Of o-phenylenediamine

Place 27 g. of o-phenylenediamine (Section IV,92) in a 250 ml. round-bottomed flask and add 17 -5 g. (16 ml.) of 90 per cent, formic acid (1). Heat the mixture on a water bath at 100° for 2 hours. Cool, add 10 per cent sodium hydroxide solution slowly, with constant rotation of the flask, until the mixture is just alkaline to litmus. Filter off the crude benzimidazole at the pump, wash with ice-cold water, drain well and wash again with 25 ml. of cold water. Dissolve the crude product in 400 ml. of boiling water, add 2 g. of decolourising carbon, and digest for 16 minutes. Filter rapidly at the pump through a pre heated Buchner funnel and flask. Cool the filtrate to about 10°, filter off the benzimidazole, wash with 25 ml. of cold water, and dry at 100°. The yield of pure benzimidazole, m.p. 171-172°, is 26 g. 

The more traditional methods of phenazine synthesis falling into the type A synthesis are altogether less satisfactory than the application of the Beirut reaction. Traditionally, Ris prepared phenazine in low yield by heating o-phenylenediamine and catechol in a sealed tube at 200 °C (1886CB2206) however, the method appears to be unsatisfactory at best and gives, in addition to phenazine, 5,10-dihydrophenazine in varying amounts (Scheme 53). Several variants of this procedure exist o-benzoquinone has been used in condensation with 0-phenylenediamine and yields as high as 35% have been reported, and 1,2,3,4-tetrahydrophenazine has been prepared by condensation of o-phenylenediamine with cyclohexane- 1,2-dione. 

A. a-Methoxyphenasine condensation). Two hundred grams (0.42 mole) of powdered lead dioxide (Note 1) is added to a solution of 10 g. (0.07 mole) of pyrogallol monomethyl ether (p. 90) in 3 1. of dry benzene in a 1-gal. narrow-necked acid bottle. The bottle and contents are placed in a shaking machine and shaken for 10-20 minutes (Note 2). The reddish brown solid is filtered through an 11-cm. Buchner funnel, and the filter cake is washed once with 400 ml. of benzene. To this filtrate there is added, immediately and with mechanical stirring, a solution of 6 g. (0.06 mole) of o-phenylenediamine (Note 3) in a mixture of 80 ml. of glacial acetic acid and 200 ml. of benzene. The solu-... 

Reaction of o-phenylenediamine and n-butyl glyoxylate gives quinoxalin-2-onc in excellent yield with 4-nitro-o-phcnylcncdiaminc (5) a mixture of 6- and 7-nitro-quinoxaIin-2-ones, (6) and (7), is obtained. ... 

Condensation of o-phenylenediamine or xV-methyl-o-phenylcne-diamine with alloxan (8) in neutral solution gives the ureides (9) and (10), respectively However, reaction of o-phenylenediamine with 1,3-dimethylalloxan (13) yields quinoxalin-3-one-2-carboxymethyl-amide (14), rather than the dimethyl ureide. Methylation of (9) in acetone in the presence of potassium carbonate gives the spiro-hydantoin (11). 

The reaction of o-diamines with w-nitroacetophenone in the presence of sodium dithionite furnishes 2-phenylquinoxalines, and reaction of o-phenylenediamine with p-N0..C,-.H4C0CH2X02 similarly gives 2- (4 -nitrophenyl) quinoxaline ... 

Cyano derivatives of (18) are prepared by reaction of o-phenylenediamine with o-CcH4(CO)2N(CH2) COC(CN)z=NCGH4NMe2-p. Hydrolysis of the latter compounds give intermediates of the type o-Cr,H4(CO)2N(CH2) COCOCN which on condensation with o-phenylenediamine yield 3-phthalimidoalkylquinoxalin-2-ones, ... 

Only one example in this category has been described in recent years (as of 2003). Treatment of o-phenylenediamine (396) with 3,4,5,6-tetrachloropyridazine (397) in A-methylpyrrolidine at 115°C for 17 h gave a separable mixture of products, one of which was 2,3-bis(benzimidazol-2-yl)quinoxaline (398) (unstated yield). The structure (398) was confirmed by X-ray analysis,and a mechanism for its formation was suggested. ... 

