N-Methylanthranilic acid

Both these acids are colourless, but the spots of each acid on a filter-paper strip show up in ultraviolet light as intense blue fluorescent zones. They can also be detected, but considerably less sensitively, by spraying with ethanolic ferric chloride solution, which gives with N-methylanthranilic acid a purple-brown coloration. 

N-Methylanthranilic acid is very readily prepared (p. 222). Prepare a sample of this acid and recr> stallise it 2 or 3 times from ethanol until it has m.p. 177" and is pure . 

Record the Rp values of the two acids under the above conditions the anthranilic and the N-methylanthranilic acid should have Rp values of 0-28 and 0 55 respectively. 

In the sjmthesis of evodiamine effected by Asahina and Ohta,i N-methylanthranilic acid was converted by ethyl chloroformate into N-methylisatoic anhydride, which, on treatment with 3- -aminoethylindole, furnished 3-/3-o-methylaminobenzoylaminoethylindole (III), and this with ethyl orthoformate at 175-180° gave dZ-evodiamine, m.p. 278°, convertible by boiling alcoholic hydrogen chloride into Zsoevodiamine, m.p. 147°, as shown above. 

B-Chloro-N-methylanthranilic acid Bromoethylamine hydrobromide Calcium carbonate Sodium hydroxide Phosphorus oxychioride... 

A) Preparation of 4-Acetyl-7-Chloro-1,2,3,4-Tetrahydro-1-Methyl-5H-1,4-Bemodiazepin-5-one A mixture of 68.5 g (0.37 mol) of 5-chloro-N-methylanthranilic acid, 51 g (0.51 mol) of calcium carbonate, 76 g (0.37 mol) of bromoethylamine hydrobromide and 2.5 liters of water was stirred and heated under reflux for 3 hours. A solution of 23.4 g (0.26 mol) of anhydrous oxalic acid in 250 ml of water was slowly added to the refluxing mixture. The precipitated calcium oxalate was filtered off, and the filtrate adjusted to pH 7 with concentrated ammonium hydroxide. The filtrate was then concentrated to dryness in vacuo and the residue heated on the steam bath with 400 ml of 6 N ethanolic hydrogen chloride until the residue was crystalline. Filtration gave 122 g of N-(aminoethyl)-5-chloro-N-methylanthranilic acid hydrochloride as a solid. 

Incorporation of anthranilic acid at the N-terminus instead of /3-alanine, led to the amidine (69). Finally, the cyclol (70) was obtained in 33% yield from the analog having N-methylanthranilic acid this reaction also gave the 10-membered cyclotripeptide in 17% yield (84TL5201). 

Daidone and co-workers cyclized the diazonium salt derived from N-pyrazolylbenzamide 173 to obtain, in addition to other products, a small amount of pyrazolodiazocine, 174 (R = Ph) (80JHC1409). Rahman condensed 3-chloro-4-aryl-1,2,4-triazoles with N-methylanthranilic acid to afford triazoles 175 (R = H, Me R = Me). Conversion of this compound to the acid chloride, followed by cyclization with aluminum chloride,... 

A convenient synthesis of quinazolines has been reported, and has been applied to the synthesis of representative alkaloids of the quinazoline group (Scheme 5).27 The procedure depends on the formation of sulphinamide anhydrides (23) from the reaction of anthranilic acids with thionyl chloride and the generation in situ of the iminoketens (24). Addition of the latter to the imine (25) or to 2-piperidone, for example, afforded alkaloid (27). Arborine (26) was prepared similarly from N-methylanthranilic acid application of the method to the synthesis of rutecarpine is described in Chapter 11. 

Baumert, A., Kuzovkina, N. and Groger, D. (1985) Activation of anthranilic acid and N-methylanthranilic acid by cell-free extracts from Ruta graveolens tissue cultures. 

METHYL-o-ANISIDINE see MGO750 p-METHYL ANISOLE see MGPOOO 9-METHYLANTHRACENE see MGP750 METHYL ANTHRANILATE (FCQ see APJ250 N-METHYLANTHRANILIC ACID, METHYL ESTER see MGQ250... 

