P-Nitrophenyl isocyanate

British Drug Houses Ltd. or Matheson Laboratory reagent-grade phenyl isocyanate was used without further purification. When using other isocyanates, care should be taken to ensure their purity as the yield is greatly dependent upon this, commercially available p-nitrophenyl isocyanate being a case in point. 

The yields from the reactions, carried out at room temperature and a pressure of 2-4 at, increase with increasing electronegativity of the substituent X. The yield with phenyl isocyanate is 13%, with p-chlorophenyl isocyanate 55% and with p-nitrophenyl isocyanate it is 100%. Primary and secondary carba-moylphosphines cannot be isolated even when equi-molar quantities of phosphine and isocyanate are used. Their intermediate formation is probable but apparently they are more reactive towards isocyanates than phosphine itself. Similarly, phosphine does not react with free cyanic acid whereas primary and secondary phosphines react with cyanic acid, as with isocyanates, to form the corresponding carbamoylphosphines Attempts to make phosphine react with phenyl isothiocyanate did not succeed... 

In the case of aromatic isocyanates, electron-withdrawing groups increase the rate of carbodiimide formation in proportion to their electron-withdrawing power. Electron-releasing groups tend to inhibit the reaction. p-Nitrophenyl isocyanate reacts almost explosively to yield the carbodiimide when catalyzed [5]. o-Chlorophenyl isocyanate reacts seven times as fast as the o-methyl analog [33]. 

An abnormal aza-Wittig reaction is observed in the reaction of a polymer bound iminophosphoranes with electron poor isocyanates, such as p-nitrophenyl isocyanate. With aliphatic isocyanates the regular aza-Wittig reaction occurs. ... 

The submitters report a similar yield on a scale three times that illustrated here. This method has been employed for the preparation of the 4-methyl- (100%, m.p. 143° from ethyl acetate), 4-i-butyl- (100%, m.p. 147° from ethyl acetate), and 4-p-nitrophenyl-l-carbethoxysemicarbazide (90%, m.p. 219° from methanol). Because of the impure nature of commercial p-nitrophenyl isocyanate, the produet from that reaction may be contaminated with 2 -nitrophenylurea. It can be used in this impure form for preparing the corresponding urazole, as the contaminant is alkali insoluble. 

In an earlier procedure for the preparation of p-nitrophenyl isocyanate a solution of the free base in ethyl acetate is added gradually to ethyl acetate saturated with phosgene while fresh phosgene is passed into the reaction mixture yield 85-95%. 

An ethereal soln. of peroxybenzoic acid added to a stirred ethereal soln. of p-nitrophenyl isocyanate containing a little pyridine benzoyl N-(p-nitro-phenyl)carbamoyl peroxide. Y 55%. F. e. s. R. Okazaki and O. Simamura, Chem. Commun. 1969, 1308. 

The reaction of phenyl isocyanate (145, R = CeHs) with TMSA (146), followed by desilylation of the product 147 (R = CeHs) with water provides phenylcarbamoyl azide (148, R = CeHs), l-phenyl-A -tetrazoUne-5-one (150, R = CeHs) and its phenylcarbamoyl derivative 151 (R = CeHs). The appropriately generated products and yields are greatly dependent on the reaction conditions. The reaction of TMSA (146) with 1 equivalent of phenyl isocyanate (145, R = CeHs) in dry benzene at 50-60 °C for 24 hours provides phenylcarbamoyl azide (148, R = CeHs) in 57% yield, while the same reaction performed without solvent gives phenylcarbamoyl azide (148, R = CeHs), l-phenyl-A -tetrazoline-5-one (150, R = CeHs) and its phenylcarbamoyl derivative 151 (R = CeHs) in 21%, 8% and 28% yield respectively. In contrast, the reaction of 2 equivalents of TMSA (146) with phenyl isocyanate as well as with p-methoxyphenyl, p-chlorophenyl and p-nitrophenyl isocyanate 145 without solvent at reflux temperature for 24 hours affords the corresponding 1-aryl-A -tetrazohne-5-ones 150 in good yields. This method for the preparation of l-aryl-A -tetrazohne-5-ones 150 consequently is superior to the earher described approach [102] in terms of both yields and the simple procedure. 

