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AZ9RBAYCAN KIMYA JURNALI № 2 2017
UDC 547;547:544,16;547:544,12
CRiSTALLiK AND MOLEKULYAR STRUKTURE OF 2,2,6,6-TETRAMETiL-4-HiDROKSi PiPERiDiN HiDROXLORiDE
A.A.Medjidov, P.A.Fatullayeva, Onur §ahin*, B.Yalcin**
*Sinop University, Scientific and Technological Research Application and Research Center,
57000 Sinop, Turkey
**Fakultet of Art and Sciense Department of Chemistry of Marmara University,Istanbul-Tukey Institute of Catalysis and Inorganic Chemistry, NAS of Azerbaijan
ajdarmedjidov@gmail.com
Received 06.01.2017
The reaction of carboxymethylation and amidation of 2,2,6,6 tetramethyl-4-hydroxy piperidine with chlorace-tic acid and oxalyl chloride was investigated. It was shown that instead of the expected derivatives of amino-acetic acid and diamide hydrochloride the formation of 2,2,6,6-tetramethyl-4-hydroxyoxy piperidine hydrochloride takes place. The molecular and crystalic structures of obtained compound were determined.
Keywords: sterical hindered amine, chloracetik acide, oxalyl chloride, acylation, of 2,2,6,6-tetramethyl-4-hydroxy piperidine hydrochloride, X-ray structure.
The reactions of acylation and carboxymethylation of secondary amines are widely used in organic synthesis. The carboxymethylation of primary and secondary amines with chloroacetic acid is carried out usually in water solutions of alkaline at 800C [1]. The reaction with oxalyl chloride usually leads to the formation of amides [2].
This paper describes studies on the interaction of 2,2,6,6-tetramethyl-4-hydroxy piperidine (TMHP) with chloracetic acid and oxalyl chloride. The hydrochloride of TMHP is formed in both cases instead of the expected derivatives of aminoacetic acid and diamide hydrochloride. Crystallic and molecular structure of synthesized 2,2,6,6-tetramethyl-4-hydroxy piperidine hydrochloride was studied by X-ray analysis.
Experimental part
Initial 2,2,6,6-tetramethyl-4-hydroxypipe-ridin (TMHP) was synthesized according to known method [3]. Chloroacetic acid and ox-alylchloride were used (SIGMA-Aldrich).
Reaction of TMHP with chloroacetic acid. A mixture of 0.01 mol (1.56 g) TMHP and 0.01 mol (0.96 g) chloroacetic acid were pounded in porcelain mortar. Then the solution 0.02 mol (0.8 g) sodium hydroxide in 30 ml water was added and this mixture was refluxed within 20 hours. Then the solution was evaporated to dry and the rest was extracted by ethyl alcohol. The obtained crystals were dried and
recrystallized from benzol:ethanol mixture 1:1. Colourless crystals TMHP hydrochloride (1) with m.p. > 2500C suitable for X -ray analysis was obtained.
Found,
C 55.72, H 10.45, N 7.12.
C9H20NOCL Calculated, %: C 55.80, H 10.40, N 7.23.
1H-NMR (400 MHz, CD3OD) 5 4.17 (m, 1H), 3.88 (s, 2H), 3.34 (s, 1H), 2.07 (7=10 Hz, 2H, 1.53 (7=8 Hz) 1.529 (s, 3H).
Reaction of TMHP with oxalylchlo-ride. 0.01 mol (1.27 g) of oxalylchloride was added to the solution of 0.01 mol (1.56 g) TMHP in 30 ml dioxane by mixing on magnetic stirrer. Then 150 ml of water was added and this mixture was left for night. Next day the dropped-out white deposit was filtered and dried on air and recrystallized from mix of ben-zol:ethanol 1:1. The colourless crystals with m.p. > 2500C were obtained.
Thus, interaction between TMHP and chlo-roacetic acid occurs according to the scheme:
H°^N-H + ClCH2C°°H-
л
\
H _ Cl
+ HOCHCOOH.
H
It is undoubted that reaction of carbox-ymethylation of TMHP by chloroacetic acid doesn't proceed because of sterically hindrance of secondary amino group by methyl groups. The similar behavior of sterically hindranced amines was observed at direct reductive amination of aldehydes and ketones to obtain the amines with additional alkyl group. It was shown that the yield of reaction products of reductive amination depends on number and the nature of substituents at amine group. For example, diizopropylamine is not active in similar reaction [4].