The sole recent example in this category is the condensation (in hot aqueous ethanolic sodium hydrogen carbonate) of o-phenylenediamine (399) with tA-tert-butyl 2-hydroxy-3-oxo-l,2,6-piperidinetricarboxylate (400) to give tcrt-butyl 3-[3-(tcrt-butoxycarbonyl)-3-(tcrt-butoxycarbonylamino)propyl]-2-quinoxalinecarboxy-late (401) in 87% yield. ... 

This category is represented in the facile reaction of o-phenylenediamine (408) with 4-benzoyl-5-phenyl-2,3-dihydro-2,3-thiophenedione (409) (in toluene at 20°C for 30 min) to afford 3-(a-benzoyl-p-mercaptostyryl)-2(l//)-qumoxalinone (410) in 98% yield " also in the complicated reaction of 3-methyl-2,2,4-trinitro-2,5-dihydrothiophene 1,1-dioxide (411) with 2 equiv of ethyl 4-aminobenzoate (412) (in acetonitrile but no further details) to give ethyl 2-(p-ethoxycarbonylphenyl)-3-(l-methyl-2-nitrovinyl)-6-quinoxalinecarboxylate (413) in 51% yield.Several... 

According to the H-NMR spectra in DMSO - de, benzodiazepine 69 exists as a 4 1 mixture of tautomers A and A. Benzodiazepin-2-one 69 is formed due to the substitution of the hydroxyl group of coiunarin 67 by one of the amino groups of o-phenylenediamine and the C - O bond cleavage in the py-rone ring upon reaction with the second amino group. 

Benzannulated NHPs are straightforwardly accessible from AUV-disubsti luted o-phenylenediamines either via base-induced condensation with substituted dichlorophosphines [25] or PC13 [26], or via transamination with tris(dialkylamino) phosphines [13, 14, 27], respectively. An analogous NH-substituted derivative was obtained in low yield via transamination of o-phcnylcncdiaminc with ethoxy-bis(diethylamino)phosphine [28], and condensation of o-phenylenediamine with excess tris(diethylamino)phosphine furnished a l,3-bis(phosphino)-substituted heterocycle [29], Intermediates with one or two NH functions were detectable by spectroscopy but could not be isolated in pure form under these conditions. However, 2-chloro-benzo-l,3,2-diazaphospholene and the corresponding 1-phenyl derivative were prepared in acceptable yield via condensation of PC13 with o-phenylenediamine under microwave irradiation [30], or with A-phenyl-o-phenylenediamine under reflux [27], respectively, in the absence of additional base. The formation of tetrameric benzo-NHPs during transamination of A-alkyl-o-phenylenediamines with P(NMe2)3 has already been mentioned (cf. the section entitled 1,3,2-Diazaphospholes and 1,3,2-Diazaphospholides ). 

Since there appeared to be strong evidence for a nonthermal effect in this type of reaction, we repeated the reaction of o-phenylenediamine 34 (Scheme 4.13, Rj = R2 = H) with ethyl acetoacetate 35 (R = CH3) [19], which was one of the reactions reported by Soufiaoui [53] to give the diazepine only on MW heating. However, when the same reaction mixtures were heated forlO min with the same temperature profile, almost identical yields of the diazepines were obtained by MW and classical heating. Later, this was also found to be the case in the reaction of 34 with ethyl benzoylacetate 35 (R = Ph). 

The perinone ring system is thus formed by condensation with aromatic o-di-amines. Reaction of o-phenylenediamine with the monoanhydride is typically achieved in glacial acetic acid at 120°C. A mixture of the cis and trans isomers evolves, which appear as mixed crystals ... 

A more direct, one-step approach to phenazines 84 is possible via condensation of o-phenylenediamines 82 with o-benzoquinones 83 that can be generated in situ from oxidation of the specific catechols. As reactions of substituted o-phenylenediamines with substituted o-benzoquinones inevitably suffer from regioselectivity problems, this method is bound to have a limited range of... 

Reaction of dehydro-L-ascorbic acid and its analogs with two molecules of o-phenylenediamine or its substituted derivative gave the quinoxaline... 

