Excess Of Hydrazine Hydrate Research Articles

Pyrazolo‐Fused Quinoline Analogues: Synthesis of 1H‐Pyrazolo[3,4‐b]quinolines and 3‐Amino‐1H‐pyrazolo[3,4‐b]quinolines from 3‐Formyl and 3‐Cyano‐2‐chloroquinolines.

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Termolecular one-pot synthesis of symmetrical azines of 4-acetyl-3-arylsydnones. Hydrazone and azine derivatives of 4-acetyl-3-arylsydnones, their spectral characterization and biological properties

Hydrazones of 4-acetyl-3-arylsydnones (2a-o) were prepared by heating 4-acetyl-3-arylsydnones (1α-o) with excess of hydrazine hydrate and the corresponding symmetrical azines (3a-o) were obtained by a termolecular reaction of 4-acetyl-3-arylsydnones with hydrazine hydrate (2: 1 ratio). Hydrazones and azines were screened for their antimicrobial activity and few of these compounds exhibit inhibitory action more than the reference drugs used.

2‐Acylamino‐3‐chloroacrylonitriles, Promising Reagents for Heterocyclization.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of some new azo pyrazolo[1,5- a]pyrimidine-thieno[2,3- b]pyridine derivatives and their application as disperse dyes

The 3-amino-4,6-disubstituted-thieno[2,3- b]pyridines were diazotized and coupled with 3-aminocrotononitrile to give the 3-(2-hydrozone-3-ketimino-butyronitrile)-4,6-disubstituted-thieno[2,3- b]pyridines which can react with 85% excess hydrazine hydrate to afford the corresponding 3-(5-amino-3-methyl-pyrazol-4-yl)-azo-4,6-disubstituted-thieno[2,3- b]pyridines. The 3-(2-methyl-5,7-disubstituted-pyrazolo[1,5- a]pyrimidine-3-yl)azo-4,6-disubstituted-thieno[2,3- b]pyridine dyes were obtained by the cyclocondensation reaction of 3-(5-amino-3-methyl-pyrazol-4-yl)-azo-4,6-disubstituted-thieno[2,3- b]pyridines with the appropriate 1,3-diketones under acidic condition. The dyes were applied to polyester fibers and their spectral characteristics and fastness properties measured.

2-Acylamino-3-chloroacrylonitriles, Promising Reagents for Heterocyclization

2-Acylamino-3-chloroacrylonitriles prepared by treating available N-(1,2,2-trichloroethyl)amides of carboxylic acids with sodium cyanide readily undergo cyclization in the presence of excess hydrazine hydrate. The cyclization products, 5-amino-4-acylaminopyrazoles, were applied to the synthesis of new imidazo[4,5-c]pyrazole and pyrazolo[1,5-a]pyrimidine derivatives.

Stereoselective ring opening of dimethyl 5-aryl-2,3-dihydro-3,3 dimethyl-1-oxo-1H,5H-pyrazolo[1,2–a]pyrazole-6,7-dicarboxylates with hydrazine hydrate. Synthesis of rel-(4'R,5'S)-3-[5-aryl-3,4bis (hydrazino-carbonyl)]-4,5-dihydro-1H-pyrazol-1-yl)-3-methylbutanohydrazides

Reactions of dimethyl 5-aryl-2,3-dihydro-3,3-dimethyl-1-oxo-1H,5H-pyrazolo[1,2–a]pyrazole6,7-dicarboxylates 3a–e with excess of hydrazine hydrate gave propanohydrazides 5a–e in 70– 99% yields. The ring opening of pyrazolo[1,2–a]pyrazole-6,7-dicarboxylates 3a–e proceeded stereoselectively, furnishing the rel-(4'R,5'S)-isomers of 3-[5-aryl-3,4-bis(hydrazinocarbonyl)4,5-dihydro-1H-pyrazol-1-yl)-3-methyl-butanohydrazides 5a–e. The X–ray structure of 5a was determined.

Synthesis and Transformations of 4-Phosphorylated 2-Alkyl(aryl)-5-hydrazinooxazoles

Treatment of 1-phosphorylated 2,2-dichloroethenylcarboxamides with excess hydrazine hydrate gives in high yields phosphorylated derivatives of 2-alkyl(aryl)-5-hydrazinooxazoles containing the P(O)(OCH3)2, P(O)(OC2H5)2, and P+(C6H5)3ClO4- groups in the 4-position of the ring. The presence of the hydrazine group in these oxazole derivatives was confirmed not only by the spectral data, but also by the reactions with p-toluic aldehyde, p-toluic chloride, and phenyl isothiocyanate.

