FR2495147A1 - 6-Alkoxy:carbonyl:hydrazino-3 -substd.-amino-pyridazine(s) - and use as intermediates in prepn. of 6-hydrazino-3-substd.-amino-pyridazine(s) - Google Patents

Abstract

Substd. pyridazines of the formula (VI) in which R9, R10 and R11 are each methyl are new. They are intermediates in the conversion of halopyridazines of the formula (V) to hydrazinopyridazines of the formula (I) by reaction with an appropriate alkylcarbazate at a temp. above 50 deg.C in an organic solvent to form (VI) followed by mild acidic hydrolysis of (VI) to form (I), which may be isolated as an acid-addition salt. In the formulae, R5 and R6 are each independently H, 1-6C alkyl, 3-6C alkenyl, 3-6C alkynyl, 1-6C hydroxyalkyl, (1-4C alkoxy)- (1-6C alkyl), (2-4C alkanoyloxy)- (1-6C alkyl), phenyl opt. substd. with 1 to 3 substituents selected from Cl, F, Br, 1-4C alkyl and 1-4C alkoxy, methylenedioxyphenyl, or phenyl-(1-4C alkyl) opt. substd. in the phenyl ring as above, or NR5R6 is a fully or partially hydrogenated 5- to 7-membered heterocyclic ring which may contain a further hetero atom selected from O, N and S and may bear one or two substituents selected from 1-4C alkyl, OH, 1-4C hydroxyalkyl and phenyl opt. substd. by 1 to 3 substituents selected from Cl, F, Br, OH, 1-4C alkyl and 1-4C alkoxy; R7 and R8 are each H or together represent a fused-on benzene ring; R9, R10 and R11 are each 1-4C alkyl; and HY is an inorganic acid. (I) are known antihypertensive agents and are also intermediates for other antihypertensive agents. The present process for their prepn. avoids the use of hydrazine (hydrate) which is poisonous, corrosive and inflammable; and also gives increased yields over some of the known processes.

Description

 The present invention relates to a novel process for preparing 6-amino-3-hydrazino pyridazine derivatives.

et leurs sels formés avec des acides, ou les symboles R5 et Rb representent indépendamment un atome d'hydrogène ou un radical alkyle(C1-C6) alcényle(C3-C6), alcynyle(C3-C6), hydroxyalkyle(C1-C6), a lcoxy(C1-C4)- alkyle(C1-06), alcanoy oxy(C1-04)alkyle(C1-C6), phényle, phényle subs titué par 1 à 3 substituants choisis indépendamment parmi les radicaux chloro, fluoro, bromo, alkyle(C1-C4) et alcoxy(Cl-C4), phenyle substitué par un radical mSthylènedioxy, ou phenylalkyle(C-C4) dont le cycle. phenyle peut être substitué comme ci-dessus, ou R et R5 peuvent former ensemble avec l'atome d'azote adjacent, un hétérocycle pentagonal 9 heptagonal entièrement ou partiellement hydrogéné qui peut contenir un hétéro-atome supplementaire choisi parmi l'oxygène, l'azote et le soufre et porter 1 ou 2 substituants choisis parmi les radicaux alkyle(C1-C4) > hydroxy, hydroxyalkyle(Cl-C4), phényle et phényle substitué par 1 à 3 substituants choisis indépendamment parmi les radicaux chloro fluoro, brome, hydroxy, alkyle(C1-C4) et alcoxy (C1-C4), et R et R8 représentent des atomes d'hydrogène ou forment ensemble un radical butadiène-1,3-ylène formant un système benzo condensé avec le cycle pyridazine. On peut citer comme exemples de sels formés avec des acides des composés répondant à la formule I ci-dessus, les chlorhydrates, bromhydrates, iodhydrates, sulfates, phosphates, oxalates, tartrates, citrates, malates et analogues. A partir de ces sels, on peut obtenir les bases libres correspondantes en traitant le sel choisi avec une quantité équimoleculaire d'une base appropriée, telle que par exemple un hydroxyde alcalin.Les sels d'addition d'acides des composés de formule I peuvent être préparés en traitant la base libre avec une proportion équimoléculaire de l'acide prédéterminé. Les composés de formule I qui, du point de vue chimique, sont des dérivés d'amino-6 hydrazino-3 pyridazine, ainsi que les sels correspondants, sont utiles comme antihypertenseurs comme décrit par exemple dans les brevets belges n 687 855 et n 744 626, dans le brevet britannique n 1 373 548 et dans Progressa in Drug Research, Vol. 20, pages 203-205, publié par E. Juker,
Birkhauser Verlag, Bâle 1976.More particularly, the invention relates to a new process for preparing compounds of general formula

