DE1817016A1 - New piperidine derivatives - Google Patents

Description

Cologne, JL8. December 1968 Kl / Ax / fa

Yoshitomi Pharmaceutical Industries Ltd., 35 Hiranomachi 3-chome, Higashiku, Osaka (Japan)

New_piperidine derivatives

The invention "relates to new therapeutically valuable piperidine derivatives the formula

(I)

in which X ¹ and X ^{2 are} H, Gl, methyl, methoxy, methylthio, trifluoromethyl or acetyl, Y is -0-, -S-, -SOp-, -OH ₂ -, -CH ₂ -OH ₂ - , -OH = CH-, -NH- or -N (CH,) -, A for -OH ₃ -, -CH ₂ -OH ₂ -, = 0H0H _5? -0-CH ₂ - or -0-CH ₂ -OH ₂ -, where -0- is bonded directly to the nitrogen atom, and R is a benzyl radical or alkylreat with 1 to 4 carbon atoms, for example methyl, ethyl, propyl - or is butyl radical «,

The compounds of the formula (I) are prepared by reacting compounds of the formula

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(II)

in which Z is an alkali metal or -OH, with a compound of the formula

-4— A-Q (III)

I -4-

in which Q is a halogen atom (e.g. "B <> oil, Br or I) or an organic sulfonyloxy _{radical, Z 0} B _{0 is} a methylsulfonyloxy or p-tolylsulfonyloxy radical«,

The reaction is preferably carried out in an inert solvent such as benzene, toluene, xylene, dfoxane, dimethylformamide, or in a mixture of these solvents. The reaction temperature is determined depending on the respective starting compounds and other reaction conditions, but the reaction is usually carried out at room temperature or elevated temperature, ζ _e B * approximately at the boiling point of the solvent used »If Z stands for OH, the reaction is advantageous in the presence of a Deacidifying agent carried out. Suitable deacidifying agents are, for example, inorganic or organic alkali metal compounds or basic compounds, Z ₀ B ₀ sodium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide or pyridino

The starting compounds of formula (II) in which Z is an alkali metal, are prepared, for example 1) by reacting the corresponding compound in which Z is hydrogen with an alkali metal amide such as sodium amide _e, in an inert solu-

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solvent or 2) by reacting a compound of the formula

(IV)

in which R is a lower alkyl radical with an alkali amide in, an inert solvent.

Further starting compounds of the formula (II) in which Z is for -OH is "for example by catalytic reduction a compound of the formula

(V)

in which R is a lower alkyl radical, in the presence of hydrogen and Raney-Uicke] /, where ^ for ^ nT ^ dration and simultaneous cyclization take place.

The piperidine derivatives of the formula (I) prepared in this way can be mixed with various inorganic or organic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, oxalic acid, maleic acid, fumaric acid, tartaric acid, o- (p-hydroxybenzoyl) benzoic acid, o «- ( p- (o-Hydroxyphenyl) phenyl) benzoic acid and 4 ¹ , 4 "-dihydroxytriphenylmethane-2" * carboxylic acid, acid addition salts or / alkyl halides, such as methyl iodici, form quaternary ammonium salts ©

9 0 9 8 3 2/1575

■ - 4 -

The compounds of formula (I) and their pharmaceutically, harmless acid addition salts have antihiatamine and antitremorin effects, as shown, for example, by the following experiments «

1> Anti-stamine effect .

Male guinea pigs weighing 400 to 600 g each received none for 18 hours. Food and were then sacrificed "The intestine was isolated and in a Magnus cup (Ϊ0 el, Xösung Tyrode, pH 7.6 to 7.8, 37 ⁰ C, air) and stimulated with histamine. The results were recorded on the kymograph. The PA ₂ value was calculated from the contraction of the intestine which had been pretreated for 5 minutes with a test compound according to the Ύοη JM van Eos sum method (Archives Internationales de Pharmacodynamie et de ee Therapy, 143, 299 * 330, 1963 ) - PA ₂ is the negative value of the logarithm of the molar concentration of the test compound which reduces the effect of the double histamine doses on the contraction activity of the guinea pig intestine to the effect of a single dose.

