Furoxans, nitro derivatives

By a similar procedure, Snyder Boyer (Ref 3) prepd 3,4-Bis(m-nitrobenzoyl) -furoxan, wh crysts, mp 150°. They also prepd the respective Azines of the p-nitro deriv, orn-yel crysts, mp 252° and of the m-nitro deriv -bright yel crysts, mp 251°... 

Analogous high-yield cyclizations were reported with l-amino-2-nitro-derivatives of pyridines and isoquinolines, which gave the corresponding furoxans [53,54], Anilines oxidized in the presence of indoles afforded Schiff s bases from 2- and/or 3-position in low yield [55], An unexpected rearrangement occurred on treatment of l-phenyl-4-methyl-5-aminopyrimidinone with DIB and catalytic amounts of nickel dichloride, resulting in the formation of an imidazole derivative [56] ... 

The resistance of the furoxan ring to chemical attack allows derivatives to be prepared via the reactions of the substituents (Section 4.22.3.4). Carboxylic acids are available by permanganate oxidation of methyl derivatives or by hydrolysis of the corresponding esters reaction with ammonia affords carboxamides. Acylfuroxans provide a source of hydroxyalkyl compounds by reduction, and oximes, for example, via nucleophilic addition. Acylation and oxidation of aminofuroxans allows the amide and nitro derivatives to be prepared. Nucleophilic displacements of nitro substituents can take place, but can be somewhat hazardous on account of the explosive nature of these compounds. Alkoxy derivatives are formed with sodium alkoxide, while reaction with thiolate anions yields sulfides, from which sulfones can be synthesized by peracid oxidation. Nitrofuroxans have also been reduced to... 

In contrast to halogenation, nitration of indoxazene-3-acetic acid with fuming nitric acid at 0°C furnishes a mixture of nuclear (31 R1 = C02H, R2 = N02) (24%) and side-chain (32 R1 = H) nitration products together with a small amount (9%) of the furoxan 33.47 At room temperature a more complex mixture is obtained, consisting of the 5-nitroindoxazene-3-carboxylic acid (24%), the dinitro- and trinitromethyl derivatives (32 R1 = H and N02, respectively), and 6-nitroindoxazene-3-aldehyde (4%). As with bromination, the ester 30 (R1 = H, R2 = Me) and the corresponding 3-acetonitrile behave differently from the parent acid in that nitration yields only the 5-nitro derivatives (31 R2 = N02, R1 = C02Me and CN, respectively). 

Acetyl- and 3-formylbenzo[6]thiophen have been nitrated under conditions similar to those used for the acid. Although treatment of the 3-acetyl derivative with concentrated nitric acid in acetic acid containing 10% of sulphuric acid led to furoxan formation, reaction with potassium nitrate in concentrated sulphuric acid at 0 °C, or with a cold mixture of fuming nitric acid and acetic anhydride, gave rise to substitution at all four available positions in the benzene ring. Similar results were obtained with the 3-formyl derivative. In addition, with the last-mentioned method, appreciable amounts of deacetylation and deformylation, leading to the 3-nitro-derivative, were observed. Attempted bromination of both 3-acetyl- and 3-formyl-benzo[6]thiophen by means of bromine in acetic acid failed. ... 

In 1960 a new access to nitrile oxides was provided by dehydration of primary nitro compounds 4, achieved with 2 equiv of phenyl isocyanate, which is converted into diphenylurea, beside the substituted furoxan isoxazole derivatives are obtained in the presence of suitable dipolarophiles (Scheme 8.1) [6,7]. This method for the synthesis of isoxazoles has become popular in turn and both methods have been widely employed over the past 50 years the subject has been repeatedly reviewed [8-15]. 

Pyrido[2,3-c]furoxan (4-azabenzofuroxan, 31) is prepared by pyrolysis of the nitropyridotetrazole (30) (concerning its tauto-merism, see Section I1I,C). Some derivatives of 31 are also known (see Table I). Unsuccessful attempts to make pyrido[3,4-c]furoxan audits A -oxide have been reported, although its 7-nitro and 6,7-benzo (16) derivatives have been prepared. Hydrazine and 3,4-diaroylfuroxans give the diarylpyridazinofuroxans (32). ... 