and their salts with acids, or the symbols R5 and Rb independently represent a hydrogen atom or a (C1-C6) alkyl (C3-C6) alkenyl, (C3-C6) alkynyl, (C1-C6) hydroxyalkyl radical alkoxy (C1-C4) -alkyl (C1-C6), phenyl, phenyl substituted with 1 to 3 substituents independently selected from chloro, fluoro, bromo; , (C1-C4) alkyl and (C1-C4) alkoxy, phenyl substituted with methyl (methylene) radical, or phenyl (C1-C4) alkyl whose ring. phenyl may be substituted as above, or R and R5 together with the adjacent nitrogen atom may form a heptagonal, fully or partially hydrogenated, pentagonal heterocycle 9 which may contain an additional hetero atom selected from oxygen, nitrogen and sulfur and carry 1 or 2 substituents selected from alkyl (C1-C4)> hydroxy, hydroxyalkyl (C1-C4), phenyl and phenyl substituted with 1 to 3 substituents independently selected from chloro fluoro, bromo, hydroxy , (C1-C4) alkyl and (C1-C4) alkoxy, and R and R8 represent hydrogen atoms or together form a butadiene-1,3-ylene radical forming a benzo-fused system with the pyridazine ring. Examples of salts formed with acids are compounds of formula I above, hydrochlorides, hydrobromides, hydroiodides, sulfates, phosphates, oxalates, tartrates, citrates, malates and the like. From these salts, the corresponding free bases can be obtained by treating the chosen salt with an equimolar amount of a suitable base, such as, for example, an alkaline hydroxide. The acid addition salts of the compounds of the formula I can be prepared by treating the free base with an equimolar proportion of the predetermined acid. The compounds of formula I which, from the chemical point of view, are derivatives of 6-amino-3-hydrazinopyridazine and the corresponding salts are useful as antihypertensives as described, for example, in Belgian Pat. Nos. 687,855 and 744. 626, in British Patent No. 1,373,548 and in Progressa in Drug Research, Vol. 20, pages 203-205, published by E. Juker,
Birkhauser Verlag, Basel 1976.

oÙ R5, 6 R7 et R8 ont la même signification que ci-dessus, R
R, R1, R2 et 3, qui peuvent être semblables ou différents, représentent indépendamment un atome d'hydrogène ou un radical alkyle (C1-C4), et R4 représente un atome d'hydrogène ou un radical alkyle.The compounds of formula I, in addition to their antihypertensive action, are also useful as intermediates in the synthesis of the compounds described in South African Patent No. 67/7803 and in the preparation of N-pyrrolylpyridazinamines of Formula II

where R5, R7 and R8 have the same meaning as above, R
R, R1, R2 and 3, which may be the same or different, independently represent a hydrogen atom or a (C1-C4) alkyl radical, and R4 represents a hydrogen atom or an alkyl radical.

 (C1-C4), (C1-C4) alkylamino> bis-alkylamino (C1-C4) alkanoyl (C1-C4), halogenalkanoyl (C1-C4), (C1-C4) alkoxycarbonyl or benzyloxycarbonyl.

 The N-pyrrolylpyridazinamines of formula II are described in European Patent Application Publication No. 9555 as antihypertensive agents. The processes for the preparation of the compounds of formula I which are known from the chemical literature (for example those described in British Patent No. 1157,642 and in Belgian Patent No. 744,626) comprise a first reaction stage which is the condensation of a dihalogeno3,6 pyridazine with a suitable primary or secondary amine to obtain the corresponding 6-amino-3-halogeno pyridazine derivative.