2 »Antitremorin effects .

Female mice of the dd strain of 20 to 25 g each were divided into groups of 6 animals each. Thirty minutes after a test compound was injected subcutaneously, each mouse received 15 mg of tremorin hydrochloride per kg of body weight by intraperitoneal injection. After 20 minutes it was examined whether tremor and salivation were present - The dose that was effective in half of the animals is given as -BDc ₀ *

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ΐ e s tverbindung Antihi s tamin-
■ -effect, pA ₂ Antitremorin
■ effect,
Bp ₅₀ (mg / kg) A. 7.69 8.2 B ^ 8.20 0.7 σ 10 D. 6.2 E ■ ' 7.72 7.6 Έ 7.81 20th G 7.5 H 7.7 30th I. 3.1

Ai 7-ChIOr-IO- (2- (1 -methyl-2-piperidyl) ethyl) -10,11-

dihydro ~ .5H-di benzo (Td, e) (1,4) diazepin-11-one maleate Bj 7-Oiilor-10- (1-methyl-2-piperidyl) methyl-10, ll-dihy-

αΓο-5Η-αχΐ3βηζο (^, Θ) (1, 4) diazepin-11-one fumarate 0 j 7-methoxy-10- (2- (1-methyl-2-piperidyl) ethyl) -10,11-

dihydro-dilDenzoCtJif) (1,4) thiazepin-11-one fumarate D: 10- (2- (1-methyl-2-piperidyl) ethyl) -8-trifluoro-methyl-10,11-dihydro-dibenzo (b, f) (1,4) thiazepin-11-one-

fumarate
Egg 7-chloro-10- (1 -methyl-3-piperidyl} _methy 1-10,11-

dihydro-SH-dilDenzoCb, e) (1,4) diazepine «r« 11-one-fumarate F: 7-0hlor-10- (2- (1-methyl-2-piperidyl) ethyl) ^ 10,

1 i-dihydro-diTDenzoCb ^) (1,4) thiazepine-11-one fumarate Gs 8-methyl-10 "(i-methyl-2-piperidyl) methoxy-10, 11-

dihydro-dilDenzo (^ b, f) (1,4) thiazepine «11-one-fumarate Hs 5-methyl-10- (1-methyl-2-piperidyl) methoxy-10, 11-

dihydro-5H-di'benzo (T3, e) (i, 4) diazepin-11-one oxalate I i 1O- (2-methy1-2-pipe ridy1) ethoxy) -10,11-dihydrof) ("1 , 4) thiazepine-11-one oxalate.

7-chloro «-10- (1-methyl-2-piperidyl) -me thy 1-10,11 -dihydro-5H-dibenzo (" b, e) (1,4) diazepine-1 I ^ on-fumarate has the following acute toxicity:

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LD ^ ing / kg (male dd ~ mouse)

oral 670

intraperitoneally 255

The compounds (I) according to the invention and their pharmaceuticals Suitable acid addition salts can be used as such as anti-Parkinson agents and antihistamine agents or in the form of a pharmaceutical preparation mixed with a suitable conventional carrier or excipient orally or by injection can be administered without harm to the recipient »Me pharmaceutical preparations can die Form of tablets, granules, powder, capsules, injection solutions, etc. for oral or parenteral administration habeno Of these preparations are tablets and solutions for injection particularly preferred. The choice of carrier depends on the preferred dosage form, the solubility of the Connections and local pharmaceutical practice. Below is an example of the preparation to take given when the compound (i) according to the invention for pharmaceutical purposes.

1 mg tablet j Compound I 1 mg Lactose 78 mg strength 20 mg Magnesium stearate 1 mg

The usual ^T agesdosis the compound (I) or its salt is in the range of about 2 to 15 mg for adults. In the case of tablets which each contain 1 mg of the compound (i) or its salt, 2 to 15 tablets are thus given daily.

