Patented Oct. 11, 1949 2,484,785 UNITED STATES PATENT OFFICE 1,4-DHYDRAZINO-PHTHALAZINE AND ITS ACD SALTS Jean Druey, Riehen, Switzerland, assignor to Ciba Pharmaceutical Products, Inc., Summit, N. J. No Drawing. Application December 6, 1948, Se ria No. 63,861. In Switzerland December 19, 194 4 Claims. (C. 260-250) 2 The present invention relates to new hydrazine hydrazine and the like. These hydrazines may derivatives of compounds containing a pyridazine also be used in the form of their salts. The re ring, and has especial relation more particularly action with the hydrazine is advantageously con to 1:4-dihydrazino-phthalazines. These com ducted in the presence of a diluent, and, if de pounds possess valuable pharmacological proper sired, also in the presence of a condensing agent, ties. Thus, for example, 1:4-dihydrazino in which case it may also be carried out in the phthalazine brings about a fall in blood pressure presence of a catalyst Such as copper powder. of eSpecially long duration. They can be used as The reduction, for example, of the nitramine medicaments or as intermediate products. compounds, in accordance with the invention to It has been found that the said derivatives can O form the hydrazines, may be brought about, for be obtained by converting into hydrazino groups, example, catalytically or by means of zinc dust Simultaneously or in succession, two substituents in the presence of caustic Soda Solution. The which are convertible into hydrazino groups and hydrazines so obtained easily form salts with which are present in Ortho-position to the two inorganic or organic acids, as for example with ring nitrogen atoms in a compound containing a 5 hydrohalic acids, such as hydrochloric acid, sui pyridazine ring. Thus, a compound containing furic acid, phosphoric acid, thiocyanic acid, meth a pyridazine ring and, in Ortho-position. With re anesulfonic acid, hydroxy ethaneSulfonic acid, Spect to each ring nitrogen atom, an exchange acetic acid or tartaric acid. able substituent-for example, an esterified The following examples illustrate the inven hydroxyl group, especially a halogen atom, or 20 tion, the parts being by weight unless otherwise an alkoxy, aryloxy or thioether group, which stated, and the relationship of parts by weight two Substituents may be different from one an to parts by Volume being the same as that of other-may be reacted with a hydrazine. Dihy the gram to the cubic centimeter: drazino-pyridazine compounds are also obtained Eacample 1 25 in accordance with the invention by treating with 6.6 parts of 1-chloro-4-methoxy-phthalazine a reducing agent a compound which contains a (melting at 108-109° C., and obtained from pyridazine ring and also contains substituents, for i:4-dichloro-phthalazine and Sodium methylate) example, nitramino groups which are convert ible into hydrazino groups by reduction. By in are introduced into a warm mixture of 25 parts troducing the hydrazino groups in succession it 30 by Volume of hydrazine hydrate and 25 parts by is possible to form hydrazino groups which differ Wolume of absolute ethyl alcohol. Dissolution from One another, in which case the two above occurs immediately. After being heated for 2 mentioned forms of the process may be combined. hours on the Water-bath, the whole is cooled and As compounds which contain a pyridazine ring crystallization sets in. By filtering with Suction and which are disubstituted in the Ortho-posi 35 and washing with ethyl alcohol there are obtained tions with respect to the nitrogen atoms there are about 5 parts of 1:4-dihydrazino-phthalazine, an used, more especially, those which contain an Orange colored compound of the formula, aromatic nucleus, in particular, phthalazines, NNE Thus, use may be made, for example, of 1:4-di chloro-phthalazine, 1-chloro-4-methoxy-phthal 40 azine, 1-chloro-4-ethoxy-phthalazine, 1-chloro 4-phenoxy-phthalazine, 1:4-dimethylmercapto phthalazine, 1:4-dinitramino-phthalazine, and also corresponding phthalazines which contain NEINEI. Substituents in the aromatic nucleus. which crystallizes from water in fine small As hydrazines there are used hydrazine itself needles and melts at about 180° C. The corre or substitution products thereof, including those sponding dihydrochloride is obtained with in which one nitrogen atom forms part of a ring, 2N-hydrochloric acid. It crystallizes with a small for example, of a piperidine or morpholine ring. amount of water of crystallization and melts Thus, use may be made of the following hydra 50 unsharply with decomposition at about 255° C. zines: Hydrazine, methylhydrazine, asymmetri In an analogous manner, there can be obtained cal dimethyl-hydrazine, symmetrical dimethyl other salts, for example of Sulfuric acid, phos hydrazine, propyl-hydrazine, allyl-hydrazine, phoric acid, thiocyanic acid, methanesulfonic N-methyl-N-butyl-hydrazine, N-amino-piperi acid, hydroxy ethanesulfonic acid, acetic acid dine, N-amino-morpholine, 3-methyl-cyclohexyl 55 or tartaric acid. 2,484,785 3 4 Instead of 1-chloro-4-methoxy-phthalazine, which the hydrochloride melts at about 150° C.), the corresponding 4-ethoxy-compound may be which when heated to about 150° C. undergoes used as starting material. The latter is obtained further conversion into 1:4-dihydrazino-phthal from 1:4-dichloro-phthalazine in ethyl alcohol azine melting at 180° C. in the presence of sodium ethylate, and melts at Having now disclosed the invention, what is 78° C. claimed is: When 1:4-diphenoxy-phthalazine (melting at 1. A compound selected from the group con 222 C., and obtained from 1:4-dichloro-phthal sisting of 1:4-dihydrazino-phthalazine and its azine and Sodium phenolate) is used as Starting: acid salts. material, the reaction with hydrazine hydrate is 2. 1:4-dihydrazino-phthalazine. advantageously conducted at a raised tempera 3. An acid salt of 1:4-dihydrazino-phthalazine. ture in a bomb tube. 4. The dihydrochloride of 1:4-dihydrazino Eacample'2'' phthalazilets JEAN DRUEY. By the action of hydrazine hydrate on 1:4- . . dichloro-phthalazine under mild conditions there. No references cited. is obtained 1-hydrazino-4-chlorophthalazine (of