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ISSN 2522-1841 (Online) ISSN 0005-2531 (Print)
UDC 547.569+547.436
SYNTHESIS OF NEW AMINOMETHYL AND ORGANYLSULPHIDE DERIVATIVES OF PIPERIDINO-2-HYDROXYPROPANETHIOL-3
V.M.Farzaliyev, Sh.R.Aliyev, R.F.Mammadova, R.M.Babai, Q.M.Quliyeva
A.Guliyev Institute of Chemistry of Additives, NAS of Azerbaijan [email protected] Received 05.03.2018
At interaction of hydrogen sulphide with piperidino-2,3-epoxyprorane there is formed piperidino-2-hydroxypropanthiol-3. The latter reacts by Mannich with formaldehyde and secondary aliphatic and heterocyclic amines, as well with organic halogenide, forming respectively aminomethyl and organyl-sulphide derivatives of piperidino-2-hydroxypropanethiol-3. Composition and structure of synthesized compounds are confirmed by elemental analysis and method NMR.
Keywords: epychlorohydrine, piperidine, formaldehyde, butyl bromide, hydrogen sulphide, aminomethyl derivatives, organylsulphide derivatives.
It is known that the epoxy compounds formed as a result of the interaction of compounds having an active hydrogen atom with epychloro-hydrine and sodium hydroxide under treatment by hydrogen sulphide lead to compounds in which the sulphohydryl group is attached to the terminal carbon atom of the propane chain. Analysis of the literature [1-5] shows that such types of compounds have been relatively not enough investigated. However, such compounds may be synthons for the preparation of novel N- and S-containing compounds that are widely used as biologically active compounds [6], as well as ad-
ditives for lubricating oils [7].
In the beginning, piperidino-2,3-epoxy-propane was prepared according to the known method [8]. Then by treatment of piperidino-2,3-epoxypropane with hydrogen sulphide, piperidi-no-2-hydroxypropanthiol-3 (I) was synthesized. By acting on the latter as synthon by formalin and secondary aliphatic, heterocyclic amines, and also organyl halogenides, the corresponding aminomethyl (II a-d) and organylsulphide (III a-d) derivatives were obtained. The reactions were carried out according to the following schemes:
n^7 + h2s
'o
I + CH2O + hnr2
OH
II a-d
NR.2,
nr2 = -n (c2h5)2 (a), -n(c4h9)2 (b), -n< ^o (c), -n
(d) ;
I + R-Hal
OH III a-d
R = C4H (a), C7H15 (b), CH2COOH (c), CH-CH2OH (d), Hal = Br, I, Cl.
1
Physicochemical characteristics of the obtained compounds are presented in the Table. The composition and structure of the obtained ami-nomethyl derivatives of piperidino-2-hydroxy-propanethiol-3 and organylsulphides are confirmed by elemental analysis and spectral methods.
Experimental part
1 1 ^
NMR spectra of XH and C were taken on a Bruker AV-300, spectrometer at a working frequency of 80 MHz. As a solvent SDCl3 was used, the internal standard - hexamethyldisilox-ane (HMDS) [9].
Piperidino-2-hydroxypropanethiol-3 (I). 15 g (0.1 mole) of piperidino-2,3-epoxypropane dissolved in 50 ml of ethyl alcohol and 0.3 g of NaOH dissolved in 15 ml of water were placed in a three-necked flask. The reaction mixture was cooled to a temperature of +50C and hydrogen sulphide was fed into the mixture for an hour. After completion of the reaction the mixture was extracted by benzene and dried over anhydrous sodium sulphate. After distillation off the solvent, 15.3 g (82%) of compound I was isolated by distillation under vacuum.
Spectrum (compounds I, Figure 1) NMR 1H, 5, ppm: 1.38 tt (2H, -CH2CH2CH2-), 1.49 tt (4H, -CH2CH2CH2-), 2.27 d (2H, -CH2-SH), 2.30 OH
d (2H, >NCH9- CH -), 2.51 tt (4H, -CH2NCH2-),
2.76 s (1H, SH), 3.71 m (1H, CH).
