DE2140550C3 - 2-Benzoylalkylbenzomorphans, process for their preparation and pharmaceuticals - Google Patents

Description

2. Process for the preparation of 2-benzoylalkylbenzomorphanes according to claim 1, characterized in that a benzomorphane of the general formula II is used in a manner known per se

MR

(Π)

in which R, Ri, R ₂ , R5, R ₆ and R _{7 have} the above meaning, with a compound of the general formula III

40 and optionally the resulting 2-Benzoyialkylbenzomoiphan of the general formula I converted into a salt by reaction with an inorganic or organic acid.

3. Medicament with analgesic effect, containing a compound according to claim 1.

C- (CH ₂ J ₁₁ -X (III)

in which R ₃ , R ₄ and n have the above meaning, X is a halogen atom and Y is an oxygen atom or an ethylenedioxy group, condenses and, if Y is the ethylenedioxy group, the resulting ethylene ketal of 2-benzoylalkylbenzomorphane of the general formula IV

HR ₇

Analgesics of the benzomorphan group are known. One of the therapeutically most important representatives of this The class of compound, phenazocine, has an extraordinarily high analgesic effect in animal experiments Effect, but research has shown that the "addictive capacity" of this compound is consistent with the high analgesic intensity. The depressive effects of phenazocin on the The respiratory function is at least as great as that of an equianalgesic dose of morphine (cf. and Ru schig, "Arzneimittel", Vol. 1, pages 342 to 348, Verlag Chemie, 1968).

The object of the invention is to provide new 2-benzoylalkylbenzomorphanes with analgesic properties to create the disadvantages of the known benzomorphans do not exhibit. This object is achieved by the invention.

The invention thus relates to 2-benzoylalkylbenzomorphanes of the general formula I.

35

in which R, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ , R ₇ and η have the above meaning, cleaves hydrolytically

45 in which R represents a hydrogen atom, a Ci_ ₃ alkoxy radical, a hydroxyl, nitro or amino group, Ri and R2 represent a hydrogen atom or a Ci -3 alkyl radical, but in the event that Ri _{denotes the Ci _ 3} alkyl radical , R ₂ does not represent this radical, R ₃ and R ₄ , which are identical or different, are hydrogen or halogen atoms or Ci_3-alkoxy radicals, R5 is a hydrogen atom or a methyl group, Re is a hydrogen atom or a Ci _3-alkyl radical and R _{7 is} a hydrogen atom or a Ci-3-alkyl radical and π has the value 3 or 4, and their salts with acids.

In preferred 2-benzoylalkylbenzomorphanes of the general formula I, R is a hydrogen atom, a hydroxyl group or a C 1 -3 alkoxy group and R 1 is a C 1 _-3 alkyl group.

In a further group of preferred 2-Benzoylalkylbenzomorphanen of the general formula I R, represents a hydrogen atom, a hydroxyl group or a C ₃ _ -AIkoxyrest.

The invention also relates to a process for the preparation of 2-benzoylalkylbenzomorphanes general formula I, which is characterized

β one in a known manner a benzomorphane r general formula II

MR

(H)

ι the R, Ri. R2, Rs, Ηβ and R ₇ the above meaning n, with a compound of the general formula II!

15th

VC- (CH ₂ ) "- X (IU)

in which R3, R * and η have the above meaning, X is a halogen atom and Y is an oxygen atom or an ethylenedioxy group, condenses and, if Y is the ethylenedioxy group, the resulting ethylene ketal of 2-benzoylalkylbenzomorphane of the general formula IV

HR ₇

35

40

in which R, Ri, R2, R3, R4, Rs, R6, R7 and π the above Have meaning, hydrolytically cleaves and optionally the 2-benzoylalkylbenzomorphan obtained general formula I by reaction with an inorganic or organic acid in a salt 4 ;; convicted.

The reaction of the benzomorphane of the general formula II with the compound of the general formula III is usually carried out in an inert organic solvent such as η-hexane, benzene, toluene, xylene, chloroform, dimethylformamide, methanol, ethanol or isopropanol. Preferably the reaction is conducted in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium amide, sodium hydride, pyridine or triethylamine, carrying out the reaction may proceed at temperatures of 20 to 200 ⁰ C, preferably 60 to 15O ⁰ C, be performed. The reaction product is isolated in the usual way

If Y is the ethylene dioxy group, the corresponding ethylene ketal of 2-benzoylalkylbenzomorphans must be used the general form! IV are hydrolytically cleaved. The hydrolysis takes place according to the usual Methods with an acid. The hydrolysis becomes 6 "; preferably in a solvent such as water, an alcohol such as methanol, ethanol, propanol,> 1 or butanol, and preferably at Temperatures carried out from room temperature to the boiling point of the solvent used. Catalytic amounts of acid are necessary for hydrolysis. Examples of acids that can be used are Mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid, or organic acids such as acetic acid.

