Sodium anthranilate

The reagent consists of a 3 per cent aqueous solution of pure sodium anthranilate. 

Anthranilic acid. Cadmium ( > 100 mg in 150 mL). Add 3 per cent sodium anthranilate solution to the boiling solution (neutral or weakly acid). Filter and wash the precipitate with 50mL of diluted reagent (1 20), then with ethanol. Dry at 105-110 °C and weigh as Cd(C7H602N)2 (Section 11.21). 

Substituted phenacyl anthranilates were prepared by reaction of sodium anthranilate with substituted phenacyl halides in DMF. The phenacyl esters were cyclized in polyphosphoric add or by heating to give the respective substituted 2-aryl-3-hydroxyquinoline-4(l. -ones in high yield <95CCC(60)1357>. 

In this method, a polymer is prepared which has certain struc-tiiral features which can be chemically transformed to dye structures in one or more steps. Perhaps the most common class of dyes that have been so synthesized on a polymer backbone is the azo dyes, which are simply formed by the coupling of a polymeric aryl diazon-ium salt with an activated aromatic system. The former are prepared from polymeric aromatic amines by diazotization. Thus polymers and copolymers of 2,2 -di vinyl benzidine (XVl) have been diazotized and coupled with sodium naphthionate, sodium anthranilate and sulfanilic acid to give polymeric azo dyes which act as pH indicators,... 

Anomerization of carbohydrate derivs. 29, 215 Anthracene s. Sodium/-Anthranils s. 2,1-Benzisoxazoles Anthranol esters 29, 921... 

Required Anthranilic acid, 20 g. anhydrous sodium carbonate, 7 5 g, sodium nitrite, 12 g. concentrated hydrochloric acid, 190 ml. crystalline copper sulphate, 50 g. concentrated ammonia, 85 ml, hydroxylamine hydrochloride, 14-5 g. (or hydroxylamine sulphate, 17-4 g.) acetic acid, 10-20 ml,... 

A) Diazotisation of Anthranilic Acid, Dissolve 20 g. of anthranilic acid in a solution of 7 5 g. of anhydrous sodium carbonate in 200 ml. of water contained in a 400 ml. beaker, (The mixture may be warmed very gently with stirring to obtain a solution more rapidly, and then cooled.) Add slowly 12 g. of sodium nitrite and cool the stirred solution below 10 , Pour this cold solution slowly on to a vigorously stirred mixture of 40 ml, of concentrated hydrochloric acid and 120 g. of crushed ice in a 600 ml. beaker. 

This preparation illustrates the use of dimethyl sulphate to convert a primary amino group into the secondary monomethylamino group, without the methy-lation proceeding to the tertiary dimethylamino stage. The methylation of anthranilic acid is arrested at the monomethylamino stage by using i-i molecular equiN alents of sodium hydroxide and of dimethyl sulphate. The reactions can be considered as ... 

Dissolve 2 g. of anthranilic acid in 12 8 ml. of 5% aqueous sodium hydroxide, or in 16 ml. of A -NaOH solution in a 50 ml. conical flask. (It is essential that the concentration of the hydroxide solution is accurately known.) Add i-6 ml. of dimethyl sulphate, and shake the securely-stoppered flask vigorously. 

Diazotisation. Dissolve 0 2 g. of anthranilic acid in about 4 ml. of dil. HCl and cool in ice-water. To this solution, add slowly about I ml. of cold 20% sodium nitrite. solution and divide the cold diazonium solution thus prepared into two portions A and B. 

The reaction is applicable to the preparation of amines from amides of aliphatic aromatic, aryl-aliphatic and heterocyclic acids. A further example is given in Section IV,170 in connexion with the preparation of anthranilic acid from phthal-imide. It may be mentioned that for aliphatic monoamides containing more than eight carbon atoms aqueous alkaline hypohalite gives poor yields of the amines. Good results are obtained by treatment of the amide (C > 8) in methanol with sodium methoxide and bromine, followed by hydrolysis of the resulting N-alkyl methyl carbamate ... 

Anthranilic acid. This substance, the ortho amino derivative of benzoic acid, may be conveniently prepared by the action of sodium hypobromite (or sodium hypochlorite) solution upon phthalimide in alkaline solution at 80°. The ring in phthalimide is opened by hydrolysis to phthalamidic acid and the latter undergoes the Hofmann reaction (compare Section 111,116) ... 