13C NMR spectrum, 5, ppm: 24.14
(-CH7CH7CH7-), 25.97 (-CH7CH7CH7-), 29.25
OH
(-CH2-SH), 54.72 ( >NCH2- CH -), 65.03
OH
(-CH2NCH2-), 67.39 (- Cl-).
Piperidino-2-hydroxypropyl-3-piperidyl-methyl sulphide (II d). To 6.2 ml of a 20%
aqueous solution of formaldehyde, there were added dropwise at 20-250C 4 g (0.04 mol) of piperidine, then 6 g (0.04 mol) of piperidino-2-hydroxypropanthiol-3 (I) in 50 ml of benzene. In this cose increase in temperature from 25 to 350C was observed, the mixture was stirred for 4 hours at a temperature of 75-800C. After completion of the reaction 28% sodium hydroxide solution (1g
NaOH + 2.5 ml H2O) was added to the mixture. Then the benzene solution was washed twice with water and dried with sodium sulphate, then after distillation of benzene the non-distilled liquid (II d) was extracted.
Compounds (II a-c) were similarly obtained, the characteristics of which are given in the Table.
Spectrum (compound II d, Figure 2) NMR 1H, Ô, ppm: 1.44 tt (4H, -CH2CH2CH2-), 1.55 tt (8H, -CH2CH2CH2-), 2.35 d (2H, -CH2-S-),
oh
2.40 d (2H, > NCH?- CH -), 2.56 tt (8H, -CH2NCH2-), 3.51 s (2H, -SCH2-N <), 3.78 m (1H, CH).
13C NMR spectrum, Ô, ppm: 24.28 (-CH2CH2CH2-), 25.97 (-CH2CH2CH2-), 41.11
OH
(-CH2-S-), 52.64 ( >NCH2 -CH- ), 55.20 (-CH2NCH2-), 64.25 (-SCH2-N <), 68.83 OH
(- CH - ).
Piperidino-2-hydroxypropyl-3-butylsul-phide (IIIa). In a 100 ml three-necked flask equipped with a stirrer, reflux condenser and dropping funnel, 6 g (0.03 mol) of piperidino-2-hydroxypropanethiol-3 (I), 30 ml of isopropyl alcohol and 3.6 g (0.03 mol) of butyl bromide were placed. While stirring at room temperature, a 32% solution of NaOH (1.04 g NaOH + 2.2 ml of H2O) was added dropwise to the mixture, and then the mixture was stirred at 75-800C for 6 hours. After completion of the reaction, the product was extracted by benzene, washed with water, dried over Na2SO4. After distillation the solvents, the residue was distilled in vacuum.
Compounds (IIIb-d) were singularly synthesized. Their characteristics listed in the table.
Spectrum (compound IIIa, Figure 3) NMR 1H, Ô, ppm: 0.87 t (3H, CH3CH2-), 1.32 m (4H, -CH2CH2CH3), 1.37 tt (2H, -CH2CH2CH2-); 1.48 tt (4H, -CH2CH2CH2-), 2.24 t (2H, -S-CH2-CH2-), 2.35 d (2H, -CH2-S-), 2.39 d
OH
(2H, > NCH2- CH ), 2.52 dd (-CH2NCH2-), 3.75 m (1H, CH) .
Fig.1. Spectrum (compound I ) NMR 1H piperidino-2-hydroxypropanethiol-3.
Fig.1. C NMR spectrum piperidino-2-hydroxypropanethiol-3 (I).
M ГО ffi О О Г- LO M
О <У> г- Г- "чО г—I с— со
СО г- Г- Г-- lO Ю "Ч1 'Ч'
ГО ГО 00 ГО ГО О-) СО Г)
ПЧ-ЮЮттОГО^СМОНОС^О СО иною (^С^ЮТО^ФЮЮЮчГ'Т^'Ч'^'З'ГОГОГОГОГО
СМ СМ СМ СМ СМ СМ СМ CM <N CN CM CM СМ СМ СМ О ] см СМ СМ С\]
^ 1 1 ' .......