Recyclization of 2-Aryl-4-cyano-5-hydrazinooxazoles

The available 2-benzoylamino-3,3-dichloroacrylonitrile and its analogs when treated with excess hydrazine hydrate convert to 2-aryl-4-cyano-5-hydrazinooxazoles. The products are fairly stable in usual conditions but undergo recyclization on heating in acetic acid to give previously unknown derivatives of 2-methyl-1,3,4-oxadiazole with a 5-acylamino(carbamoyl)methyl substituent, whose structure was established by spectroscopy and X-ray diffraction. An important role in this complex transformation is probably played by prototropic forms of 4-cyano-5-hydrazinooxazoles, viz. hydrazones of substituted 2-oxazolin-5-ones which are not aromatic and thus can be cleaved with acetic acid and then recyclize.

Multiple-Batch, Wolff−Kishner Reduction Based on Azeotropic Distillation Using Diethylene Glycol

The Huang−Minlon (Wolff−Kishner) procedure for deoxygenating aldehydes and ketones is improved by recycling excess hydrazine hydrate instead of distilling to increase the reaction temperature. This procedural change provides lower reaction and distillation temperatures and a short reaction time. It is applicable to those examples which are compatible with a refluxing mixture of diethylene glycol, hydrazine hydrate, and alkali and yield a product forming an azeotropic bilayer with diethylene glycol and hydrazine hydrate. The apparatus essential to these operational changes is described. Multibatch runs reusing reagents (alkali, diethylene glycol, and some retained hydrazine hydrate) show that high yields and product purity remain unchanged throughout this repetitive process and that accumulation of nonvolatile residue is minimal over a series of multiple runs applied to 2‘-acetonaphthone and dimethoxybenzaldehydes. This suggests that a continuous process, utilizing these techniques, could be developed.

A simple one step synthesis of new 3,5‐disubstituted‐4‐amino‐1,2,4‐triazoles

AbstractA number of symmetrically 3,5‐disubstituted 4‐amino‐1,2,4‐triazoles have been prepared by the reaction of aromatic nitriles with hydrazine dihydrochloride or sulfate with an excess of hydrazine hydrate in ethyl ene or diethylene glycol under a nitrogen atmosphere. The structures of the new triazoles derivatives were confirmed by analytical and spectral data.

Novel syntheses of symmetrical 2,5-diaryl-1,3,4-oxadiazoles and 1,4-phenylenebis-1,3,4-oxadiazoles

The reactions of trichloromethylarenes with excess hydrazine hydrate in ethanol gives symmetrical 2,5-diaryl-1,3,4-oxadiazoles in 68–96% yields. The reaction of 1,4-bis(trichloromethyl)benzene with acylhydrazines in an ethanol-pyridine mixture gives the corresponding substituted or unsubstituted 1,4-phenylenebis-1,3,4-oxadiazoles in 35–51% yields. The mass spectra of 2,5-diaryl-1,3,4-oxadiazoles and 1,4-phenylenebis-1,3,4-oxadiazoles were studied.

