5- Methylanthranilate

The first of the two experiments given below illustrates the separation of amino-acids, now an almost classic example of the use of paper chromatography the second illustrates the separation of anthranilic acid and iV-methylanthranilic acid. Both experiments show the micro scale of the separation, and also the fact that a mixture of compounds which are chemically closely similar can be readily separated, and also can be identified by the use of controls. 

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. 

Finally spray the paper with neutral 1% ethanolic ferric chloride solution the methylanthranilic acid spot develops a purple-brown coloration, whereas the anthranilic acid gives only a very faint pink coloration. 

The isolation of the. V-methylanthranilic acid is greatly facilitated by the fact that in cold water it is appreciably less soluble than anthranilic acid, and very much less soluble than A A -dimethylanthranilic acid. 

The iV-methylanthranilic acid rapidly separates. Cool the mixture in ice-water, filter off the acid at the pump, wash thoroughly with water and drain. The crude acid if now dried weighs 1 5 g. and has m.p. 166-170°. 

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. 

Methylanthranilic acid, which has been found as an ester in similar oils, melts at 179°, and forms an acetyl derivative melting at 186°. 

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. 

The key intermediate 2-thioxo-3-phenylquinazohn-4(3H)-one was prepared by adding carbon disulfide and sodium hydroxide solution simultaneously to a vigorously stirred solution of aniline 7 in dimethylsulfoxide over 30 min stirring was then continued for an additional 30 min. Dimethylsulfate was added to the reaction mixture whilst stirring at 5-10°C after which it was stirred for another 2 h and then poured into ice water to obtain a soHd dithiocarbamic acid methylester 6. The compoimd 6 and methylanthranilate 5 when refluxed in ethanol for 18 h yielded the desired 2-thioxo-3-substituted quinazolin-4(3H)-one 4. The product obtained was cycUc and not an open chain thiourea 5a. It was confirmed by its value, high melting point, and its... 

Ferreres, F., Giner, J. M., and Tomas-Barberan, F. A. (1994c). A comparative study of hesperetin and methylanthranilate as markers of the floral origin of citrus honey. /. Sci. Food Agric. 65, 371-372. 

Evidence from nanosecond flash photolysis studies indicates that an oxa-ziridine precursor to the diazoketone is unlikely. Photoelimination of nitrogen is also observed in 4-methyl-1,2,3-benzotriazine 3-oxide and affords 3-methylanthranil a mechanism involving loss of nitrogen from an intermediate oxaziridine has been proposed.74... 

In the first class, different fluorophores were bound to the amino terminus of ferrioxamine B including NBD, Af-methylanthranilic acid (MA) and l-cyanobenz[/]isoindole (CBI) to form 185, 186 and 187, respectively. The NBD-DFO was examined for the determination of Fe(III) under physiological conditions and monitoring the interaction with ferritin and transferrin. 

Two similar syntheses have been reported by Ziegler and co-workers (487) and Kametani et al. (488,489). Reaction of N-methylisatic anhydride (584) with thioacetamide afforded glomerin (60) in 58% yield (487). The other synthetic route is as follows The sulfinamide (585), prepared from N-methylanthranilic anhydride and thionyl chloride, was treated with acetamide and propionamide to afford glomerin (60) and homoglomerin (61), respectively (Scheme 72) (488,489). 

Various 1-(1-naphthyl)-1,2,3-triazoles with electron-withdrawing groups at the 4- and/or 5-pos-itions (e.g. (135)) are synthesized from 1-azidonaphthalene and alkynes <87JCS(P1)413>. l-(Naphthyl)-benzotriazoles (127) are prepared by cycloaddition of the appropriate 1-azidonaphthalenes to benzyne or substituted benzynes, generated from 3-methylanthranilic acid. l-(l-Naphthyl)-naphthotriazole is similarly prepared by cycloaddition to 2,3-dihydronaphthalene. 1,3-Dipolar cycloadditions of 8-azidoquinolinone with benzyne and DMAD give benzotriazoles and triazoles (e.g., (130)), respectively <87JCS(Pi)403>. 

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). 

The main components are limonene (65-75%) and q-terpinene (16-22%). The characteristic feature of mandarin oil is its content of a-sinensal (0.2-0.5%), methyl A-methylanthranilate (0.3-0.6%, which is responsible for fluorescence), and long-chain unsaturated aliphatic aldehydes [369, 370a, 370d, 370e, 381, 394c, 414-421b]. 

Petitgrain oils are obtained by steam distillation of the leaves of citrus trees. The oils derived from the bitter orange tree are the most important. Other petitgrain oils (mandarinier, citronnier, and bergamottier) are less important. Petitgrain oil mandarinier is a source of natural methyl A -methylanthranilate, which is present at a concentration of nearly 50%. Petitgrain oils are essential constituents of eau de cologne. 

Scheme 23.22 Some nitrogen-containing flavour compounds produced by microorganisms, a Methylanthranilate formation from N-methyl methylanthranilate 1 Trametes sp., Polyporus sp. b Different pyrazines produced with microorganisms in optimised media 2 mutant strain from Pseudomonas perolens ATCC 10757 3 Bacillus subtilis, Brevibacterium linens 4 mutant strain of Corynebacterium glutamicum...

Methylanthranilate, which occurs in small quantities (0.5-3 mg L" ) [87] in a large number of blossom essential oils, grapes and citrus oils is mainly used... 

Citrus reticulata Blanco C. reticulata Blanco, var. chachiensis Jiu Hong, Chen Pi (Orange) (external layer of pericarp) Citral, geraniol, linalool, methylanthranilate, stachydrine, putrescine, apyrocatechol, naringin, poncirin, hesperidin, neohespiridin, nobiletin.33 Expectorant, antitussive, treat indigestion, an antiemetic agent. 

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