X-Ray diffraction analysis. Suitable crystal was selected for data collection which was performed on a D8-QUEST diffractometer equipped with a graphite-monochromatic MoXa-radiation at 296 K. The structures were solved by direct methods using SHELXS-97 [5 ] and refined by full-matrix least-squares methods on F2 using SHELXL-97 [5] from within the WINGX [6] suite of software. All non-hydrogen atoms were refined with anisotropic parameters. The H atoms of C atoms were located from different maps and then treated as riding atoms with C-H distances of 0.96-0.97 A. All other H atoms were located in a difference map refined subject to a DFIX restraint. Molecular diagrams were created using MERCURY [7]. Supramolecular analyses were made and the diagrams were prepared with the aid of PLATON [8, 9]. Details of data collection and crystal structure determinations are given in Table 1.
Supplementary Material. Crystallo-graphic data for the structural analysis has been deposited with the Cambridge Crystallographic Data Centre, CCDC No. 1045481. Copies of this information may be obtained free of charge from the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44-1223336033; e-mail: deposit@ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.uk).
The molecular and crystallic structure of compound 1. The molecular structure of 1 with the atom labeling is shown in Figure 1. The asymmetric unit of 1 consists of four independent cation molecules and four chloride ani-
ons. The four cation molecules share common structural features. Each pipyridine ring adopts a chair conformation with puckering parameters [9]: Q = 0.545 A, 9 = 7.95° and 9 = 164.77° in Cg1, Q = 0.530 A, 9 = 6.96° and 9 = 176.74° in Cg2, Q = 0.539 A, 9 = 172.80° and 9 = 1.536° in Cg3 and Q = 0.533 A, 9 = 6.59° and 9 = 193.41° in Cg4. The cations and anions are connected to one another via N-H—Cl and O-H—Cl hydrogen bonds (Table 2) and form alternating cation-anion layer-like structures. The combination of N-H-Cl, O-H-Cl and N-H—O hydrogen bonds generates a chain of edge-fused R3(10) and R7(30) rings running parallel to the ac plane (Figure 2).
Table 1. Crystal data and structure refinement parameters
Empirical formula C9H20NOCI
Formula weight 193.71
Crystal system Monoclinic
Space group P21/c
a (A) 10.1177 (18)
b (A) 12.408 (2)
c (A) 34.712 (6)
P O 90.532 (6)
V (A3) 4357.7 (13)
Z 16
Dc (g cm-3) 1.181
^ (mm-1) 0.31
9 range (°) 3.1-28.3
Measured refls. 76468
Independent refls. 10300
Rint 0.069
S 1.25
R1/wR2 0.134/0.345
Apmax/Apmm (eA-3) 0.72/-0.67
Table 2. Hydrogen bonds parameters (Ä)
D-H-A D-H H---A D---A D-H-A
O1-H1-C11 0.81 (2) 2.33 (3) 3.138 (5) 169 (9)
O2-H2-C12 0.82 (2) 2.26 (2) 3.082 (5) 174 (8)
O3-H3C---C13 0.82 (2) 2.25 (3) 3.057 (5) 169 (8)
O4-H4---C14 0.82 (2) 2.31 (2) 3.128 (6) 174 (10)
N1-H1A---C141 0.87 (2) 2.34 (2) 3.212 (5) 178 (7)
N1-H1B-C12 0.87 (2) 2.26 (2) 3.128 (5) 173 (6)
N2-H2C---Cl1ii 0.87 (2) 2.35 (2) 3.204 (5) 168 (6)
N2-H2D---O3 0.86 (2) 2.04 (2) 2.898 (6) 175 (6)
N3-H3A---C14111 0.86 (2) 2.34 (2) 3.192 (5) 167 (6)
N3-H3B---O2iv 0.86 (2) 2.08 (3) 2.925 (6) 166 (6)
N4-H4C---Cl1ii 0.86 (2) 2.36 (2) 3.216 (5) 171 (6)
N4-H4D---C13 0.87 (2) 2.26 (2) 3.119 (5) 169 (6)
Symmetry codes: (i) x+1, -y+3/2, z+1/2; (ii) x, -y+3/2, z-1/2; (iii) x, -y+3/2, z+1/2; (iv) x—1, y, z.
