Novel Cinnamoyles Piperazines and Homopiperazines, the Method of Preparing Them and Their Application in Therapeutics

The present invention relates to certain cinnamoyl piperazine and homopiperazine compounds.

The compounds of the invention have the formula (I) ##STR1## in which ##STR2## is selected from the group consisting of ##STR3## 4-fluorophenyl, 3,5-dimethoxyphenyl, 3,4-methylenedioxyphenyl, ##STR4## in which R.sub.14 is hydrogen or linear or branched alkyl having 2 or 3 carbon atoms, and ##STR5## and in which

I. when ##STR6## the parameters (n, R.sub.1, X, m) are selected from the group consisting of (1, OH, oxygen, zero), (2, OH, oxygen, zero), (1, H, oxygen, zero), (1, OH, S, zero), ##STR7## and (1, OH, oxygen, 1), and in which A. when (n, R.sub.1, X, m) is (I, OH, oxygen, zero), Ar is selected from the group consisting of ##STR8## in which R.sub.10 is acetyl, acetamido or N-methylcarbamoylamino, ##STR9## in which q is 1 or 2 and R.sub.10 has the same meaning as defined above, ##STR10## and in which 1. when Ar is ##STR11## R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are selected from the group consisting of

a. R.sub.3 .dbd.R.sub.4 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, and R.sub.2 is chloro, fluoro, acetamido, acetyl, cyano, methoxy, methyl, allyl or allyloxy,

b. R.sub.2 .dbd.R.sub.4 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, and R.sub.3 is acetamido, methyl, acetyl, cyano, methoxy or chloro,

c. R.sub.2 .dbd.R.sub.3 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, and R.sub.6 is chloro, cyano, nitro, methylthio, benzoyl, ethyl carboxylate, methyl, linear or branched alkyl having from 3 to 5 carbon atoms, cyclohexyl, alkanoyl in which the alkyl has from 1 to 3 carbon atoms, alkanoylamino in which the alkyl has from 1 to 3 carbon atoms, carboxamido, N-methylcarboxamido, cyanomethyl, carboxamidomethyl or N-methylcarbamoylamino,

d. R.sub.3 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, R.sub.2 is fluoro and R.sub.4 is acetyl,

e. R.sub.3 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, R.sub.2 is chloro and R.sub.4 is nitro, acetyl, or N-methylcarbamoylamino,

f. R.sub.3 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, R.sub.2 is methyl and R.sub.4 is chloro, acetyl, acetamido or N-methylcarbamoylamino,

g. R.sub.3 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, R.sub.2 is methoxy and R.sub.4 is acetyl, propionyl, formyl, cyano, acetamido, or N-methylcarboxamido,

h. R.sub.4 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, and R.sub.2 and R.sub.3 are methoxy,

i. R.sub.3 .dbd.R.sub.4 .dbd.R.sub.5 .dbd.H, and R.sub.2 and R.sub.6 are methoxy,

j. R.sub.2 .dbd.R.sub.4 .dbd.R.sub.6 .dbd.H, and R.sub.3 and R.sub.5 are methoxy,

k. R.sub.2 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, and R.sub.3 and R.sub.4 together are methylenedioxy.

l. R.sub.2 .dbd.R.sub.5 .dbd.R.sub.6 .dbd.H, R.sub.3 is methyl and R.sub.4 is nitro, acetamido or N-methylcarbamoylamino,

m. R.sub.2 .dbd.R.sub.6 .dbd.H, and R.sub.3, R.sub.4 and R.sub.5 are methoxy,

n. R.sub.2 .dbd.R.sub.6 .dbd.H, R.sub.3 and R.sub.5 are methyl, and R.sub.4 is chloro,

o. R.sub.5 .dbd.R.sub.6 .dbd.H, R.sub.2 and R.sub.3 are methoxy and R.sub.4 is N-methylcarbamoylamino,

p. R.sub.3 .dbd.R.sub.5 .dbd.H, R.sub.2 and R.sub.6 are chloro, and R.sub.4 is acetyl or N-methylcarbamoylamino,

q. R.sub.3 .dbd.R.sub.5 .dbd.H, R.sub.2 and R.sub.6 are methoxy and R.sub.4 is acetyl, ethyl carboxylate or N-methylcarbamoylamino, and

r. R.sub.6 .dbd.H, R.sub.3, R.sub.4 and R.sub.5 are methoxy and R.sub.2 is acetyl,

and in which

2. when Ar is ##STR12## p, R.sub.7, R.sub.8 and R.sub.9 are selected from the group consisting of a. p=2, R.sub.7 .dbd.R.sub.8 .dbd.H, and R.sub.9 is hydrogen, hydroxy, acetoxy, methoxy, methyl, ethyl, cyano, acetyl, n-butyroyl, alkoxycarbonyl in which the alkoxy is linear or branched and has from 2 to 5 carbon atoms, cyclohexyloxycarbonyl, carboxamido, N-methylcarboxamido, N-cyclohexylcarboxamido, N-phenylcarboxamido, alkanoylamino in which the alkyl is linear or branched and has from 1 to 5 carbon atoms, cyclohexylcarbonylamino, benzoylamino, N-alkylcarbamoylamino in which the alkyl is linear or branched alkyl and has from 1 to 5 carbon atoms, N-cyclohexylcarbamoylamino, N-phenylcarbamoylamino, N-(paramethoxy-phenyl)-carbamoylamino, N,N-dimethylcarbamoylamino, morpholinocarbonylamino, N,N'-dimethylcarbamoylamino, ethoxycarbonylamino, hydroxymethyl, cyanomethyl, ethyl acetate, carboxamidomethyl or N-methylcarboxamidomethyl,

b. p=2, R.sub.7 .dbd.R.sub.9 .dbd.H, and R.sub.8 is acetyl,

c. p=2, R.sub.8 .dbd.R.sub.9 .dbd.H, and R.sub.7 is acetamido,

d. p=1 or 3, R.sub.7 .dbd.R.sub.8 .dbd.H, and R.sub.9 is hydrogen, acetyl, acetamido or N-methylcarbamoylamino,

B. when (n, R.sub.1, X, m) is (2, OH, oxygen, zero), Ar is selected from the group consisting of phenyl, ##STR13## in which R.sub.11 is hydrogen or methoxy, and ##STR14## in which R.sub.10 has the same meaning as previously, C. when (n, R.sub.1, X, m) is (1, H, oxygen, zero), Ar is ##STR15## in which R.sub.12 is acetyl, acetamido, N-methylcarboxamido or N-methylcarbamoylamino,

D. when (n, R.sub.1, X, m) is (1, OH, S, O), Ar is phenyl, metamethoxyphenyl, paratolyl, ##STR16## in which R.sub.11 is hydrogen or methoxy, or ##STR17## in which R.sub.13 is hydrogen or acetyl, E. when (n, R.sub.1, X, m) is ##STR18## Ar is phenyl, and F. when (n, R.sub.1, X, m) is (1, OH, oxygen, 1), Ar is phenyl,

II. when ##STR19## is 4-fluorophenyl, 3,5-dimethoxyphenyl, 3,4-methylenedioxyphenyl, or ##STR20## the parameters (n, R.sub.1, X, m) are (1, OH, oxygen, zero) and Ar is ##STR21##

III. when ##STR22## the parameters (n, R.sub.1, X, m) are (1, OH, oxygen, zero) and Ar is ##STR23## and the pharmacologically acceptable salts thereof.

The process for preparing the compounds of formula (I), except for the 7 following compounds of formula (I):

the compound of formula (I) in which ##STR24## the compound of formula (I) in which X represents the methylamino group ##STR25## the compound of formula (I) in which Ar is ##STR26## the four compounds of formula (I) in which R.sub.1 represents the hydrogen atom,

consists in condensing a piperazine or a homopiperazine of formula (II) ##STR27## in which n assumes the values 1 and 2 and ##STR28## has the same meanings as ##STR29## in formula (I) except for the value ##STR30## with an epoxy of formula (III): ##STR31## in which Ar' has the same meaning as Ar in formula (I), except for the value ##STR32## and X' represents oxygen or sulphur, or with 2,3-epoxy-1-benzyloxy propane, to obtain the compound of formula (I) in which m=1.

This condensation is carried out preferably in ethanol with reflux.

Following the same process as above, but from suitable reagents, the compound corresponding to formula (Ia): ##STR33## will be prepared.

The novel compounds of formula (II), particularly those corresponding to formulae (IIb) and (IIa). ##STR34## in which ##STR35## represents the following aromatic groups ##STR36## are obtained by condensation of the compounds of formulae (IV) and (IVa): ##STR37## in which R" has the same meanings as in (IIa) respectively, with homopiperazine and piperazine. This condensation is carried out preferably in solution in acetic acid.

The compounds of formula (IVa), particularly those in which ##STR38## are obtained by action of thionyl chloride, in a toluen solution on corresponding cinnamoic acids of formula (V): ##STR39## in which R'.sub.14 represents the ethyl and isopropyl groups.

The compounds (V) are obtained by saponification of the ethyl esters of the corresponding cinnamoic acids of formula (VI): ##STR40## in which R'.sub.14 has the same meaning as in (V).

The compounds of formula (VI) were used in the crude state and are prepared by action of ethyl iodide or of isopropyl iodide on the ethyl ester of sinapic acid, in solution in acetonitrile and in the presence of potassium carbonate.

The compounds of formula (III): ##STR41## are partially novel and particularly those in which X' represents an oxygen atom and the Ar' radical represents:

(a) a mono or polysubstituted phenyl nucleus ##STR42## in which R'.sub.2, R'.sub.3, R'.sub.4, R'.sub.5 and R'.sub.6 represent simultaneously the following values:

R'.sub.3 .dbd.R'.sub.5 .dbd.R'.sub.6 .dbd.H; R'.sub.2 .dbd.F; R'.sub.4 .dbd.COCH.sub.3

R'.sub.3 .dbd.R'.sub.5 .dbd.R'.sub.6 .dbd.H; R'.sub.2 .dbd.OCH.sub.3 ; R'.sub.4 .dbd.COCH.sub.3, COEt

R'.sub.3 .dbd.R'.sub.5 .dbd.R'.sub.6 .dbd.H; R'.sub.2 .dbd.Cl; R'.sub.4 .dbd.COCH.sub.3, NO.sub.2

R'.sub.2 .dbd.R'.sub.5 .dbd.R'.sub.6 .dbd.H; R.dbd..sub.3 .dbd.CH.sub.3 ; R'.sub.4 .dbd.NO.sub.2, NH--CONH--CH.sub.3

R'.sub.5 .dbd.R'.sub.6 .dbd.H; R'.sub.2 .dbd.R'.sub.3 .dbd.OCH.sub.3 ; R'.sub.4 .dbd.NHCONH--CH.sub.3

R'.sub.3 .dbd.R'.sub.5 .dbd.H; R'.sub.2 .dbd.R'.sub.6 .dbd.Cl; R'.sub.4 .dbd.COCH.sub.3, NHCONHCH.sub.3

R'.sub.3 .dbd.R'.sub.5 .dbd.H; R'.sub.2 .dbd.R'.sub.6 .dbd.OCH.sub.3 ; R'.sub.4 .dbd.COCH.sub.3, COOEt, or NHCONHCH.sub.3

R'.sub.6 .dbd.H; R'.sub.3 .dbd.R'.sub.4 .dbd.R'.sub.5 .dbd.OCH.sub.3 ; R'.sub.2 .dbd.COCH.sub.3

R'.sub.2 .dbd.R'.sub.3 .dbd.R'.sub.5 .dbd.R'.sub.6 .dbd.H; R'.sub.4 .dbd.CH.sub.2 --CN

(b) a heterocycle of formula ##STR43## in which p, R'.sub.7, R'.sub.8 and R'.sub.9 assume the following values: p=2; R'.sub.7 .dbd.R'.sub.8 .dbd.H; R'.sub.9 represents the methoxy, acetoxy, methyl, cyano, acetyl, n-butyroyl, alkoxycarbonyl in which the alkyl is linear or branched and comprises 2 to 5 carbon atoms, cyclohexyloxycarbonyl, carboxamido, N-methylcarboxamido, N-cyclohexylcarboxamido, N-phenylcarboxamido, alkanoylamino whose linear or branched alkyl has 1 to 4 carbon atoms, cyclohexylcarbonylamino, benzoylamino, N-alkylcarbamoylamino whose linear or branched alkyl has from 1 to 5 carbon atoms, N-cyclohexylcarbamoylamino, N-phenylcarbamoylamino, N-(paramethoxyphenyl)carbamoylamino, N,N-diethylcarbamoylamino, morpholino carbonylamino, N,N'-dimethyl carbamoylamino, ethoxycarbonylamino, hydroxymethyl, cyanomethyl, ethylacetate, carboxamidomethyl or N-methylcarboxamidomethyl.

p=2; R'.sub.7 .dbd.R'.sub.9 .dbd.H; R'.sub.8 represents the acetyl group.

p=2; R'.sub.8 .dbd.R'.sub.9 .dbd.H; R'.sub.7 represents the acetamido group.

p=1 or 3; R'.sub.7 .dbd.R'.sub.8 .dbd.H; R'.sub.9 represents the acetyl, acetamido or N-methylcarbamoylamino groups.

(c) a naphthalene nucleus of the type ##STR44## in which R.sub.10 represents the acetyl, acetamido or N-methylcarbamoylamino groups.

(d) a heterocycle of the type ##STR45## in which q and R'.sub.10 assume simultaneously the following values: q=1 in which case R'.sub.10 represents the acetamido and N-methylcarbamoylamino groups

q=2 in which case R'.sub.10 represents the acetyl, acetamido or N-methylcarbamoylamino groups.

(e) the group ##STR46## and --X' represents a sulphur atom and the Ar' radical represents:

(f) an aromatic group ##STR47## in which R.sub.11 represents the hydrogen atom or the methoxy group. (g) a heterocycle of the type ##STR48## in which R.sub.13 represents the hydrogen atom or the acetyl group.