These compounds are generally isolated and characterized and then reacted with a large excess of highly concentrated hydrazine hydrate to obtain the 6-amino-hydrazino-3-pyridazine derivatives.

 The above methods have several disadvantages which are essentially due to the use of large amounts of concentrated hydrazine hydrate as a reaction component in the second reaction stage. As is well known from the chemical literature (see for example the eighth edition of the Merck Index, p. 539, 1968) and practical experience, hydrazine, the anhydrous state as well as the reactive hydrated form, is a very potent compound. toxic, which causes delayed eye irritation and is easily ignited. It corrodes glass, rubber and certain stainless steels and must be used under strictly controlled reaction conditions, for example in the absence of air and traces of certain metal cations (eg iron, molybdenum and the like) to avoid explosions. It is therefore obvious that the industrial use of highly concentrated hydrazine poses various difficult problems from the technical point of view and from the point of view of safety.

 The method of the invention overcomes the disadvantages of the prior art.

 One of the advantages of the process of the invention over those previously described is the replacement of hydrazine, or hydrazine hydrate very concentrated, by a derivative of carbazate alkyl (C4-C13) which removes the risks and disadvantages mentioned above.

 According to the methods of the prior art, some of the products, depending on the nature of R5 and R6, are obtained with low yields while, according to the new process of the invention, the yields are considerably increased.

oÙ R5, R6, R7 et R8 ont la même définition que ci-dessus, R9, R10 et
R11 representent indépendamment des radicaux alkyles(C1-C4)? X repré- sente un radical chloro, bromo ou iodo et HY représente un acide minéral tel que l'acide chlorhydrique, sulfurique, phosphorique et similaires.The reaction scheme is as follows
DIAGRAM

where R5, R6, R7 and R8 have the same definition as above, R9, R10 and
R11 independently represent (C1-C4) alkyl radicals? X represents a chloro, bromo or iodo radical and HY represents a mineral acid such as hydrochloric acid, sulfuric acid, phosphoric acid and the like.

 The first stage is the preparation of the 3-halogeno pyridazinamine-6 derivatives where the halo radical is a chloro, bromo or iodo radical. According to British Patent No. 1,115,642, the amine of formula HNR5R6 is allowed to react with the appropriate 3,6-dihalo-pyridazine of formula III at a temperature of between 90 and 150 ° C. in the presence of a solvent or without a solvent at melting temperature. The compounds of formula IV thus obtained are recovered according to the usual techniques.

The second step is the preparation of an acid addition salt of the compound IV by reaction of the amino-substituted halogeno-3-pyridazine derivative at the 6-position with an excess of a mineral acid
HY, such as hydrochloric acid, sulfuric acid, phosphoric acid and the like.

 The product of formula V thus obtained is then reacted with a (C4-C13) alkyl carbazate to give the amino-substituted pyridazinyl-3 carbazate at the 6-position.

 The characteristic of the alkyl carbazate derivatives which can be used in the process of the invention is the ease of hydrolysis under mildly acidic conditions, so that as soon as they have reacted with 6-halogeno-pyridazinamine 3 chosen, the hydrolysis can be easily carried out to obtain the hydrazino derivative of formula I.