0.025 $ solution for injection

Compound I 0.5 mg

Water »to make up to 2 ml.

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Currently preferred embodiments of the invention Described in the following examples · In these examples, parts by weight relate to parts by volume as jee Grams to cubic centimeters.

example 1

To a solution of 4.8 parts by weight of 7 ^ ChlorvlO, 11 "" dihydro-5H-dibenzo (b, e) (1,4) diazepin-11-one in 4-0 parts by volume of anhydrous dioxane are 0.9 wt The mixture is refluxed for 3 hours. After adding 3-9 parts by weight of 2- (1-methyl-2-piperidyl) ethyl chloride, the Gemisoh is refluxed for 5 hours. The reaction mixture is cooled, filtered and concentrated. The residue is dissolved in benzene and extracted with 10 # hydrochloric acid. The acid layer is made alkaline with aqueous ammonia. The oil layer formed after separation is mixed with chloroform, and the chloroform layer is washed with water and then dried over sodium sulfate. The chloroform is distilled off and the remaining brown oil is crystallized from ethanol, 6 parts by weight of colorless crystals of 7-chloro-10- (2- (1-methyl-2-piperialyl) ethyl) «10,11-dihydro-SH -dibenzo- (b, e) (1,4) ~ diazepin ~ 11-one with a melting point of 189 to 19O ⁰ C can be obtained. The maleate of this compound obtained by treatment with maleic acid in ethanol melts at 178 to 181 ° C.

Example 2

a) To a solution of 24.5 parts by weight of 7-chloro-10, 11-dihydro-SH-dibenzoCbjeHl, 4) diazepin-II-one 4.1 parts by weight of sodium amide are added to 200 parts by volume of dioxane. The Gemisoh is refluxed for 3 hours.

b) 2.4 parts by weight of metallic sodium are added to 180 parts by volume of liquid ammonia. The mixture is stirred for 1.5 hours. After adding 13.4 parts by weight of 1-methyl-2-piperidylmethanol, the mixture is stirred for a further 1 _{t for} 5 hours. The ammonia is then distilled off. After adding 100 parts by volume of anhydrous toluene, the Gemisoh is 2 hours on

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Heated to reflux and then ^{cooled to 5 to 10 0} O. A solution of 19 parts by weight of p-toluenesulfonyl chloride in 40 parts by volume of toluene at 5 to 10 ⁰ C is added dropwise to the mixture o After the addition is complete, the mixture is 30 minutes at 10 to 15 ° 0 stirred and then filtered «,

c) The filtrate, the 1-methyl-2 ^ piperidyl-methyl-p «toluene sulfonate contains, becomes the refluxed mixture

drips

Zzüge "*", which contains the sodium salt of the compound 7-chloro "* 10, 11 ~ dihydro-5H-dibenzo (b, e) (1, e) diazepin-11-one, mentioned under a). The resulting mixture is refluxed for 6 hours, cooled, filtered and concentrated. The oily residue is crystallized from ethyl acetate, whereby 16 parts by weight of colorless crystals of 7-chloro-10- (1-methyl-2-piperidyl) methy1-10,11-dihydro-5H-dibenzo (b, e) (1 , 4) 5 obtained diazepin-11-one of melting point 173 to 175 ⁰ C *. ' The fumarate of this compound melts at 216 ⁰ C, the hydrochloride at 192-195 ⁰ C, the 4 ^l -Hydrohybenzophenon-2-carboxylatmonohydrat at 161 to 165 ⁰ C, the 4 ^l - (o-hydroxyphenyl) benzophenone-2-carboxylatmonohydrat at 168-171 ⁰ C and ^4,4-2-ll -Dihydroxytriphenylmethan carboxylatmonohydrat at 173 to 176 ⁰ C.