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A.A.MEDJiDOV et al.
Fig. 1. The molecular structure of 1 showing the atom numbering scheme. The H atoms have been omitted for clarity.
Fig. 2. Part of the crystal structure of 1, showing the formation of R53(10) and R77(30) rings by the N-H-Cl, O-H-Cl and N-H—O hydrogen bonds.
Thus, it is shown that interaction of TMHP with chloracetic acid and oxalyl chloride produces hydrochloride of TMHP instead of the expected N-methylencarboxy-2,2,6,6-tetrame-thyl-4-hydroxy piperidine and corresponding diamide. This phenomena can be explained by methyl groups volume shielding at the amino group, which create steric hindrance for direct carboxymethylation and amidation.
References
1. Дятлова Н.М.. Комплексоны и комплексы металлов. М.: Химия, 1988. 544 с.
2. Вейганд Хильгетаг. Методы эксперимента в органической химии. М.: Химия, 1969. 775 с.
3. Розанцев Э.Г. Стабильные иминоксальные радикалы. М.: Химия, 1970. 190 с.
4. Pobichaund A., Nait Ajjou A. First example of direct reductive amination of aldehydes with primary and secondary amines catalyzed by water-soluble transition metal catalysts // Tetrahedron Lett. 2006. V. 47. P. 3633-3636.
5. Sheldrick G.M. A short history of SHELX //Acta Crystallogr. Sect. A. 2008. V. 64. P. 112-122.
6. Farrugia L.J. WinGX suite for small-molecule single-crystal crystallography // J. Apply. Crystallogr. 1999. V. 32. P. 837-838.
7. Macrae C.F., Edgington P.R., McCabe P., Pidcock E., Shields G.P., Taylor R., M. & van de Streek Towler. Mercury: visualization and analysis of crystal structures // J. Appl. Crystallogr. 2006. V. 39. P. 453-457.
8. Spek A.L., Platon-Squeeze // Acta Crystallogr. Sect. D. 2009. V. 65. P. 148-155.
9. Cremer D., Pople J.A. General definition of ring puckering coordinates // J. Am. Chem. Soc. 1975. V. 97. P. 1354-1358.
КРИСТАЛЛИЧЕСКАЯ И МОЛЕКУЛЯРНАЯ СТРУКТУРЫ 2,2,6,6-ТЕТРАМЕТИЛ-4-ГИДРОКСИПИПЕРИДИНГИДРОХЛОРИДА
А.А.Меджидов, П.А.Фатуллаева, Онур Шаген, Б.Ялчин
Изучена реакция карбоксиметилирования и амидирования 2,2,6,6-тетраметил-4-гидроксипиперидина хлорук-сусной кислотой и оксалилхлоридом. Показано, что вместо ожидаемых производных аминокислоты и диамида образуется гидрохлорид 2,2,6,6-тетраметил-4-гидроксипиперидина. Изучены молекулярная и кристаллическая структуры этого соединения.
Ключевые слова: стерически затрудненные амины, ацилирование, хлоруксусная кислота, оксалил хлористый, рентгеновая структура 2,2,6,6-тетраметил-4-гидроксипиперидингидрохлоридa.
2,2,6,6-TETRAMETiL-4-HiDROKSiPiPERiDiN HiDROXLORlDiN MOLEKULYAR УЭ KRiSTALLiK
QURULU§U
Э.Э.Mэcidov, P^.Fatullayeva, Onur §ahin, B.Yalfin
2,2,6,6-tetrametil-4-hidroksipiperidinin xlorsirka tur§usu va oksalilxloridla karboksimetillaijma va amidla§ma reaksiyalari öyranilmi§dir. Gostarilmi§dir ki, gözlanilan amintur§u va diamid töramalari avazina 2,2,6,6-tetrametil-4-hidroksipiperidin birla§masi amala galir. Bu birla§m§nin kristallik va struktur qurulu§u öyranilmi§dir.
Agar sözlar: f3za h3r3k3ti g3tinls§dirilmi§ aminhr, asill3§m3, xlorsirks tur§usu, oksalil xlorid, 2,2,6,6-tetrametil-4-hidroksipiperidinhidroxloridin rentgen strukturu.