■41 LO СО CTi СМ О OD CM
VjQ LO LO LO Ю LO
\—i а~\ ««р см
ррш
(МП^ООМПМСОЧ'ЮЮтОПШСМОНОСМ^ОПННООЗЧЮ^ОЗО^
o^r-r-^Hr-fOHOUJioroHaioo^cTir- LO ч'ооспмптооанх'чгм
<0 ГО ГО СО ГО ГО ГО Г) ГО СМ СМ СМ СМ СМ <М СМСМСМСМСМСМСМСМСМСМСМСМСМСМгНгЧгЧ
Fig.2. 13C NMR spectrum piperidino-2-hydroxypropyl-3-piperidylmethyl sulfide (IId).
Fig.2. Spectrum (compound IId ) NMR lH piperidino-2-hydroxypropyl-3-piperidylmethyl sulfide.
Fig.3. Spectrum (compound IIIa ) NMR 1H piperidino-2-hydroxypropyl-3-butylsulfide.
Fig.3.
Spectrum (compound IIIa ) NMR 1H piperidino-2-hydroxypropyl-3-butylsulfide. AZERBAIJAN CHEMICAL JOURNAL № 4 2018
13C NMR spectrum, S, ppm: 13.65 (CH3CH-), 21.89 (CH3CH2-), 24.18 (-CH7CH7CH-), 26.01 (CH7CH7CH7-), 31.75 (-CH3CH2CH2-), 32.65 (2H, -S-CH2-CH2-),
OH OH
37.03 ( CH-CH2-S-), 54.69 ( >NÇH2-CH-), 63.76
OH
(ÇH2NCH2-), 66.26 (- CH-).
Piperidino-2-hydroxypropyl-3-carboxy-methylsulphide (IIIc). In a 100 ml three-necked flask equipped with a stirrer, reflux condenser and dropping funnel, there were placed 4.3 g (0.05 mol) of morochloroacetic acid neutralized with a 4% solution of NaOH (1.8 g NaOH + 44 ml H2O), 30 ml of isopropyl alcohol and 8 g (0.05 mole) piperidino-2-hydroxypropanethiol-3 (I) and stirred at room temperature. 32% solution of NaOH (1.6 g NaOH + 3.5 ml H2O) to the reaction mixture was added dropwise. The mixture was then stirred at 70-750C for 6 hours. The obtained reaction mass was hydrolyzed with 0.5 g of hydrochloric acid. After completion of the reaction, the product was extracted with benzene, washed with water, after distillation of benzene non-distillated liquid (IIIc) was recovered. The characteristic is given in the Table.
References
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2. Urinov U.K., Maksumova O.S. Studying of the Complex Compounds, formed by molecules of morpholine betaine and urea // Austrian J. Technical and Natural Sciences-Vienna. 2015. No 3-4. P. 70-75.
3. Urinov U.K., Maksumova O.S., Abdulmalikova Kh.B. O reaktcii vzaimodeistviia mocheviny s pikhlorgidrinom // Austrian J. Technical and Natural Sciences-Vienna. 2016. № 3-4. P. 141-145.
4. Sharifova S.K. O napravleniiakh reaktcii epi-khlorgidrina s kislotami, spirtami i aminami // Azerb. him. zhum. 2010. № 2. S. 139-146.
5. Bespalko Iu.N., Shved E.N., Oleinik N.M. Osobennosti kataliticheskogo povedeniia osno-vanii v reaktcii alifaticheskikh karbonovykh kislot s a-okisiu. // Teor. i eksper. himiia. 2008.T. 44. Vyp. 5. S. 292-297
6. Mashkovskii M.D. Lekarstvennye sredstva. M. Novaia volna, 2002. T. 1, 2. 736; 688 s.
7. Latiuk V.I., Kelarev V.I., Koshelev V.N., Korenev K.D. Sulfidy riada sim-triazina kak maslorastvori-mye ingibitory korrozii // Himiia i tekhnologiia topliv i masel. 2002. № 5. S. 23-26.