Example 3

0.9 parts by weight of sodium amide are added to a solution of 5-8 parts by weight of methyl ~ o - * (2-amino-5-methoxyphenylthio) benzoate in 40 parts by volume of dioxane. The mixture is refluxed for 4 hours. 3.9 parts by weight of 2- (H ^ ethyl * -2-piperidyl). The resulting mixture is refluxed for 5 hours and then treated in the manner described in Example 1. Crystallization from diisopropyl ether gives 5.6 parts by weight of colorless 7 "methoxy-10- (2- (1-methyl-2 -piperidyl) ethyl) -10,11-dihydrodibenzo (b, f) - (1,4) thiazepin-11-one from melting point 104 to 107 ⁰ O obtained »The fumarate of this compound melts at 131.5 ⁰ C. -

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Example 4

The sodium salt of 8 «tri-fluoromethyl-10,11-dihydrodibenzo (b, f) (1,4) thiazepin-11-one is prepared by 0.9 parts by weight. Sodium amide to a solution of 6.5 weight parts by _e methyl-o "(2" * amino "4 ~ Trifluo: methylphenylthio) are added benzoate in 40 parts by volume of dioxane and the mixture is heated for 4 hours at Rüokfluss". By reacting the sodium salt with 3.9 parts by weight of 2- (1-methyl-2-piperidyl) ethyl chloride, 7.6 parts by weight of oily 10- (2- (1-methyl-2-piperidyl) ethyl) are obtained ) "F.8"! * Trifluorme thy 1-10,11 <-dihydrodibenzo (b, f) (1,4) thia * zepin-11-one obtained The fumarate of this compound melts at 129 ⁰ O.

Example 5

A solution of 5.4 parts by weight of 8-methyl "-" 10,11-dihydrodibenzo (b, f) (1 _> 4) thiazepine * "41." 0.9 part by weight of sodium amide is added. The mixture is heated under reflux for 3 hours and then concentrated to about 60 parts by volume. 3> 9 parts by weight of 2 "(T-methyl-2""piperidyl) ethyl chloride are added to the residue . The mixture is refluxed for 5 hours. The reaction mixture is then treated in the manner described in Example 1 to give a light brown Gl (6.1 parts by weight) «. The oil is dissolved in ether and treated with alcoholic hydrochloric acid, whereby crystals of 8 «methyl ~ 10- (2 - * (1 ~ methyl-2rPiperidyl) ethyl)« 10,11-dihydrodibenzo (b, f) (1,4) «Thiazepin-11-one-5,5-dioxydhydrochloriämonohydrat can be obtained. After recrystallization from an isopropanol / ether mixture, the product melts at 137 ⁰ O ₀

Example 6

A sodium salt and a p-toluenesulfonate are _{prepared in the manner described in Example 2 (a) or e} (b), where a) 4.1 parts by weight of 5.6 ~ dihydromorphanthridin * -6 ~ one, 40 parts by volume of dioxane and 0.9 parts by weight of sodium amide and b) 2.7 parts by weight of i-methyl-2-piperidylmethanol, 40 parts by volume of liquid ammonia, 0.48 parts by weight of metallic sodium, 3 »8 wt _o -

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Parts of p-toluenesulfonyl chloride and 30 parts by volume of toluene are used o The reaction of the sodium salt and the p-toluenesulfonate is carried out in the manner described in Example 2 (c) " _o After the reaction, the mixture is cooled, filtered and concentrated. The remaining oil is dissolved in toluene dissolved and extracted with 10 ^ hydrochloric acid. The aqueous layer is made alkaline with aqueous ammonia. The oil which separates out is extracted with chloroform, washed with water and dried over sodium sulfate. The light brown oil, which remains after removal of the chloroform by distillation, is dissolved in ethanol. By adding ethanolic hydrochloric acid, a precipitate separates out, which is recrystallized from methanol, with 4.2 parts by weight of 5- (1- methyl-2-piperidyl) methyl-5,6-dihydromorphanthridine werdeno -6-on-hyärochlorid of melting point 261-263 ⁰ C.

