes by Pd(OAc)2 in acetic acid. p-Methoxy toluene gave a 96% yield of p-methoxybenzyl acetate, and p-nitrotoluene gave only 2% p-nitrobenzyl acetate, in agreement with either an electrophilic substitution or electron transfer mechanism. More mechanistic studies are necessary to clear up these anomalies. Steric effects may play an important role in these reactions. 

Sandmeyer reaction, 24, 22 Saponification, of an ester, 26, 30 with sodium cyanide, 26, 54 of ethyl linoleate, 22, 78 of ethyl linolenate, 22, 84 of natural oils, 22, 75, 79, 82 of p-nitrobenzyl acetate, 24, 81 Screen, protective, 22, 97 Seal, rubber tube, for stirrer shaft, 21, to... 

Other reactions. p-Nitrobenzyl acetate is formed by displacement from the halide. ... 

Nitrobenzoyl chloride, 624 p-Nitrobenzoyl chloride, 286, 736, 743, 866 p-Nitrobenzyl acetate, 1026 p-Nitrobenzyl alcohol, 304, 598 p-Nitrobenzyl bromide, 736, 737 p-Nitrobenzyl chloride, 736,1026, 1201 p-Nitrobenzyl tosylate, 736... 

The value of the Hammett equation in estimating reaction rates is illustrated as follows. Suppose it is required to know the rate of alkaline hydrolysis of p-nitrobenzyl acetate in 56% acetone at 25°C. p for the general reaction is +0.760 and the rate constant for the hydrolysis of benzyl acetate is 6.995 X 10 1 mole" sec". The substituent constant for p-nitro is +0.778. The required rate constant is obtained from the equation ... 

Preparation of 7-amino-3-chloro-3-cephem-4-carboxylic acid To a solution of 750 mg (1 55 mmol) of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride in 20 ml of tetrahydrofuran and 40 ml of methanol was added a suspension of 750 mg of prereduced 5% palladium on carbon catalyst in 20 ml of ethanol and the suspension was hydrogenated under 50 psi of hydrogen at room temperature for 45 minutes. The catalyst was filtered and washed with THF and water. The filtrate and catalyst washes were combined and evaporated to dryness. The residue was dissolved in a water-ethyl acetate mixture and the pH adjusted to pH 3. The insoluble product was filtered and triturated with acetone. The product was then dried to yield 115 mg of 7-amlno-3-chloro-3-cephem-4-carboxylic acid. 

A solution of 218 g. (1.12 moles) of />-nitrobenzyl acetate (p. 79) in 500 ml. of hot methanol is prepared in a 2-1. flask. To the hot solution is added 380 g. (1.43 moles) of a 15% solution of sodium hydroxide. The alkali should be added slowly at first with shaking to prevent too vigorous boiling. After standing for 5 minutes, the mixture is poured with vigorous hand stirring into 4.5 kg. of a mixture of cracked ice and water. The precipitate is collected on a Buchner funnel and recrystallized from 3 to 3.7 1. of hot water with the aid of 15 g. of Norite. The alcohol is dried at 60° to 65° in an oven for several hours and bottled (Note 1). The yield of slender, nearly colorless needles amounts to 110-121 g. (64-71%) the product melts at 92-93° (Note 2). 

The photodecarboxylation of nitrophenyl acetate in aqueous media was also investigated recently89 -92, especially with respect to the kinetic and spectral properties of the photogenerated p-nitrobenzyl carbanion its triplet state (Xmax ca 290 nm) was identified to have a lifetime of 90 nanoseconds at pH > 5.0. The proposed reaction mechanism following 266-nm laser excitation of p-nitrophenyl acetate is summarized in Scheme 792. 

Preparation of p-Nitrostyrene The monomer p-Nitrostyrene was prepared by the procedure of Broos and Anteunis (27) using p-nitrobenzyl bromide as starting material. The crude monomer was purified by column chromatography using a 9 1 hexane/ethyl acetate mixture as eluting solvent to yield 78% of p-nitrostyrene. 

Reagents. NaCl (Spectrum Chemical Co.) was fired 4 h at 550 °C in a muffle furnace to remove trace organic contaminants. Acetonitrile (HPLC grade J. T. Baker), dichloromethane (Burdick and Jackson), 5-dimethylamino-l-naphthalenesulfonyl chloride (dansyl chloride Aldrich), O-p-nitrobenzyl-N,N -diisopropylisourea (PNBDI Regis), and N-succinimidyl-p-nitrophenyl acetate (SNPA Regis) were used as purchased. 

The formal total synthesis of the novel /3-lactam antibiotic thienamycin has been accomplished from an isoxazoline derivative generated by [3 + 2] dipolar cycloaddition <79H(l2)l 183). Reaction of the nitrile oxide derived from 3-nitropropanal dimethyl acetal with methyl crotonate gave the isoxazoline (477) regio- and stereo-selectively. The isoxazoline was converted to amino ester (478) by hydrogenation and then to /3-lactam (479) by ester saponification and ring closure with DCC. Treatment of (479) with p-nitrobenzyl chloroformate and reaction of the derived acetal (480) with excess N-p-nitrobenzyloxycar-bonylcysteamine gave thioacetal (481), a compound which has previously been converted into ( )-(8S )-thienamycin (Scheme 106). 

The esters produced by these derivatizing reagents usually enable the sensitive determination of their parent acids in foods, with detection limits occasionally comparable to those provided by intrinsically more sensitive techniques, such as electrochemistry. The UV (254 nm) and electrochemical detection (1.1 V) limits of the p-nitrobenzyl derivatives of lactic, formic, and acetic acid are the same, and are equal to 1.8, 0.9, and 1.1 ng, respectively (45). 

Cognate preparations. p-Nitrobenzaldehyde. This preparation is an example of the Sommelet reaction in which the hexaminium salt is isolated. Dissolve llg (0.13mol) of hexamethylenetetramine in 70ml of chloroform (CAUTION) and add 11.4 g (0.067 mol) of p-nitrobenzyl chloride or 14.4 g of p-nitrobenzyl bromide (Expt 6.28). Heat the mixture under reflux on a steam bath for 4 hours a precipitate gradually separates. Replace the reflux condenser by a condenser set for distillation and distil off about 35 ml of solvent. Add 35 ml of acetone, cool in ice, collect the precipitate by suction filtration and dry it in the air. Heat the hexaminium salt thus obtained under reflux for 1 hour with 100 ml of 50 per cent acetic acid then add 100 ml of water and 25 ml of concentrated hydrochloric acid and continue the refluxing for 5-10 minutes. Cool the solution in ice, collect the crystals of p-nitrobenzaldehyde and dry them in a vacuum desiccator. The yield is 6.4 g (63%), m.p. 106 °C. The p.m.r. spectrum is noted in Expt 6.117. 

In this directed evolution experiment, increased thermostability was accompanied by an increase in catalytic activity at all temperatures (Fig. 6), as measured on the substrate used during screening, jfr-nitrophenyl acetate. Variant 8G8 is 3.7 times more active than wild type at the wild-type Topt the improvement is 4.5-fold at 8G8 s new Topt of 60°C. Activity was allowed to decrease in the first generation (variant 1A5D1 was an intermediate product of a separate evolution experiment to increase p-nitrobenzyl esterase activity in aqueous organic solvent and differs from wild type at five positions), but was recovered in later generations. 

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