The compounds of formula (III) result from the condensation of the phenols of formula (VII):

in which X' and Ar' have the same meanings as in formula (III), with epichlorohydrin or epibromohydrin. This condensation is carried out preferably with reflux in acetone or acetonitrile in the presence of potassium carbonate.

The compounds of formula (VII) above are partially novel and they are prepared following different methods according to the nature of X' and Ar.

More exactly:

(1) The compounds of formula (VII) corresponding to formulae (VIIa), (VIIb), (VIIc): ##STR49## in which R".sub.2, R".sub.3, R".sub.5 and R".sub.6 assume simultaneously the following values:

R".sub.3 .dbd.R".sub.5 .dbd.R".sub.6 .dbd.H; R".sub.2 .dbd.CH.sub.3

R".sub.5 .dbd.R".sub.6 .dbd.H; R".sub.2 .dbd.R".sub.3 .dbd.OCH.sub.3

R".sub.3 .dbd.R".sub.5 .dbd.H; R".sub.2 .dbd.R".sub.6 .dbd.Cl

R".sub.3 .dbd.R".sub.5 .dbd.H; R".sub.2 .dbd.R".sub.6 .dbd.OCH.sub.3 ##STR50## in which q assumes the values 1 or 2, are obtained by action of methyl isocyanate, in a chloroform solution, respectively on the amino phenols of formulae: ##STR51## in which the values R".sub.2, R".sub.3, R".sub.5 and R".sub.6 have the same meanings as in (VIIa), ##STR52## in which q assumes the values 1 or 2. (2) The compounds (VII) corresponding to the formula (VIId): ##STR53## in which q assumes the values 1 or 2, are obtained by condensation of acetic anhydride on the (VIIIc) compounds in an aqueous solution.

(3) The compounds (VII) corresponding to formulae (VIIe) and (VIIf): ##STR54## in which R.sub.13 represents the hydrogen atom or the acetyl group are obtained by treatment with a solution of NaOH in methanol of compounds of formulae (IX) and (IXa) ##STR55## in which R.sub.13 represents the hydrogen atom or the acetyl group.

The (IX) and (IXa) compounds are obtained by thermal transposition of compounds (X) and (Xa) ##STR56## in which R.sub.13 has the same meanings as in (IXa).

The (X) and (Xa) compounds are themselves obtained by condensatin of N,N-dimethylthiocarbamoyl chloride with phenols of formulae: ##STR57## (4) The compounds of formula (VII) corresponding to formula (VIIk) ##STR58## in which p, R".sub.7, R".sub.8 and R".sub.9 assume simultaneously the following values:

p=2; R".sub.7 .dbd.R".sub.8 .dbd.H; R".sub.9 represents the acetoxy, cyano, alkoxy carbonyl in which the alkyl is linear or branched and comprises 2 to 5 carbon atoms, cyclohexyloxy carbonyl, carboxamido, N-methyl carboxamido, N-cyclohexyl carboxamido, N-phenyl carboxamido, alkanoylamino whose alkyl is linear or branched and has 2 to 5 carbon atoms, cyclohexylcarbonylamino, benzoylamino, N-alkylcarbamoylamino whose alkyl is linear or branched and has 1 to 5 carbon atoms, N-cyclohexylcarbamoylamino, N-phenylcarbamoylamino, N-paramethoxyphenyl carbamoylamino, N,N-dimethyl carbamoylamino, morpholinocarbonylamino, N,N'-dimethylcarbamoylamino, ethoxycarbonylamino, hydroxymethyl, cyanomethyl, ethyl acetate, carboxamidomethyl and N-methylcarboxamidomethyl,

p=1 or 3; R".sub.7 .dbd.R".sub.8 .dbd.H; R".sub.9 then represents the acetyl, acetamino or N-methylcarbamoylamino groups,

are obtained by hydrogenolysis, in the presence of palladium on charcoal, of compounds of formula (XI) ##STR59## in which p, R".sub.7, R".sub.8 and R".sub.9 have the same meanings as in (VIIk).

(5) The (VII) compound corresponding to the formula (VIIl) ##STR60## is obtained by the transposition of Fries of the compound of formula (XII) ##STR61## (6) The (VII) compound corresponding to formula (VIIm) ##STR62## is obtained by a Beckmann rearrangement, in an acetic acid medium, in the presence of hydrochloric acid, of the compound of formula (XIII) ##STR63##

Compound (XIII) is itself obtained by action of hydroxylamine on the compound of formula (VIIi) ##STR64## (7) The compound of formula (VII) corresponding to formula (VIIn) ##STR65## is obtained by hydrogenolysis, in the presence of palladium on 5% charcoal, of the compound of formula (XIp) used in the crude state ##STR66##

The compounds of formula (XI) above, necessary in the preparation of the compounds of formula (VIIk) are partly novel and are obtained by different processes depending on the nature of p, R".sub.7, R".sub.8 and R".sub.9.

Similarly, the compound of formula (XIa) is novel: ##STR67## which can be used for the synthesis of a compound of formula (VIIk'), which is known: ##STR68## More exactly: (1) The compound corresponding to formula (XIa) ##STR69## is obtained by action of methyl sulfate on the compound of formula (XIV) ##STR70##

The compound (XIV) is obtained by action of potassium carbonate on the following compound (XIb) ##STR71## which is itself obtained by Baeyer Williger reaction on the compound of formula (XV) ##STR72##

The novel compound (XV) is obtained by action of benzyl chloride, in solution in acetonitrile or acetone, in the presence of potassium carbonate, on the compound (VIIi): ##STR73## (2) The compounds (XI) corresponding to the formula (XIc): ##STR74## in which R.sub.15 represents the ethyl, isopropyl, tertbutyl, n-pentyl, or cyclohexyl groups are obtained:

when in (XIc) R.sub.15 represents the isopropyl, t-butyl, n-pentyl, and cyclohexyl groups, by a synthesis in two stages which consists in treating the compound of formula (XVI) ##STR75## with thionyl chloride, then by reacting the crude product thus obtained with alcohols of formula (XVII):

in which R.sub.15 has the same meaning as in formula (XIc), except for the ethyl group, and

when in (XIc) R.sub.15 represents the ethyl group, by action of ethanol in the presence of hydrochloric acid, on the compound of formula (XVI).

The compound of formula (XVI), also novel, is obtained by oxidation by the iodine-pyridine complex, in the presence of soda, of the compound of formula (XV): ##STR76## (3) The (XI) compounds corresponding to the formula (XId): ##STR77## in which R.sub.16 represents either the hydrogen atom or the methyl, cyclohexyl or phenyl groups are obtained:

when R.sub.16 assumes the above meanings, except for the methyl group, by a two-stage synthesis which consists in treating the compound of formula (XVI) with thionyl chloride, then in reacting on the crude product thus obtained the amines of formula (XVIII)

in which R.sub.16 represents the hydrogen atom or a cyclohexyl or phenyl group, and

when R.sub.16 represents the methyl group, from the compound of formula (XVI) following the process of mixed anhydrides (with methylamine).

(4) The compounds (XI) corresponding to formula (XIe): ##STR78## in which R.sub.17 represents either a linear or branched alkyl group having from 2 to 5 carbon atoms, or the cyclohexyl group, or the phenyl group, are obtained by action of acid chlorides of formula (XIX):

in which R.sub.17 has the same meanings as in (XIe), on the compounds of formula (XX): ##STR79## in a tetrahydrofuran medium. (5) The compounds of formula (XI) corresponding to formula (XIf): ##STR80## in which p and R.sub.18 assume simultaneously the following values: p=2; R.sub.18 represents either a linear or branched alkyl group having 1 to 5 carbon atoms or the cyclohexyl, phenyl or paramethoxyphenyl groups,

p=1 or 3; R.sub.18 represents the methyl group,

are obtained by action of isocyanates of formula (XXI):

on the compounds of formula (XX) above and (XXa) ##STR81## in which p' assumes the values 1 or 3. (6) The compound (XI) corresponding to formula (XIg): ##STR82## is obtained by action of ethyl chloroformate on the compound of formula (XX) above.

The compounds of formulae (XX) and (XXa) used in the synthesis given under items (4), (5) and (6) above are novel and are obtained by hydrolysis, with potash (KOH) in ethanol, of the compounds of formula (XIh) ##STR83## in which p assumes the values 1, 2 or 3.

The compounds of formula (XIh) are, for their part, obtained:

either by a Beckmann rearrangement, in an acid medium, of the compounds of formula (XXII): ##STR84## in which p' assumes the values 1 or 3. or by action of benzyl chloride on the compound of formula (VIIm): ##STR85## in an acetone solution, in the presence of potassium carbonate.

The compounds of formula (XXII) above are obtained by action of hydroxylamine on the compounds of formula (XIi): ##STR86## in which p' assumes the values 1 or 3.

The compounds of formula (XIi) are obtained by action of a di-iodated or dibrominated derivative of formula (XXIII):

or

in which p' assumes the value 1 or 3, on the compound of formula (XXIV): ##STR87## in solution in dimethyl sulfoxide or N,N-dimethylformamide in the presence of potash (KOH).

Compound (XXIV) is obtained by action of benzyl chloride on gallacetophenone.

(7) The compound (XI) corresponding to formula (XIj): ##STR88## is obtained by action of methyl isocyanate on compound (XXV): ##STR89## Compound (XXV) is obtained by a synthesis in two steps which consists in treating the compound of formula (XX) with a mixture of formaldehyde and 5,5-dimethylhydantoin in an ethanol solution, then in reacting on the crude reaction product, sodium borohydride in solution in dimethylsulfoxide, at a temperature of 100.degree. C.

(8) Compound (XI) corresponding to formula (XIk): ##STR90## is obtained by action of morpholine at reflux on the compound of formula (XIg): ##STR91## (9) Compound (XI) corresponding to formula (XIl): ##STR92## is obtained by action of N,N-dimethylcarbamoyl chloride on the compound of formula (XX).

(10) Compound (XI) corresponding to formula (XIm): ##STR93## is obtained by action of sodium cyanide on the compound of formula (XXVI): ##STR94## Compound (XXVI) is obtained by action of thionyl chloride on compound (XIp), hereafter described.

(11) Compound (XI) corresponding to formula (XIn): ##STR95## is obtained by treating compound (XIm): ##STR96## by potash (KOH) in solution in t-butanol. (12) Compound (XI) corresponding to formula (XIo): ##STR97## is obtained by action of methylamine following the mixed anhydride method on the compound of formula (XXVII): ##STR98## Compound (XXVII) is obtained by saponification with an aqueous solution of NaOH of compound (XIm).

(13) Compound (XI) corresponding to formula (XIp): ##STR99## is obtained by reduction with the double hydride of lithium and aluminum of the compound of formula (XIc), in which R.sub.15 represents the ethyl group.

(14) Compound (XI) corresponding to formula (XIq): ##STR100## is obtained by action of phosphorous pentachloride on the compound (XId) in which R.sub.16 represents the hydrogen atom.

(15) Compound (XI) corresponding to formula (XIr): ##STR101## is obtained by action of ethanol, in the presence of hydrochloric acid, on the compound of formula (XXVII): ##STR102##

The process for the preparation of the compounds of formula (I) in which: ##STR103## consists in hydrolyzing the acetoxy group of compounds of formulae (Ia) and (Ib) ##STR104## with an alcohol solution of sodium bicarbonate.

The compounds of formulae (Ia) and (Ib) are obtained by a process identical to that used for the synthesis of compounds of formula (I) previously described.

The process for the preparation of the compounds of formula (I) in which X represents the methylamino group: ##STR105## consists in condensing an epoxy of formula (IIIh): ##STR106## with N-methylaniline in an alcohol medium.

The compound of formula (IIIh) is obtained by condensing epibromohydrin on 3,4,5-trimethoxy cinnamoylpiperazine of formula (IIc): ##STR107## in solution in acetonitrile, in the presence of potassium carbonate.

The process for the preparation of compounds of formula (I), in which R.sub.1 represents the hydrogen atom consists in condensing piperazine of formula (IIc) above with a chlorinated derivative of formula (XXVIII): ##STR108## in which R.sub.12 represents the acetyl, acetamido, N-methyl carboxamido or N-methylcarbamoylamino groups in solution in acetonitrile, in the presence of potassium carbonate.

The novel compounds of formula (XXVIII) are obtained by condensation of 1-bromo-3-chloropropane with the phenols of formula (VII):

in which X' represents the oxygen atom and Ar' is ##STR109## in which R.sub.12 has the same meanings as in formula (XXVIII).

The following preparations are given by way of example to illustrate the invention.

Code number: 770 993

A mixture of 9.2 g of 3,4,5-trimethoxy cinnamoyl piperazine and 6.2 g of 1-(2-methyl-4-acetylphenyl)-2,3-epoxy propane in 65 ml of ethanol was brought to reflux for 4 hours. The solvent was evaporated and the residue was chromatographed on a silica column eluted by chloroform-methanol: 98%/2% mixture and 12 g of an oil was obtained which was dissolved in acetone. Then, a gaseous current of dry hydrochloric acid was passed until an acid pH was obtained, then the precipitate obtained was filtered.

Yield: 45%

Melting Point: 140.degree. C.