The reaction is usually complete in about 30 minutes to 2 hours

The 2-benzoylalkylbenzomorphanes are used to prepare the salts of the general formula I by customary methods with an organic or inorganic Acid, such as formic acid, acetic acid, butyric acid, malic acid, fumaric acid, succinic acid, glutamic acid, Tartaric acid, oxalic acid, citric acid, lactic acid, glycolic acid, gluconic acid, glucuronic acid, saccharic acid, Ascorbic acid, benzoic acid, phthalic acid, salicylic acid, glyceric acid, anthranilic acid, cholic acid, picolinic acid, Picric acid, tropic acid, indole acetic acid, barbituric acid, Sulfamic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, Hydrobromic acid, hydroiodic acid, sulfuric acid or phosphoric acid.

The 2-Benzoylalkylbenzomorphane of the general formula I in which R ₂ represents a Ci _ ₃ alkyl group, are used in the as-configuration (R ₂ = α-form) and in the trans configuration (R2 = ß-form) before. These two diastereoisomers can be separated from one another and purified by customary fractional crystallization, fractional distillation or column chromatography.

Each of these diastereoisomers can also be obtained by condensation of the corresponding cis or trans-Ben homorphan of the general formula II prepared with the compound of the general formula III will.

Each of these diastereoisomers has asymmetric ones Carbon atoms, so that there are four different optically active 2-benzoylalkylbenzomorphanes of the general Formula I obtained by customary methods for the cleavage of optical isomers, namely the (-t -) - cis-, (-) -cis-, (+) - trans- and (-) -trans-forms.

The benzomorphanes of the general formula II used in the process according to the invention are selected from the corresponding 2-methyl-6,7-benzomorphane derivatives prepared by demethylation.

The 2-benzoylalkylbenzomorphans according to the invention and their salts with acids are valuable Analgesics with a calming effect that surprisingly showed no tendency to become addictive in animal experiments exhibit. The following experiments have shown this.

1. Determination of abstinence syndrome

(cf. Folia pharmacologica Japonica, Vol. 54 [1958], p. 120)

For each experimental group, 20 male rats (Wistar strain; initial body weight 150 g) used.

The compounds listed in Table I were administered subcutaneously to rats twice daily for a period of time administered from 4 weeks. After discontinuation of the compounds, the rats develop abstinence syndrome determined on the basis of body weight loss. If one of the investigated compounds shows an abstinence syn drom, takes the body weight of the rat

clearly. The symbols in Table I have the following meanings:

+ 4 + strong decrease in body weight (about 5%),

+ + moderate weight loss, + slight weight loss, - no weight loss.

The results are summarized in Table I. Table I.

Test connection

Dose of abstinence

img / kg, sc / day syndrome for 4 weeks

2'-hydroxy-2- [y- (p-fluoro-20 -

benzoyl) -n-propyl] -

5-methyl-6,7-benzo-

morphan

2'-hydroxy-2- [y- (p-fluoro-20 -

benzoyl) -n-propyl] -

6,7-benzomorphan

2- (y-benzoyl-n-propyl) - 20 -

5-methyl-6,7-benzo-

morphan

2- [y- (p-fluorobenzoyl) - 20 -

n-propyl] -5-methyl-

6,7-benzomorphan

2- [y- (p-fluorobenzoyl) - 20 -

n-propyl] -6,7-benzo-

morphan

«-2'-hydroxy-2,5,9-tri- 20 ++

methyl-6,7-benzomorphan

(US-PS 31 38 603)

Morphine 20 +++

2'-methoxy-2-carbamyl-20 +

5-phenyl-6,7-benzomorphane

(OE-PS 2 61 126)

Iso-2'-hydroxy-5,9-di-20 ++

methyl-2- (0-phenethyl) -

6,7-benzomorphan

(US-PS 29 59 594)

From the results it can be seen that the compounds of the invention, in contrast to the known compounds do not cause abstinence symptoms after weaning.

0.6 percent aqueous acetic acid solution is caused. The syndrome is characterized by intermittent contractions of the abdomen, twisting and turning of the body and stretching the Hind legs.