Example 7 to 17

In the manner described in Example 1, the compounds mentioned below are prepared from the corresponding sodium salt of the formula (II) and the corresponding 1-substituted piperidylalkyl chloride prepared?

(7) lO- (2- (1-methyl-2 'piperidyl) ethyl) -Lo, ll-dihyärodibenzo (b f) (1,4) oxazepine-11-one of boiling point 176 to 18O ⁰ C / 0, 03 mm Hg ₀

(8) 7-Chloro-5 «methyl-10- (2- (1-methyl-2-piperidyl) ethyl) -10,11-dihydro-5H-dibenzo (b, e) (1,4) diazepine« 11 -on, its maleate melts at 135 to 137 ° C.

(9) 10- (2- (1 -Benzy 1 ^ .2-piperidy 1) ethy 1) «10,11 -d ihy dr o-5H« dibenzo (b, e) (1,4) diazepine ~ 11- on from melting point 140 to 141.5 ⁰ C.

(10) 10- (2- (1 «methyl-2-piperidyl) ethyl) -10, ll-dihydro-5H-dibenzo (b, e) (1,4) diazepin-11-one with a melting point of 134 to 136 ⁰ C (recrystallized from toluene).

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(11) 2,7-dichloro-10- (2- (1-methyl-2-piperidyl) ethyl) -10,11 «dihydro-5H-dibenzo (b, e) (1,4) diazepine-11- on; Melting point of the fumarate 151 Ma 154 ⁰ Co

(12) 7-chloro-10- (2 ~ (1-methyl-2-piperidyl) ethyI) -IO, 11-dihydrodibenzo (b, f) (1,4) thiazepin-11-one, melting point 127 "to 128 ⁰ O (from hexane); melting point of the fumarate up to 150 ° 0.

(13) 7-chloro-10- (1-methyl-.2-piperidyl) methyl-10, 11-dihydrodibenzo (b, f) (1,4) thiazepine1-one with a melting point of 135 "to 138 ⁰ C (from Iigroin ) j Melting point of the fumarate 205.5 to 208 ⁰ C.

(14) 8 "methylthio" lO '(1-methyl-2-piperiäyl) _methyl-Lo> 11-dihydrodibenzo (b, f) (1,4) thiazepine-11 "one maleate, melting point 201 Ma 204 ⁰ C.

(15) 8 ~ acetyl-10- (1-methy 1-2-piperidyl) methyl «10,11-

, 4) thiazepin-11-one maleate from melting point 199 to 201 ⁰ O.

(16) 5- (1-methyl-2-piperidyl) methyl-5,6-dihydrodiT3enz- (b, f) azpcin-6-one fumarate with a melting point 169 "171 ⁰ C bia

(17) 5 «(1-methyl-2-piperidyl) methy1-5,6,11,12-tetra-

f) azooin-6-one fumarate from melting point 161 to

164 ⁰ G.

Examples 18-20

On the example. 1 are the following Compounds from the corresponding sodium salt of Formula (II) and the corresponding 1-substituted piperiayl-alkyl-p-toluenesulfonate manufacturedj

(18) 7-Chloro-10- (1-methy1-3-piperidyl) methy1-10,11-dihydro-SH-dibenzo (b, e) (1,4) diazepin-11-one from melting point 202 to 204 ° C (from ethyl acetate); Melting point of the fumarate

C. 9098 32/157 5

(19) 7-chloro ~ 10- (1- (1-methyl-2-piperidyl) ethyl) -lO, lldihydro <* 5H «* dibenzo (b, e) (1,4) diazepine with a melting point of 176 to 178, 5 ^° C; Melting point of the fumarate 173 ₉ 5 to 175 ⁰ Co

