Anthranilic diazotation

The angularly fused pyridazino[l,6- ]quinazolines were prepared by tandem [6+0 (a), 6+0 (7)] cyclization of functionalized, diazotized anthranilic acid derivatives. Depending on the order of reacting ethyl benzoylacetate, malonitrile, and the diazotized anthranilonitrile, the pyridazino[l,6- ]quinazolines 103 or 105 were obtained by alkaline or thermal cyclizations, respectively (Scheme 11) <2001T1813>. 

Benzyne generated in situ by diazotization of anthranilic acid adds readily to aminides 172 to provide cycloadducts 171. Introduction of a nitro group into para position of the phenyl ring on the nitrogen terminus of the 1,3-dipole (X2 = N02) stabilizes the system and results in higher yields of product 171 (70% vs. 50% forX2 = H). Electron-deficient imines react also with aminides 172, but the yields of isolated adducts 173 are relatively low (10-26%) (Scheme 19) <2003ARK(vii)110>. 

Methyl red was first prepared 1 by diazotization of anthranilic acid in alcoholic solution, the product being allowed to react with dimethylaniline in the same solvent. It has been stated 2 that this process does not work satisfactorily and yields a different product, of brownish-red color. 

Anisole, chlorination with sulfuryl chloride, 47, 23, 49,16 Anisole, /i-a-mcHLORO-, 49,16 Anthranilic acid, diazotization with isoamyl nitrite and trichloroacetic acid, 48,13, IS... 

Fig. 1. Structures of some bilirubin conjugates and nature of the azo derivatives obtained by treatment with diazotized ethyl anthranilate. From Fevery et al. (F5), by kind permission of the Editor of The BiochemicalJoumal.

Diazotized ethyl anthranilate (pH 2.6, 30 BCR minutes, room temperature) ... 

Compernolle, F., Jansen, F. H., and Heirwegh, K. P. M., Mass-spectrometric study of the azopigments obtained from bile pigments with diazotized ethyl anthranilate. Biochem. J. 120, 891-894 (1970). 

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>. 

Diazotization of anthranilamide and its derivatives is the most common and widely exploited reaction for the preparation of 1,2,3-benzo-triazine derivatives. The reasons for this are 3-fold (i) many nuclear substituted anthranilic acid derivatives are readily available (ii) the diazotization reactions generally proceed smoothly and in high yield, and the product triazinones are usually very stable and easily handled and (iii) many 3-substituted l,2,3-benzotriazin-4(3i/)-ones have been found to possess a wide range of pronounced pharmacological activity, while others undergo a number of very interesting chemical transformations, and hence a very large number of these compounds have been prepared. 

Acylhydrazides of anthranilic acid (35, R = NHCOR ) give 3-acylamino-l,2,3-benzotriazin-4(3H)-ones (10, R = NHCOR on treatment with nitrous acid. The triazine hydroxamic acid (40) and its benzo-substituted derivatives are available by diazotization of the corresponding o-aminobenzohydroxamic acids. The pyrido[2,3-e]triazine analog (41) was prepared similarly from 3-aminoisonicotino-hydroxamic acid, but the isomeric 2-aminonicotinohydroxamic acid failed to react under the same conditions to give 42. ... 

When benzyne is generated by aprotic diazotization of anthranilic acid in boiling 1,2-dimethoxyethane in the presence of substituted benzene-2-diazo 1-oxides (o-quinonediazides), dibenzofurans are obtained in moderate yields (Scheme 64). ... 

The thermal decomposition of diazotized anthranilic acid in acetone led to carbazole 328 as well as to 329, benzoic acid, and o-biphenylene. The 329... 

The melting point of the />-toluenesulfonylanthranilic acid is not a good criterion of purity because the />-toluenesulfonic acid salt of anthranilic acid has about the same value. The neutral equivalents are widely different 154 for the salt and 291 for p-toluenesulfonylanthranilic acid. The compound obtained in this preparation gives a negative test for anthranilic acid on diazotization and treatment with alkaline /3-naphthol solution. The probable impurity is the sodium salt of -toluene-sulfonylanthranilic acid. 

Diphenic acid has been prepared by the reduction of diazotized anthranilic acid with cuprous ion,5 Ullman coupling of potassium... 

The two heterocyclic rings of this system (485) were formed upon coupling salts of diazotized anthranilic acid (87JHC227) or diazotized anthranilic acid ester (88MI1) with butenonitriles. 

B. Diazotization of Anthranilic Acid.—To 100 g. (0.73 mole) of anthranilic acid (m.p. 143-1440) in a 1.5-I. beaker arranged for vigorous mechanical stirring and efficient external cooling are added 300 cc. of distilled water and 133 cc. of glacial acetic acid (2.3 moles) (Note 1). A solution of 51 g. of sodium nitrite (0.74 mole) in 200 cc. of distilled water is slowly added from a separatory funnel during about forty minutes (Note 2). 

In almost all samples of commercial anthranilic acid, even though showing the correct melting point, a small amount of insoluble material remains on diazotization. The clear liquor should be removed from this by decantation. 

Diphenic acid was first prepared by oxidizing phenanthrene-quinone with chromic acid.1 Many later workers2 have modified this process in minor details. Vorlander and Meyer 3 were the first to prepare diphenic acid from diazotized anthranilic add and cuprous oxide, but their process is not well adapted to large scale preparation. Inasmuch as pure phenanthrene is now very difficult to obtain in quantity, the present process was devised for relatively large scale operation. 

Lester Friedman and Frauds M. Logullo prepared substituted benzynes by diazotizing substituted anthranilic acid. This is a mild, room-temperature reaction which permits simultaneous reactions of the benzynes with suitable acceptors to prepare halogen. —NO , — ClL. and —OCH3 derivatives. They have also prepared new heterocyclic arynes, such as 3-pyridine from 3-amino-isonicotinic add. 

Carboxy-phenyl] 3(oder l) cyanguanyl -triazen-(l) 2- [Cyanoguanyl-triazeno] -benzoesaure or [2-Carboxy-benzoldiazo] dicyandiamid in Ger), HOOC.C6H4,N N.NH.C-( NH).NH.CN mw 232.20 N 36.20% yel crysts (from MeOH), mp dec ca 98° readily sol in hot ale si sol in benz, eth or chlf insol in w was prepd by treating diazotized anthranilic acid with dicyandiamid in alksoln.Its Silver salt... 

V-Hydroxycarbazole (326) was first postulated (64JOC2808) as an intermediate in the reaction of benzyne with nitrosobenzene, which gave N-phenylcarbazole. Later it was obtained in 1% yield from diazotized anthranilic acid and nitrosobenzene, while tetrahalogenated benzynes,... 

Diphenic acid has been prepared by the reduction of diazotized anthranilic acid with cuprous ion,6 Ullman coupling of potassium o-bromobenzoate,6 and oxidation of phenanthrene or phen-anthrenequinone with various oxidizing agents.7 The latter methods have been reviewed recently.7 The ozonolysis method has also been carried out in solvents 8 that do not react with the zwitterion intermediate. ... 

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