 According to the process of the invention, an excess of (C 4 -C 13) alkyl carbazate, preferably about 2 to 3 molar proportions, is added to a solution of the 6-halo-6-amino acid addition salt. pyridazine is suitable in an appropriate inert organic solvent, that is a solvent in which the reagents are sufficiently soluble for the reaction to proceed but which does not itself react with the functional groups of the reagents or products Finally, these solvents are advantageously chosen from alkanols containing 3 to 6 carbon atoms, such as propanol, butanol, isobutanol, pentanol-1, pentanol-2, pentanol-3 and methyl-3. 2-pentanol, 4-methyl-3-pentanol, hexanol-2-hexanol or 3-hexanol, 5 to 7-carbon cyclolscanols, such as cyclopentanol, cyclohexanol or cycloheptanol, glycols containing 2 to 4 carbon atoms and mono- or di-alkyl ethers or esters ( C1-C4), for example ethylene glycol, bis (2-methoxyethyl) ether, monomethyl ether or ethylene glycol monoethyl ether, ethylene glycol monoisopropyl ether, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,3-propanediol monoacetate, 1,3-propanediol monoethyl ether, 1,2-butanediol, butanediol-2 3 or 2,3-butanediol monomethyl ether and benzyl alcohol. The preferred solvents are alkanols having 4 or 5 carbon atoms and ethers of mono- and di-alkyl (C1-C2) ethylene glycol and 1,2-propanediol.

 The reaction mixture is generally heated to a temperature above SOOC and preferably at the reflux temperature of the reaction mixture.

 The reaction is monitored by thin layer chromatography and is generally complete in 24 to 36 hours or more.

 It is not necessary to isolate the compounds of formula VI thus obtained and can be hydrolyzed directly under moderately acidic conditions.

 Generally, inorganic acids and preferably halogenated hydracids are employed.

According to a preferred embodiment, hydrochloric acid is used at a concentration of between 5% and 12%.
The hydrolysis stage also produces a hydrazine hydrazine haloge as a result of the hydrolysis of excess (C4-C13) alkyl carbazate, and other by-products. The hydrazine hydrohalide is insoluble in the concentrated hydrohalic acid whereas the main product remains soluble under these conditions, which allows the separation by filtration.

 Sometimes it is difficult to separate the main product from the byproducts only according to the abbreviated modems above.

 In this case it may be useful to prepare the 6-amino-3-pyridazine amino-substituted pyridazine in the 6-position with benzaldehyde or other suitable aromatic aldehydes. This reaction is preferably carried out under alkaline conditions such as those obtained with aqueous solutions of alkali metal carbonate or bicarbonate and the like. The hydrazone of the desired product is generally insoluble in many organic solvents in which by contrast the by-products of the reaction are soluble.

This fact can be used for purification; the main product is separated from undesired by-products by addition of one of said organic solvents or a mixture thereof. The recovery is easily carried out by filtration. Examples of such solvents are the lower alkanols having at least 3 carbon atoms, the alkyl ethers and the like. Preferred solvents are isopropyl alcohol and ethyl ether.

 The hydrazone is then hydrolyzed from the amino-substituted 6-hydrazino-pyridazine derivative in the 6-position under acidic conditions to obtain the 6-amino-6-pyridazine derivative amino-substituted in the pure and solid form.

A preferred hydrolysis agent is a halogenated hydric acid,
HX, where X has the same definition as above. According to another preferred embodiment, 5-1OZ hydrochloric acid is used for this hydrolysis.

 The stage of separation with benzaldehyde is described in Journal of Medicinal Chemistry 1975, 18, 741-746 by Pifferai et al.

(où R1 et R2 représentent un radical alkyle(Cl-C6), allyle, hydroxy-2 éthyle ou hydroxy-2 propyle) sont décrites comme agents antihypertenseurs dans le brevet belge nO 811 847 et le brevet britannique nO 1 470 747. Cependant, ces composés ne peuvent pas être utilisés comme intermédiaires dans le procédé de l'invention car contrairement à un radical alcoxy(C4-C13) carbonyle, le radical éthoxycarbonyle ne s'hydrolyse pas facilement dans les conditions modérément acides utilisées dans le procédé de l'invention.The final products of formula I thus obtained can be used as antihypertensive agents or they can be used to prepare N-pyrrolylpyridazinamines of formula II by reaction with an appropriate diketone (as described in the aforementioned European Patent Application No. 0009655) or use them as intermediates for preparing the compounds of the aforesaid South African Patent No. 67/7803. The intermediate products of formula VI are new and constitute another subject of the invention. However, the amino-substituted ethoxycarbonylhydrazipo-3-pyridazines of the formula

(Where R 1 and R 2 are (C 1 -C 6) alkyl, allyl, 2-hydroxyethyl or 2-hydroxypropyl) are described as antihypertensive agents in Belgian Patent No. 811,847 and British Patent No. 1,470,747. these compounds can not be used as intermediates in the process of the invention because unlike a (C 4 -C 13) alkoxycarbonyl radical, the ethoxycarbonyl radical does not hydrolyze easily under the mildly acidic conditions used in the process of the invention.

