Hydrazine, 1-Methyl-1-phenyl

For the mechanism of this reaction, see Robinson and Robinson,1918, H3i 639 1924, 145, 827.) The reaction is of wide application for example, the use of methyl-phenyl-hydrazine, CsH5(CHj)> -iN H, in the above reaction gives i-methyl-2-phenylindole, whereas pyruvic acid, CH CO COOH, when converted to its phenylhydrazone and then indolised, gives indole-2-carboxylic... 

Katritzky and co-workers studied the mechanism of this reaction in detail. His work involved a NMR study of 16 reactions of methyl-, phenyl-, 1,2-dimethyl-, and l-methyl-2-phenylhydrazine with /3-keto esters. In many cases starting materials, intermediates, and products were detected simultaneously. Most reactions proceed by nucleophilic addition of the less hindered hydrazine nitrogen atom to the keto carbon of the keto ester. For example, the pathway given in Scheme 3 for the reaction of methyl 3-oxobutanoate 9 with methyl- or phenyUiydrazine 2 (R = Me or Ph) was found to be dominant. The initially formed addition product 10 dehydrates to hydrazone 11, which then isomerizes to hydrazone 12. Intermediate 12 then cyclizes to pyrazol-3-one 13, which tautomerizes to the kinetically more stable pyrazol-3-otie 14 [87JCS(P2)969]. 

Dimethyl-I,l -biphenyl has been prepared by a wide variety of procedures, but few of these are of any practical synthetic utility Classical radical biarjl syntheses such as the Gomberg reaction or the thermal decomposition of diaroyl peroxides give complex mixtures of products m which 4,4 dimethyl-l.l -biphenyl is a minor constituent A radical process maj also be involved in the formation of 4,4 dimethyl-1, l -biphenyl (13%) by treatment of 4-bromotoluene with hydrazine hydrate 5 4,4 -Dimethyl-l,l -biphenyl has been obtained in moderate to good yield (68-89%) by treatment of either dichlorobis(4-methyl phenyl)tellurium or l,l -tellurobis(4-methylbenzene) with degassed Raney nickel in 2 methoxyethyl ether 6... 

In saurer Losung wird Methyl-phenyl-nitrosamin an Blei zu N-Methyl-N-phenyl-hydra-zin reduziert (80% d.Th.)4. Analog verhalten sich Dialkyl-nitrosamine ( — 0,9 V, bis 82% d.Th.) in alkoholischer Salzsaure5. Zur Hcrstellung von N,N-Dimethyl-hydrazin aus dem N-Nitroso-Derivat s.ds. Handb., Bd. X/2, S. 42 (zuN,N-Dialkyl-hydrazinen s.Lit.6). 

Nitro-2-hydrazinotoluene, It golden-yel or orn-yel ndls with a violet tinge (from ale), mp 179-80° diffc sol in hot ale xylene was prepd by heating the K salt of N-[4-Nitro-2-methyl-phenyl] -hydrazine-N,N -disul-fonic acid with coned HC1 (Refs 1 3) 3-Nitro-4-hydmzinotoluene, dk-red ndls (from eth), mp 110—11° v sol in acet sol in eth, chlf benz si sol in petr eth was prepd by diazotizing 2-nitro-4-methylaniline with Zn chloride HC1. Its Hydrochloride salt, C7H9N3O2+HCI, orn-red ndls or plates (from w) dec at 190-91° (Refs 2 4)... 

The stereoselective synthesis of both trans-88 and cis isomers 89 of pyrazo-lines was reported in [62] (Scheme 2.22). The configuration of the reaction products depends on the conditions of the cyclocondensation involving unsaturated ketones 87 and methyl(phenyl)hydrazines or (thio)semicarbazide. In boiling pyridine the treatment yields only raws-pyrazolines, while reaction in ethanol with catalytic amounts of hydrochloric acid leads mainly to the cis... 