C]Tryptophan gave inactive alkaloids but tritiated 2,4-dihydroxy-quinoline (34) and its N-methyl derivative were incorporated into (47) (0.009 % and 0.020% respectively) an early route had suggested the derivation of what was essentially (34) from tryptophan. Radioisotope dilution showed the presence of both these quinoline precursors together with iV-acetyl- and N-methyl-anthranilic acid in A. baueri. A satisfactory incorporation of N-methylanthranilic acid into (47) was found in Evodia xanthoxyloides, and this, together with its natural occurrence, indicates that early methylation may be important in the biosynthesis of acridone alkaloids. 

There are a few tetra- and pentacyclic analogues. Benzo analogues of 245 were prepared from pyridine-2,3-dicarboxylic acid anhydride and a tetralin derivative under conditions of the Friedel-Crafts reaction (85JCR(S)338). Pentacyclic compounds 258 (R = H or Me) were prepared from the bis adduct of anthranilic (or N-methylanthranilic) acid to 1,4-benzoquinone, followed by cyclization in concentrated sulfuric acid (55JCS4440 66CB1991). 6-Methylquinoline-5,8-dione dimerized in the presence of ethanolic IV-methyl-cyclohexylamine to 259 in very low yield and the dimerization is interpreted as two base-catalyzed addition reactions and three oxidation steps (71JCS(C)1253). 

Dreyer and Brenner 62) isolated two new quinazoline alkaloids from seed husks of Zanthoxylum arborescens. The major compound, C17H16N2O2 exhibits a blue fluorescence on TLC. In the H-nmr spectrum the downfield aromatic quartet at 8 8.12 (J = 7.1 Hz) and a one-proton triplet at 8 7.8 (J = 7 Hz), each further split (J = 1 Hz) suggest the presence of four adjacent aromatic protons on an ortho-substituted benzene ring. The aromatic quartet farthest downfield at 8 8.12 indicates the presence of a / r/-related carbonyl group. Two two-proton multiplets (8 2.93—4.40) are consistent with the presence of a 2-phenylethyl system. Other nmr data, in light of the mass spectrum, suggest the presence of an N-methylanthranilic acid system. These characteristics could be assembled in two different ways, leading to structures (7) (Chart 1) and (31). C-spectroscopy and synthesis from N-methylisatoic anhydride and 2-phenylethylamine finally allowed elucidation of the structure. The synthetic product, l-methyl-3-(2 -phenylethyl)-lH,3H-quinazolin-2,4-dione (7) was identical with the alkaloid. 

A second alkaloid from the mother liquors of the major constituent, had prominent infrared absorptions at 1700, 1660 and 1620 cm its H-nmr spectrum exhibited many similarities to that of the major component. The aromatic region contained an A2B2 system (8 6.90 and 7.20) as well as signals associated with an N-methylanthranilic acid system. Two three-... 

H-nmr 5 2.53 (3H, s, NMe) and 5.90 (IH, s, C3-H). The structure of (67) was partially revealed by alkaline hydrolysis which yields N-methyl-anthranilic acid and 3,4-dihydro-p-carboline. Boiling alcoholic potassium hydroxide degrades (67) to N-methylanthranilic acid, carbon dioxide and tryptamine. When boiled with alcoholic hydrochloric acid (67) yields optically inactive isoevodiamine [evodiamine hydrate (74)] which can be recyclized with acetic anhydride or oxalic acid to optically inactive evodiamine. (67) can be converted to rutaecarpine via the dry hydrochloride of (74), which, on heating, yields (63). The chemistry of evodiamine has been reviewed by Armarego (6) see also (25, 94, 134, 169). 

Synonyms 2-Methylamino methyl benzoate N-Methylanthranilic acid, methyl ester Methyl methylaminobenzoate Methyl 2-methylaminobenzoate Methyl N-methyl-2-ami nobenzoate... 

Methyl 2-anthranilate. See Methyl anthranilate Methyl anthranilate hydroxycitronellal. See Hydroxycitronellal methyl anthranilate N-Methylanthranilic acid, methyl ester. See Dimethyl anthranilate... 

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