(20) 7-Ohlor ~ 10 »(1-n-butyl-2-piperidyl) methy1-10,11-dihydro-5H ~ dibenzo (b, e) (1,4) diazepin-11-one with a melting point of 185 to 186 ⁰ O (from ethyl acetate) \ Melting point of the fumarate 196 to 197.5 ⁰ C ₀

Example 21

~ To a solution of 5 percent by _e parts of 7-chloro-10-hydroxy-10,11-dihydrodibenzo (b, f) (1,4) thiazepine-11-one in 50 parts by volume of dimethylformamide is added dropwise within 1 hour under stirring _Ä at 40 ⁰ C 1.2 parts by weight sodium methoxide. After adding 3.3 parts by weight of 1-methyl-2 "piperiäylmethylchlorid the mixture is ^{heated to 50 to 60 0} C for 6 hours and then poured into a large amount of ice water. The separated oil is mixed with benzene. The benzene layer is extracted with dilute hydrochloric acid, the aqueous layer is made alkaline with potassium carbonate, and the deposited oil is extracted with benzene and dried over sodium sulfate. The benzene is distilled off and the residue is recrystallized from ethyl acetate, which contains a small amount of methanol, 7-chloro «* 10- (1« methyl-2-piperidyl) methoxy-lO, 11-dihydrodibenzo (b, f) ( 1,4) th ± azepin-11-one of melting point 144 to 145 ⁰ C in a yield of $ 73 is obtained.

Example 22

The experiment described in Example 1 is carried out with 4.8 parts by weight lO-Hydroxy-10,11 ~ dihydrodibenzo (b, f) - (i, 4) thiazepine- * 11-one, 50 parts by weight of dimethylformamide, 3 parts by weight of potassium carbonate and 4.5 parts by weight! • »• Benzyl ^ -. piperidylmethyl chloride repeated. The oily 10- (1-benzyl-3-piperidyl) methoxy-10, 11-dihydrodibenzo- (b, f) (1,4) thiazepin-11-one obtained in this way is dissolved in 50 parts by weight of benzene · 5 parts by weight of methyl iodide are added to the solution. The mixture is left to stand overnight at room temperature, a precipitate separating out. The precipitation will

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recrystallized from ethanol, meth; iodide of melting point 213 to 214 ⁰ O being obtained in a yield of $ 68.

Examples 23 to 32

In the manner described in Example 1, the following are made Connections made j

(23) 8 ^ methylthio-10 "(1 Hnethyl-2-.piperidyl) methoxy-10, 11 ~ dihydrodibenzo (b, f) (1,4) thiazepine-11 ~ on 'oxalate, melting point 133-134 ⁰ Co

(24) 8 "methyl ~ lO ~ (1 ~ methyl ~ 2-piperidyl) methoxy ~ lO, 11-dihydrodibenzoibjf) (1,4) thiazepine-11-one fumarate with a melting point of 203 ⁰ Oo

(25) 7 ~ methoxy «10 ~ (1-methyl-2-piperidyl) methoxy ~ 10,11-dihydrodibenzo (b, f ) (1,4) thiazepines! 1-on-oxalate from Melting point 108-109 ° 0.

(26) 2,7-dichloro-10- (1-methyl-2-piperidyl) methoxy-10, ll "dihydrodibenzo (b, f) (1,4) thiazepine" * 11-one oxalate with 1 molecule of crystal ethanol, Melting point 121 to 122 ⁰ C.

(27) iO ~ (1-methyl-2-piperidyl) methoxy «10,11-dihydrodibenzo (b, f) (1,4) thiazepine 11« on <»5,5 ~ dioxide oxalate with a melting point of 203 to 204 ⁰ C.

(28) 10- (1-methyl-2-piperidyl) ethoxy-10, ll-dihydrodibenzo (b, f) (1,4) oxazepin-11-one oxalate with a melting point of 150 to ⁰

(29) 5-methyl-10 "(1-methyl-2" piperidyl) methoxy-10, ll-

, 4) diazepin ^ -11-one ~ oxalate from

Melting point 158 to 159 ⁰ C.