Some new approaches to the synthesis of pyridazino[3,4-c]pyridazines have been described. The pyrazolopyridazino[3,4-c]pyridazines (13 R = OMe, Me) and (14) are prepared by the reaction of /i-aroyl-a-(3-methyl-5(4//)-oxo-l-phenyl-4-pyrazolyl)propionic acid (12) with hydrazine or phenyl-hydrazine in butanol (Scheme 2) <90IJC(B)72>. 

Aus Methyl-phenyl-phosphinsaure-chlorid kann unter den gleichen Bedingungen das ent-sprechende Ilydrazid nicht isoliert werden. Die direkte Umsetzung von zwei Molen Me-thyl-phenyl-phosphinsaure-chlorid und drei Molen Hydrazin zum l,2-Bis-[methyl-phe-nyl-phosphoryl]-hydrazin (Schmp. 253—255°) gelingt dagegen zu 76 bzw. 65%765 767 ... 

Die Hydrazinolyse von Phosphinsaure-estern ist stark Iosungsmittelabhangig. So reagiert z.B. Methyl-phenyl-phosphinsaure-methylester in Ether nicht mit Hydrazin, in Methanol dagegen erhalt man das erwartete Methyl-phenyl-phosphinsdure-hydrazid zu 62% 786. 

Amino-3-methoxy-2-(3-pyridyl-methylen-amino)-E15/2, 1809 [(NC)2CH-NH2 + R-CHO] Azetidin 3-Azido-4-(4-methyl-phenyl)-2-oxo- E16b, 371 (Nj-C-CO-Cl + Imin) Furazan 4-(Anilinomethylen-amino)-3-methyl- E8c, 673 (NH2 -> N=CH —NH —Ar) Hydrazin l,2-Bis-[2-pyrrylme-thylen]- -1-oxid X/2, 121 1 H-(Imidazo 1,2-a]-l,3,5-benzotriaze-pin), 10-Hydroxy-2,3-dihydro E9d, 476 [1 -(2-NH2 — Ar) — 2-imino — imidazolidin/COCl2) Imidazo[4,5-f indazol 5,6-Dimethyl-... 

Benzopyrone reagieren analog zu (2-Hydroxy-phenyl)-1 H-pyrazolen,185 1191,1364, i365, 1377 [tabellarische Zusammenstellung s. Bd.Vl/lc, S. 397/398 sowie S. 453, 1460 (1976) und Bd.X/2, S.6798 (1968)], 2-Methyl-4-thiono-4H-l-benzopyran gibt mit Hydrazin bzw. Phenyl-hydrazin 3(5)-(2-Hydroxy-phenyl)-5(3)-methyl- bzw. 5-(2-Hydroxy-phenyl)-3-methyl-l-phe-nyl-lH-pyrazol [s. Bd. IX, S. 725 (1955)]. 3-Formyl-4H-l-benzopyrone geben mit Phenyl-hydr-azin 4-(2-Hydroxy-benzoyl)- -phenyl -1 H-pyrazole1186 ... 

C HkN, Benzyliden-[methyl-phenyl> methylen]-hydrazin 7, 2W. Benzyliden-[4-methyl-benzyIiden] hydrazin 7, m 1159. 

Similar levels of regiocontrol were observed in the condensation of A- N,N-diethylamino)-l,l,l-triflnoro-3-phenyl-3-buten-2-one and methyl-, phenyl-, and p-nitrophenyl hydrazines in acetonitrile (58-83 % yield). With methylhydrazine, the major isomer was the 3-triflnoromethyl-l-methyl-4-phenylpyrazole (ratio 2.5 1), whereas with phenylhydrazine, the 5-trifluromethylpyrazole analogue was the predominant component in a 11 1 mixture of isomers. This regioisomer was the only product observed when p-nitrophenylhydrazine was used [38]. 

When ethyl acetoacetate is warmed with an equivalent quantity of phenyl-hydrazine, the compound (I), which is not a true hydrazone, is first formed this undergoes ring formation (II) with loss of ethyl alcohol upon further heating. The product (II) is N or l-phenyl-3-methyl-5-pyrazolone. 

