Methyl acetate phenylhydrazine

The l-[(2-aminophenyl)methyl]-l-phenylhydrazines (38), prepared from phenylhydra2dne and 2-nitrobenzyl chloride, readily cyclized with either triethyl orthoacetate or orthopropionate in refluxing glacial acetic acid to give the 4,5-dihydro-3 f-l,3,4-benzotriazepines (39) (ca. yield) (Equation (2)) <85JHC1105>. 

Dissolve 0 3 ml. of glacial acetic acid in 2 ml. of water in a 25 ml. conical flask, and add 0 4 ml. (0 44 g.) of phenylhydrazine. Mix thoroughly to obtain a clear solution of phenylhydrazine acetate and then add 0 2 ml. (0 21 g.) of benzaldehyde. Cork the flask securely and shake the contents vigorously. A yellow crystalline mass of the hydrazone soon begins to separate. Allow to stand for 15 minutes, with occasional shaking, and then filter the solid product at the pump, wash first with very dilute acetic acid and then with water, and finally drain thoroughly. Recrystallise the material from rectified or methylated spirit, the benzaldehyde phenylhydrazone being thus obtained in fine colourless needles, m.p. 157 yield, 0 4 g. 

Mix 6 2 ml. (6 4 g.) of pure ethyl acetoacetate and 5 ml. of pure phenylhydrazine in an evaporating-basin of about 75 ml. capacity, add 0 5 ml. of acetic acid and then heat the mixture on a briskly boiling water-bath (preferably in a fume-cupboard) for I hour, occasionally stirring the mixture with a short glass rod. Then allow the heavy yellow syrup to cool somewhat, add 30-40 ml. of ether, and stir the mixture vigorously the syrup may now dissolve and the solution shortly afterwards deposit the crystalline pyrazolone, or at lower temperatures the syrup may solidify directly. Note. If the laboratory has been inoculated by previous preparations, the syrup may solidify whilst still on the water-bath in this case the solid product when cold must be chipped out of the basin, and ground in a mortar with the ether.) Now filter the product at the pump, and wash the solid material thoroughly with ether. Recrystallise the product from a small quantity of a mixture of equal volumes of water and ethanol. The methyl-phenyl-pyrazolone is obtained... 

Dissolve 0-2 g. of fructose in 10 ml. of water, add 0-6 g. of cw-methyl-phenylhydrazine and sufficient rectified spirit to give a clear solution. Since the fructose may not be quite pure, warm the mixture slightly, allow to stand, preferably overnight, so that any insoluble hydrazones may separate if present, remove them by filtration. Add 4 ml. of 50 per cent, acetic acid to the filtrate it will become yellow in colour. Heat the solution on a water bath for 5-10 minutes, and allow to stand in the dark until crystalUsation is complete it may be necessary to scratch the walls of the vessel to induce crystalUsation. Filter the crystals and wash with water, followed by a little ether. RecrystaUise the orange-coloured methylphenylosazone from benzene m.p. 152°. 

A solution of 4% aq. H2SO4, (301) was heated to 50"C over 30-60 min. Nitrogen was bubbled through the solution during this time. 4-(Cyano-methyl)phenylhydrazine hydrochloride (1080g, 4.77 mol) was added as a solid to the heated mixture. After it had dissolved, A,A-dimethyl-4,4-dimethoxy-butanamine (965 g, 5.98 mol) was added over a period of 30 min. The mixture was then heated at reflux for 2 h. The reaction mixture was cooled and diluted with portions of 30%o aq. NH4OH (21 total) over 0.5 h at a rate to maintain the temperature at 25-30°C. The product was then extracted into isopropyl acetate (3 x 101). The solution was concentrated to 31 which led to a precipitate which was isolated by filtration and washed with cold isopropyl acetate to give 827.4 g (76%) of product. 

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). 

Turanose Phenylosazone. A mixture of 4 g. of turanose, 2 ec. of water, and 1 co. of phenylhydrazine was warmed on the steam-bath until solution was complete. To the cooled solution was added 3.5 cc. of phenylhydrazine and 4 cc. of glacial acetic acid, and the mixture returned to the steam-bath for one hour. At the expiration of this time, 40 cc. of warm 60% alcohol was added and, upon cooling, a rapid crystallization of the osazone occurred. The osazone was recovered by filtration and washed with absolute alcohol followed by ether to yield 4.2 g. (69%) of lemon-yellow needles. The osazone is soluble in hot water and separates on cooling as jelly-like particles, but water is not a satisfactory solvent for its purification. It was recrystallized from 15 parts of 95% alcohol with good recovery, as needles which melted with decomposition at 200-205° and rotated [ ]d +24.5° - +33.0° (24 hours, constant value c, 0.82) in a mixture of 4 parts of pyridine, by volume, and 6 parts of absolute ethyl alcohol. In methyl cellosolve (ethylene glycol monomethyl ether) solution it rotated C< 3d" + 44.3°— + 48.5° (24 hours, constant value c, 0.80). 

To 21.6 g phenylhydrazine dissolved in 300 ml 0.3N sulfuric acid, add 9.8 g concentrated sulfuric acid. Add dropwise with stirring and heating at 100°, 11.6 g methyl-beta-formyl-propionate in 300 ml 0.3 N sulfuric acid and continue heating six hours to get 14 g indole-3-acetic acid. Convert to the dialkyltryptamine as already described. 