 The invention is illustrated by the following nonlimiting examples.

Example 1
Hydrazino-6-dihydrochloride N, N-bis (methoxyethyl) amino-3-pyridazine.

 A) 149 g (1 mole) of 3,6-dichloropyridazine are added slowly to 26.4 g (2 moles) of bis (2-methoxyethyl) amine heated to 1400C.

 Heating was continued with stirring for a further 5 hours, then the reaction mixture was allowed to warm to room temperature, dissolved in 600 ml of ethyl acetate and washed twice with water (300 ml).

 The organic solvent was distilled off in vacuo and the residue was purified by vacuum distillation (115-1180c / 0.53 mbar). 100 g of 3-chloro-bis (2-methoxyethyl) -amino-6-pyridazine are obtained; yield about 40.7%; F. 33-340C.

 B) 100 g of the product obtained as above are dissolved in 200 ml of methanol and acidified by adding a solution of hydrochloric acid in ethyl ether. The solvent is removed by boiling in vacuo and the residue is crystallized from acetonitrile.

 Yield 84 g (83%) of 3-chloro-bis (2-methoxyethyl) amino-6-pyridazine hydrochloride; Mp 130-1320C.

 C) 72 g (0.0545 mol) of tertbutyl carbazate 9 are added to a solution of 65 g (0.23 mol) of 3-chloro-bis- (2-methoxyethyl) -amino-pyridazine hydrochloride in 9CO ml of 2-methoxyethylene glycol.

 After boiling at reflux temperature for 26 hours, the mixture is allowed to warm to room temperature and the solvent is evaporated in vacuo.

 The residue is dissolved in 10% hydrochloric acid, heated for a few minutes at 50-80 ° C, dried again in vacuo, 37% hydrochloric acid is added and filtered.

 The hydrazine hydrochloride is recovered on the filter, the filtrate is distilled in vacuo, the resulting residue is dissolved in water, basified with sodium carbonate and extracted with toluene (300 ml x 3).

 D) 6 g of benzaldehyde are added to the aqueous alkaline solution and the reaction mixture is kept hot in a water bath for 15 minutes and then filtered. The filtrate is discarded, the solid is dissolved on the filter in methanol and then the methanol is distilled off in vacuo, the residue is taken up in isopropanol and precipitated with ethyl ether.

 (N → N-bis (2-methoxyethyl) amino) -6-pyridazinylbarsaldehyde hydrazone is recovered and crystallized from 95% methanol; yield 34.5 g (45.6A); Mp 138-1390C.

 E) The above product (32.5 g) is dissolved in 100 ml of 37% hydrochloric acid and 400 ml of water and dried in vacuo.

This operation is repeated until there is no reaction with 2,4-diphenylhydrazine. The residue is dissolved in boiling isopropanol and precipitated with ethyl ether.

 29.9 g (96.5X) of the desired compound are obtained; F. 1950C (decomposition).

Example 2
Hydrazino-6 (N, N-bis (ethyl) amino] -3-pyridazine dihydrochloride.

 A) 3-chloro-bis (ethyl) amino-6-pyridazine is known (see Schonback and Klamstein Monatsh Chem., 99, 15 (1968).

 B) To form 3-chloro-bis (ethyl) amino-6-pyridazine hydrochloride, hydrochloric acid is bubbled into a solution of 3-chloro-bis (ethyl) amino-6-pyridazine in propan-2-ol.

Mp 134-135 ° C (after recrystallization from a mixture of 2-propanol and ethyl ether); yield about 90%.

