2,1,3-Benzoxadiazoles

Dipping sointion II Dissolve 0.1 g NBD-chloride (7-chloro-4-nitrobenzofurazan, 7-chloro-4-nitro-2,l,3-benzoxadiazole) in 50 ml ethanol. 

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. 

The structure of 1,2,3-benzoxadiazole (4.16) bears some resemblance to Wallis and Dunitz s structure (4.14, Fig. 4-1) for quinoline-8-diazonium-l-oxide, as the latter structure has a tendency towards forming a five-membered heteroaromatic ring. The two compounds are, however, different with respect to the involvement of an N(2) and an N(l) diazo atom. The 1,2,3-benzoxadiazole structure is consistent with the bands observed in the 9.45 to 12.37 eV range in the photoelectron spectrum,... 

Benzotriazoles, see Triazoles 1,2,3-Benzoxadiazole 74f., 136 Benzoxathiete 270 Benzylideneaniline, comparison with... 

Although derivatives of 2,1,3-benzoxadiazole have been used extensively to make quinoxalines (see Section 1.6.7), the corresponding selena and thia systems have been paid scant attention for that purpose. However, 5-chloro-4-nitro-2,l,3-benzoselenadiazole (456) has been used as a convenient source of 4-chloro-3-nitro-1,2-benzenediamine (457) (HCl + HI, 20°C, 2 h 88%), which was then converted into 6-chloro-5-nitro-2,3(l//,4//)-quinoxalinedione (458) (oxalic acid, 2M HCl, reflux, 2.5 h 23%). ° In addition, irradiation of 2,1,3-benzoselenadiazole (460, X = Se) or 2,1,3-benzothiadiazole (460, X = S) with dimethyl acetylenedicarboxy-late afforded, among other products, dimethyl 2,3-quinoxalinedicarboxylate (459)... 

There is an extensive literature on the use of 2,1,3-benzoxadiazole 1-oxide [often called benzofuroxanie) (BFO) (462)] as a substrate for the primary synthesis of quinoxaline 1,4-dioxides and occasionally quinoxaline mono-A -oxides or even simple quinoxalines. Very few substituted derivatives of the parent substrate (462) have been employed in recent years. The general mechanism clearly involves a fission (usually amine-catalyzed) of the oxadiazole ring followed by reaction with an ancillary synthon. The following examples are divided according to the type of synthon employed. 

Benzoxadiazole 1-oxide (467) gave 2,3-dimethylquinoxaline 1,4-dioxide (466) (AcEt, NHs-MeOH, 40-50°C, 5 h 90% also many homologs simi-... 

CHjAc, BuNHj, MeOH, 20°C, 12 h 83%), 2/.cr.zyi 2-benzyl-3-phenyl-quinoxahne 1,4-dioxide (469) [(PhCH2)2CO, NaNH2, Et20, °C, h 52%]. 5,6-Dichloro-2,l,3-benzoxadiazole 1-oxide (470) and a-(methylthio)acetone gave 6,7-dichloro-2-methyl-3-methylthioquinoxahne 1,4-dioxide (471) (NHa-MeOH, 20°C, 12 h 30%) many analogs likewise. ... 

Benzoxadiazole 1-oxide (473) gave 2-acetyl-3-methylquinoxaline 1,4-dioxide (472) (AC2CH2, NaOH, EtOH, 55°C, 90 min, then 20°C, 12 h 54% or AC2CH2 on Si02 gel, 20°C, 7 days 58%), 2-benzoyl-3-methylquinoxaline 1,4-dioxide (474) (BZCH2AC on 3A molecular sieve,... 

BzCH2C(=0)CH2Ph, neat EtjN, 20°C, 24 h 21%) ° 5,6-Difluoro-2,l,3-benzoxadiazole 1-oxide (476) gave 2-acetyl-6,7-difluoro-3-methylquinoxaline 1,4-dioxide (477) (AC2CH2, neat Et3N, 5°C, 1 h, then 20°C, 1 h 72% analogs likewise). ° = ... 

Benzoxadiazole 1-oxide (481) with 3-acetyltetrahydro-2-furanone (2-acetyl-butyrolactone 482) gave 2-(2-hydroxyethyl)-3-methylquinoxaline 1,4-diox-ide (483) (KOH, MeOH-HaO, 20°C, 24 h 50%) but with 2-acetylacetaldehyde dimethyl acetal (484), in the presence of morpholine as base, it gave 2-(2-morpholinovinyl)quinoxaline 1,4-dioxide (485) (PhH, reflux, water separation, 9 h 47%) ... 

Diiluoro-2,l,3-benzoxadiazole 1-oxide and ethyl acetoacetate gave ethyl 6,7-difluoro-3-methyl-2-quinoxalinecarboxylate 1,4-dioxide (486) (neat... 

Benzoxadiazole 1-oxide (490) gave either 2-phenylquinoxaline 4-oxide (491) [PhCH=CHC(=0)Me, HN(CH2)4, MeCN, reflux, 24 h 35% note deacylation] or 2-acetyl-3-phenylquinoxalme 4-oxide (492) [PhCH - -... 

Benzoxadiazole 1-oxide (494) gave methyl 3-methyl-2-quinoxalinecar-boxylate 1,4-dioxide (493) [MeC(NH2)=CHC02Me, MeOH, reflux, 30 h or 2-methylquinoxahne 1,4-dioxide (495) (Me3SiCH2CH= CHNH2, dioxane-MeOH, 50°C, 15 min, then reflux, 10 min 41% note desilylation as well as deamination). ... 

Benzoxadiazole 1-oxide (497) and malononitrile gave 3-amino-2-quinox-alinecarbonitrile 1,4-dioxide (498) (EtsN, MeaNCHO, 25°, 90 min 75% EtsN, MeaNCHO, 0°C 10°C, 4 h 15% f EtsN, Me2NCHO, 0°C 20°C, 24 h 75%)7 Symmetrically substituted substrates afforded products like 3-amino-6,7-dunethyl-2-quinoxalinecarbonitrile 1,4-dioxide (499), but unsym-metric substrates usually gave two isomeric products, such as 3-amino-6/7-... 

Benzoxadiazole 1-oxide (501) and methyl 2-(triphenylphosphoranyli-dene)propionate gave several products from which methyl 2-quinoxalinecar-boxylate (503), probably formed via the intermediate (502), was isolated (PhH, reflux, 6 h 4%). ... 

Benzoxadiazole 1-oxide (462) and styrene (463 R = Ph) gave 2-phenyl-quinoxaline 1,4-dioxide (464, R = Ph) (CHCI3, reflux, >30 h 43%) 2-p-methoxyphenylquinoxaline 1,4-dioxide (464, R CfiFTtOMe-p) (58%), 2-(pyridin-4-yl)quinoxaline 1,4-dioxide (464, R pyridin-4-yl) (35%), and other such quinoxalines were made similarly.1035... 

Dichloro-2,l,3-benzoxadiazole 1-oxide (470) and a-(methylthio)acetone gave 6,7-dichloro-2-methyl-3-methylthioquinoxahne 1,4-dioxide (471) (NH3-MeOH, 20°C, 12 h 30%) 483 many analogs likewise.1086... 

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