Empirical formula: C.sub.28 H.sub.37 ClN.sub.2 O.sub.7

Molecular weight: 549.05

By the same process, but from corresponding reagents, the compounds of formula I, given in the following Table I, were obtained, except for the compounds of formula I in which R.sub.1 .dbd.H which are obtained with the process of Example 3, for the compounds of code number 770 274 and 780 120 (obtained in Example 2) and 770 495 (obtained in Example 4). ##STR110## CodeNumber ##STR111## n R.sub.1 X m A.sub.r Form EmpiricalFormula Mole-cularweight Meltingpoin t(.degree.C.) Yield% ELEMENTARYANALYSISCHN 770993 ##STR112## 1 OH Oxygen 0 ##STR113## HCl C.sub.28 H.sub.37 ClN.sub.2 O.sub.7 549.05 140 45 Cal. %Obt. % 61.2561.12 6.796.62 5.105.04 770194 ##STR114## " " " " ##STR115## oxalate C.sub.29 H.sub.32 N.sub.2 O.sub.12+ 3/2 H.sub.2 O 627.59 118 71 C al. %Obt. % 55.5055.85 5.625.48 4.464.71 770199 ##STR116## " " " " " " C.sub.28 H.sub.31 FN.sub.2 O.sub.10+ 4/5 H.sub.2 O 588.96 136 79 Cal. %Obt. % 57.1056.97 5.585.28 4.764.88 770504 ##STR117## " " " " " " C.sub. 32 H.sub.40 N.sub.2 O.sub.13 660.56 191 58 Cal. %Obt. % 58.1757.87 6.106.13 4.244.29 770538 ##STR118## " " " " " Base C.sub.28 H.sub.34 N.sub.2 O.sub.8 526.57 168 63 Cal. %Obt. % 63.8663.56 6.516.41 5.325.01 770727 ##STR119## " " " " " HCl C.sub.31 H.sub.41 ClN.sub.2 O.sub.9+ 5/3 H.sub.2 O 651.14 145 27 Cal. %Obt. % 57.1857.45 6.866.42 4.304.39 770276 ##STR120## " " " 1 ##STR121## HCl C.sub.26 H.sub.35 ClN.sub.2 O.sub.6 + 2/3 H.sub.2 O 519.02 170 90 Cal. %Obt. % 60.1660.04 7.066.75 5.405.55 770307 " " " " 0 ##STR122## HCl C.sub.30 H.sub.41 ClN.sub.4 O.sub.3+ H.sub.2 0 655.133 172 65 Cal. O %bt. % 55.0054.80 6.626.57 8.558.49 770312 " " " " " ##STR123## HCl C.sub.31 H.sub.41 ClN.sub.2 O.sub.10+ 2/3 H.sub.2 O 649.111 156 94 Cal. %Obt. % 57.3657.45 6.576.60 4.324.11 770382 " " " " " ##STR124## HCl C.sub.30 H.sub.40 ClN.sub.3 O.sub.9+ 1 1/6 H.sub.2 O 643.120 180 87 C al. %Obt. % 56.0255.99 6.646.54 6.536.45 770386 " " " " " ##STR125## HCl C.sub.29 H.sub.38 ClN.sub.3 O.sub.9+ 1,5 H.sub.2 O 635.099 180 65 Cal. %Obt. % 54.8455.00 6.516.27 6.626.61 770458 " " " " " ##STR126## HCl C.sub.27 H.sub.35 ClN.sub.2 O.sub.7 535.02 132 59 Cal. %Obt. % 6 60.610.67 6.596.53 5.245.18 770483 " " " " " ##STR127## Oxalate C.sub. 33 H.sub.44 N.sub.4 O.sub.13 704.714 200 95 Cal. %Obt. % 5 6.2455.96 6.296.29 7.957.86 770487 " " " " " ##STR128## Oxalate C.sub.30 H.sub.39 N.sub.3 O.sub.12+ 1/2 H.sub.2 O 642.64 170 36 C al. %Obt. % 56.0755.94 6.286.08 6.546.52 770488 " " " " " ##STR129## " C.sub.29 H.sub.36 N.sub.3 O.sub.10+ 3/5 H.sub.2 O 596.40 115 36 Cal. O %bt. % 58.4058.53 6.125.75 7.057.13 770525 " " " " " ##STR130## Oxalate C.sub.32 H.sub.41 N.sub.3 O.sub.14+ 1/2 H.sub.2 O 700.68 162 96 C al. %Obt. % 54.8555.02 6.045.97 6.005.89 770529 " " " " " ##STR131## " C.sub.36 H.sub.41 N.sub.3 O.sub.13+ 3/5 H.sub.2 O 734.521 177 93 Cal. %Obt. % 58.8659.05 5.795.40 5.725.96 770533 " " " " " ##STR132## " C.sub.36 H.sub.47 N.sub.3 O.sub.13+ 3/4 H.sub.2 O 743.372 195 98 Cal. %Obt. % 58.1758.15 6.586.40 5.655.72 770545 " " " " " ##STR133## " C.sub.32 H.sub.41 N.sub.3 O.sub.13+ 2/5 H.sub.2 O 682.878 165 100 Cal. %Obt.% 56.2855.98 6.176.00 6.156.18 770581 " " " " " ##STR134## Oxalate C.sub.29 H.sub.36 N.sub.3 O.sub.11+ 1/5 H.sub.2 O 629.626 178 52.5 Cal. %Obt. % 52.3255.14 6.246.31 6.676.66 770585 " " " " " ##STR135## Base C.sub.28 H.sub.33 N.sub.3 O.sub.8 539.568 154 82.5 Cal. %Obt. % 62.3262.25 6.166.26 7.797.80 770590 " " " " " ##STR136## Oxalate C.sub.31 H.sub.38 N.sub.2 O.sub.13+ 3/5 H.sub.2 O 657.44 172 18 C al. %Obt. % 56.6356.86 6.015.85 4.264.13 770601 " " " " " ##STR137## " C.sub.34 H.sub.45 N.sub.3 O.sub.13+ 4/5 H.sub.2 O 718.136 177 97.5 Cal. %Obt. % 56.8657.06 6.546.32 5.855.72 770610 " " " " " ##STR138## " C.sub.33 H.sub.43 N.sub.3 O.sub.13+ 1/5 H.sub.2 O 693.301 190 100 Cal. %Obt. % 57.1757.42 6.316.17 6.066.05 770614 " " " " " ##STR139## " C.sub.34 H.sub.45 N.sub.3 O.sub.13 707.724 203 100 Cal. %Obt. % 58.0357.74 6.456.25 5.975.91 770622 " 2 " " " ##STR140## HCl C.sub.30 H.sub.39 ClN.sub.2 O.sub.9+ 1/5 H.sub.2 O 639.51 85 17 Cal. %Obt. % 56.3456.10 6.716.78 4.384.14 770630 " 1 " " " ##STR141## Oxalate C.sub.33 H.sub.44 N.sub.4 O.sub.13 704.714 198 90 Cal. %Obt. % 56.2455.93 6.296.37 7.95 8.14 770634 " " " " " ##STR142## Oxalate C.sub.34 H.sub.46 N.sub.4 O.sub.13+ 3/5 H.sub.2 O 729.549 175 90 Cal. %Obt. % 55.9755.75 6.526.33 7.687.59 770692 " " " " " ##STR143## Oxalate C.sub.33 H.sub.43 N.sub.3 O.sub.13+ 2/3 H.sub.2 O 701.709 192 99 Cal. %Obt. % 56.4856.48 6.376.34 5.995.90 770711 " " " " " ##STR144## Oxalate C.sub.34 H.sub.46 N.sub.4 O.sub.13 718.740 168 65 Cal. %Obt. % 56.8156.86 6.456.56 7.80 7.96 770738 " " " " " ##STR145## Oxalate C.sub.27 H.sub.35 N.sub.3 O.sub.7+ 1.78 (COOH).sub.2+ 1.75 H.sub.2 O 699.96 119 23 Cal. %Obt. % 52.2352.11 6.045.69 6.005.84 770855 " " " " " ##STR146## HCl C.sub.28 H.sub.38 ClN.sub.3 O.sub.8+ 2 H.sub.2 O 616.10 173 73 Cal. %Obt. % 54.5854.56 6.606.49 7.246.92 770858 " " " " " ##STR147## HCl C.sub.28 H.sub.39 ClN.sub.2 O.sub.6 535.06 204 68 Cal. %Obt. % 6 62.853.09 7.357.54 5.245.20 770859 " " " " " ##STR148## HCl C.sub.29 H.sub.41 ClN.sub.2 O.sub.6+ 1/6 H.sub.2 O 552.09 210 94 Cal. %Obt. % 63.0963.13 7.557.47 5.025.29 770898 " " " " " ##STR149## Base C.sub.28 H.sub.38 N.sub.4 O.sub.7+ 3/5 H.sub.2 O 553.42 136 41 Cal. %Obt. % 60.7660.40 7.147.38 10.129.21 770831 " " " " " ##STR150## Oxalate C.sub.36 H.sub.47 N.sub.3 O.sub.13 729.760 207 54 Cal. %Obt. % 59.2559.08 6.496.38 5.766.08 770844 " " " " " ##STR151## Base C.sub.27 H.sub. 35 N.sub.3 O.sub.7+ 1 H.sub.2 O 531.59 103 46 Cal. %Obt. % 61.0060.81 7.027.25 7.918.08 770848 " " " " " ##STR152## Oxalate C.sub.36 H.sub.41 N.sub.3 O.sub.13+ 1/3 H.sub.2 O 729.717 173 100 Cal. %Obt. % 59.2558.97 5.765.69 5.765.48 770854 " " " " " ##STR153## HCl C.sub.28 H.sub.37 ClN.sub.2 O.sub.7+ 9/4 H.sub.2 O 589.58 114 45 Cal. %Obt. % 57.0457.12 7.106.81 4.754.77 770963 " " " " " ##STR154## HCl C.sub.26 H.sub.33 N.sub.3 O.sub.8+ 6/5 HCl+ 3/5 H.sub.2 O 570.11 155 53 Cal. %Obt. % 54.7754.76 6.265.93 7.377.22 770966 " " " " " ##STR155## " C.sub.26 H.sub.34 Cl.sub.2 N.sub.2 O.sub.6 541.46 122 52 Cal. %Obt. % 5 7.6757.63 6.336.26 5.174.90 770992 " " " " " ##STR156## Base C.sub.29 H.sub.40 N.sub.4 O.sub.9 588.64 172 44 Cal. %Obt. % 59.1758.91 6.856.55 9.529.35 771014 " " " " " ##STR157## HCl C.sub.27 H.sub.34 Cl.sub.2 N.sub.2 O.sub.6 552.46 191 70 Cal. %Obt. % 58.3858.06 6.536.39 5.045.03 771031 " " " "" ##STR158## Oxalate C.sub.33 H.sub.40 N.sub.4 O.sub.11+ 1/6 H.sub.2 O 671.685 204 67 Cal. %Obt. % 59.0158.71 6.055.96 8.348.40 771036 " " " " " ##STR159## HCl C.sub.31 H.sub.38 ClN.sub.3 O.sub.7 600.095 225 84 Cal. %Obt. % 62.0461.93 6.386.09 7.007.11 771076 " " " " " ##STR160## Base C.sub.27 H.sub.36 N.sub.3 O.sub.7+ 2/3 H.sub.2 O 525.58 80 29 Cal. %Obt. % 61.7062.25 6.967.05 7.807.87 771077 " " " " " ##STR161## " C.sub.28 H.sub.37 N.sub.3 O.sub.7 545.61 92 83 Cal. %Obt. % 61.6361.94 7.217.01 7.707.70 771124 " " " " " ##STR162## Base C.sub.25 H.sub.30 ClN.sub.3 O.sub.8 535.97 152 82 Cal. %Obt. % 56.0255.71 5.645.71 7.847.53 771149 " " " " " ##STR163## HCl C.sub.32 H.sub.43 ClN.sub.4 O.sub.10+ 2 H.sub.2 O 715.185 182 98 Cal. %Obt. % 53.7454.11 6.026.48 7.837.52 771153 " " " " " ##STR164## " C.sub.30 H.sub.41 ClN.sub.4 O.sub.7+ 4/5 H.sub.2 O 619.529 200 85 Cal. %Obt. % 58.1657.95 6.936.86 9.049.33 771157 " " " " " ##STR165## Oxalate C.sub.33 H.sub.44 N.sub.4 O.sub.11+ 2/5 H.sub.2 O 679.920 200 76 Cal. %Obt. % 58.2958.32 6.646.49 8.248.14 771233 " " " " " ##STR166## Oxalate C.sub.32 H.sub.42 N.sub.4 O.sub.13+ 5/6 H.sub.2 O 705.701 168 45 Cal. %Obt. % 54.4654.55 6.245.93 7.947.72 771238 " " " " " ##STR167## HCl C.sub.30 H.sub.41 ClN.sub.4 O.sub.9+ 7/6 H.sub.2 O 658.136 188 36 Cal. %Obt. % 54.7554.74 6.646.55 8.518.21771281 " " " " " ##STR168## " C.sub.27 H.sub.34 ClN.sub.3 O.sub.7+ H.sub.2 O 566.04 186 78 Cal. %Obt. % 57.2957.24 5.416.10 7.427.34 771306 " " " " " ##STR169## " C.sub.30 H.sub.40 ClN.sub.3 O.sub.7+ 5/3 H.sub.2 O 620.128 185 78 Cal. %Obt. % 58.1057.81 7.046.72 6.786.63 780044 " " " " " ##STR170## HCl C.sub.29 H.sub.37 ClN.sub.2 O.sub.10+ 1 1/6 H.sub.2 O 630.078 205 28 Cal. %Obt. % 55.2855.35 6.135.95 4.454.44 780009 " " " " " ##STR171## " C.sub.28 H.sub.37 ClN.sub.2 O.sub.9+ 4/5 H.sub.2 O 595.461 178 38 Cal. %Obt. % 56.4756.51 6.536.58 4.704.43 7800044 " " " " " ##STR172## " C.sub.31 H.sub.42 ClN.sub.3 O.sub.7+ 3/2 H.sub.2 O 631.151 185 56 Cal. %Obt. % 58.9959.19 7.196.81 6.666.66 780128 " " " " " ##STR173## " C.sub.31 H.sub.41 ClN.sub.2 O.sub.7+ 4/5 H.sub.2 O 603.523 150 60 Cal. %Obt. % 61.6961.79 7.126.79 4.644.68 771309 " " " " " ##STR174## Oxalate C.sub.30 H.sub.40 N.sub.4 O.sub.11+ 0.95 H.sub.2 O 649.77 184 48 Cal. %Obt. % 55.4555.80 6.506.35 8.628.56 771315 " " " " " ##STR175## HClC.sub.31 H.sub.37 N.sub.2 O.sub.7 Cl+ H.sub.2 O 603.095 210 30 Cal. O %bt. % 61.7361.86 6.526.20 4.654.64 771318 " " " " " ##STR176## Oxalate C.sub.32 H.sub.36 N.sub.2 O.sub.7+ 1.17(COOH).sub.2 665.97 170 23 Cal. %Obt. % 61.9361.91 6.115.84 4.214.12 771348 " " " " " ##STR177## " C.sub.30 H.sub.39 N.sub.3 O.sub.11+ 3/5 H.sub.2 O 628.45 180 51 Cal. O %bt. % 57.3357.06 6.456.14 6.696.70 780138 " " " " " ##STR178## HCl C.sub.26 H.sub.33 ClN.sub.2 O.sub.8 536.998 199 30 Cal. %Obt. % 58.1558.03 6.196.39 5.225.47 780150 " " " " " ##STR179## OxalateC.sub.30 H.sub.38 N.sub.2 O.sub.12 618.62 212 71 Cal. %Obt. % 58.2458.43 6.196.46 4.534.69 780189 " " " " " ##STR180## " C.sub.27 H.sub.35 ClN.sub.4 O.sub.7+ 6/5(COOH).sub.2+ 1/2 H.sub.2 O 680.09 120 37 Cal. %Obt. % 51.9251.345.645.58 8.238.08 780223 " " " " " ##STR181## HCl C.sub.35 H.sub.43 ClN.sub.4 O.sub.10+ 0.6 H.sub.2 O 725.992 155 30 Cal. %Obt. % 57.9057.96 6.146.19 7.727.60 780225 " " " " " ##STR182## Oxalate C.sub.29 H.sub.37 N.sub.3 O.sub.9 + 0.5(COOH).sub.2+ H.sub.2 O 634.654 154 40 Cal. %Obt. % 56.7756.87 6.356.38 6.626.86 780241 " " " " " ##STR183## HCl C.sub.30 H.sub.39 ClN.sub.2 O.sub.9+ H.sub.2 O 625.101 183 81 Cal. O %bt. % 57.6457.90 6.616.50 4.484.35 780267 " " " " " ##STR184## Base C.sub.28 H.sub.38 N.sub.2 O.sub.6 498.600 110 59 Cal. %Obt. % 6 67.447.17 7.687.77 5.625.78 780269 " 2 " " " ##STR185## HCl C.sub.29 H.sub.39 ClN.sub.2 O.sub.8+ 3/4 H.sub.2 O 592.59 106 46Cal. %Obt. % 58.77 58.55 6.896.43 4.734.53 780272 " " " " " ##STR186## Oxalate C.sub.32 H.sub.41 N.sub.3 O.sub.13+ 5/6 H.sub.2 O 690.686 130 30 Cal. %Obt. % 55.6455.75 6.236.33 6.085.90 780292 " 1 " " " ##STR187## " C.sub.29 H.sub.36 Cl.sub.2 N.sub.4 O.sub.11 687.52 200 30 Cal. %Obt. % 50.6650.38 5.285.49 8.158.18 780301 " " " " " ##STR188## "C.sub.35 H.sub.46 N.sub.2 O.sub.14 718.734 146 93 Cal. %Obt. % 58.4858.58 6.456.48 3.903.92 780302 " " " " " ##STR189## HCl C.sub.29 H.sub.39 ClN.sub.2 O.sub.7 563.17 158 19 