A 0.6 percent aqueous acetic acid solution was administered intraperitoneally to the mice. 20 minutes before the compounds to be investigated were administered to the injection of the acetic acid solution. For control purposes animals were used which were injected intraperitoneally with acetic acid solution only. the Number of mice that have no pain response (curvature syndrome) was noted. To determine the analgesic activity, the number of Contractions of the abdomen during 12 minutes after the injection of the acetic acid solution were counted. Both In animals of the control group, the number of contractions was 30. The compounds examined are considered effective when the number of contractions is 3 or less. The ED50 was calculated according to Litchfield - Wilcoxon. The results are summarized in Table II.

Table II

Test connection

2. Determination of the analgesic effect

Groups of 5 animals each were used for each experiment. The following experiments were carried out accomplished:

a) Curvature test (cf. Folia Pharmacologica, Japonica, Vol. 56 [I960} p. 83).

Male mice (ICR strain; 20 to 25 g in weight) were used for these experiments. The curvature test is based on the specific antagonism of analgesics against the typical curvature syndrome, which is caused by intraperitoneal injection of a curvature LD50,
syndrome test mg / kg
ED50, mg / kg, se

2'-hydroxy-2 - [)> - (p-fluoro-2.0> 270

benzoyl) -n-propyl] -5-methyl-

6,7-benzomorphan

2'-hydroxy-2-O (p-fluoro-1,4> 270

benzoyl) -n-propyl] -6,7-benzo-

morphan

2- (γ-Benzoyl-n-propyl) -5-methyl-6,7-benzomorphane

2 - [)> - (p-fluorobenzoyl) -n-pro-

pyl] -5-methyl-6,7-benzo-

morphan

2- [y- (p-fluorobenzoyl) -

n-propyl] -6,7-benzomorphane

2'-methoxy-2-carbamyl-> 160

5-phenyI-6,7-benzomorphane

(OE-PS 2 61 126)
50

2'-hydroxy-2-carbamyl-> 160> 250

5-phenyl-6,7-benzomorphane

(OE-PS 2 61 126)

2'-hydroxy-2- [y- (p-fluoro-4.1 270

benzoyl) -n-propyi] -5,9-dimethyl-6,7-benzomorphane
(NL-CS 69 19 358)

9.0 > 270 6.0 > 270 7.0 > 270 0 250

In contrast to other morphine and 6,7-benzomorphane derivatives, the compounds of the invention show no adverse side effects such as rigor, ataxia, convulsions, vomiting, and respiratory depression. In Experiments on male dogs of the Beagle strain weighing 8 to 12 kg (10 animals per group) were carried out Respiratory depression and the effect of nausea were investigated. The results are in Tables IH and IV compiled.

Table IU
Respiratory depression

Test connection dose
mg / kg,
in the Respiratory
depression 2'-hydroxy-2- [y- (p-fluoro-
benzoyl) -n-propyl] -5-methyl-
6,7-benzomorphan 20th
40
80 - 2'-hydroxy-2- [y- (p-fluoro-
benzoyl) -n-propyl] -6,7-benzo-
morphan 20th
40
80 - <x-2'-hydroxy-2,5,9-trimethyl-
6,7 -benzomorphane 20th depression Morphine 20th depression Table IV Emetic effect Test connection Dose,
mg / kg,
in the Emetic
effect

2'-hydroxy-2- [y- (p-fluoro- 20th benzoyl) -n-propyl] -5-methyl- 40 6,7 -benzomorphane 80 2'-hydroxy-2- [y- (p-fluoro- 20th benzoyl) -n-propyl] -6,7-benzo- 40 morphan 80 Ä-2'-hydroxy-2 5 9-trimethyl- 20th 6,7-benzomorphan Morphine 20th

b) Randall-Selitto test (see Arch. int. Pharmacodyn., Vol. 113 [1957], p. 233).

In this test, the analgesic effect of the compounds to be investigated is artificial determined inflammation. This method is based on the principle that inflammation causes the Sensitivity to pain is increased and that this increased sensitivity is modified by analgesics can be. The inflammation lowers the pain response threshold, and it lowers it Pain response threshold is set by analgesics

s increased.

Male rats (Wistar strain, 80 to 100 g in weight) were used. Those listed in Table V were used Compounds were given to the rats 2 hours after the injection of 0.1 ml of a 20 percent brewer's yeast suspension administered into the foot surface of the right foot. The pain threshold was considered to be the one on the Pressure applied to the foot measured in mm Hg, which is required to generate an escape reaction (fidgeting) is. The extent of the analgesic effect is expressed as a percentage increase in the pain threshold of the treated Rats calculated at the mean pain threshold of untreated rats

c) Bradykinin test (cf. J. Pharm, Pharmacol., Vol. 18 [1966], p. 135).