Phenyl-3,6-dihydro-l,3,4-oxadiazin-2-one (50) is a high temperature blowing agent used primarily for polycarbonates (qv). It is prepared by the reaction of a-hydroxyacetophenone and methyl carbazate (52), made from hydrazine and dimethyl carbonate (175) ... 

Methyl>1,5-dlphsnyl-1,2,4-triazole (3), A mixture of phenyl hydrazine hydrochlonde 1 (14 5 g, 0.11 moQ, N-acetytbenzamide 2 (16.5 g, 0.1 moQ and NaOAc (10 g, 0.12 mol) in AcOH (30 mL) was refluxed for 10 h. The product was made elkaline wNaOH solution and extracted with Et20 Evaporation gave a pale yellow oil which slowly sofidiTied, mp 80-61 0. Recrystallization from 90% EtOH and petroleum ether afforded IS 4 g of 3 (76%). 

Deactivation (weak) from the adjoining ring does not prevent facile disubstitution of 4-methyl- and 4-phenyl-2,7-dichloro-1,8-naphthyridines wdth alkoxides (65°, 30 min), p-phenetidine (ca. 200°, 2 hr), hydrazine hydrate (100°, 8 hr), or diethylaminoethylmer-captide (in xylene, 145°, 24 hr) mono-substitution has not been reported. Nor does stronger deactivation prevent easy 2-oxonation of 5,7-dimethoxy-l-methylnaphthyridinium iodide wdth alkaline ferricyanide via hydroxide ion attack adjacent to the positive charge and loss of hydride ion by oxidation. 

Condensation of ethyl acetoacetate with phenyl hydrazine gives the pyrazolone, 58. Methylation by means of methyl iodide affords the prototype of this series, antipyrine (59). Reaction of that compound with nitrous acid gives the product of substitution at the only available position, the nitroso derivative (60) reduction affords another antiinflammatory agent, aminopyrine (61). Reductive alkylation of 61 with acetone in the presence of hydrogen and platinum gives isopyrine (62). Acylation of 61 with the acid chloride from nicotinic acid affords nifenazone (63). Acylation of 61 with 2-chloropropionyl chloride gives the amide, 64 displacement of the halogen with dimethylamine leads to aminopropylon (65). ... 

Aeridin laBt sich dureh Phenyl-hydrazin in DMF (5 Stdn. 130°) in 72%iger Ausbeute zu 9,9 -Bi-acridanyl reduzieren. N-Methyl-acridiniumjodid liefert entspreehend (30 Min. Koehen in Athanol od. Erhitzen auf 110° in DMF) JO, 10 -Dimethyl-9,9 -bi-acridanyl (73 bzw. 88% d.Th.)11. 

Ethyl formate34,52 or orthoformate5 3,54 reacts with two equivalents of phenylhydrazine to yield 1,5-diphenylformazan (11) the reaction takes place under acidic conditions and involves an oxidation. Under basic conditions, ethyl nitrate reacts at the methylene position to yield 3-methyl-1,5-diphenylformazan (37) which can also be obtained from the reaction of phenyl-azoethane (38) with isoamyl nitrite (Scheme 4).8,68 Aryl hydrazines react with a variety of s-triazines (39) to yield 1,5-diaryl formazans with hydrogen, methyl, or phenyl groups in the 3-position as in 40 (Eq. 6).56 Hydrazines have also been reported to react with benzotrichloride55,658 and sym-diamino tetrazine659 to yield formazans. 

Refluxing of hydrazine 60 in acetic acid in the presence of sodium acetate resulted in the formation of 6-methyl-3-oxo-8-phenyl-3,4-dihydro-2/7-pyrimido[6,l-r-][l,2,4]triazine-9-carbonitrile 61 in good yield <1997IJB269> (Equation 2). 

The synthetically versatile 6-amino-7-cyano-l,4-dihydro-3-methyl-l-phenyl-4-thioxothiopyrano[4,3-c]pyrazole 107 has been used for the synthesis of several bicyclic and tricyclic systems. For example, reaction with hydrazine gives 108, which can be used to generate tricycles 109-111 (Scheme 8) <2002H(57)1121>. 

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