8. Zeinalov S.B., Kiazimova T.N., Sharifova S.K. Epikhlorgidrin. Baku: Elm, 2000. 188 s.
9. Balci M. Nuclear Magnetic Resonance Spektros-copy. METU Press. Ankara. 2000. 458 p.
PiPERiDiN-2-HiDROKSiPROPANTiOL-3-ÜN YENi AMiNOMETiL УЭ ORQANiLSULFiD
TÖROMOLORiNiN SiNTEZi
V.M.Farzaliyev, §.R.Oliyev, RF.Mammadova, R.M.Babayi, Q.M.Quliyeva
Piperidin va epixlorhidrin asasinda ahnmi§ piperidin-2,3-epoksipropanin qalavi mühitinda hidrogen sulfidla qar§iliqli tasirindan piperidin-2-hidroksiprorantiol-3 alinmüjdir. Sonuncudan sinton madda kimi istifada etmakla Mannix re-aksiyasi §araitinda formaldehid va ikili alifatik, heterotsiklik aminlarla kondensla§masindan bir sira aminometil va orqanil halogenidlarla reaksiyalarindan isa bir sira orqanilsulfid töramalari sintez edilmi§dir. Alinmi§ birla§malarin qurulu§u va tarkibi NMR spektroskopiya üsulu va element analizi ila tasdiq edilmi§dir.
Agar sözlzr: epixlorhidrin, piperidin, formaldehid, butilbromid, hidrogen sulfid, aminometil ШгэтэЬп, orqanilsulfid ШгэтэЬп.
СИНТЕЗ НОВЫХ АМИНОМЕТИЛЬНЫХ И ОРГАНИЛСУЛЬФИДНЫХ ПРОИЗВОДНЫХ ПИПЕРИДИНО-2-ГИДРОКСИПРОПАНТИОЛ-3
В.М.Фарзалиев, Ш.Р.Алиев, Р.Ф.Мамедова, Р.М.Бабаи, Г.М.Кулиева
При взаимодействии в щелочной среде пиперидин-2,3-эпоксипропана, полученного на основе пиперидина и эпихлоргидрина, с сероводородом, синтезирован пиперидин-2-гидроксипропантиол-3. Пользуясь последним как синтоном, в условиях реакции Манниха при конденсации формальдегида и вторичных алифатических, гетероциклических аминов получен ряд аминометильных, а реакциями с органилгалогенидами - ряд органил-сульфидных производных. Состав и структура синтезированных соединений подтверждены данными элементного анализа и методом ЯМР.
Ключевые слова: эпихлоргидрин, пиперидин, формальдегид, бромистый бутил, сероводород, аминометильные производные, огранилсульфидные производные.
The yields, constants and elemental analysis data of piperidino-2-hydroxypropanethiol-3 (I) and its aminomethyl (IIa-d) and organylsulphide derivatives (IIIa-d)
№ compounds Yield, % Thoi^ 0C df n20 nD Found/calculated, % Brutto formula mrd Found/calculated, %
C H N S
I 82 115-117 (3mm) 1.0321 1.4978 54.82 55.24 9.78 9.42 7.99 8.47 18.29 18.70 C8H17NOS 49.77 50.22
II a 78 Non-permeating clear liquid 0.9552 1.4768 59.95 60.35 10.84 11.16 10.76 10.45 12.31 12.70 Q3H28N2OS 77.00 77.36
II b 68 n " 0.9466 1.4892 64.50 65.00 11.46 11.05 8.85 8.54 10.13 9.84 C17H36N2OS 96.55 96.03
II c 80 n " 1.0632 1.5117 57.40 56.90 9.13 9.55 9.81 10.21 12.13 11.68 C13H26N2O2S 77.41 77.00
II d 85 n " 1.0364 1.5220 61.72 62.02 10.36 10.15 10.28 10.59 11.77 12.18 C14H28N2OS 80.24 79.97
III a 85 134-135 (2 mm) 0.9921 1.4953 62.29 61.93 10.89 10.61 6.05 6.41 13.86 13.47 c12h25nos 68.05 68.81
III b 88 162-163 (1.5 mm) 0.9516 1.4878 65.88 65.37 11.43 11.92 5.42 4.96 11.72 11.41 C15H31NOS 82.77 82.66
III c 87 Non-permeating clear liquid 1.1254 1.4932 51.48 51.00 8.21 8.49 6.00 6.28 13.74 14.14 C10H19NO3S 60.27 60.66
III d 85 n " 1.1167 1.5302 55.27 54.84 8.81 9.03 6.45 6.83 14.75 14.28 Q0H21NO2S 60.69 61.20