Synthesis of polycyclic pyridazinediones as chemiluminescent compounds

AbstractReactions of 1,3‐disubstituted 5‐aminopyrazole‐4‐carbonitrile derivatives 3a‐o with dimethyl acetylenedicarboxylate in the presence of potassium carbonate in dimethyl sulfoxide gave the corresponding dimethyl 1,3‐disubstituted pyrazolo[3,4‐b]pyridine‐5,6‐dicarboxylates 4a‐o which were allowed to react with excess hydrazine hydrate under ethanol refluxing conditions followed by heating at 250‐300° to give 1,3‐disubstituted 4‐amino‐1H‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyridazine‐5,8(6H,7H)‐diones 7a‐s in good yields. Similarly, 1,3‐disubstituted 4‐hydroxy‐1H‐pyrazolo[4′3′:5,6]pyrido[2,3‐d]pyridazine‐5,8(6H,7H)‐diones 10a‐c were obtained from alkyl 1,3‐disubstituted 5‐aminopyrazole‐4‐carboxylates 8a‐c. These tricyclic pyridazine derivatives were alternatively synthesized from 4‐hydroxypyrrolo[3,4‐e]pyrazolo[3,4‐b]pyridine‐5,7‐diones 13a‐c prepared by reactions of 5‐aminopyrazoles (8e‐g) with methyl 1‐methyl‐4‐methylthio‐2,5‐dioxo‐1H‐pyrrole‐3‐carboxylate (11a) followed by the Gould/Jacobs reaction.1‐Methyl‐4‐methylthio‐2,5‐dioxo‐1H‐pyrrole‐3‐carbonitrile smoothly reacted with 2‐aminobenzimidazoles to give the corresponding 5‐amino‐3‐methyl‐1H‐pyrrolo[3′4′:4,5]pyrimido[1,2‐a]benzimidazole‐1,3(2H)‐diones 16a‐e, which were readily converted to the desired 12‐aminopyridazino[4′,5′:4,5]pyrimido‐[1,2‐a]benzimidazole‐1,4(2H,3H)‐diones 17a‐e in good yields. Other pyridazinopyrimidine derivatives were also obtained by the reaction of the corresponding 2‐aminoheterocycles with the maleimide in good yields.Substituted anilines reacted 11b in refluxing methanol to give the corresponding methyl 4‐phenylamino‐1‐methyl‐2,5‐dioxo‐1H‐pyrrole‐3‐carboxylates 25a‐e which were converted in good yields to 2‐methylpyrrolo[3,4‐b]quinoline derivatives 26a‐e by heating in diphenyl ether. Reaction of 26a‐c with hydrazine hydrate gave 10‐hydroxypyridazino[4,5‐b]quinoline‐1,4(2H,3H)‐diones 27a‐e in good yields. The desired 10‐aminopyridazino[4,5‐b]pyridazine‐1,4(2H,3H)‐diones 30a‐e were obtained in good yields by the chlorination of 4a‐e with phosphorus oxychloride followed by aminolysis with 28% ammonium hydroxide.Some pyridazino[4,5‐a][2.2.3]cyclazine‐1,4(2H,3H)‐diones 37a,b as luminescent compounds were synthesized via several steps from indolizine derivatives. The key intermediates, dimethyl 6‐dimethylamino[2.2.3]cyclazine‐1,2‐dicarboxylates 34, 36, were synthesized by the [8 + 2] cycloaddition reaction of the corresponding 7‐dimethylaminoindolizines 33, 35 with dimethyl acetylenedicarboxylate in the presence of Pd‐C in refluxing toluene.Some were found to be more efficient than luminol in light production. 4‐Amino‐3‐methylsufonyl‐1‐phenyl‐1H‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyridazine‐5,8(6H,7H)‐dione (7r), 10‐hydroxypyridazino[4,5‐b]‐quinoline‐1,4(2H,3H)‐diones 27a‐e, and 10‐aminopyridazino[4,5‐b]quinoline‐1,4(2H,3H)‐diones 30a‐e showed the greatest chemiluminescence intensity in the presence of hydrogen peroxide peroxidase in a solution of phosphate buffer at pH 8.0.

An efficient synthesis of symmetrical 2,5-diaryl-1,3,4-oxadiazoles

The interaction of trichloromethylarenes with excess hydrazine hydrate in alcohols leads to symmetrical 2,5-diaryl-1,3,4-oxadiazoles in 68–98% yields.

Synthesis of Unsymmetrical 5,5'-Disubstituted 2,2'-Bipyridines(1).