This test measures the degree of inhibition of bradykinin-induced behavior in the test animals, namely, turning the head clockwise, flexing the right limbus and increasing breathing and the Motility, determined by the compound being tested.

If at least two of the three behaviors are suppressed, the connection is considered effective viewed.

Male rats (Wistar strain, about 300 g in weight) were used. 30 minutes after subcutaneous Administration of the compound to be investigated was through a polyethylene cannula 0.2 to 0.4 Micrograms of bradykinin injected into the common carotid artery.

d) Electric shock test (see J. H. Burn et al., Biological Standardization, 1950, p. 316).

In this test, the tail of a mouse is electrically stimulated. The time is determined until the Mouse screams. If the mouse treated with the compound to be tested during 3 Minute stimulus duration does not emit screams, the connection is considered to be effective.

Male mice (dd-k strain, 50 to 20 g in weight) were used. 30 minutes after subcutaneous Administration of the compound to be tested was started with the experiment.

The results are shown in Table V.

Table V

Test connection

Bradykinin test ED50,
mg / kg, se

Randall-Selitto test

Dose, mg / kg, se pain threshold,

Electric shock test, ED50,
mg / kg, se

2'-Hydroxy-2- [y- (p -fluorobenzoyl) -n-propyl] -5-methyl-6,7-benzomorphane

2'-Hydroxy-2- [y- (p -fluorobenzoyl) -n-propyl] -6,7-benzomorphane

2- (γ-Benzoyl-n-propyl) -5-methyl-6,7-benzomorphane

2- [y- (p-fluorobenzoyl) -n-propyl] -5-methyl-6 7-benzomorphane

8.0 10 30.7 4.6 20th 62.6 40 79.7 80 92.8 7.3 10 42.0 3.8 20th 74.2 40 72.2 80 100.2 25.4 21.5 19.5 14.0

709 652/17

continuation

i,

Test connection

2- [y- (p-Fluorobenzoyl) -n -propyl] -6,7-benzomorphane

2'-methoxy-2-carbamyl-5-phenyl-6,7-benzomorphane
(OE-PS 2 61 126)

2'-Hydroxy-2- [y- (p -fluorobenzoyl) -n-propyl] -5,9-dimethyl-6,7-benzomorphane (NL-OS 69 19 358)

Bradykinin Rundall-Selitto-Tcst Pain- Electric shock Tesl EDiO, schwcllc,% Test, ED-, 0, mg / kg, se Dose, mg / kg, se mg / kg, se 8.9 18.8 6.4 13.5 > 40 20th 15.7 > 80 40 53.3 80 160

9.1

The valuable properties of the 2-benzoylalkylbenzomorphanes of the general formula I are presumably based primarily on the 2-benzoylalkyl side chain. These properties are not found in either morphine or other 6,7-benzomorphans.

For the production of medicaments, the compounds of the invention can be used in the form of their salts in sterile water or an equivalent amount of a pharmacologically acceptable acid, provided the free Base is used, or in a physiologically acceptable aqueous medium, such as physiological Saline solution, dissolved, and dispensed into ampoules. The compounds of the invention can also in dosage units of 1 to 15 mg together with other conventional carriers and auxiliaries, such as Calcium carbonate, starch, lactose, talc, magnesium or gum arabic, in tablets or capsules processed for oral administration.

The examples illustrate the invention.

example 1

2'-Hydroxy-2- [y- (p -fluorobenzoyl) -n -propylene] -5-methyl-6,7-benzomorphane

1.1 2'-Hydroxy-2- [4 "- (p-fluorophenyl) -4", 4 "-ethylenedioxy-n-butyl] -5-methyl-6,7-benzomorphane

A mixture of 0.8 g of 2'-hydroxy-5-methyl-6,7-benzomorphane, 0.5 g of sodium bicarbonate, 1.06 g of 4- (p-fluorophenyl) -4,4-ethylenedioxy-1-chlorobutane and 15 ml of dimethylformamide is heated to 130 to 155 ° C. for _{3V for 2 hours and stirred.} The precipitate formed is filtered off and the filtrate is evaporated under reduced pressure. The residue is mixed with water and extracted with diethyl ether. The combined ether extracts are dried over sodium sulfate and evaporated. The specified product remains as a viscous liquid.