Phenylglycine-o-carboxylic acid. In a 750 ml. round-bottomed flask, fitted with a reflux condenser, place 14 g. of anthranilic acid (Section IV,170), 10 g. of chloroacetic acid, 20 g. of anhydrous sodium carbonate and 200 ml. of water. Reflux the mixture for. 3 hours, then pour into a beaker, cool, render shghtly acid with concentrated hy dro-chloric acid, and allow to stand overnight. Filter off the crude acid and wash it with water. Recrystalhse from hot water with the aid of a little decolourising carbon, and dry the acid at 100°. The yield of phenyl-glycine-o-carboxyhc acid, m.p. 208°, is 12 g. 

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

Dihydroxyquinazoline (benzoylene urea) has been prepared by fusing urea with anthranilic acid or better from 2-ureidobenzoic acid. It can also be prepared from o-ethoxycarbonylaminobenzoni-trile and sodium methoxide followed by hydrolysis (see 5d). 

Indazoles can be considered as either azaindoles or azaisoindoles depending on the reader s prejudice. Benzydamine (54) represents a drug with this heterocyclic nucleus. Alkylation of the amine of anthranilic acid methyl ester with benzyl chloride in the presence of sodium acetate gives 52. Treatment with nitrous acid leads to the nitrosoamine, which cyclizes spontaneously to the 3-ketoindazole system, 53. This intermediate forms an ether of its enol form on heating the sodium salt with 3-dimethylaminopropyl chloride. There is thus obtained benzydamine (54), a fairly potent nonsteroidal antiinflammatory agent with significant antipyretic and analgesic properties. 

Nucleophilic aromatic substitution of the anthranilic acid derivatives, 72, on ortho-bromonitrobenzene affords the diphenyl-amine, 73. The ester is then saponified and the nitro group reduced to the amine (74). Cyclization of the resulting amino acid by heat affords the lactam (75). Alkylation on the amide nitrogen with 2-dimethylaminoethyl chloride by means of sodium amide affords dibenzepine (76). ... 

Interaction of substituted arenediazonium salts with potassium O. O-diphenylphosphorodithioates gave a series of solid diazonium salts which decomposed explosively when heated dry [10], The unique failure of diazotised anthranilic acid solutions to produce any explosive sulfide derivatives under a variety of conditions has been investigated and discussed [6]. Preparation of diaryl sulfides from interaction of diazonium and thiophenoxide salts led to violent explosions, attributed to presence of some arenediazo sulfide during subsequent distillation of the diaryl sulfides. Precautions are detailed [11]. A safe method of preparation of diaryl sulfides from diazonium tetralluoroborates and sodium benzenethiolate in DMF is now available [12],... 

Benzocyclobutenone was first prepared from 1 -bromobenzocyclobutene by hydrolysis followed by chromium trioxide oxidation.3 More recent procedures involve hydrolysis of 1,1-dichloro- or 1,1-dimethoxybenzocyclobutene which in turn have been obtained through cycloaddition of the appropriate 1,1-disubstituted ethylenes to benzyne generated either from anthranilic acid through diazotization5 6 or from bromobenzene through sodium amide treatment.7.3 Benzocyclobutenone has... 

Reduction of aromatic carboxylic acids to alcohols can be achieved by hydrides and complex hydrides, e.g. lithium aluminum hydride 968], sodium aluminum hydride [55] and sodium bis 2-methoxyethoxy)aluminum hydride [544, 969, 970], and with borane (diborane) [976] prepared from sodium borohydride and boron trifluoride etherate [971, 977] or aluminum chloride [755, 975] in diglyme. Sodium borohydride alone does not reduce free carboxylic acids. Anthranilic acid was reduced to the corresponding alcohol by electroreduction in sulfuric acid at 20-30° in 69-78% yield [979],... 

One of the early steps in an allergic reaction consists in the release of a series of endogenous compounds referred to as mediators from sensitized cells. The finding in the early 1960s that cromolyn sodium, still the only approved drug of this class, blunts this reaction has led to an intense search for additional examples. It is of interest that a relatively simple anthranilic acid derivative has shown mediator-release inhibiting activity. Reaction of 3,4-dimethoxybenzalde-hyde (167) with isatoic anhydride 168 gives the condensation product 169, which, upon hydrolysis, affords tranilast (170) (43]. 

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