The preparation of unsymmetrical 6,6′-disubstituted 2,2′-bipyridines has generally occurred by the stepwise mono-N-oxidation,2 followed by a Boekelheide-type rearrangement3 or by a coupling of different pyridine precursors;4 both procedures are plagued with difficulties. It was, however, demonstrated5 that, in THF at -60 °C with 1 equiv of butyllithium, 6,6′-bis(hydroxymethyl)-2,2′bipyridine2 was transformed to the monoalkoxide, which was trapped as the monomesylate in an overall 96% yield. This procedure takes advantage of the different solubility characteristics of the intermediates vs the starting material; this monolithium alkoxide is insoluble under these specific reaction conditions. Application of this general procedure was used6 to afford 6-(bromomethyl)-6′-(hydroxymethyl)-2,2′-bipyridine, which was subsequently converted to functionalized oligobipyridines. In that we needed unsymmetrical 5,5′-disubstituted 2,2′-bipyridines for the synthesis of specifically located binding loci within dendrons, we herein describe the use of similar solubility differences of the intermediate(s) to prepare 5′-amino2,2′-bipyridine-5-carboxylic acid in excellent overall yield from the symmetrical diethyl 2,2′-bipyridine-5,5′-dicarboxylate. The synthesis of 5,5′-diamino-2,2′-bipyridine from diethyl 2,2′-bipyridine-5,5′-dicarboxylate (2) had been previously reported by Whittle.7 The desired diester 2 was prepared by refluxing neat ethyl nicotinate 1 with palladium on charcoal for 6 days under a partial vacuum; the catalyst and starting ester were removed and recycled (Scheme 1). Diester 2 was isolated in ca. 35% yield on the first cycle, and its simple NMR spectra supported the structure. By taking advantage of the low solubility of carbohydrazides, the exclusive formation of the monocarbohydrazide 3 was achieved by the use of approximately 1.5 equiv of hydrazine and by adjusting either the polarity of the solvent system (ethanol/toluene) or the reaction temperature (80 °C). The monocarbohydrazide 3 precipitated under these conditions and was obtained in 85% yield. Although 3 is nearly insoluble in many organic solvent, its 1H NMR spectrum in DMSO clearly showed two doublets (J ) 2 Hz) at δ 9.1 and 9.2 for the two different 6,6′-pyH, respectively, confirming the unsymmetrical substitution pattern. Treatment of 2 with excess hydrazine hydrate under more drastic conditions afforded (100%) the symmetrical dicarbohydrazide 4, which is insoluble in most common organic solvents. Reaction of monocarbohydrazide 3 with NaNO2 in concentrated HCl gave (ca. 100%) the corresponding carbazide 5, whose IR spectrum clearly demonstrates the presence of the characteristic carbazide stretch at 2181 and 2143 cm-1 as well as the shift (13C NMR) from δ 163.8 to 171.0 for the carbonyl groups supporting the conversion. Subsequent Curtius rearrangement of carbazide 5 provided (82%) urethane 6; the 13C NMR for 6 shows the expected upfield shift from δ 171.0 to 153.3 for the urethane moiety. Saponification of 6 afforded (89%) the desired 5′-amino-2,2′-bipyridine-5-carboxylic acid hydrochloride 7 supported by the carbonyl absorption at δ 176.0 and the disappearance of the peak for the urethane carbonyl. The bright yellow salt is soluble in aqueous base but shows only very low solubility in organic solvent other than DMSO. In order to enhance the solubility characteristics, the amino acid 7 was subjected to Fischer esterification conditions affording the ethyl ester 8, as a pale yellow solid. The enhanced organic solubility and the appearance of the typical ethyl absorption in the NMR spectra support the assigned structure. Application of the selective reactivity due to solubility differences has great potential in the preparation of unsymmetrical heterocycles8 and is being pursued in other N-heterocyclic functionalizations.

Synthesis and chemiluminescence of 1,3-disubstituted pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyridazine-5,8(6h,7h)-diones and related compounds

Reactions of 1,3-disubstituted 5-aminopyrazole-4-carbonitrile derivatives (3a-o) with dimethyl acetylenedicarboxylate in the presence of potassium carbonate in dimethyl sulfoxide gave the corresponding dimethyl 1,3-disubstituted pyrazolo[3,4-b]pyridine-5,6-dicarboxylates (4a-o) which were allowed to react with excess hydrazine hydrate in ethanol under reflux followed by heating at 250–300 °C to give 1,3-disubstituted 4-amino-1H-pyrazolol [4′,3′:5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-diones (7a-s) in good yields. These tricyclic pyridazine derivatives were evaluated for chemiluminescence. Some were found to be more efficient than luminol in light production. 4-Amino-3-methylsufonyl-1-phenyl-1H-pyrazolo [4′,3′:5,6]pyndo[2,3-d]pyridazine-5,8(6H,7H)-dione(7r) showed the greatest chemiluminescence intensity derivatives in the presence of H2O2, peroxidase, in a solution of phosphate buffer pH 8.0