IR absorption ν ^: 1600, 1580, 1505, 1220, 1155, 1040, 840.

1.2 2'-Hydroxy-2- [y- (p -fluorobenzoyl) -n-propyl] -5-methyl-6,7-brenzomorphan

A mixture of 1.7 g of the compound prepared according to 1.1, 8 ml of methanol, 4 ml of water and 0.8 ml of concentrated hydrochloric acid is ^{heated to 79 to 81 °} C. for 1 hour and stirred. The mixture is then treated with 0.05 g of decolorizing charcoal and filtered. The filtrate is evaporated under reduced pressure, the residue is made alkaline with aqueous ammonia solution

45

5 °

55 made and extracted with diethyl ether. The combined ether extracts are evaporated to dryness. The residue is recrystallized from acetone. The product melts at 169.5 to 171.5 ° C.
IR absorption v ^c ^ _m " : 1690, 1600, 1505.

Example 2

2 - [)> - (p-Fluorobenzoyl) -n -propyl] -5-methyl-6,7-benzomorphane

2.1 2- [4 "- (p-fluorophenyl) -4", 4 "-ethylenedioxyn-butyl] -5-methyl-6,7-benzomorphane

A mixture of 1.87 g of 5-methyl-6,7-benzomorphane, 1.0 g of sodium bicarbonate, 2.45 g of 4- (p-fluorophenyl) -4,4-ethylenedioxy-1-chlorobutane and 20 ml of dimethylformamide is used for 4 hours heated to 110 to 145 ⁰ C unc stirred. The mixture is then strongly concentrated under reduced pressure, and water is added. There; The mixture is extracted several times with benzene, the combined benzene extracts are washed with water, dried over sodium sulfate and evaporated under reduced pressure. You get there; specified product.

IR absorption Km? «*: 1600, 1502, 1220, 1158, 1040 840,760,680.

2.2 2- [y- (p-fluorobenzoyl) -n-propyl] -5-methyl-

6,7-benzomorphan

A mixture of 3.6 g of the compound obtained according to 2.1, 40 ml of methanol and 15 ml of water is mixed with 5 ml of concentrated hydrochloric acid, heated under reflux for 1 hour, then treated with decolorizing charcoal and filtered. The filtrate is evaporated under reduced pressure, the residue is made alkaline with aqueous ammonia solution and extracted with dichloromethane. The extract is washed with water, dried over sodium sulfate and evaporated. The residue is distilled under reduced pressure. The product boils at 170 to 198 ^° CA): Torr.

IR absorption vmLi _P : 1678, 1592, 1230, 1156, 837 760.

The free base, dissolved in diethyl ether, is reacted with anhydrous hydrogen chloride gas. The hydrochloride is recrystallized from a mixture of acetone and methanol. F. 219 to 220 ⁰ C.

IR absorption V ^ m _n - 1688.1600.

Example 3

2 - (}> - Benzoyl-n-propyl) -5-methyl-6,7-benzomorphane

A mixture of 0.47 g of 5-methyl-6,7-benzomoiphane, 0.3 g of sodium bicarbonate and 10 ml of dimethylformamide 0.46 g of γ-chlorobutyrophenone are added. The resulting mixture is heated to 130 to 160 ° C. for 4 hours heated and stirred. The mixture is then evaporated, water is added to the residue and extracted with diethyl ether. The combined ether extracts are washed with water over sodium sulfate dried, treated with decolorizing charcoal and evaporated. The residue is obtained by reacting with anhydrous hydrogen chloride gas converted into the hydrochloride, which after recrystallization from a Mixture of acetone and ethyl acetate at 218 to 22Γ C melts

IR absorption vf ^ _ma : 2500 (broad), 1685, 1598, 1580, 1212.

20th

Example 4

2'-Hydroxy-2- [y- (p-fluorobenzoyl) -n-propyl] -

6,7-benzomorphan 2 ;;

4.1 2'-Hydroxy-2- [4 "- (p-fluorophenyl) -4", 4 "-ethylenedioxy-n-butyl] -6,7-benzomorphane

A mixture of 0.45 g of 2'-hydroxy-6,7-benzomorphane, 0.3 g of sodium bicarbonate and 10 ml of dimethylformamide is mixed with 0.64 g of 4- (p-fluorophenyl) -4,4-ethylenedioxy-1-bromobutane and heated 3V ₂ hours at 130 to 150 ° C and stirred the precipitate formed is filtered off, the filtrate evaporated and the residue treated with water the mixture is extracted with diethyl ether and the combined ether extracts evaporated to dryness, it remains behind the specified product as an oil.