Cal. %Obt. % 6 61.841.56 6.986.95 4.975.11 780346 " " " " " ##STR190## HCl C.sub.28 H.sub.36 ClN.sub.3 O.sub.9+ 3/5 H.sub.2 O 604.858 168 43 Cal. %Obt. % 55.6055.82 6.206.21 6.957.12 780353 " " " " " ##STR191## Oxalate C.sub.29 H.sub.35 FN.sub.2 O.sub.11+ 3/5 H.sub.2 O 617.39 125 33 Cal. %Obt. % 56.4156.33 5.915.79 4.544.76 780357 " " " " " ##STR192## " C.sub.31 H.sub.42 N.sub.4 O.sub.13 678.68 125 12 Cal. %Obt. % 54.8555.06 6.246.55 8.268.25 780359 " " " " " ##STR193## " C.sub.31 H.sub.40 N.sub.2 O.sub.13+ 1/5 H.sub.2 O 652.25 188 34 Cal. O %bt. % 57.0856.94 6.246.13 4.294.21780308 " " " " " ##STR194## HCl C.sub.28 H.sub.35 ClN.sub.2 O.sub.9+ 0.33 H.sub.2 O 585.038 192 70 Cal. %Obt. % 57.4857.53 6.156.32 4.794.64 780329 " " " " " ##STR195## Base C.sub.27 H.sub.34 N.sub.2 O.sub.8 514.55 135 21 Cal. %Obt. % 63.0262.70 6.666.85 5.445.51 780333 " " " " " ##STR196## Oxalate C.sub.36 H.sub.46 N.sub.2 O.sub.14+ 1/2 H.sub.2 O 739.752 172 97 Cal. %Obt. % 58.4558.41 6.406.35 3.793.89 780339 " " " " " ##STR197## " C.sub.29 H.sub.34 Cl.sub.2 N.sub.2 O.sub.11 657.49 175 39 Cal. %Obt. % 52.9753.06 4.914.85 4.264.12 780361 " " " " " ##STR198## Oxalate C.sub.32 H.sub.42 N.sub.2 O.sub.14+ H.sub.2 O 696.69 200 40 Cal. %Obt. % 55.1655.45 6.376.15 4.023.71 780369 " " " " " ##STR199## HCl C.sub.32 H.sub.43 ClN.sub.2 O.sub.10+ H.sub.2 O 675.158 195 90 Cal. %Obt. % 56.9256.64 6.826.50 4.153.84 780373 " " " " " ##STR200## Oxalate C.sub.33 H.sub.42 N.sub.2 O.sub.14+ 0.9 H.sub.2 O 706.896 130 80 Cal. %Obt. % 56.0756.35 6.245.91 3.963.95 780374 " 2 " " " ##STR201## HCl C.sub.30 H.sub.41 ClN.sub.4 O.sub.9+ 1.9 H.sub.2 O 671.347 185 65 Cal. %Obt. % 53.6753.43 6.736.52 8.358.30 780384 " 1 " Sulfur " ##STR202## HCl C.sub.29 H.sub.37 ClN.sub.2 O.sub.8 S+ 3/5 H.sub.2 O 619.934 192 73 C al. %Obt. % 56.1856.45 6.216.10 4.524.52 780389 " " " " " ##STR203## " C.sub.27 H.sub.35 ClN.sub.2 O.sub.7 S 567.089 171 50 Cal. %Obt. % 57.1856.96 6.226.55 4.944.90 780393 " " " Oxygen " ##STR204## " C.sub.30 H.sub.40 ClN.sub.3 O.sub.9+ 2/5 H.sub.2 O 629.307 180 94 Cal. %Obt. % 57.2556.96 6.536.23 6.686.41 780401 " " " " " ##STR205## Oxalate C.sub.29 H.sub.35 ClN.sub.2 O.sub.11 623.04 135 42 Cal. %Obt. % 5 5.9055.77 5.665.69 4.504.53 780409 " " " " " ##STR206## HCl C.sub.28 H.sub.37 ClN.sub.4 O.sub.9+ H.sub.2 O 627.081 156 62 Cal. O %bt. % 53.6253.67 6.116.19 8.949.04 780411 " " " " " ##STR207## Oxalate C.sub.33 H.sub.44 N.sub.2 O.sub.10 628.698 194 43 Cal. %Obt. % 63.0462.78 7.057.09 4.464.76 780415 " 2 " " " ##STR208## HCl C.sub.28 H.sub.37 ClN.sub.4 O.sub.7 549.05 232 52 Cal. %Obt. % 6 61.251.28 6.796.58 5.104.83 780448 " 1 " " " ##STR209## Oxalate C.sub.31 H.sub.40 N.sub.2 O.sub.12 632.65 165 64 Cal. %Obt. % 58.8558.63 6.376.29 4.434.32 780452 " " " " " ##STR210## Oxalate C.sub.30 H.sub.37 N.sub.2 O.sub.9 569.61 185 56 Cal. %Obt. % 63.2563.10 6.546.76 4.925.01 780455 " " " S " ##STR211## " C.sub.29 H.sub.36 N.sub.2 O.sub.10 S+ H.sub.2 O 622.68 152 56 Cal. %Obt. % 55.9356.08 6.155.98 4.504.71 780456 " " " Oxygen " ##STR212## HCl C.sub.30 H.sub.41 ClN.sub.4 O.sub.9+ 2 H.sub.2 O 673.149 177 85 Cal. %Obt. % 53.5253.57 6.746.28 8.328.11 780474 " " " S " ##STR213## Oxalate C.sub.30 H.sub.38 N.sub.2 O.sub.11 S+ 3/5 H.sub.2 O 645.49 157 22 Cal. %Obt. % 55.8256.10 6.126.36 4.344.66 760382 " " " Oxygen " ##STR214## HCl C.sub.28 H.sub.37 ClN.sub.2 O.sub.8 565.05 170 63 Cal. %Obt. % 5 59.519.77 6.606.66 4.965.09 760385 " " " " " ##STR215## HCl C.sub.27 H.sub.35 ClN.sub.4 O.sub.7+ 2 H.sub.2 O 571.05 130 59 Cal. %Obt. % 56.7856.76 6.886.68 4.914.96 760389 " " " " " ##STR216## HCl C.sub.26 H.sub.33 ClN.sub.3 O.sub.6+ 1/2 H.sub.2 O 528.01 130 64 Cal. %Obt. % 59.1459.29 6.496.49 7.968.18 760390 " " " " " ##STR217## HCl C.sub.26 H.sub.35 ClN.sub.2 O.sub.7+ 3/4 H.sub.2 O 536.55 163 70 Cal. %Obt. % 58.2558.15 6.736.60 5.225.03 760392 " " " " " ##STR218## HCl C.sub.26 H.sub.35 ClN.sub.2 O.sub.7+ H.sub.2 O 541.03 197 45 Cal. %Obt. % 57.7257.79 6.896.68 5.184.92 760393 " " " " " ##STR219## " C.sub.27 H.sub.37 ClN.sub.2 O.sub.8+ H.sub.2 O 571.05 120 77 Cal. %Obt. % 56.7856.80 6.886.93 4.904.86 760394 " " " " " ##STR220## Oxalate C.sub. 31 H.sub.38 N.sub.2 O.sub.13+ 1/3 H.sub.2 O 652.63 195 47 Cal. %Obt. % 57.0557.13 5.975.85 4.294.24 760455 " " " " " ##STR221## HCl C.sub.27 H.sub.35 ClN.sub.2 O.sub.7+ H.sub.2 O 554.03 117 74 Cal. %Obt. % 58.5358.33 6.916.30 5.065.23 760476 " " " " " ##STR222## HCl C.sub.25 H.sub.32 Cl.sub.2 N.sub.2 O.sub.6 527.44 158 77 Cal. %Obt. % 56.9356.80 6.126.30 5.315.16 760501 " " " " " ##STR223## Base C.sub.26 H.sub.31 N.sub.3 O.sub.6 481.53 137 50 Cal. %Obt. % 64.8564.62 6.496.52 8.738.61 760506 " " " " " ##STR224## HCl C.sub.28 H.sub.39 ClN.sub.2 O.sub.9+ 1/2 H.sub.2 O 592.07 215 55 Cal. %Obt. % 56.8056.71 6.816.53 4.734.97 760507 " " " " " ##STR225## HCl C.sub.26 H.sub.35 ClN.sub.2 O.sub.6 S+ 1/4 H.sub.2 O 543.58 195 51 Cal. %Obt. % 57.4457.44 6.586.52 5.155.44 760519 " " " " " ##STR226## HCl C.sub.27 H.sub.35 ClN.sub.2 O.sub.8+ H.sub.2 O 569.04 190 80 Cal. %Obt. % 56.8957.34 6.556.62 4.924.80 760520 " " " " " ##STR227## HCl C.sub.25 H.sub.32 Cl.sub.2 N.sub.2 O.sub.6+ H.sub.2 O 545.45 152 48 C al. %Obt. % 55.0554.90 6.286.29 5.144.95 760529 " " " " " ##STR228## HCl C.sub.26 H.sub.33 ClN.sub.2 O.sub.8+ 1/3 H.sub.2 O 536.99 178 25 Cal. %Obt. % 57.5157.53 6.256.51 5.165.15 760538 " " " " " ##STR229## HCl C.sub.25 H.sub.32 ClN.sub.3 O.sub.8+ 2/5 H.sub.2 O 545.19 195 40 Cal. %Obt. % 55.0754.72 6.065.95 7.717.59 760542 " " " " " ##STR230## Base C.sub.27 H.sub.35 N.sub.3 O.sub.7+ 2 H.sub.2 O 549.61 115 31 Cal. %Obt. % 59.0059.03 7.156.64 7.657.68 760580 " " " " " ##STR231## HCl C.sub.27 H.sub.37 ClN.sub.2 O.sub.8+ 1/2 H.sub.2 O 562.05 190 76 Cal. %Obt. % 57.6957.74 6.826.69 4.974.96 760619 " " " " " ##STR232## HCl C.sub.24 H.sub.32 ClFN.sub.2 O.sub.6+ 1/2 H.sub.2 O 519.99 197 67 Cal. %Obt. % 57.7458.00 6.406.38 5.395.09 760620 " " " " " ##STR233## HCl C.sub.27 H.sub.37 ClN.sub.2 O.sub.8+ 4/5 H.sub.2 O 567.45 184 85 Cal. %Obt. % 57.15 57.37 6.866.75 4.945.03 760700 ##STR234## 1 OH Oxygen 0 ##STR235## HCl C.sub.30 H.sub.39 ClN.sub.2 O.sub.10+ H.sub.2 O 641.10 175 62.5 Cal. %Obt. % 56.2056.26 6.456.37 4.374.29 760705 " " " " " ##STR236## Base C.sub.28 H.sub.36 N.sub.2 O.sub.9 544.58 100 12 Cal. %Obt. % 61.7561.44 6.666.57 5.144.84 760710 " " " " " ##STR237## Oxalate C.sub.31 H.sub.39 N.sub.3 O.sub.13+ 5/4 H.sub.2 O 684.17 160 37 C al. %Obt. % 54.4254.65 6.116.00 6.146.10760781 " " " " " ##STR238## HCl C.sub.30 H.sub.41 ClN.sub.2 O.sub.10+ 4/3 H.sub.2 O 649.12 138 62 Cal. %Obt. % 55.9155.10 6.786.45 4.324.40 760784 " " " " " ##STR239## HCl C.sub.26 H.sub.33 ClN.sub.3 O.sub.6+ 1/2 H.sub.2 O 528.01 130 64 Cal. %Obt. % 59.1459.29 6.496.49 7.968.18 760847 " " " " " ##STR240## Oxalate C.sub.30 H.sub.38 N.sub.2 O.sub.12+ 2/5 H.sub.2 O 625.83 148 72 C al. %Obt. % 57.5757.55 6.256.04 4.484.46 760852 " " " " " ##STR241## HCl C.sub.30 H.sub.39 ClN.sub.2 O.sub.7+ 3/4 H.sub.2 O 588.59 130 43 Cal. %Obt. % 61.1261.21 6.726.94 4.724.76 760866 " " " " " ##STR242## " C.sub.31 H.sub.41 ClN.sub.2 O.sub.9+ H.sub.2 O 640.93 142 49 Cal. %Obt. % 58.0957.91 6.786.72 4.374.17 760868 " " " " " ##STR243## Oxalate C.sub.31 H.sub.39 N.sub.3 O.sub.13+ 3/2 H.sub.2 O 724.28 136 70 C al. %Obt. % 53.0353.10 5.845.75 5.805.94 760892 " " " " " ##STR244## Base C.sub.29 H.sub.39 N.sub.3 O.sub.7+ 2/3 H.sub.2 O 553.64 108 40 Cal. %Obt. % 62.9162.99 7.347.28 7.597.53 760986 " " " " " ##STR245## HCl C.sub.29 H.sub.37 ClN.sub.2 O.sub.7+ 4/5 H.sub.2 O 575.47 168 11 Cal. %Obt. % 60.5260.38 6.766.61 4.874.86 770056 " " " " " ##STR246## Base C.sub.27 H.sub.36 N.sub.4 O.sub.7 528.59 >200 12 Cal. %Obt. % 6 61.351.06 6.867.00 10.6010.25 770058 " " " " " ##STR247## HCl C.sub.26 H.sub.34 ClN.sub.3 O.sub.7+ 1/2 H.sub.2 O 545.02 143 48 Cal. %Obt. % 57.2957.23 6.476.36 7.717.49 770059 " " " S " ##STR248## " C.sub.26 H.sub.35 ClN.sub.2 O.sub.5 S 523.08 200 55 Cal. %Obt. % 5 59.709.61 6.746.82 5.365.34 770060 " " " " " ##STR249## " C.sub.25 H.sub.33 ClN.sub.2 O.sub. 5 S 509.05 154 56 Cal. %Obt. % 58.9858.68 6.536.55 5.505.59 770073 " " " Oxygen " ##STR250## Oxalate C.sub.30 H.sub.38 N.sub.2 O.sub.12+ 1/3 H.sub.2 O 625.83 155 65 C al. %Obt. % 57.6857.60 6.246.17 4.494.30 770077 " " " " " ##STR251## Base C.sub.29 H.sub.38 N.sub.4 O.sub.9+ 1/2 H.sub.2 O 595.63 155 50 Cal. %Obt. % 58.4758.45 6.606.48 9.419.27 770081 " " " " " ##STR252## HCl C.sub.34 H.sub.47 ClN.sub.4 O.sub.9+ 3/4 H.sub.2 O 704.72 168 42 Cal. %Obt. % 57.9457.90 6.946.85 7.957.91 770085 " " " " " ##STR253## " C.sub.34 H.sub.41 ClN.sub.4 O.sub.9+ 4/5 H.sub.2 O 699.57 168 32 Cal. %Obt. % 58.3758.54 6.145.89 8.018.13 770112 " " " S " ##STR254## " C.sub.25 H.sub.35 ClN.sub.2 O.sub.6 S 539.08 152 83 Cal. %Obt. % 5 57.927.68 6.546.38 5.205.08 770135 " " " Oxygen " ##STR255## Base C.sub.27 H.sub.35 N.sub.3 O.sub.7+ 4/5 H.sub.2 O 527.99 130 56 Cal. %Obt. % 61.4261.39 6.996.91 7.968.02 770142 " " " " " ##STR256## Oxalate C.sub.31 H.sub.40 N.sub.2 O.sub.12 632.65 200 47 Cal. %Obt. % 58.8558.94 6.376.35 4.434.55 770188 " " " " " ##STR257## HCl C.sub.29 H.sub.36 ClN.sub.3 O.sub.8 590.05 140 52 Cal. %Obt. % 5 59.039.12 6.155.83 7.126.99 760939 " " H " " ##STR258## Base C.sub.29 H.sub.36 N.sub.2 O.sub.8 540.59 134 18.5 Cal. %Obt. % 64.4364.10 6.716.77 5.185.00 771163 " " H " " ##STR259## Oxalate C.sub.31 H.sub.39 N.sub.3 O.sub.12+ 1/2 H.sub.2 O 654.654 211 50 Cal. %Obt. % 56.8757.07 6.166.13 6.426.34 771172 " " " " " ##STR260## " C.sub.31 H.sub.39 N.sub.3 O.sub.12 645.646 195 83 Cal. %Obt. % 57.6657.35 6.096.12 6.516.64 780040 " " " " " ##STR261## HCl C.sub.29 H.sub.39 ClN.sub.4 O.sub.8+ 7/4 H.sub.2 O 638.619 145 60 Cal. %Obt. % 54.5354.24 6.706.36 8.778.66 780404 ##STR262## " OH " " ##STR263## Base C.sub.27 H.sub.34 N.sub.2 O.sub.7+ 3/5 H.sub.2 O 509.37 60 71 Cal. %Obt. % 63.6663.70 6.976.96 5.505.83 760388 ##STR264## 2 """ ##STR265## HCl C.sub.26 H.sub.35 ClN.sub.2 O.sub.6 507.01 175 20 Cal. %Obt. % 6 61.591.09 6.95 7.07 5.535.74 760502 " 1 " " " ##STR266## " C.sub.26 H.sub.35 ClN.sub.2 O.sub.6+ 3/4 H.sub.2 O 520.52 150 78 Cal. %Obt. % 59.9960.32 6.877.12 5.385.50 760503 " " " " " ##STR267## " C.sub.28 H.sub.37 ClN.sub.2 O.sub.7+ 1/2 H.sub.2 O 588.06 138 65 Cal. %Obt. % 60.2660.56 6.886.86 5.025.00 760504 " " " " " ##STR268## " C.sub.25 H.sub.32 Cl.sub.2 N.sub.2 O.sub.6+ 2/3 H.sub.2 O 539.45 160 67 Cal. %Obt. % 55.6655.40 6.236.33 5.195.25 760505 " " " " " ##STR269## HCl C.sub.26 H.sub.35 ClN.sub.2 O.sub.6+ H.sub.2 O 525.03 180 81 Cal. %Obt. % 59.4759.70 7.107.00 5.345.24 760518 " " " " " ##STR270## " C.sub.28 H.sub.37 ClN.sub.2 O.sub.6+ 1/2 H.sub.2 O 542.06 163 85 Cal. %Obt. % 62.0462.13 7.077.35 5.175.02 760521 " " " " " ##STR271## " C.sub.26 H.sub.35 ClN.sub.2 O.sub.6+ H.sub.2 O 525.03 184 78 Cal. %Obt. % 59.4759.55 7.106.74 5.345.08