(30) 5 * «methyl-7 * .chlor« 10- (1-methyl-2-piperidy 1) methoxy 10,1-dihydro-iH-dll-benzoibje) (1,4) diazepine-11-one oxalate with 1 molecular crystal-Methyläthy ketone!, melting point 115 to 118 ^Q C, 9 0 9832/1575 "

(31) 10- (2- (i-methyl-2 «piperidyl) ätiioxy) -10, ll-dihydrodibenzo (b, f) (1,4) thiazepine-11-one oxalate $ Melting point

_V 32) 8-Trifluoromethyl-10- (1-methy1-3-piperidyl) methoxy-10, ll-dihydrodibenz, o (b, f) (1, 4) thiazepine-11-one oxalate with a melting point of 12O ⁰ G ₀

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Claims (12)

Claims 1) Compounds of the general formula (D 1 2 wherein each of the radicals X and X is hydrogen, chlorine, methyl, methoxy, methylthio, trifluoromethyl or acetyl, the radical Y -0-, -S-, -SO ₂ -, "CHg-, -CH ₂ -CH ₂ -, - CH = CH-, -NH- or -N (CH ₃ ) -, A -CH ₂ -, -CH ₂ -CH ₂ -, = CHCH ,, -0-CH ₂ - or -0-CH ₂ -CH ₂ -, where -0- is bonded directly to the nitrogen atom, and finally R is benzyl or alkyl having 1 to 4 carbon atoms. 2) Compounds according to claim 1 in the form of their pharmaceutical compatible acid addition salts. 5H-dibenzo (b, e) (1,4) diazepin-II-one. 4) 7-chloro-10- (1-methyl-2-piperidyl) methyl-10, ll-dihydro-5H-dibenzo (b, e) (1,4) diazepine-l1-oh. 5) 7-Methoxy-10- (2- (1-methyl-2-piperidyl) ethyl) -10,11-dihydrodibenzo (b, f) (1,4) thiazepin-II-one. 6) 10- (2- (1-methyl-2-piperidyl) ethyl) -10,11-dihydro-dibenzo- (b, f) (1,4) thiazepin-II-one. 909832/1575 7) 7-chloro-10- (l-methyl-3-piperidyl) methyl-10, ll-dihydro- ·. 5H-dibenzo (b _J) e) diazepin-II-one. 8) 7-chloro-10- (2- (1-methyl-2-piperidyl) ethyl-10,11-dihydrodibenzo (b, f) (1,4) thiazepin-11-one. 9) 8-Methyl-10- (1-methyl-2 ^ iperidyl) methoxy-10, ll-dihydrodibenzo (b, f) (1,4) thiazepin-11-one. 10) 5-Methyl-10- (1-methyl-2-piperidyl) methoxy-10, ll-dlhydro-5H-dibenzo (b, e) (1,4) diazepin-II-one. 11) 10- (2- (1-methyl-2-piperidyl) ethoxy) -10, ll-dihydro-dibenzo (b, f) (l, 4) thiazepin-ll-one. 12) Process for the preparation of piperidine derivatives of the general formula (D 1 2 wherein each of the radicals X and X is hydrogen, chlorine, methyl, methoxy, methylthio, trifluoromethyl or acetyl, the radical Y -0-, -S-, -SO ₂ -, -CH ₂ -, -CH ₂ -CH ₂ -, -CHoCH-, -NH- or -N (CH,) -, A -CHg-, -CHg-CHg-, ^ CHCH ,, -O-CHgöder -0-CH ₂ -CH ₂ -, where -O- is bonded directly to the nitrogen atom, and finally R is benzyl or alkyl having 1 to 4 carbon atoms, characterized in that compounds of the general formula 909832 / 157b COPY (ID wherein Z is an alkali metal or an OH group and X and X have the above meaning with compounds of the general formula Q- (in) wherein Q is halogen or an organic sulfonyloxy radical and A has the meaning above. 909032/1575 COPY