Startg. O-alkyllactim allowed to react at room temp, with p-nitrophenyl isocyanate 2-methoxy-2,3-pentamethylene-l-(4-nitrophenyl)-l,3-diazetidin-4-one. Y 87%. F.e. s. U.Kraatz, Tetrah. Let. 1973, 1219. 

Aromatic isocyanates react with regular olefins only in the presence of metal catalysts. For example, reaction of ethylene with phenyl isocyanate in the presence of liganded nickel (o) catalysts under argon in THF at -20 °C affords a five-membered ring metalla-cycle, which on hydrolysis gives a Af-substituted carboxylic acid amide. Heating of the metallacycle causes jS-elimination with formation of Af-substituted acrylic acid amides Diolefines and allenes also undergo this reaction with phenyl isocyanate. From 1,1-bis-p-dimethylaminophenylethylene and p-nitrophenyl isocyanate a linear 1 1 adduct is obtained... 

The reaction of aromatic amines with phosgene to produce isocyanates has wide applicability. The example of the preparation of p-nitrophenyl isocyanate illustrates the general procedure. Even complex aromatic amines such as fluorescein amine may be subjected to the reaction to produce fluorescein isocyanate, which has found some application in biochemical research. 

A soln. of p-nitrophenyl isocyanate and triethylamine in benzene satd. with phosphine under Ng, then shaken 4 hrs. at 30-60 lbs./sq. in. tris-(p-nitro-phenylcarbamyl)phosphine. Y 91-100%. F. e. with lower yields s. S. A. Buckler, J. Org. Ghem. 24, 1460 (1959). 

About two-thirds of the carbon tetrachloride is distilled. The solution is cooled, and the crystals of />-nitrophenyl isocyanate are filtered as quickly as possible in order to avoid prolonged exposure of the compound to the moisture of the air. By concentration of the mother liquor a further crop is obtained. The product is recrystallized from dry carbon tetrachloride and is obtained in the form of light yellow needles melting at 56-57° (Note 6). The yield after one recrystallization is 152-170 g. (85-95 P r cent of the theoretical amount) (Note 7). 

Examples of synthesis of five-membered heterocycles following this strategy are limited in number. An approach to 1,3,4-triazoles involves bonding of C-l and C-3 of vinyl isocyanate 150 to both nitrogen atoms of aromatic hydrazines (78JOC402) (Scheme 37). The reaction was run at room temperature and gave quantitatively regioisomer 151 or a mixture of 151 and 152 when p-nitrophenyl and phenylhydrazine, respectively, were employed. 

C7H3FN203 4-ftuoro-2-nitrophenyl isocyanate 90774-51- 25.00 1.5571 2 9708 C7H4CIN03 p-nitrobenzoyl chloride 122-04-3 25.00 1.4903 2... 

A second route (Method B in Scheme 36) involves the reaction of triphosgene with the deprotected terminal amine, providing chloroformamides that lose HCl to give isocyanates. A urea derivative is formed by adding an anthranilate or an an-thranilic acid derivative. Alternatively, an activated carbamate can be produced from p-nitrophenyl chloroformate as the reactive intermediate (Method C in Scheme 36). 

There has been continued interest in the synthesis of oxazoles from a-diazo carbonyl compounds and nitriles catalyzed by Lewis acids. The BFa-catalyzed reaction of a-diazoacetophenones or methyl p-nitrophenyldiazoacetate with chloroacetonitrile affords 5-aryl-2-chloromethyloxazoles or 2-chloromethyl-5-methoxy-4-(p-nitrophenyl)oxazole, respectively (Equation (19)) <89BCJ618>. The former products react with primary, secondary, and tertiary amines by nucleophilic displacement of the chloride group. Methyl or ethyl isocyanate may be used as the nitrile component to prepare... 

Sodiiim phenylacetylene, reaction with p-nitrophenyl-propiolyl chloride, 615 Stilbazoles, -carboxy-prep-aration from pyridine aldehydes, 342, 343 stereochemistry, 342, 343 -cyano-preparation from pyridine aldehydes, 343 stereochemistry, 343 stereochemistry of, 348, 349 synthesis, 348, 349 Strecker reaction, preparation of 2-cyanomethylfurans, 666 Strecker synthesis, of pyri-dine-side chain nitriles, 362, 535-538 Streptonigrin, 626 Styryl isocyanates, reaction with ynamines, 639 6-Substituted-2,4-bis(alky 1-... 

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