A variety of methods have been developed for the preparation of substituted benzimidazoles. Of these, one of the most traditional methods involves the condensation of an o-phenylenediamine with carboxylic acid or its derivatives. Subsequently, several improved protocols have been developed for the synthesis of benzimidazoles via the condensation of o-phenylenediamines with aldehydes in the presence of acid catalysts under various reaction conditions. However, many of these methods suffer from certain drawbacks, including longer reaction times, unsatisfactory yields, harsh reaction conditions, expensive reagents, tedious work-up procedures, co-occurrence of several side reactions, and poor selectivity. Bismuth triflate provides a handy alternative to the conventional methods. It catalyzes the reaction of mono- and disubstituted aryl 1,2-diamines with aromatic aldehydes bearing either electron-rich or electron-deficient substituents on the aromatic ring in the presence of Bi(OTf)3 (10 mol%) in water, resulting in the formation of benzimidazole [119] (Fig. 29). Furthermore, the reaction also works well with heteroaromatic aldehydes. 

Benzotriazole and its derivatives are usually obtained by diazotization of o-phenylenediamines as discussed in Section 4.01.8.3 and in CHEC-1 <84CHEC-i(5)722>. Substituted o-phenylenediamines (e.g., 849) similarly give 1-substituted benzotriazoles (850) upon treatment with NaNOz (Equation (87)) <92JHC1519>. 1-Arylbenzotriazoles are alternatively synthesized from the cycloaddition of an aryl azide to benzyne or substituted benzynes, generated from the diazotization of anthranilic acid or its appropriately substituted derivatives (Scheme 169) <86CC399,87JCS(Pl)403, CHEC-i>. 

Reaction of o-phenylenediamines with Se(IV) reagents continues to be the method of choice for the synthesis of 2,1,3-benzoselenadiazoles. Selenium dioxide is commonly used <84HCA574,... 

The hemoglobin-catalyzed oxidation of o-phenylenediamine to 2,3-diaminophenazine (100), in phosphate-citric acid buffer at pH 5.0, shown in equation 30, is the basis for a kinetic method for determination of H2O2, in a FIA system, measuring at 425 mn by the stopped-flow method. The LOD is 9.2 nM, with RSD 2.08% at 0.5 p,M and linearity in the 50 to 3500 nM range . This colorimetric method was proposed for development as a standard procedure in the Republic of China for determination of H2O2 in foodstuffs . ... 

A benzannulated pyrazino[2,3-,y][l,2]thiazine has been prepared by coupling of o-phenylenediamine with a thiazine-4,5-dione (Equation 179) <1992AP461>. 

Stronger bases or acids promote the cyclization of the 1 1 adduct, 51, to pyrazines and, as was shown for the case of o-phenylenediamine, 1 equivalent or more of a strong acid both catalyzes and directs the course of the condensation by promoting the loss of ammonium ion. Strong acid catalysis is described in more detail in the following section (72JOC4136). 

The dibenzo[6,/][l,4]diazocine system (216) has been obtained by condensation of o- phenylenediamines with o-diaroylbenzenes in the presence of acid catalysts under very specific conditions (68CC1202, 75S246). In the presence of AICI3 or TsOH the diben-zodiazocines are formed in 70% yields different conditions lead to formation of o-amino-arylisoindoles. Racemization of an optically active aldehyde (216 R = CHO) has A[Pg.675]

A. Quinoxaline. One hundred thirty-five grams (1.25 moles) of o-phenylenediamine is dissolved in 2 1. of water, and the solution is heated to 70°. With stirring, a solution of 344 g. (1.29 moles) of glyoxal-sodium bisulfite (Note 1) in 1.5 1. of hot water (about 80°) is added to the o-phenylenediamine solution. The mixture is allowed to stand for 15 minutes and then is cooled to about room temperature and 500 g. of sodium carbonate monohydrate (Note 2) is added. The quinoxaline separates as an oil or as a crystalline solid if the mixture is sufficiently cool. The... 

Mercaptobenzoxazole, m.p. 193-195°, can be prepared in 80% yield by a similar procedure, using o-aminophenol in place of o-phenylenediamine. 

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