C) 55.5 g (0.25 mole) of the above product and 82.5 g (0.625 625 mole) of tert-butyl carbazate are reacted as in
C) of Example 1 and the bis (ethyl) amino-6-pyridazinyl-3H-2 hydrazinecarboxylic acid tert-butyl ester is hydrolyzed as described in the second part of C) of Example 1 .

 D) 62.5 g of benzaldehyde are then added to the above reaction product as described in D) of Example 1 to obtain 20.9 g of (bis (ethyl) amino-6-pyridazinyl] -2-benzaldehyde hydrazone .

Yield 31.2%; F. 200-2050C. This compound was also obtained by Pifferi et al. (J. of Medicinal Chemistry, 18, 741-746).

 The yields from 3-chloro-6-bistyl-6-pyridazine indicated in the above-mentioned article are 15% (see Table IV, page 744), whereas, according to the process of the invention, a yield of about 28% from the same product.

 E) The desired product is obtained from the above compound as in E) of Example 1 (yield 99X); F. 235-238 C (decomposition).

Example 3 Hydrazino-6-hydrazino-6-dihydrochloride (4-morpholinyl) amino-3-pyridazine.

 A) 3-chloro-4-morpholin-4-pyridazine is known (see E. Bellasio et al., "I1 Farmaco" Ed., Sc 24, 912 (1962).

 B) 30 g (0.15 mole) of the above product are dissolved in methanol and acidified by addition of a solution of hydrochloric acid in ethyl ether.

 150 ml of ethyl ether are added to form a precipitate which is collected and crystallized from isopropanol to obtain 27 g (76% yield) of chloro-3 (4-morpholinyl) pyridazine hydrochloride. F. 197-2080C.

 C) 23.6 g (0.1 mole) of the above product and 33.4 g (0.25 mole) of tert-butyl carbazate are reacted as described in C) of Example 1.

 D) 25 g of benzaldehyde are added to the product of the reaction above according to the procedures described in D) of Example 1 to obtain 11.6 g of (4-morpholinyl) -6-pyridazinyl-3-benzaldehyde-hydrone ( 41%); F. 278-280C

 E) 9.1 g of the desired product are obtained from 10 g of the above product, according to the procedures described in E) of Example 1. Yield 964; F. 231-233 C.

 Naturally, various modifications may be made by those skilled in the art to the devices or methods which have just been described solely by way of nonlimiting examples without departing from the scope of the invention.

Claims (10)

1. Process for preparing 3-hydrazino-pyridazinamine-6 derivatives having the formula

 and their acid addition salts, wherein the symbols R5 and R6 independently represent a hydrogen atom or an alkyl (C6), alkenyl (C3-C6), alkynyl (C3-C6), hydroxyalkyl (C1-C6) radical ), alkoxy (C1-C4) -alkyl (C1-C6), alkanoyloxy (C2-C4) alkyl (C1-C6), phenyl, phenyl substituted with 1 to 3 substituents independently selected from chloro, fluoro, bromo, alkyl radicals (C1-C4), alkoxy (C1-C4), phenyl substituted by a methylenedioxy radical or phenylalkyl (C1-5C4) whose phenyl ring may be substituted as above, or R and R6, with the nitrogen atom adjacent, may also form a heptagonal hexagonal heterocycle wholly or partially hygrogen which may contain an additional heteroatom selected from oxygen, nitrogen and sulfur and carry 1 or 2 substituents selected from alkyl radicals (C1-C4), hydroxy, hydroxy (C1-C4) alkyl, phenyl or phenyl substituted with 1 to 3 substituents independently selected from the radicals loro, fluoro, bromo, hydroxy, (C1-C4) alkyl and (C1-C4) alkoxy and R7 and R8 represent hydrogen atoms or together form a butadiene-1,3-ylene radical forming a benzo-condensed system with the pyridazine ring, which consists in reacting a formula derivative