Code number: 770 274

A mixture of 9.6 g (0.0155 mole) of 1-[3-(4-acetyl-2,3-ethylenedioxy)phenoxy-2-hydroxy]propyl-4-(3,5-dimethoxy -4-acetoxy cinnamoyl)piperazine (Ib) (used in the crude state) and of 3.9 g (0.0465 mole) of sodium bicarbonate in 60 cm.sup.3 of ethanol was brought to reflux for 5 hours. Then, the solvent was evaporated, the residue was taken up in acetone and a solution of 1.4 g (0.0155 mole) of oxalic acid in acetone was added. After filtering 6.3 g of product were obtained.

Yield: 65%

Melting point: 110.degree. C.

Empirical formula: C.sub.30 H.sub.36 N.sub.2 O.sub.13 +3/4 H.sub.2 O

Molecular weight: 646.12

By the same process, but from the compound of formula (Ib) ##STR272## Code No. 780 004, 1-[3-(4-hydroxy-2,3-ethylenedioxy) phenoxy-2-hydroxy]propyl-4-(3,4,5-trimethoxy-cinnamoyl)piperazine, hydrated chlorhydrate was obtained.

Code Number: 780 120

Yield: 22%

Melting Point: 174.degree. C.

Empirical formula: C.sub.27 H.sub.37 ClN.sub.2 O.sub.10

Molecular weight: 585.04

Code number: 760 939

1st step: 3-(4-acetyl-2,3-ethylenedioxy)phenoxy-1-chloropropane (XXVIII)

This compound was obtained following the same working method as 3-(4-acetamido-2,3-ethylenedioxy) phenoxy-1-chloropropane of code number 771 171 for which:

A mixture of 25 g of 5-acetamido-8-hydroxy-benzodioxan, of 50 g of potassium carbonate and of 35.5 ml of 1-bromo-1-chloropropane in 500 ml of acetonitrile was brought to reflux for three hours. After filtering, evaporating and recrystallizing in ethanol, 30 g of product were obtained.

Yield: 88%

Melting point: 163.degree. C.

NMR spectrum (DMSO) .delta. ppm:

6.51, d; 7.22, d; 4.20, s:

6 benzodioxan protons

9.31, s and 2.00. s: NH-COCH.sub.3

IR spectrum: NHCOCH.sub.3 bands at 1660-1555 and 3380 cm.sup.-1.

By the same process, but from the corresponding reagents, the compounds of formula (XXVIII) shown in Table II below are obtained.

2nd step: 1-[3-(4-acetyl-2,3-ethylenedioxy)phenoxy]-propyl-4-(3,4,5-trimethoxycinnam oyl)-piperazine (I)

A mixture of 15.3 g (0.05 mole) of 3,4,5-trimethoxycinnamoyl piperazine, of 13.6 g of 3-(4-acetyl-2,3-ethylenedioxyphenoxy)-1-chloropropane, used in the crude state, and of 20.7 g of potassium carbonate in 100 ml of acetonitrile was brought to reflux for 12 hours. Then, the solvent was filtered and evaporated, the residue was filtered on a silica column, eluted with chloroform and the product obtained was crystallized in ether. 5 g of product was obtained.

Yield: 21%

Melting point: 134.degree. C.

Empirical formula: C.sub.29 H.sub.36 N.sub.2 O.sub.8

Molecular weight: 540.59

By the same process, but from the corresponding reagents, the compounds of formula I, shown in Table I, and bearing the code numbers 771 163, 771 172 and 780 040 were obtained.

Code number: 770 495

1st step: 1-(2,3-epoxypropyl)-4-(3,4,5-trimethoxycinnamoyl)piperazine.

Code number: 770 319

A solution of 61.2 g of 3,4,5-trimethoxycinnamoyl piperazine, 137 g of epibromhydrin and 138 g of potassium carbonate in 300 ml of acetonitrile was brought to reflux for 8 hours. Then, the solvent was evaporated and the residue chromatographed on a silica column. Eluted with chloroform, the product was obtained which was crystallized in ethyl ether. Weight: 26.4 g.

Yield: 36%

Melting point: 126.degree. C.

Empirical formula: C.sub.19 H.sub.36 N.sub.2 O.sub.5

Molecular weight: 362.41

2nd step: 1-(3-N-methylanilino-2-hydroxy)propyl-4-(3,4,5-trimethoxycinnamoyl)piperaz ine, hydrated oxalate.

A solution of 3.62 g (0.01 mole) of 1-(2,3-epoxypropyl-4-(3,4,5-trimethoxycinnamoyl)piperazine (IIIh) and 1.07 g (0.01 mole) of N-methylaniline in 20 ml of ethanol was brought to reflux for 93 hours. The solvent was evaporated, the residue was taken up in chloroform, extracted with an aqueous solution of methane sulfonic acid, the aqueous phase was basified with sodium bicarbonate, extracted with chloroform, the solvent was evaporated, the residue was taken up in 40 ml of acetone and 0.75 g of oxalic acid in solution in 10 ml of acetone was added. After filtering, 1.9 g of product were obtained.

Yield: 34%

Melting point: 154.degree. C.

Empirical formula: C.sub.29 H.sub.38 N.sub.3 O.sub.11

Molecular weight: 615.427

Code number: 770 125

To a toluene solution of 20 g of parafluoro cinnamoic acid was added 20 cm.sup.3 of thionyl chloride and the mixture was brought to 70.degree.-80.degree. C. for 1 hour.

The solvents were evaporated and the residue (14 g) was slowly added to a solution of 13.2 g of piperazine in 150 ml of acetic acid. They were left in contact for 3 days at room temperature, then the solvent was evaporated, the residue was taken up in a mixture of chloroform and dilute hydrochloric acid, decanted and the aqueous phase was basified with a concentrated NaOH solution, extracted with chloroform, washed with water, the solvent was evaporated and the residue filtered on silica. 14.5 g of product were obtained.

Yield: 81%

Melting point: 90.degree. C.

NMR spectrum:

.delta. ppm=6.82, d, and 7.68, d, (J.dbd.16Hz)--CH.dbd.CH--

=7.52, m, and 7.08 m, aromatic protons

=3.62, m 2.91, m: and 1.92, s, piperazinic protons.

