4-nitrobenzyl chloroformate

Chloroethyl Alkyl (Me,Et) 4-Nitrobenzyl chloroformate Phenyl chloroformate Phenyl chlorothionofoirnate ohioroformates chloroformates (NZ-CI)... 

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). 

For further variations of the Z group and related properties see Table 2 and previous reviews on this subject.t 1 Most of these protecting groups are introduced by procedures similar to those described for the synthesis of N-Z derivatives, either with the corresponding chloroformates, azido formates or mixed carbonates. However, these reagents are usually not commercially available, except for 4,5-methoxy-2-nitrobenzyl chloroformate, 4-nitro-benzyl chloroformate, and the 4-methoxybenzyl carbazate [Z(OMe)-NHNH2] as precursor of Z(OMe)-N3. 

The nitrobenzyl caibonates were prepared to protect a secondary hydroxyl group in a thienamycin precursor. The o-nitrobenzyl carbonate was prepared from the chloroformate (DMAP, CH2CI2, 0° - 20°, 3 h) and cleaved by irradiation, pH 7. The p-nitrobenzyl carbonate was prepared from the chloroformate (—78°, n-BuLi, THE, 85% yield) and cleaved by hydrogenolysis (H2/Pd-C, dioxane, H2O, EtOH, K2HP04). It is also cleaved by electrolytic reduction. ... 

Kinetics and Mechanism of Reactions of Bis (methyl-2,2 -dimercaptodiethyl-amine) dinickel(II) with Alkyl Halides. The rates of reaction of [Ni2 CH3N-(CH2CH2S)2 2], structure III, with methyl iodide, benzyl bromide, benzyl chloride, p-chlorobenzyl chloride, and p-nitrobenzyl chloride have been studied as functions of temperature and concentration in chloroform (3). Absorbance measurements were utilized to determine the rates. All experiments were conducted with excess alkyl halide (20 to 1000 times the initial concentration of complex). Jicha and Busch (18) were able to isolate alkylated complexes of the composition... 

On the other hand, the dilute solution of poly(p-benzyl-L-aspartate) in chloroform or dichloromethane gives a weak but existant CD band centered at 252 nm. A large positive CD band at 222 nm means that poly(p-benzyl-L-aspartate) (PBLA) exists in the left-handed a-helical form. Poly(y-p-nitrobenzyl-L-glutamate) also shows a definite negative CD band around 275 nm, even if the concentration of the polymer... 

Dibenzyl diselenide crystallises from alcohol in yellow needles, which are slightly deeper in colour than those of the p-nitrobenzyl compound, and melt at 92° to 93° C. Exposure to light for an hour or so causes the crystals to turn red. The selenide readily dissolves in hot alcohol, but is only sparingly soluble in ether, insoluble in water. Oxidation with fuming nitric acid converts it into benzyl seleninic acid, and boiling with copper or mercury in suspension precipitates selenium. Boiling with iodine in chloroform solution gives the tetra-iodide, M.pt. 98° C. the tetrabromide melts at 137° C.5... 

Aziridine traces in aqueous solution can be determined by reaction with 4-(/>-nitrobenzyl)pyridine [1085-48-5] and potassium carbonate [584-08-7]. Quantitative determination is carried out by photometric measurement of the absorption of the blue dye formed (367,368). Alkylating reagents interfere in the determination. Aziridine traces in the air can be detected discontinuously by absorption in Folin s reagent (l,2-naphthoquinone-4-sulfonate) [2066-95-5] (369,370) with subsequent chloroform extraction and hplc analysis of the red dye formed (371,372). The detection limit is ca 0.1 ppm. Nitrogen-specific thermal ionization detectors can be used for continuous monitoring of the ambient air. 

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. 

To a 1 liter flask containing dimethylformamide at 0°C, was added 24.8 g sodium N-(2-methoxycarbonyl-l-methylvinyl)-D-a-phenylglycine (prepared from sodium D-a-phenylglycine and methyl acetoacetate). The mixture was cooled to -40°C and methyl chloroformate (7.5 ml) and dimethylbenzylamine (0.26 ml) added. After stirring for 25 minutes, p-nitrobenzyl 7-aminodesacetoxycephalosporanate (32.8 g) in the form of its hydrochloride salt was added, followed by triethylamine (12.1 ml) and dimethylformamide (140 ml) over a period of 20 minutes. The reaction mixture was stirred for 2 hours at -25°C to -35°C, then warmed to 0°C and water (32 ml) added. To the resultant solution, hydrochloric acid (54 ml) was added followed by zinc (21.8 g) in portions over a period of 5 minutes, the temperature being maintained at 5°C to 10°C. Further hydrochloric acid (35 ml) was added and the solution stirred at 15°C to 20°C for 7 hours. 

An ice-cold soln of 4-nitrophenyl chloroformate (9.0 g, 45 mmol) in acetone (25 mL) was added dropwise to a soln of nitrobenzyl alcohol (7.8 g, 50 mmol) and pyridine (3.6 g, 45 mmol) in acetone (25 mL) with stirring. The product began to precipitate immediately after the last portion was added. The mixture was then poured into H2O (300 mL) and stirred for 15 min with cooling in ice water. The product was then filtered, washed with H2O, and dried yield 13.8 g (96%). Recrystallization (MeOH/CHCb) afforded the product as light yellow crystals, mp 132 °C. 

Reductions. Reports of rather simple reductions by indium keep appearing of tx-halocarbonyl compounds in water with ultrasound assistance, of p-nitrobenzyl ethers and esters, disulfides, amine IV-oxides, and organic azides in alcoholic solvents in the presence of NH4CI. When the azide reduction is carried out in DMF the products can be directly converted to carbamates by having a chloroformate ester in the reaction vessel. ... 

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