Bartók, Mihály

Felföldi, K.

Karahanov, R. A.

Molnár, Árpád

English

Felföldi K.

Molnár Árpád

Bartók Mihály

Karahanov R. A.

University of Szeged

CHEMISTRY OF 1,3-BIFUNCTIONAL COMPOUNDS, XXV* SYNTHESIS OF SOME ESTERS CONTAINING SUBSTITUTED PIPERIDINE AND TETRAHYDROPYRIDINE SKELETONS By K. FELFÖLDI, Á. MOLNÁR, M. BARTÓK and R. A. KARAKHANOV Department of Organic Chemistry, Attila József University, 6720 Szeged, Hungary (Received September 30, 1980) The synthesis and pharmacologic characteristics of 3-piperidinyl esters were reported earlier [1]. The present paper describes the synthesis of 43 esters containing substituted piperidine and tetra-hydropyridine skeletons. Most of the new esters display a coronary vasodilator effect. In this work esters of TV-substituted-4-piperidinol and various 4-substituted-piperidinyl and tetrahydropyridinylpropyl esters were synthetized. Some 7V-alkyl-4-piperidinyl esters are known to exhibit valuable pharmacological properties, e.g. local anaesthetic, reserpine-like, parasympatholytic, hypotensive, ganglion blocker, and central nervous system tranquillizing effects [2—8]. It is similarly known [9] that the l-(3-aroylpropyl)-4-aryl-l,2,3,6-tetrahydropyridines display analgetic, spasmolytic and central nervous system tranquillizing effects. The new compounds we have prepared were subjected to pharmacological investigation in the Pharmacological Laboratory of the Gedeon Richter Pharmaceutical Works. Mainly the coronary vasodilator effect was found to-be significant, particularly in the case of 18, 7V-(3-methylbutyl)-4-piperidinylxanthene-9-carboxylate. Experimental The temperature values given in the Tables have not been corrected. The courses of the reactions and the purities of the end-products were examined by, among others, thin-layer chromatography. Of the compounds used, 4-piperidinol, 4-(pyr-rolidinyl-l)-piperidine, 4-(piperidinyl-l)-piperidine and l,4-dioxa-8-azaspiro [4,5]-decane were Fluka products, while 4-phenyltetrahydropyridine, 4-/?-chlorophenyltetra-hydropyridine and 4-hydroxy-4-/?-chlorophenylpiperidine were made available by the Gedeon Richter Pharmaceutical Works. The aminoalcohols were prepared by reacting the appropriate secondary amine with alkyl halide or with 3-chloropropyl alcohol [1, 10, 11], and purified by distillation or recrystallization. The A^-cyanoethyl-4-pipe-* Part XXIV: see reference [11]. 178 К. FELFÖLDI, Á. MOLNÁR, M. BARTÓK and R. A. KARAKHANOV Table I N-substituted-4-piperidinols No. R в.р. CQ Hgmm "в Yield % 1* СНз 110—114 20 1.4750 58 2 ^ с н - с н 2 -СИ3 84—86 5 1.4674 62 3 СНЗ / С Н - ( С Н 2 > 2 -с н 3 124—126 2 1.4710 75 4 СН2=СН-СН2-98—100 8 1.4907 79 5 с н = с н - с н 2 - 111—113ь — 35 6 H O - Q M C H 2 ) 3 - 202—204" — . 40 " Lit. [12]: b.p. 113—114 °C (23 Hgmm) ь Melting point ridinol necessary for the preparation of esters 25 and 26 was obtained by the reac-tion of acrylonitrile and 4-piperidinol [11]; the reaction product was acylated wit-hout further purification. The esters were obtained from the reaction of the appro-priate aminoalcohol and acid halide, and purified by recrystallization from ethanol. References [1] Felföldi, K„ A. Molnár, M. Bartók: Acta Chim. (Budapest) 90, 75 (1976). {2] Brit. pat. 899 605 (1962); C. A. 59, 7497f (1963). [3] Renz, J., J. P. Bourquin: Swiss! pat. 383 777 (I960); C. A. 62, 7734f (1965). [4] Ganellin, C. R., R. G. W. Spickett: J. Med. Chem. 8, 619 (1968). [5] Biel, J. H.: U. S. pat. 2 856 407 (1958); C. A. 53, 5292a (1959). [6] Coon, S. B., D. Papa: J. Org. Chem. 20, 774 (1955). [7] Moffet, R. B.: J. Med. Chem. 7, 319 (1964). [8] Cusic, J. W.: U. S. pat. 2 650 230 (1953); C. A. 48, 11500c (1954). [9] Janssen, P. A. J.: J. Med. Pharm. Chem. 1, 281 (1959). U. S. pat. 2 973 363 (1961); C. A. 35, 15514e (1961). [10] Felföldi, K., A. Molnár, M. Bartók: Acta Chim. Budapest 91, 333 (1976). [11] Felföldi, K., M. Laszlavik, M. Bartók, E. Kárpáti: Acta Phys. et Chem. Szeged, preceding paper. [12] McElvain, S. M„ K. Rorig: J. Am. Chem. Soc. 70, 1820 (1948). ХИМИЯ 1,3-БИФУНКЦИОНАЛЬНЫХ СОЕДИНЕНИЙ, XXV СИНТЕЗ НЕКОТОРЫХ ЭФИРОВ, ИМЕЮЩИХ ЗАМЕЩЕННЫЕ ПИПЕРИДИНОВЫЕ И ТЕТРАГИДРОПИРИДИНОВЫЕ СКЕЛЕТЫ К. Фелфелди, А. Молнар, М. Барток и Р. А. Караханов В работе описан синтез 43 эфиров, имеющих замещенные шшеридиновые и тетра-гидропиридиновые скелеты. Болшинство синтезированных эфиров обладает венечным вазо-Дилятаторкым действием. Table ii Z—CH2—CHS—CH2—OH No. z B.p. C O Hgmm M.p. (°C) Yield % Formula Analysis Calc./Found C H N 7 O-G . 168—172/1 — 75 CuHiaNO 78.50 78.25 7.52 7.72 6.53 6.82 8 178—184/1 189—190* 65 Methoiodide C13H21C1IN0 45.76 45.40 5.37 5.39 3.65 3.65 9 HO •. — 106—107 236—238* 74 CuHaoClNOa 62.33 62.12 7.47 7.45 5.19 5.27 10 0 0 158—160/1.5 57—58 70 c12h21n2o 68.10 67.71 11.30 11.43 13.20 13.60 11 q - q - 152—154/1 38—40' 70 c13h26n2o 69.00 68.87 11.60 11.53 12.37 12.52 12 c x > ' — 84—85 45 C10HiaNO, 59.70 59.65 9.53 9.45 6.96 6.72 * Melting point of methioiodide 180 К. FELFÖLDI, Á. MOLNÁR, M. BARTÓK and R. A. KARAKHANOV X I u - o I o i ó I <r G á s (N fS r- r"i vo vö u s . o z u a u I X o / \ m . X o u I a 4- O | 3B vo 1— a d o <N o z ö e) X n ct u o z N u «1 a u 0 1 x o / \ X u X o V X o X u X o o z u a U vo vo o o O W-1 ín o VO VD r— VO o\ r-vo vo in in u I a r i t— o z o a u © q f a vo o <N ¥ I X o o z o e a" u o z ö a u x o x o 'U. X o CHEMISTRY OF 1,3-BIFUNCTIONAL COMPOUNDS, XXIII 181: 1 8 2 К. FELFÖLDI, Á. MOLNÁR, M. BARTÓK and R. A. K A R A K H A N O V CHEMISTRY OF 1,3-BIFUNCTIONAL COMPOUNDS, XXIII 183: 4.24 4.40 3.57 4.03 3.41 3.65 3.41 4.03 3.27 3.68 3.27 4.06 3.18 3.42 2.98 3.05 7.19 7.18 6.95 6.80 6.68 6.88 —с о •ч- гч v© vö ^ m o\ t -«n vi о vo •Ч; сч »ri vi «о 1 00 VO vi V"» сл ЧО VO vi vi «О Г4 ЧО ЧО vi vi ОО ^ VÖ \¿ — r-> fS Tt V© V¿ r - o Г-; 00 O m O <N 00 00 Ov — VO 00 ov О ""! я OÔ ОО «о »л CTv Tf C-l fS ЧГ VO VO Г- f i 3 S Г- in Ч о ЧО 3 00 Tf 00 ЧО 00 оо VI v> оо о\ 00 ЧО 00 оо Vi vi О О Оч ó ov vo vs CS vo f - ЧО 00 oo «/"» 1Л —1 o ЧО ЧО OÖ OO vi v* Vi VJ v> fS oi os Vi Vi 00 00 ГЧ o Vï VÏ m t— а~ Л psj t -m r -r -M 00 ö 7 Ж о\ t -N vo a i vo 00 t -аД г -о оо G 7 a óv г -vo G 7 \o ÍN 00 a ! 00 Vi — VO U <s a 1 < s S o) o _ ЧО Urs a 1 »41 00 M V*, CN •Ч-— VI (J«N а 1 M ei O z d Ö a ф и M o z N 4 e* se 0* o Cl О z ö е* а, е» и я О Z о и а с* и о z Ii-с* и •rß « и о z И-Ü о эв е« и o z Ö «1 a N « и •a O z ея и a и o» o C4 z « и O a" 6> U el o 04 z и M 99 a о С4 и n O «4 z M q a o J m X О 1 9 а » а р г r X o m 5 f ? 5 < r » p L í ¡ £ o ç r ° 1 V о i "i 1 "1 но 1 *| 1 1 1 "1 1 "1 Ф 0 1 ."1 1 Î « r -Cí 90 Cl 9\ о о ** тг M •ч- t») 5 V) •ч- vo •4-Table IV (cnntinned) ' ' Formula Analysis No. z X M.p. C O Calc./Found C H N 48 tt - O ' C19H20O2FN2O2 2"HC1 262—265 56.05 55.85 7.09 7.25 6.88 7.12 49 » 0 6 0 Ca„H31ClaN203 2 HCI 242—245 63.28 62.95 6.95 7.27 5.67 5.31 50 GO- - o 2 HCI 260—262 59.65 59.45 8.05 8.14 6.94 6.81 51 tt -P CH3 CjiHjiCljNjOj 2 HCI 258—262 60.43 60.18 8.21 8.31 6.70 6.74 52 -Q och3 Ca iH3 1ClaN s03 2 HCI 261—264 58.40 58.20 7.15 7.35 6.47 6.45 53 tt •Q-' C20H31CI:FN2O2 2 HCI 273—276 57.01 56.85 7.40 7.31 6.65 6.78 54 c X > - C17Ha3CIFN04 HCI 209—211 55.46 55.26 6.44 6.25 — 55 tt - Q CF3 C18H23C1F3N04 HCI 177—178 52.76 52.95 5.66 5.86 — 

Chemistry of 1,3-bifunctional compounds 25. : Synthesis of some esters containing substituted piperidine and tetrahydropyridine

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Chemistry of 1,3-bifunctional compounds 25. : Synthesis of some esters containing substituted piperidine and tetrahydropyridine

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