By the same process but from the corresponding reagents were obtained: 3,4,5-trimethoxycinnamoyl homopiperazine chlorhydrate (IIb) code number: 760 360;

Yield: 73%

Melting point: 164.degree. C.

Empirical formula: C.sub.17 H.sub.25 ClN.sub.2 O.sub.4 +H.sub.2 O

Molecular weight: 374.859

the compounds of formula (IIa) appearing in Table III below, and the 4-acetoxy-3,5-dimethoxycinnamoyl piperazine (IIa) which is used in the crude state for the synthesis of compound (Ia) used in Example 2.

Code number: 770 431

A solution of 100 g of ethyl ester of sinapic acid, 208 g of ethyl iodide and 184 g of potassium carbonate in 1500 ml of acetonitrile was brought to reflux for 6 hours. The solution was filtered, the filtrate was evaporated and the residue was crystallized which was dissolved in a solution of 36 g of NaOH in 360 ml of water.

It was brought to reflux for 2 hours, then washed with chloroform, acidified with concentrated hydrochloric acid and extracted with chloroform. The solvent was evaporated and the oil obtained was crystallized in isopropyl ether.

18.5 g of product were obtained

Yield: 20%

Melting point: 120.degree. C.

NMR spectrum:

.delta. ppm=6.71, d; and 7.62, d, (J=16Hz):--CHOCH

7.08 s, aromatic protons

3.82, s,: 2 CH.sub.3 O

By the same process, but from the corresponding reagents, 4-isopropoxy-3,5-dimethoxycinnamoic acid (V) was obtained which was used in the crude state in the synthesis of the compound of formula (IIa), code number 770 623, appearing in Table III.

Code number: 770 584

A mixture of 31 g of 5-cyano-8-hydroxy-1,4-benzodioxan (VII) (Code number 770 583), 38.35 g of epibromhydrin and 133 g of potassium carbonate in 300 ml of acetonitrile was brought to reflux for 12 hours. The mixture was filtered, the product then crystallized in the filtrate, it was filtered out and recrystallized in acetonitrile.

31.6 g of product were obtained.

Yield: 79%

Melting point: 167.degree. C.

Empirical formula: C.sub.12 H.sub.11 NO.sub.4

Molecular weight: 233.116

By the same process but from the corresponding reagents, the compounds of formula (III), appearing in Table IV below, were obtained as well as the following compounds of formula III:

-1-(2-acetyl-3,4,5-trimethoxyphenoxy)-2,3-epoxy-propane

-1-(4-cyanomethylphenoxy)-2,3-epoxypropane

-1-(4-n-propylcarbonyl-2,3-ethylenedioxyphenoxy)-2,3-epoxypropane

-1-(5-acetyl-2,3-ethylenedioxyphenoxy)-2,3-epoxy-propane

-2,3-epoxy-7-propoxy-4-acetamidoindane

which are used in the crude state in the synthesis of the corresponding compounds of formula I, appearing in Table I, following the process used in Example I.

Code number: 770 702

To a suspension of 2-methyl-4-hydroxy aniline (12.3 g) in 300 cm.sup.3 of chloroform was slowly added 59.cm.sup.3 of methyl isocyanate. They were left in contact for 3 hours at room temperature, then the solvent was evaporated and the residue crystallized in ethanol.

5.5 g of product were obtained.

Yield: 30%

Melting point: 198.degree. C.

Empirical formula: C.sub.9 H.sub.12 N.sub.2 O.sub.2

Molecular weight: 182.20

By the same process, but from the corresponding reagents, compounds of formula (VIIa), code numbers 770 920, 780 290, 780 355, the compound of formula (VIIb) code number 771 029 and the compounds of formula (VIIc), code numbers 771 151 and 771 155, shown in Table V below, were obtained.

Code number: 771 304

A mixture of 25 g of 7-hydroxy-4-amino indane and of 8 ml of acetic anhydride in 400 ml of iced water was stirred for 30 minutes. After filtering, the precipitate was washed with water and ethyl ether and was recrystallized in isopropanol.

25 g of product were obtained.

Yield: 78%

Melting point: 220.degree. C.

Empirical formula: C.sub.11 H.sub.13 NO.sub.2

Molecular weight: 191.22

By the same process, but from the corresponding reagents, the compound of formula (VIId) of code number 700 042 and shown in Table V below, was obtained.

Code Number: 780 472

1st step: 1-N,N-dimethylthiocarbamoyloxy-2-methoxy-4-acetylbenzene (X)

Code Number: 780 470

A solution of 3.3 g of acetovanillone, of 2.9 g of dimethyl thiocarbamoyl and of 8.2 g of potassium carbonate in 80 cm.sup.3 of acetonitrile was brought to 70.degree. C. for 30 minutes. After filtering, the solvent was evaporated and the residue recrystallized in ethanol. 3.3 g of product were obtained.

Yield: 66%

Melting point: 130.degree. C.

NMR spectrum:

.delta. ppm=7.54, m & 7.11, d, (J=9 Hz):aromatic protons

=3.82, s --OCH.sub.3

=3.21, s, and 3.15, s,: ##STR410## =2.56, s,: COCH.sub.3

By the same process, but from the corresponding reagents, the following compounds of formula (Xa) were obtained:

5-N,N-dimethylthiocarbamoyloxy-1,4-benzodioxane

Code Number: 780 385

Yield: 98%

Melting point: 98.degree. C.

Empirical form.: C.sub.11 H.sub.13 NO.sub.3 S

Molecular weight: 239.39

5-N,N-dimethylthiocarbamoyloxy-8-acetyl-1,4-benzodioxane

Code Number: 780 380

Yield: 75%

Melting point: 149.degree. C.

Empirical formula: C.sub.13 H.sub.15 NO.sub.4 S

Molecular weight: 281.32

2nd step: 1-N,N-dimethylcarbamoylthio-2-methoxy-4-acetylbenzene (IX)

Code Number: 780 471

Under a flow of argon, 13 g of 1-N,N-dimethylthiocarbamoyloxy-2-methoxy-4-acetylbenzene, obtained in the preceding step were heated for 35 minutes at 250.degree. C. Then, the residue was chromatographed on a silica column. After elution with chloroform 6 g of product were obtained.

Yield: 46%

Melting point: 116.degree. C.

NMR spectrum:

.delta. ppm=7.57, s, aromatic protons

=3.91, s,: --OMe

=3.03, s,: ##STR411## =2.52, s,: COCH.sub.3

By the same process, but from the corresponding reagents, the following compounds of formula (IXa) were obtained:

5-N,N-dimethylcarbamoylthio-1,4-benzodioxane

Code Number: 780 386

Yield: 59%

Melting point: 78.degree. C.

NMR spectrum:

.delta. ppm=6.98, m; and 4.22, s: benzodioxane protons

=3.02, s, ##STR412##

IR spectrum: band at 1640 cm.sup.-1 ##STR413##

5-N,N-dimethylcarbamoylthio-8-acetyl-1,4-benzodioxane

Code Number: 780 381

Yield: 39%

Melting point: 155.degree. C.

Empirical formula: C.sub.13 H.sub.15 NO.sub.4 S

Molecular weight: 281.32

3rd step: 2-methoxy-4-acetylthiophenol (VIIe)

Code Number: 780 472

A solution of 5.6 g of 4-N,N-dimethylthiocarbamoyloxy-3-methoxy acetophenone obtained in the previous step, 2.6 g of soda (NaOH) in 210 ml of methanol and 60 ml of water was brought to reflux for two hours. Then, the solvents were evaporated, the residue was taken up in water, washed with ethyl acetate, the aqueous phase was acidified with concentrated hydrochloric acid, extracted with chloroform which was dried and the solvent was evaporated. 3.5 g of product were obtained.

Yield: 87%

Melting point: 50.degree. C.

NMR spectrum:

.delta. ppm=7.20, m: aromatic protons

=4.16, s: --SH

=3.96, s,: --OMe

=2.57, s,: --COCH.sub.3

By the same process, but from the corresponding reagents, the compounds of formula (VIIf), code numbers 780 387 and 780 382, shown in Table V below, were obtained.

Code Number: 770 829

A solution of 34.5 g of 5-benzyloxy-8-N-cyclohexylcarboxamido-1,4-benzodioxane (XIId), code number 770 828, in presence of 6.8 g of palladium on 5% charcoal was hydrogenolysed in an autoclave at room pressure and temperature. Once the absorption of hydrogen was completed, and after filtration, the filtrate was evaporated.

Yield: 92%

Melting point: 182.degree. C.

NMR spectrum:

.delta. ppm=7.24, d; 6.48, d, (J=10 Hz) and 4.18 s,: benzodioxane protons

=7.62, d, (J=7 Hz): --COHN--

=10.1, m,: --OH

=3.78, m and 1.5, m,: ##STR414##

By the same process, but from the corresponding reagents, the compounds of formula (VII), corresponding to formula (VIIk) shown in Table V below, were obtained.

Code Number: 750 769

A solution of 44.4 g (0.2 mole) of 8-n-propyl carbonyloxy-1,4-benzodioxane in 240 ml of nitrobenzene was cooled to a temperature of less than 10.degree. C. and 40 g (0.3 mole) of aluminum chloride were slowly added. It was left for 48 hours at room temperature, diluted with water, the organic phase was decanted, the solvent was evaporated, and the residue was chromatographed on a silica column. With toluene-chloroform mixtures, 27 g (61%) of 5-hydroxy-6-n-propylcarbonyl-1,4-benzodioxane were eluted. Then, with a 90% chloroform-10% methanol mixture, 5 g of 5-hydroxy-8-n-propylcarbonyl-1,4-benzodioxane were eluted.

Yield: 11%

Melting point: 84.degree. C.

Empirical formula: C.sub.12 H.sub.14 O.sub.4

Molecular weight: 222.23

Code number: 750 548

1st step: 5-hydroxy-8-acetyl-1,4-benzodioxane oxime (XIII)

Code number: 750 527

A solution of 19.4 g (0.1 mole) of 5-hydroxy 8-acetyl-1,4-benzodioxane (VIIi) and 10.4 g (0.15 mole) of hydroxylamine hydrochloride in 50 ml of pyridine and 50 ml of ethanol was brought to reflux for 7 hours. Then, the solvents were evaporated and the residue crystallized in water. 12 g of product were obtained.

Yield: 55%

Melting point: 145.degree. C.

Empirical form.: C.sub.10 H.sub.11 NO.sub.4 1/2H.sub.2 O

Molecular weight: 218.20

2nd step: 5-hydroxy-8-acetamido-1,4-benzodioxane

250 ml of acetic acid were saturated with gaseous hydrochloric acid, then 20.9 g (0.1 mole) of 5-hydroxy-8-acetyl-1,4-benzodioxane oxime, obtained in the previous step, were added. It was brought to reflux for 5 hours, then the solvents were evaporated, the residue was crystallized in water and recrystallized in ethanol. 7 g of product were obtained.

Yield: 33%

Melting point: 170.degree. C.

Empirical formula: C.sub.10 H.sub.11 NO.sub.4

Molecular weight: 209.20

Code number: 760 844

A solution of 14.7 g (0.05 mole) of 5-benzyloxy-8-hydroxymethyl-1,4-benzodioxane (XIp) code number 760 701, crude, non-crystallized, in 300 ml of absolute alcohol was hydrogenolysed at room pressure and temperature, in the presence of 3 g of palladium on 5% charcoal. Once the absorption of hydrogen was completed, the catalyst was filtered and the solvent was evaporated. A liquid was obtained.

NMR spectrum:

.delta. ppm=8.90, s, 1 phenolic proton

=6.42 and 6.21, d, (J=10 Hz)

=4.17, s,: benzodioxane protons

=1.98, s,: --CH.sub.3

Code number: 780 006

1st step: 5-benzyloxy-8-acetyl-1,4-benzodioxane (XV)

Code Number: 760 694

A suspension of 97 g (0.5 mole) of 5-hydroxy-8-acetyl-1,4-benzodioxane (VIIi), of 127 g (1 mole) of benzyl chloride and 155 g (1.12 mole) of potassium carbonate in 150 ml of absolute alcohol was brought to reflux for 24 hours. After filtration the solvent was evaporated, the residue was taken up in chloroform, washed with a solution of soda (NaOH) 1 N, the solvent was evaporated and the product was crystallized in alcohol, 135 g of product expected were obtained.

Yield: 95%

Melting point: 133.degree. C.

Empirical formula: C.sub.17 H.sub.16 O.sub.4

Molecular weight: 284.29

2nd step: 5-benzyloxy-8-acetoxy-1,4-benzodioxane (XIb)

Code Number: 780 001

To a solution of 58 g of 5-benzyloxy-8-acetyl-1,4-benzodioxane (XV) obtained in the previous step, in 300 ml of formic acid, were added, at -5.degree. C., 25 g of a 36% solution of hydrogen peroxide in 100 ml of formic acid. The mixture was left at 0.degree. C. for 72 hours then poured on a mixture of water and ice, the precipitate formed was filtered, washed in water and recrystallized in a mixture of ethyl acetate and isopropyl ether.

Yield: 89%

Melting point: 104.degree. C.

Empirical formula: C.sub.17 H.sub.16 O.sub.5

Molecular weight: 300.39

3rd step: 5-benzyloxy-8-hydroxy-1,4-benzodioxane (XIV)

Code Number: 780 005

To a solution of 58.3 g of 5-benzyloxy-8-acetoxy-1,4-benzodioxane obtained in the previous step, in 400 ml of methanol, are added 75 g of potassium carbonate, at room temperature. Then, after 30 minutes, the solution was filtered, the solvent evaporated, and the residue was taken up in water and acidified in concentrated hydrochloric acid. The precipitate obtained was filtered and recrystallized in alcohol: 47.3 g of the product were obtained.

Yield: 94%

Melting point: 131.degree. C.