Chloro- and 5-methylbenzofuroxans are readily nitrated in the 4-position the product rearranges easily to form 7-substituted 4-nitro compounds (see Section VIII), also obtained by nitration of the corresponding 4-substituted benzofuroxans. Dinitration of 5-methylbenzofuroxan is said to give a product of m.p. 133°, while the 4-methyl gives a dinitro compound m.p. 122°-123°. For other benzofuroxans to have been nitrated see refs. 19, 36, 81, 97,121. There appears to be some confusion over the site of electrophilic substitution of naphtho[l,2-c]furoxan. Early reports in the literature state that nitration gives the 5,6-dinitro derivative (47). However, sulfona-... 

A new general synthesis of 3-substituted derivatives has been reported (99MC13) (Scheme 9). Thus, the nitro group of furoxan 27 underwent a facile hydride replacement on treatment with NaBH4 in EtOH to give 3-monosubstituted furoxans 23. The result of this reaction is independent of the nature of R. 

The amino- and nitro-substituted furazans and furoxans have been studied in detail because they are useful precursors for the synthesis of new derivatives and, moreover, they can be used as starting materials for the preparation of new heterocyclic systems. 

A convenient method was developed for the synthesis of 4-amino-3-furoxancarboxylic acid azide, which is a universal synthon for the preparation of furoxan derivatives 320 (Scheme 81). This method was used for the synthesis of new azo-, azoxy-, azido-, cyano-, nitro-, carbonylamino-, and hydroxylamino-substituted furoxan derivatives that are difficult to prepare using alternative procedures <2003RCB1822>. 

Other methods can be used to prepare the furoxan system the most common are spontaneous decomposition of azidonitroolefms 26, dehydration of a-nitrooximes 25, thermolysis of o-nitro phenylazides 27 and oxidation of o-nitrosubstituted aromatic amines 28 (Scheme 6.7). All these procedures have been discussed in detail in Ref. [10]. The latter two methods are of paramount importance in the synthesis of benzofuroxan derivatives. 

The same reaction also occurs at a lower temperature. 0.665 % of the substance decomposed at 20°C to form benzotrifuroxane in 3 years 2.43% at 35°C in one year 0.65% at 50°C in 10 days and at 100°C the substance underwent complete change in 14 hr. This decomposition is not, however, autocatalytic. This reaction — the formation of furoxane derivatives from aromatic azides with nitro group in the or/Ao-position — is of a general character (Boyer al. [160]). Despite the ease with which it decomposes trinitrotriazidobenzene has not been rejected for use as an initiator. In some countries large scale experiments are in progress to examine the possibilities of developing its practical application. 

The oxidation of oximes of oj//-perfluoroaldehydes with fuming nitric acid gives furoxane derivatives, e.g. the preparation of 3,4-bis(8//-hexadecafluoro)-l,2,5-oxadiazole (V-oxide (9).128 The conversion of ketone oximes to nitro compounds is of practical importance. Hexa-fluoroacetone oxime is transformed into l,l,l,3,3,3-hexafluoro-2-nitropropane (10) using dinitrogen pentoxide liberated in situ.249... 

The reactions of the homocyclic ring of benzofuroxans, which are described in detail in Section 4.22.3.3, provide access to numerous derivatives. Nucleophilic displacement of halides is facile when activating nitro groups are present, allowing alkoxy, aryloxy, thio and amino groups to be introduced. Electrophilic substitutions, e.g. nitration, are also valuable. Further transformations may also be performed on benzo-ring substituents. Such modifications include acetoxy to hydroxy acetamido to amino and acyl halides to esters and amides. Some reactions of the substituents of monocyclic furoxans allow hetero-substituted analogues of benzofuroxans to be prepared. For example, pyridazinofuroxans are formed by condensation of diacylfuroxans with hydrazine. 

Nitro-1,2,3-triazole 1-oxide derivatives may be obtained directly from furoxans [565] (Scheme 105). 

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