IR absorption v £ | _B : 1600, 1505, 1225, 1160, 1050, 840.

4.2 2'-Hydroxy-2- [y- (p-fluorobenzoyl) -n-propyl] -

6,7-benzomorphan

A solution of 1.05 g of the compound obtained according to 2.1 in 5 ml of methanol, 2.5 ml of water and 0.5 ml of concentrated hydrochloric acid is heated to 82 to 97 ° C for 1 hour and stirred, then with 0.03 g of decolorizing carbon _: -, o treated and filtered. The filtrate is evaporated, the residue is made alkaline with aqueous ammonia solution and extracted with diethyl ether. The combined ether extracts are evaporated and the residue is recrystallized from acetone. _5S is obtained the indicated product, mp 165.5 to 169.5 ⁰ C.

IR absorption v ^ _ra ' _m ": 1680, 1600, 1503.

Example 5
2- [y- (p-fluorobenzoyl) -n-propyl] -6,7-benzomorphane 5.1 2- [4 "- (p-fluorophenyl) -4", 4 "-ethylenedioxyn-butyl] -6,7-benzomorphane

A mixture of 1.7 g of 6,7-benzomorphane, 2.5 g of 4- (p-fluorophenyl) -4,4-ethylenedioxy-1-chlorobutane, 1.01 g of sodium bicarbonate and 20 ml of dimethylformamide is brought to 125 for _{3V for 2 hours} Heated and stirred to 155 ° C.

ίο The mixture is then vigorously evaporated under reduced pressure and water is added to the residue. The mixture is extracted several times with diethyl ether. The combined ether extracts are washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and filtered. The filtrate is evaporated. The stated product remains as a liquid; π% = 1.5459.
IR absorption vJÜ,: 1602,1503,1222,1040,839.

52 2- [y- (p-Fluorobenzoyl) -n -propyl] -6,7-benzomorphane

A solution of 3.5 g of the compound obtained according to 5.1 in 50 ml of methanol and 15 ml of water becomes 5 ml of concentrated hydrochloric acid are added and heated under reflux for 1 hour and then under reduced pressure Pressure evaporated. The residue is made alkaline with aqueous ammonia solution and with diethyl ether extracted The ether extract is washed with water, dried over sodium sulfate and evaporated The residue is converted into the hydrochloride with hydrogen chloride gas after recrystallization from a mixture of methanol and acetone at 209 to 211 ° C melts

IR absorption V ^ _n : 2580, 1683, 1600, 1235, 1220, 1163,850,775.

Example 6
2- [y- (p-Methoxybenzoyl) -n -propyl] -6,7-benzomorphane

6.1 2- [4 "- (p-Methoxyphenyl) -4", 4 "-ethylenedioxyn-butyl] -6,7-benzomorphane

The compound is obtained according to Example 4.1 by reacting 1.62 g of 6,7-benzomorphane with 2.4 g of 4- (p-methoxyphenyl) -4,4-ethylenedioxy-1-chlorobutone as a liquid; πΌ ° = 1.5600.

IR absorption v ^c "1 _M ' _ig : 1600, 1505, 1243, 1167, 1030, 830.762.

6.2 2- [7- (p-Methoxybenzoyl) -n-propyl] -6,7-benzomorphane

According to Example 4.2, the compound obtained in 6.1 in accordance with the hydrochloride of the above product is converted to the melts after recrystallization from a mixture of acetone and methanol at 211.5 to 213 ⁰ C.

IR absorption v ^ L x 2500, 1670, 1600, 1575, 1250, 1220, 1179, 1020.

Claims (1)

Patent claims: 1,2-BenzoyIalkylbenzomorphane of the general formula I _D 15th in which R is a hydrogen atom, a Ci_ ₃ -alkoxy group, a hydroxyl, nitro or amino group, Ri and R2 are a hydrogen atom or a Q-3-alkyl group, but for the case that Ri is the Ci-3-alkyl group , R ₂ does not represent this radical, R3 and R ₄ , which are identical or different, are hydrogen or halogen atoms or Ci_ ₃ alkoxy radicals, R5 is a hydrogen atom or a methyl group, Re is a hydrogen atom or a Ci_ ₃ alkyl radical and R _{7 is} a hydrogen atom or a Ci _3- alkyl radical and η has the value 3 or 4, and their salts with acids.