Empirical formula: C.sub.15 H.sub.14 O.sub.4

Molecular weight: 258.25

4th step: 5-benzyloxy-8-methoxy-1,4-benzodioxane (XIa)

Code Number: 780 006

To a solution of 45 g of 5-benzyloxy-8-hydroxy-1,4-benzodioxane obtained in the preceding step and 52 g of potassium carbonate in 500 ml of acetone, there was slowly added 33.5 g of dimethylsulfate then 20 ml of a 10% solution of methanolic caustic potash. The solution was then brought to reflux for 2 hours and 30 minutes, filtered, the solvents were evaporated, the residue was taken up in ethyl ether, washed with water, dried and the solvent was evaporated. 47 g of product were obtained.

Yield: 98%

Melting point: 70.degree. C.

NMR Spectrum:

.delta. ppm=7.36, d, and 6.47, d, (J=2 Hz) and 4.23, s, benzodioxane protons

=7.35, m and 5.03, s: --CH.sub.2 --.phi.

=3.78, s,: --OCH.sub.3

Code Number: 780 370

1st step: (5-benzyloxy-1,4-benzodioxane)yl-8-carboxylic acid (XVI)

Code Number: 760 695

To a solution of 29 g (0.1 mole) of 5-benzyloxy-8-acetyl-1,4-benzodioxane (XV) obtained in the first step of Example 15, in 150 ml of pyridine were added 25.8 g (0.1 mole) of iodine. Then, the mixture was brought to 100.degree. C. for 1 hour, the excess of pyridine was driven off, the residue was taken up in water, filtered and the precipitate obtained was put in solution in 450 ml of a 50/50 alcohol-water mixture. A solution of 70 g of soda (NaOH) in 200 ml of water was slowly added, then, washing with chloroform was carried out and the precipitate formed was filtered and dissolved in an aqueous solution of soda (NaOH). Acidification was carried out up to pH.perspectiveto.1 by means of hydrochloric acid, then it was concentrated and filtered. 25 g of product were obtained.

Yield: 35%

Melting point: .perspectiveto.200.degree. C.

Empirical formula: C.sub.16 H.sub.14 O.sub.5

Molecular weight: 286.27

2nd step: 5-benzyloxy-8-isopropoxycarbonyl-1,4-benzodioxane

To a toluene solution of 31 g of (5-benzyloxy-1,4-benzodioxane)yl-8-carboxylic acid obtained in the previous step, 50 ml of thionyl chloride were added and the mixture was brought to 70.degree.-80.degree. C. for 2 hours. Then, the solvents were evaporated, the residue was dissolved in 200 ml of tetrahydrofuran, and 15 cm.sup.3 of isopropyl alcohol and 70 cm.sup.3 of triethylamine were added. The mixture was brought to 60.degree. C. for 3 hours, then the precipitate formed was filtered, the filtrate evaporated and the residue chromatographed on a silica column and eluted with chloroform. 20 g of product were obtained which was recrystallized in isopropyl ether.

Yield: 71%

Melting point: 96.degree. C.

NMR spectrum:

.delta. ppm=7.38 (d), and 6.57, d, (J=10 Hz) and 4.23, s, benzodioxane protons

=7.28, s, and 5.08 s: CH.sub.2 --.phi.

=5.09, quintet, and 1.14, d (J=6 Hz) --COO<

IR spectrum: 1710 and 1200 cm.sup.-1 band: COO<

With the same method, but from the corresponding reagents, the compounds of formula XIc was prepared, given in Table VI and bearing code numbers 780 366, 780 298 and 780 330.

Code Number: 760 696

A solution of 25 g (0.095 mole) of (5-benzyloxy-1,4-benzodioxane)yl-8-carboxylic acid obtained in the first step of Example 16, in 500 ml of alcohol and 50 ml of a solution of hydrochloric acid in 4.4 N ethanol was brought to reflux for 4 hours. Then, the solvent was evaporated, the residue was taken up in chloroform, washed with a solution of sodium bicarbonate, with water, then it was dried, and the solvent was evaporated. 26 g of ester were obtained.

Yield: 90%

IR spectrum: band at 1708 and 1200 cm.sup.-1 (COOEt)

NMR spectrum:

.delta. ppm=7.22, d; 6.51, d; (J=10 Hz) and 4.38, s,: benzodioxane protons

=7.18, s: benzylic aromatic protons

=5.20, s: O--CH.sub.2 --.phi.

=4.35, q, and 1.35, t, (J=8 Hz): COOEt.

Code Number: 770 828

To a toluene solution of 30 g of (5-benzyloxy-1,4-benzodioxane)yl-8-carboxylic acid obtained in the first step of Example 16, were added 30 cm.sup.3 of thionyl chloride and it was brought to 70.degree.-80.degree. C. for 2 hours. Then, the solvents were evaporated, the residue was dissolved in 200 ml of tetrahydrofuran and 24 ml of triethylamine and 19 ml of cyclohexylamine were added. The mixture was brought to 60.degree. C. for 3 hours and after filtration the filtrate was evaporated and the residue recrystallized in a mixture of ethyl acetate and hexane.

Yield: 82.5%

Melting point: 117.degree. C.

Empirical formula: C.sub.22 H.sub.25 NO.sub.4

Molecular weight: 367.49

With the same method, but from the corresponding reagents, the compounds of formula XId were obtained, given in Table VI and bearing the following code numbers 770 202 and 770 849.

Code Number: 760 706

To a solution cooled below 0.degree. C. of 20 g (0.07 mole) of (5-benzyloxy-1,4-benzodioxane)yl-8-carboxylic acid obtained in the 1st step of Example 16, in 200 ml of anhydrous tetrahydrofuran, 11 ml of triethylamine were added, then 6.9 ml of ethyl chloroformate. It was stirred at 0.degree. C. for 2 hours, then a gaseous flow of methylamine was passed for 90 minutes. Then, the solution was left for one hour at room temperature, the tetrahydrofuran was evaporated, the residue was taken up in chloroform, then it was washed with water, the solvent was evaporated and recrystallized in alcohol. 18 g of product were obtained.

Yield: 80%

NMR spectrum:

.delta. ppm=7.70, d; 6.60, d, (J=10 Hz) and 4.32, s,: benzodioxane protons

=7.35, s,: benzylic aromatic protons

=5.18, s,: O--CH.sub.2 --.phi.

=7.36, m, --NH--CO--

=2.91, d, (J=6 Hz); CH.sub.3 --CO--N<

Code Number: 770 542

To a solution of 30 g of 5-benzyloxy-8-amino-1,4-benzodioxane (XX); code number 760 727, in 250 ml of chloroform and 21.3 ml of triethylamine, cooled to 0.degree. C., 12.1 cm.sup.3 of propionyl chloride were slowly added. Then, it was stirred for 17 hours, washed with a solution of diluted hydrochloric acid, with water, with an aqueous solution of sodium bicarbonate, then with water, the organic phase was evaporated and the residue recrystallized in ethyl acetate.

Yield: 73%

Melting point: 139.degree. C.

NMR spectrum:

.delta. ppm=7.42, d; 6.51, d, (J=10 Hz) and 4.20, s: benzodioxane protons

=7.78, d, (J=9 Hz): --NH--CO--

=7.35, s and 5.03, s: CH.sub.2 --.phi.

=2.17, q, and 1.11, t (J=7 Hz): CO--CH.sub.2 --CH.sub.3

IR spectrum: bands at 3400, 1670 and 1510 cm.sup.-1 : --NH--CO--

With the same method, but from the corresponding reagents, the compounds of formula XIe were obtained, appearing in Table VI and bearing code numbers 770 689; 770 598; 770 611; 770 530; 770 526 and 770 607.

A solution of 34 g of 4-benzyloxy-2,3-methylene dioxy acetanilide (XIh), code number 780 343, in 120 ml of methanol was treated with 34 g of potassium hydroxide, for 11/2 hour at reflux. Then, the precipitate formed was filtered and recrystallized in isopropyl alcohol. 13.4 g of product were obtained.

Yield: 50%

Melting point: 59.degree. C.

NMR spectrum:

.delta. ppm=6.22, q, (J=9 Hz) aromatic protons of the benzodioxole group

=5.84, s, ##STR415## =7.36, s and 5.03, s,: --CH.sub.2 --.phi. =3.17, s, --NH.sub.2

With the same method, but from the corresponding reagents, were obtained the compounds of formula (XXa), code number 780 464: 6-amino-9-benzyloxy-1,5-benzodioxepine.

Yield: 82%

Melting point: 92.degree. C.

Empirical formula: C.sub.16 H.sub.17 NO.sub.3

Molecular weight: 217.29

as well as the compound of formula (XX), code number 760 727: 5-benzyloxy-8-amino-1,4-benzodioxane:

Yield: 78%

Melting point: 130.degree. C.

Empirical formula: C.sub.15 H.sub.15 NO.sub.3

Molecular weight: 257.28

Code Number: 780 343

To a suspension of 100 g of 4-benzyloxy-2,3-methylene dioxy acetophenone oxime (XXII), code number 780 342, in 500 ml of acetic acid, 500 ml of acetic anhydride were slowly added, then a gaseous flow of hydrochloric acid was passed at 10.degree. C., for 1 hour. Then, the solution was brought to 40.degree.-50.degree. C. for 5 hours, the solvents were evaporated, the residue was taken up with chloroform, then it was washed with water, the solvent was evaporated and the residue recrystallized in ethyl acetate.

Yield: 84%

Melting point: 148.degree. C.

NMR spectrum:

.delta. ppm=7.18, m and 5.18 s: --CH.sub.2 .phi.

=7.18, m (aromatic protons of the benzodioxole nucleus and of CH.sub.2 .phi.)

=5.95, s,: ##STR416## =2.09, s, CH.sub.3 --CO--N-- =6.51 d, (J=9 Hz): NH--CO--

IR spectrum: 3260, 1650 cm.sup.-1 : band --NH--CO--

With the same method but from the corresponding reagents, the compound of formula (XIh) was obtained, code number 780 463, appearing in Table VI.

Code Number: 780 342

A solution of 192 g of 4-benzyloxy-2,3-methylene dioxy acetophenone (XIi); code number 780 305 and of 64 g of hydroxylamine hydrochloride in 500 ml of pyridine and 500 ml of ethanol were brought to reflux for 2 hours. Then, the solvents were evaporated, the residue was taken up in water and the precipitate formed was filtered.

Yield: 98%

Melting point: 168.degree. C.

Empirical formula: C.sub.16 H.sub.15 NO.sub.4

Molecular weight: 285.29

With the same method, but from the corresponding reagents, 6-acetyl-9-benzyloxy-1,5-benzodioxepine oxime (XXII) was obtained, code number 780 390.

Yield: 90%

Melting point: 134.degree. C.

NMR Spectrum:

.delta. ppm=13.00, m, =N--OH

=6.51, d; 6.88, d, (J=10 Hz); 4.10, m; and 2.08, m: benzodioxepine protons

=5.17 s and 7.19, s: CH.sub.2 --.phi.

=2.20, s: --CH.sub.3

Code Number: 760 606

Following the working method described in the first step of Example 15, but from 5-hydroxy-8-acetamido-1,4-benzodioxane (VIIm), code number 750 548, 91% of product was obtained.

Melting point: 148.degree. C.

NMR spectrum:

.delta. ppm=7.35, d; 6.56, d, (J=10 Hz) and 4.24, s, benzodioxane protons

=7.36, s, and 5.07, s,: CH.sub.2 --.phi.

=7.76, d, (J=9 Hz): NH--CO--

=2.17, s,: CH.sub.3

IR spectrum: bands at 3270, and 1660 cm.sup.-1 : --NH--CO--CH.sub.3

Code Number: 770 304

For 20 hours a mixture of 25 g of 5-benzyloxy-8-amino-1,4-benzodioxane, code number 760 727, and 8 ml of ethyl isocyanate in 300 ml of chloroform was maintained at reflux. Then, the solvents were evaporated in a vacuum and the residue recrystallized in ethanol.

Yield: 80%

Melting point: 188.degree. C.

NMR spectrum:

.delta. ppm=7.41, d; 6.56, d, (J=10 Hz) and 4.19, s, benzodioxane protons

=7.38, s, and 4.97, s,: --CH.sub.2 --.phi.

=6.60, m and 7.40, m: NH--CO--NH

=3.02, q and 1.00, t, (J=7 Hz): --CH.sub.2 --CH.sub.3 --

With the same method, but from the corresponding reagents, the compounds of formula (XIf) were obtained, appearing in Table VI and bearing the code numbers 770 074, 770 480, 770 627, 770 631, 770 708, 770 078, 770 082, 770 220, 780 406 and 780 465.

Code Number: 770 522

To a solution of 30 g of 5-benzyloxy-8-amino-1,4-benzodioxane (XX), code number 760 727, in 250 ml of chloroform, 21.3 ml of triethylamine, then slowly, at 0.degree. C., 15.2 g of ethyl chloroformate were added. The solution was stirred for 7 hours, filtered and the filtrate was washed with a diluted hydrochloric acid solution, with water, with a solution of sodium bicarbonate and with water. The solvent was evaporated and the residue recrystallized in ethyl acetate.

Yield: 74%

Melting point: 108.degree. C.

NMR spectrum:

.delta. ppm=6.52, d; 7.41, d, (J=10 Hz) and 4.22, s,: benzodioxane protons

=7.38, s and 5.08, s: CH.sub.2 --.phi.

=4.10, q, and 1.14, t, (J=7 Hz): CH.sub.2 --CH.sub.3

=6.80, s, --NH--

IR spectrum: 3315 and 1692 cm.sup.-1 =NHCOOEt

Code Number: 780 305

A mixture of 140 g of 4-benzyloxy-2,3-dihydroxy acetophenone (XXIV), code number 780 304, 295 g of diiodomethane and 300 g of potassium carbonate in 1200 ml of dimethyl formamide was brought to reflux for 5 hours. After filtering, the filtrate was evaporated, the residue was taken up in a 50/50 mixture of ethyl acetate and ether, then it was washed with water, the organic phase was evaporated and the residue was crystallized in ethanol.

