Benzofurazan oxides

Checked by Arthur C. Cope, David J. Marshall, and Douglas S. Smith. 

The impure azide is dissolved in 110-120 ml. of 95% ethanol at 50-55° (Note 4), and 2 g. of activated carbon is added to aid in the removal of impurities. After being filtered through a steam-heated funnel, the warm solution is allowed to cool to room temperature, whereupon 14-15 g. of the product precipitates as light-yellow prisms, m.p. 53-55°. Concentration (Note 5) of the mother liquor to 30-40 ml. by evaporation at room temperature under an air stream causes the separation of an additional 7-8 g. of material, m.p. 52-54° (Note 6). The total yield of purified o-nitrophenylazide is 63-69%. 

If the o-nitroaniline is contaminated with -nitroaniline, as it is likely to be, the yield and quality of the o-nitrophenylazide are lowered. The submitters obtained yields of 72-80% from o-nitroanilinc melting at 70-71° obtained from the Eastman Kodak Company. The yields reported were obtained with o-nitroaniline melting at 72 73.5°. 

A large container is necessary for this reaction because of excessive frothing which accompanies the nitrogen evolution. This step should be conducted in a hood to avoid possible exposure to hydrazoic acid. 

A somewhat lower yield of benzofurazan oxide, m.p. 67-70°, is obtained if non-purified azide is used. 

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The Beirut reaction involves the condensation of benzofurazan oxide (BFO) 1 with an enamine 2 or an enolate anion 3 in an alcohol solvent to give the corresponding quinoxaline-1,4-dioxide 4. ... 

Substituted benzofurazan oxides 9 and 11 have been studied by NMR at low temperature and were observed as a mixture of tautomers, presumably interconverting via the ortho-dinitroso intermediate 10. When R = Cl, MeO, or AcO, tautomer 9 is the more stable... 

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

The benzofuroxtin [benzofurazan oxide, 3,4-benzo-l,2,6-oxa-diazole-2-oxide, or 2,1,3-benzoxadiazole-l-oxide (1)] ring system has been reviewed briefly on several occasions, notably by Kaufman and Picard,Boyer, and Behr. The mqst recent of these covers the literature until 1959, and since that date there have been many advances in the subject. This, we feel, justifies the field being covered once more, and its separation from the monocyclic 1,2,5-oxadiazole oxides—the furoxans. We consider also other furoxano-fused compounds in this chapter, subject to the limitation that the ring adjacent to the furoxan is aromatic and six-membered. 

Benzofurazan oxide is most conveniently prepared by the method herein described, which is adapted from the procedure of Green and Rowe.3 It has also been reported as an Organic Syntheses preparation 4 by way of the pyrolysis of o-ni trophenylazide. 

Benzofurazan oxide has also been prepared by the oxidation of o-nitroaniline with phenyl iodosoacetate.6 Other methods of preparation are given in reference 4. The hypochlorite oxidation method has been used in the synthesis of various substituted benzofurazan oxides.6... 

Benzidine, N,N -diethyl-, 36, 21 Benzidine dihydrochloride, 36, 22 Bcnzil, 34, 42 Benzil dihydrazone, 34, 42 Benzilic acid, 33, 37 2-Benzimidazolethiol, 30, 56 l,2-Benzo-3,4-dihydrocarbazole, 30, 91 Benzofuran, 3-methyl, 33, 43 Benzofurazan oxide, 31,14, 15 37,1 Benzoguanamine, 33,13 Benzoic acid, 32, 94 37, 21 Benzoic acid, -acetyl-, methyl ester, 32, 81... 

B. Benzofurazan oxide. A mixture of 21 g. (0.32 mole) of potassium hydroxide and 250 ml. of 95% ethanol in a 1-1. Erlenmeyer flask is heated on a steam bath until the solid dissolves (Note 1). o-Nitro-aniline (40 g., 0.29 mole) (Note 2) is dissolved in the warm alkali solution. The resulting deep red solution is then cooled to 0°, and the sodium hypochlorite solution from part A is added slowly with good stirring over the course of 10 minutes (Note 3). The flocculent yellow precipitate is collected on a large Buchner funnel, washed with 200 ml. of water, and air-dried. The crude product weighs 36.0-36.5 g. and melts at 66-71° (Note 4). The product is purified by recrystallization from a solution made up from 45 ml. of 95% ethanol and 15 ml. of water. Material insoluble in the hot solvent is removed by filtration, and the hot filtrate is allowed to cool to room temperature. The yield of yellow benzofurazan oxide is 31.6-32.5 g. (80-82%), m.p. 72-73°. 

Synthesis of quinoxaline-1,4-dioxides from benzofurazan oxide. 

A simple, efficient, one-step synthesis of quinoxaline 1,4-dioxides from the reaction of benzofurazan oxide 179 with activated alkenes such as enamines was named the Beirut reaction in honor of the city of its discovery. Developments up to 1993 were surveyed by Haddadin and Issidorides <1993H(35)1503>, who first demonstrated this reaction. The benzofurazan oxide 179 (Scheme 52) also condenses with 1,3-diketones <1995M1217, 1996JHC1057, 1999CHE459, 2003EJM791, 2005H(65)1589>, /3-keto acid derivatives <1995H(41)2203,... 

In der Benzofurazan-oxid-Reihe ist es gelungen, die o-Dinitroso-Verbindung nachzuweisen (s. S. 7 1 9)376. 

The reaction provides access to a number of quinoxaline-1,4-dioxide derivatives, by reaction of the benzofurazan oxide with 1,3-diketones, 3-ketoesters, enals, enamines, phenols and a, 3-unsaturated ketones. 

The reaction of benzofurazan oxide (605) with amines has been studied by Haddadin et al. (79T681). With diethylamine, beside other products, 3-methyl-l,2,4-benzotriazine (606) and its 4-oxide (607) were isolated, the production of which was explained by the intermediate formation of (608) and (609). 

Benzofuroxan Benzofurazan Oxide Benzodioxa-diazine or Ouinonedioxime P eroxide (formerly called "o-Dinitrosobenzene , which is incorrect) (called 3 4-Benzoi,2.5-oxdiazol-2.5 oxyd or Benz-furazan-1.3-oxyd in Ger), HC = CH-( =N-0 ... 

Claudia J. Nachef was born in Saida, Lebanon. She holds a B.S. degree from the Saint-Joseph University, Lebanon, and a M.S. degree (Doctor Jean-Yves Winum) from the University of Montpellier II, France. She is currently a research assistant at the American University of Beirut (Professor M. J. Haddadin). She worked on sulfonylureas for her M.S. degree and has been working on benzofurazan oxides, quinoxaline 1,4-dioxides, phenazines, and pyocyanins. 

Benzofurazan oxide has been prepared by a thermal decomposition of o-nitrophenylazide 4-8 by oxidation of the dioxime of o-benzoquinone by dilute nitric acid or potassium ferricyanide in alkaline solution 4 and by oxidation of o-nitroaniline with sodium hypochlorite.9 The present synthesis is a modification of the methods of Noelting and Kohn 8 and of Zincke and Schwarz.4... 

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