 where X represents a chloro, bromo or iodo radical and HY represents a mineral acid such as hydrochloric acid, sulfuric acid, phosphoric acid and the like, with a C4-C13 alkyl carbazate of the formula H2N-NH-COOC (R9R10R11) wherein R9, R10 and R11 independently represent (C1-C4) alkyl radicals in a suitable inert organic solvent, heating to a temperature above 500C and hydrolyzing the resulting intermediate under mildly acidic conditions. 2. Process according to claim 1, characterized in that 2 to 3 moles of C1-C4 alkyl carbazate are used per mole of pyridazinamine derivative. 3. Process according to claim 1, characterized in that the organic solvent is chosen from alkanols containing 3 to 6 carbon atoms, such as propanol, butanol, isobutanol, pentanol-1 and pentanol-2. 3-pentanol, 3-methyl-2-pentanol, 4-methyl-3-pentanol, 1-hexanol, 2-hexanol or 3-hexanol, cycloalkanols containing 5 to 7 carbon atoms, such as cyclopentanol, cyclohexanol or cycloheptanol, glycols containing 2 to 4 carbon atoms and the corresponding mono- or di-alkyl (C1-C4) ethers or esters, for example ethylene glycol, monomethyl ether, or ethylene glycol monoethyl ether, ethylene glycol monoisopropyl ether, ethylene glycol monoacetate, propanediol 1,3-propanediol, 1,3-propanediol monoacetate, propanediol-1 monoethyl ether , 3, butanediol-1,3, butanediol-2,3 and butanediol-2,3 monomethyl ether, benzyl alcohol, dioxane or dimethylformamide. 4. Process according to claim 1, characterized in that the temperature is the reflux temperature of the reaction mixture. 5. Process according to claim 1, characterized in that the hydrolysis is carried out with 5-129 hydrochloric acid. 6. Process according to claim 1, characterized in that the final product is conveniently prepared from the reaction mixture by conversion of the benzaldehyde or other suitable aromatic aldehyde to the corresponding hydrazone. 7. Process according to claim 1 for preparing a compound of formula I in which R 7 and R 8 represent a hydrogen atom and R5 and R6 represent (C1-C6) alkyl, (C1-C4) alkoxy (C1-C6) alkyl or R5 and R6 together with the adjacent nitrogen represent a heptagonal, fully or partially hydrogenated, pentagonal heterocycle which may contain an additional hetero-atom selected from oxygen, nitrogen and sulfur and may have 1 or 2 substituents selected from (C1-C4) alkyl, hydroxy, (C1-C4) hydroxyalkyl, phenyl or substituted phenyl radicals. with 1 to 3 substituents independently selected from chloro, fluoro, bromo, hydroxy, (C 1 -C 4) alkyl and  Alkoxy (Cl-C4). 8. A process for preparing a compound of formula I wherein R 7 and R 8 are hydrogen and R 5 and R 6 are (C 1 -C 6) alkyl, (C 1 -C 4) alkoxy (C 1 -C 6) alkyl or R 5 and R6, together with the adjacent nitrogen atom, represents a heptagonal, fully or partially hydrogenated, pentagonal heterocyclic ring which may contain an additional heteroatom selected from oxygen, nitrogen and sulfur and may have 1 to 3 substituents selected from the group consisting of alkyl radicals (C1-C4), hydroxy, hydroxy (C1-C4) alkyl, phenyl and phenyl substituted with 1 to 3 substituents independently selected from chloro, fluoro, bromo, hydroxy, (C1-C) alkyl and (C1-C) alkoxy radicals; C4), characterized in that the solvent is 2-methoxy-methanol, the temperature of the reaction mixture is the reflux temperature, the hydrolysis is carried out in 5-12X hydrochloric acid and the reaction is suitably reacted with final product with benzaldehyde or other aromatic aldehydes for form the hydrazone derivative which is separated and hydrolyzed under mild acidic conditions. 9. Process according to any one of claims 1 to 8, characterized in that the reactive alkyl carbazate (C4-C13) is tert-butyl carbazate. 10. New compounds characterized in that they fulfill the formula

 where the symbols R5, R6, R7 and R8 have the same meanings as in claim 1,