Yield: 93%

Melting point: 101.degree. C.

NMR spectrum:

.delta. ppm=6.55, d; 7.35, d, (J=10 Hz): aromatic protons of the benzodioxole nucleus

=6.00, s, ##STR417## =7.38, s and 5.18, s,: CH.sub.2 --.phi. =2.44 s,: --CH.sub.3

IR spectrum: 1670 cm.sup.-1 : --CO--CH.sub.3

With the same method, but from the corresponding reagents, the compound (XIi), code number 780 238, given in Table VI, was obtained.

Code Number: 780 304

A mixture of 349 g of gallacetophenone, 1750 g of sodium bicarbonate and 260 g of benzyl chloride in 4000 ml of acetone was stirred for 2 hours at room temperature. Then the mixture was brought to reflux for 36 hours, filtered, the solvent was evaporated and the residue was taken up in ethyl acetate and diluted in isopropyl ether. 58% of crystallized product were obtained.

Melting point: 128.degree. C.

Empirical formula: C.sub.15 H.sub.14 O.sub.4

Molecular weight: 258.26

Code Number: 771 235

First step: 5-benzyloxy-8-N-methylamino-1,4-benzodioxane (XXV)

Code Number: 771 234

A mixture of 40 g of 5-benzyloxy-8-amino-1,4-benzodioxane (XX), code number 760 727, 120 ml of formaldehyde (at 38% in an aqueous solution) and 29 g of 5,5-dimethylhydantoin in 300 ml of ethanol was brought to reflux for 12 hours. Then the solvent was evaporated, the residue was taken up in chloroform and washed by means of a diluted hydrochloric acid solution. The organic phase was evaporated and the residue dissolved in 500 ml of dimethylsulfoxide. 23 g of sodiumborohydride were slowly added, and brought to 100.degree. C. for 30 minutes. Then it was diluted in 1500 ml of water, extracted with chloroform, washed with water and the solvent evaporated. The residue was chromatographed on a silica column. Eluted with chloroform, 34% of product was obtained.

Melting point: 62.degree. C.

Empirical formula: C.sub.16 H.sub.17 NO.sub.3

Molecular weight: 271.30

Second step: 5-benzyloxy-8-N,N'-dimethyl carbamoyl amino-1,4-benzodioxane

A mixture of 22.4 g of 5-benzyloxy-8-N-methyl amino-1,4-benzodioxane, obtained from the preceding step, and 10 ml of methyl isocyanate in 100 ml of chloroform were brought to reflux for 2 hours, then the solvent was evaporated and the residue recrystallized in alcohol:

Yield: 74%

Melting point: 140.degree. C.

Empirical formula: C.sub.18 H.sub.20 N.sub.2 O.sub.4

Molecular weight: 328.36

Code Number: 771 146

A mixture of 38 g of 5-benzyloxy-8-ethoxycarbonylamino-1,4-benzodioxane (XIg), code number 770 522, and 300 ml of morpholine was brought to reflux for 16 hours, in the presence of a pinch of ammonium chloride. Then the morpholine in excess was evaporated and the residue was recrystallized in 96.degree. ethanol.

Yield: 72%

Melting point: 184.degree. C.

Empirical formula: C.sub.20 H.sub.22 N.sub.2 O.sub.5

Molecular weight: 370.39

Code Number: 771 230

To a solution of 100 g of 5-benzyloxy-8-amino-1,4-benzodioxane (XX), code number 760 727, and 100 ml of triethylamine, in 1000 ml of chloroform were slowly added 47 ml of dimethylcarbamoyl chloride, at room temperature, then it was brought to reflux for 48 hours. After filtering, the filtrate was evaporated and the residue was recrystallized in ethanol. 60 g of product were obtained.

Yield: 47%

Melting point: 142.degree. C.

Empirical formula: C.sub.18 H.sub.20 N.sub.2 O.sub.4

Molecular weight: 328.36

Code Number: 770 119

First step: 5-benzyloxy-8-chloromethyl-1,4-benzodioxane (XXVI)

Code Number: 770 188

To a solution, cooled to -10.degree. C., of 10 g (0.037 mole) of 5-benzyloxy-8-hydroxymethyl-1,4-benzodioxane (XIp), code number 760 701, in 100 ml of chloroform were slowly added 4.6 g (0.039 mole) of thionyl chloride. They were left in contact for 15 minutes, then the solvents were evaporated, the residue was taken up in chloroform, washed with a solution of sodium bicarbonate, dried and the solvent was evaporated. 10.4 g of unstable product were obtained which, after checking by chromatography on a thin silica layer, was used in the synthesis of the compound of formula (XIm), code number 770 119.

Second step: 5-benzyloxy-8-cyanomethyl-1,4-benzodioxane

A solution of 99 g (0.34 mole) of 5-benzyloxy-8-chloromethyl-1,4-benzodioxane, obtained in the previous step, 19 g (0.4 mole) of sodium cyanide and 0.5 g of sodium iodide in 1000 ml of anhydrous dimethylformamide was brought to 60.degree. C. for 45 minutes. Then the solvent was driven off in a vacuum, the residue was taken up in 600 ml of a saturated solution of sodium bicarbonate and 300 ml of chloroform, the organic phase was decanted, dried and the solvent evaporated. 85 g of product were obtained.

Yield: 89%

Melting point: 95.degree. C.

Empirical formula: C.sub.17 H.sub.15 NO.sub.3

Molecular weight: 281.29

Code Number: 770 383

To a solution of 50 g of 5-benzyloxy-8-cyanomethyl-1,4-benzodioxane, obtained in the process of Example 32, in 250 ml of t-butanol were slowly added 39 g of pulverized potassium hydroxide, then it was brought to reflux for 20 minutes. Then the mixture was poured into 500 ml of an aqueous solution of sodium chloride, extracted with chloroform, washed with water, the solvent was evaporated and the residue recrystallized in ethanol.

Yield: 90%

Melting point: 166.degree. C.

NRM spectrum:

.delta. ppm=6.51, d; 6.72, d; (J=10 Hz) and 4.30, s,: benzodioxane protons

=7.37, s, and 5.16, s=CH.sub.2 --.phi.

=5.76 m: --COCH.sub.2

=3.43, s,: --CH.sub.2 --CO--

Code Number: 770 379

First step: 2-[(5-benzyloxy-1,4-benzodioxane)yl-5] acetic acid (XXVII)

Code Number: 770 308

To a solution of 57 g of sodium hydroxide in 1 l of 50% aqueous ethanol, cooled to 0.degree. C., were added 200 g of 5-benzyloxy-8-cyanomethyl-1,4-benzodioxane, obtained with the process of Example 32, then the ethanol was distilled; a solution of hydrochloric acid was added up to acid pH, it was washed with chloroform, acidified up to pH=3 and filtered.

Yield: 78%

Melting point: 150.degree. C.

NMR spectrum:

.delta. ppm=6.43, d; 6.65, d, and 4.23, s,: benzodioxane protons

=7.38, s, and 5.08, s,: --CH.sub.2 --.phi.

=3.58, s,: --CH.sub.2 --COO--

=9.20, m, --COOH

Second step: 5-benzyloxy-8-N-methylcarboxamidomethyl-1,4-benzodioxane

To a solution of 80 g of 2-[(5-benzyloxy-1,4-benzodioxane)yl-5] acetic acid obtained in the preceding step, in 500 ml of dimethyl formamide, cooled to 0.degree. C., 50 ml of triethylamine were added, then 31 ml of ethyl chloroformate. Then a gaseous flow of methylamine was passed and the reaction was checked by chromatography on a thin silica layer. Then it was poured into iced water, the precipitate formed was filtered and taken up in chloroform. The organic phase as washed with a diluted hydrochloric acid solution, the organic phase was evaporated and the residue recrystallized in ethyl acetate. 70 g of product were obtained.

Yield: 85%

Melting point: 160.degree. C.

NMR spectrum:

.delta. ppm=6.02, d, 6.23, d (J=9 Hz) and 3.82, s,: benzodioxane protons

=6.94, s and 4.63, s,: --CH.sub.2 --.phi.

=3.02, s,: CH.sub.2 --CO--

=2.30, d, (J=5 Hz): --CH.sub.3

=5.12, m, --NH--

IR spectrum: 3295 and 1640 cm.sup.-1 : --CONH--

Code Number: 760 701

A solution of 12.8 g (0.04 mole) of (5-benzyloxy-1,4-benzodioxane)yl-5-ethyl carboxylate, obtained according to the method of Example 17, in 50 ml of anhydrous tetrahydrofuran was added to a suspension of 1.54 g (0.04 mole) of lithium hydride and aluminum in 150 ml of tetrahydrofuran and left at room temperature for 30 minutes. Then it was hydrolyzed with an aqueous solution of sodium sulfate then with a saturated aqueous solution of sodium sulfate, filtered, the solvent was evaporated and the residue recrystallized in benzene. 11 g of product were thus obtained.

Yield: 97%

Melting point: 106.degree. C.

NMR spectrum:

.delta. ppm=6.78, d; 6.51, d; (J=10 Hz) and 4.24, s,: benzodioxane protons

=7.32, s, and 5.12, s;: --CH.sub.2 --.phi.

=4.60 m, and 2.20 m,: --CH.sub.2 OH

Code Number: 770 582

To a solution of 84.5 g of 5-benzyloxy-8-carboxamido-1,4-benzodioxane (XId), code number 770 202, obtained by the method of Example 18, in 1000 ml of benzene, were added 80 g of phosphorous pentachloride. The temperature rises to 40.degree. C. after 45 minutes, the solvent was evaporated, and the residue was taken up in toluene, washed with water and the solvent was evaporated. The residue was recrystallized in ethyl acetate.

Yield: 62%

Melting point: 145.degree. C.

NMR spectrum:

.delta. ppm=6.50, d, 7.01, d, (J=10 Hz) and 4.25, s,: benzodioxane protons

=7.38 s, and 5.05 s,: CH.sub.2 --.phi.

IR spectrum: 2210 cm.sup.-1 : band --CN

Code Number: 770 309

To a solution of 72 g of 2-[(5-benzyloxy-1,4-benzodioxane)yl-8] acetic acid, obtained by the method of the first step of Example 34, in 200 ml of ethanol, were added 100 ml of hydrochloric acid in ethanol 7.5 N, then it was brought to reflux for 30 minutes. The solvent was evaporated, the residue was taken up in chloroform, then it was washed with a saturated sodium bicarbonate solution, with water, and the solvent was evaporated. 98% of crystallized product was obtained.

Melting point: 86.degree. C.

NMR spectrum:

.delta. ppm=6.40, d; 6.61, d (J=10 Hz) and 4.18, s,: benzodioxane protons

=7.36, m, and 5.03, s: --CH.sub.2 --.phi.

=3.37, s: --CH.sub.2 --COO

=4.18, q and 1.10, t, (J=8 Hz): --COO--CH.sub.2 --CH.sub.3

Table VI, in which are shown the different compounds of formula (XI), is given below.

The compounds of formula I were studied on laboratory animals and showed an antiangorous activity, as well as activities on the peripheral and cerebral circulation.

The antiangorous activity was tested on an anaesthetized dog (sodium pentobarbital 30 mg/kg/i.v.).

The consumption of oxygen in the left ventricule was estimated by the product of the coronary venous flow and the coronary arteriovenous difference in oxygen (% volume).

The coronary venous flow was measured at the coronary venous sinus by means of a modified Morawitz cannula, introduced under radioscopic control.

The arterial and coronary venous oxygenation was measured with a blood gas analyzer (IL meter 213).

The cardiac effort was estimated according to KATZ's index, by the product of the average arterial pressure and the cardiac frequency.

The cardiac frequency was estimated from the electrocardiogram recorded with D.sub.2 derivation.

The systemic arterial pressure was measured at the femoral artery with a pressure sensor (SANBORN 267-BC).

The results obtained by injecting the compounds of formula I and the following reference products: LIDOFLAZINE and AMIODARONE, are given in Table VII below. It should be noted that the compounds tested were injected intravenously with slow perfusion.

The activity on the cerebral circulation was tested on an anaesthetized dog (sodium pentobarbital 30 mg/kg/i.v.). The vertebral artery flow was measured by means of an electromagnetic perivascular or ultrasonic Doppler effect probe.

The intracerebral vascular resistance was estimated by the back pressure of the internal carotid artery.

The systemic arterial pressure was measured at the femoral artery with a pressure sensor (SANBORN 267-BC).

The increase in the extraction of cerebral oxygen was estimated by the following equation:(A-V)/A in which:

A represents the volume of oxygen in the arterial blood (% volume) measured by hemoreflectometry (KIPP and ZONEN's apparatus) and quantity determination of the haemoglobin (DRABKIN's method).

V represents the volume of oxygen in the cerebral venous blood (internal maxillary vein).

The results obtained by injecting the compounds of formula I and the following reference compounds: papaverine, naphtidrofuryl, and cinnarizine are given in Table VIII below.

It should be noted that the compounds tested were injected intravenously (rapid injection).

The activity on the peripheral circulation was studied on an anaesthetized dog (sodium pentobarbital 30 mg/kg/i.v.). The femoral artery flow was measured by means of an electromagnetic or ultrasonic perivascular Doppler effect probe.

The systemic arterial pressure was measured at the femoral artery with a pressure sensor (SANBORN-267 BC).

The results obtained by injecting the compounds of formula I and the following reference compounds: papaverine, naphtidrofuryl and cinnarizine are given in Table IX below (intravenous injection with slow perfusion).

It is evident from the preceeding results that the difference between therapeutic doses and toxic doses is sufficiently great to allow the compounds of formula I to be used in the treatment of disturbances in the cardiovascular systems, particularly as antiangorous agents and as agents active on the cerebral and peripheral circulation.

They will be administered intravenously in the form of injectable ampoules containing 60 to 120 mg of active constituent or orally in the form of tablets, pills or capsules containing 20 to 200 mg of active constituent (1 to 3 per day).