Synthesis and Chemistry of 4‐Aroyl‐3‐oxo‐ and 3‐Chloropyridazine Derivatives

Abstract4H,5H‐6‐Phenyl (1a) and 6‐p‐phenoxyphenyl (1b) pyridazin‐3(2H)‐ones were reacted with aromatic aldehydes to give 4‐arylmethylpyridazm‐3(2H)‐ones (2a‐g), Oxidation of (2a‐g) with various oxidising agents (selenium dioxide in ethanol or chromium trioxide in acetic acid) gave 4‐aroyl‐6‐arylpyridazin‐3(2H)‐ones (3a‐g). Chlorination of (3a‐g) with phosphorous oxychloride afforded 4‐aroyl‐6‐aryl‐3‐chloropyridazine (4a‐g). 1H‐3‐Aryl‐5‐phenylpyrazolo[3,4‐c]pyridazines (5a‐d) were obtained by heating (4a‐d) with excess hydrazine hydrate. Hydroxyamination of (3e‐g) with iydroxylamine gave aryl‐4(6‐p‐phenoxyphenyl‐2,3‐dihydro‐3‐oxo)pyridazinyl oxime (6a‐c). Silylation of oximes (6b & 6c) gave (7a & 7b) as acyclic compound instead of the expected seven ‐ membered ‐ ring compound (8).

Reactions of functionally substituted benzo[c]pyrylium salts. Synthesis of 5h-benzo-2,3-diazepines

5H-Benzo-2,3-diazepine derivatives are formed in the reaction of 4-ethoxycarbonylbenzo[c]pyrylium perchlorates with excess hydrazine hydrate. It was established that the key intermediate in the reaction is the 2-aminoisoquinolinium cation. A method for the recyclization of 4-cyanobenzo[c]pyrylium salts to 5H-benzo-2,3-diazepine derivatives was found.

Push‐pull‐Butadiene. XI. Darstellung und Reaktionen von Methylsulfonylnicotinonitrilen

Push‐pull‐Butadienes. XI. Syntheses and Reactions of MethylsulfonylnicotinonitrilesMethylthionicotinonitriles 1, 3, 5, 9 and 12 react with potassium permanganate to give corresponding methylsulfonylnicotinonitriles 2, 4, 6, 10 and 13, respectively. Compounds 2 can be converted with sodium ethoxide to yield diethoxynicotinonitriles 7. Similarly 4, 5 and 6 react with sodium ethoxide to give 4‐aryl‐5‐bromo‐2,6‐diethoxy‐nicotinonitriles 8. Treatment of nicotinonitriles 9, 10 or 13 with sodium ethoxide gives diethoxynicotinonitriles 11. 2 with hydrazine hydrate together afford pyrazolo[3,4‐b]pyridines 14. However, an excess of hydrazine hydrate and 2 or 6 yields hydrazinopyrazolo[3,4‐b]pyridines 15.

Trichonnethylphosphonsäuredihydrazid und 3.6-Bi8(trichlormethyl)-3.6-dioxo-1.2.4.5-tetraaza-3.6-diphosphacyclohexan / Trichloromethylphosphonic Acid Dihydrazide and 3,6-Bis(trichloromethyl)-3,6-dioxo-1,2,4,5-tetraaza-3,6-diphosphacyclohexane

Abstract The title compounds are prepared from trichloromethylphosphonic acid dichloride and excess hydrazine hydrate, and from the dihydrazide and the dichloride in the presence of triethylamine, resp. They are characterized by elemental analysis, mass spectra, 1H and 31P NMR spectra, IR and Raman data. Thin layer chromatographic experiments show that in the raw material of the ring compound two isomers (probably cis- and trans-) are present, whereas in the recrystallized product only one isomer can be detected. Attempts of a preparative separation of isomers were unsuccessfull so far due to very low concentrations of the product with the slightly higher Rf. Single crystals of the isolated ring compound decompose on irradiation with X-rays

Synthesis of 1H‐[1,2]diazepino[4,5‐b]indole derivatives

AbstractA synthesis of four 1H‐[1,2]diazepino[4,5‐b]indole derivatives and some preliminary information about their biological activity are presented. The starting materials were 2‐ethoxycarbonylindoles and 2‐ethoxy‐carbonyl‐3‐formylindoles, la, b and 2a, b, respectively. 2‐Ethoxycarbonyls la, b reacted with 1‐dimethylamino‐2‐nitroethylene and ‐2‐ethoxycarbonyl‐3‐formylindoles 2a, b in the presence of nitroalkanes (nitromethane or nitroethane) giving 3‐(2‐nitrovinyl)indoles 3a, b. Reduction of 3a, b yielded β‐(2‐oxoalkyl)indoles 4. On reaction with an excess of hydrazine hydrate, compounds 4 gave satisfactory yields of 5‐oxo‐1H‐[1,2]diazepino[4,5‐b]indoles 5.