Indole-3-Acetic Acid. Dissolve 21.6 g of phenylhydrazine in 300 ml 0.3 N sulfuric acid. To this solution add 9.8 g of coned sulfuric acid. With stirring and heating to 100°, add dropwise 11.6 g of methyl-beta-formyl-propionate in 300 ml of 0.3 N sulfuric acid. Continue the heating and gentle stirring for 6 hours to get about 14 g of indole-3-acetic acid. This is from CA, 72, 66815 (1970). 

Pyrazolo[l,5-fl]pyrimidine derivative 222, when treated with water, partially changes into 223. This reaction is assumed to proceed via attack of base at C-7 (81CPB1548 81JHC163). The C-6=C-7 double bond in 222 adds a variety of electrophiles (81CPB1548 81JHC163 83H(22)1913). Thus, treatment of 222 with acetic acid and water at 70°C affords 8-carbeth-oxy-3-substituted-7-methyl-6W-pyrazolo[ 1,5-a]-1,3-diazepin-6-one (224). Compound 222 reacts with phenylhydrazine to yield the pyrazolo[3,4-6,7]pyrazolo[l,5-n]pyrimidine derivative 225. The double bond in 222 also adds diazoalkanes to yield the pyrazolo[l,5-a]pyrimidine derivatives 226 (81CPB1548 81JHC163 83H(22)1913). 

Manninotriose (0.8 g.) was heated with 1.44 g. of phenylhydrazine hydrochloride, 0.22 g. of o-phenylenediamine, and 0.5 g. of glacial acetic acid in 20 ml. of water at 100° in a stoppered tube. After 3 hours, the reaction mixture was cooled and neutralized with 40 ml. of 0.5 N sodium hydroxide. The trisaccharide flavazole was isolated by fractional extraction of the solution with ether (to remove organic bases and colored impurities), ethyl methyl ketone (to remove traces of monosaccharide and disaccharide flavazoles, as well as other colored impurities), and butanol (which extracted the trisaccharide flavazole). Each step in the fractionation process was followed by... 

The reaction of 2-thiovioluric acid (69) with hydrazine hydrate in boiling ethanol afforded triazolopyrimidine derivative 70, but in boiling acetic acid yielded N-acetyltriazolo[4,5-d]pyrimidine derivative 71. In the same manner, the N-phenyl and A-methyl-l, 2,3-triazolo derivatives 72 and 73 were obtained through the condensation of 69 with phenylhydrazine and with methylhydrazine, respectively (91MI1) (Scheme 13). 

Color reactions Boric acid (hydroxyquinones). Dimethylaminobenzaldehyde (pyrroles). Ferric chloride (enols, phenols). Haloform test. Phenylhydrazine (Porter-Silber reaction). Sulfoacetic acid (Liebermann-Burchard test). Tetranitromethane (unsaturation). Condensation catalysts /3-Alanine. Ammonium acetate (formate). Ammonium nitrate. Benzyltrimethylammonium chloride. Boric acid. Boron trilluoride. Calcium hydride. Cesium fluoride. Glycine. Ion-exchange resins. Lead oxide. Lithium amide. Mercuric cyanide. 3-Methyl-l-ethyl-2-phosphoiene-l-oxlde. 3-Methyl-1-phenyi-3-phoipholene-1-oxide. Oxalic acid. Perchloric acid. Piperidine. Potaiaium r-butoxIde. Potassium fluoride. Potassium... 

Heterocycles Acetylacetone. N-Aminophthalimide. Boron trichloride. Dichloro-formoxime. Oicyanodiamide. Dicyclohexylcarbodiimide. Dietboxymethyl acetate. Diethyl oxalate. Diketene. Dimethylformaniide diethylacetal. Diphenyldiazomethene. Ethyl ethoxy-methylenecyanoacetate. Formaldehyde. Formamide. Formamidine acetate. Formic acid. Glyoxal. Hydrazine. Hydrazoic acid. Hydroxylamine. Hydroxylamine-O-sulfonic acid. Methyl vinyl ketone. o-Phenylenediamine. Phenylhydrazine. Phosphorus pentasullide. Piperidine. Folyphosphoric acid. Potassium diazomethanedisulfonate. Sodium ethoxide. Sodium nitrite. Sodium thiocyanate. Tetracyanoethylene. Thiosemicarbozide. Thiourea. Triethyl orthoformate. Tris-formaminomethane. Trityl perchlorate. Urea. Vinyl triphenyl-phosphonium bromide. 

Synthesis of 4-amino-2-pyrazolin-5-ones is usually achieved by treatment of an a-amido-/3-aldehydo- or /9-ketoester with hydrazines according to the classical method for preparation of 2-pyrazolin-5-ones. Variants on this procedure consist of using an a-amidoester which has /9-substituents whose reaction is equivalent to that of a /9-carbonyl substituent. Such compounds are D-benzylpenicilloic acid a-methyl ester,1027 ethyl phenylpenaldate243 and the acetal of an a-amido-/9-formyl ester.59,243 Cornforth has isomerized 2-phenyl-4-hydrazino-methylidyneoxazolidone to 4-benzamido-2-pyrazolin-5-one. The same compound was obtained by treatment of 1-ethoxyvinyl-2-phenyl-oxazolidone with phenylhydrazine.319... 

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