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AZ9RBAYCAN KIMYA JURNALI № 3 2017
UDC 547.56+543.42
INVESTIGATION OF (E)-(4-HYDROXY-2-METHYLPHENYL) ACETOPHENONE OXIME AND (E)-4-HYDROXY-2-METHYLACETOPHENONE THIOSEMICARBAZONE
IN SOLUTIONS BY NMR SPECTROSCOPY
A.M.Maharramov, A.E.Farzaliyeva, M.R.Bayramov, I.G.Mamedov
Baku State University bsu.nmrlab@mail.ru Received 25.05.2016
The presented work is devoted to the study of dynamic processes of (E)-(4-hydroxy-2-methylphenyl) ethanone oxime and (E)-4-hydroxy-2-methylacetophenone thiosemicarbazone in solutions by NMR spectroscopy.
Keywords: oxime, thiosemicarbazone, hydrogen bonds, nuclear magnetic resonance.
Introduction
NMR spectroscopy plays an important role at studying of various interactions in solutions, including hydrogen bond formations. The obtained results from these investigations have a particular importance for the chemistry, biochemistry, biophysics, etc. Besides, NMR very importance at studying of the structure of drugs and their influence mechanisms [1-12].
Oxime compounds are well known as antidotes for nerve agents, analytical reagents, etc. [13-17]. Also, thiosemicarbazones and their various derivatives have a medical and biological importance. The above indicated type compounds are widely used as antitumor, antifungal, antibacterial, antivirus, antimalarial reagents [18-21].
Therefore the presented work is devoted to the investigation of dynamic processes of (E)-(4-hydroxy-2-methylphenyl) ethanone oxime and (£)-4-hydroxy-2-methylacetophenone thiosemicarbazone molecules in solutions by NMR. Obtained results showed the existence of ani-sotropic reorientation for the (E)-(4-hydroxy-2-methylphenyl) acetophenone oxime and four rotational conformers for the (E)-4-hydroxy-2-methylacetophenone thiosemicarbazone in solutions.
Experimental part
The research of the samples were carried out by using Bruker AVANCE 300 NMR spectrometer with BVT 3200 temperature regulator (working frequencies of 300 MHz for
1H and 75 MHz for 13C and Software TopSpin 2.1). Acetone-d6, DMSO-d6, CCU and D2O as solvents were used at NMR investigations.
Spin-lattice relaxation times are measured by the inversion-recovery method:
- at 1800 pulse inverts the magnetization to the z-axis,
- during the following delay time, relaxation along the longitudinal plane takes place,
- magnetization come back to the original equilibrium z-magnetization,
- a read 900 pulse creates transverse magnetization,
- acquisition is performed as usual.
The activation energies of intramolecular mobility have been calculated by the formula
E = 19.13[7<1) T2)/(T2) - T1) ] lg (T|2) / T(1}). where T1 and T2) are temperatures and T(1) and T(2) are relaxation times (E)-(4-hydroxy-2-me-thylphenyl) acetophenone oxime (I) was obtained at ethanol boiling temperature (reaction time 3 hours, 0.02 mol 4-hydroxy-2-methylacetophenone, 0.29 mol NH2OH-HCl and 40 ml of ethanol) [22]. Yield - 47%, Tmdt -196-1970C. 1H NMR (DMSO-d6. 5, m.h.): 1.9 s (3H, CH3), 2.35 s (3H, CH3), 6.6-7.3 (3H, arom.), 9.72 s (1H, OH), 11.3 s (1H, N-OH). 13C NMR (DMSO-d6; 5, m.h.); 18,1 (CH3), 22.94 (CH3), 113.6 (CH, arom.), 115.3 (CH, arom.), 123.3 (C, arom.), 129.3 (CH, arom.), 139.3 (C, arom.), 153.2 (C=N, azomethine), 159.6 (C-O).
INVESTIGATION OF (E)-(4-HYDROXY-2-METHYLPHENYL) ACETOPHENONE
13
(E)-(4-hydroxy-2-methylacetophenone thio- NMR (DMSO-d6, 5, m.h.): 19.02 (CH3), 24.83
semicarbazone (II) was obtained (reaction time 5 hours, 1 mmol 4-hydroxy-2-methylacetophenone, 1 mmol thiosemicarbazone) at ethanol boiling temperature [22]. Yield - 76%, Tmeit - 185-1870C, lH NMR (DMSO-d6, 5, m.h), 2.03 s (3H, CH3), 2.13 s (3H, CH3), 6.7-6.98 (3H, arom.), 7.92 d (2H, NH2), 8.4 s (1H, OH), 9.75 s (1H, NH). 13C
(CH3), 112.93 (C, arom.), 114.29 (C, arom.), 117.67 (CH, arom.), 124.49 (C, arom.), 128.44 (CH, arom.), 151.89 (C=N, azomethine), 158.69 (C-O, arom), 178.07 (C=S).
The synthesis scheme of compounds are given below.
NH 2OHHCl
NH, -NH-C-NH,
N-OH
N-NH
Discussions
Firstly, (E)-(4-hydroxy-2-methylphenyl) acetophenone oxime (I) was investigated. Obtained results confirmed the formation of one isomer between the reaction 4-hydroxy-2-methylacetophenone and hydroxylamine hydro-chloride. Subsequently spin-lattice relaxation
1 13
(T1) type was calculated for the H and C nucleus in 5% acetone-d6 solution for different groups at 220C and 500C and the results given in Table.
As can be seen from the table, the values of intramolecular activation energy in two
1 13
different methyl groups (for 1H and 13C nucleus) are different (5.29 and 6.96; 5.69 and 6.12 kJ/mol).
This shows the existence of anisotropic reorientation for the investigated molecule in solution.
jj—NH2
S
T1 relaxation time (for 1H and 13C nucleus, in sec) of the (£)-1-(4-hydroxy-2-methylphenyl) acetophenone oxime (I) CH3- and CH-groups and activation energy of intramolecular mobility
Frag- CH3- and Nucleus T1, T1, ^a•>
ment CH-positions 220C 500C kJ/mol
CH3 Ar-CH3 1H 2.33 2.81 5.29
CH3 =C-CH3 1H 3.23 3.95 5.69
CH3 Ar-CH3, 13C 6.01 7.69 6.96
CH3 =C-CH3, l3C 9.98 12.39 6.12
CH CH 13C 3.74 - -
CH CH 13C 4.37 - -
CH CH 13C 5.06
(T - 220C and 500C) in the 5% acetone-d6 solution
Table data for the CH-groups of aromatic ring having different relaxation time also confirm the presence of anisotropic reorientation. NMR studies showed the formation of intramolecular hydrogen bounds between the oxime molecules.
In continuation of the researches (E)-(4-hydroxy-2-methylacetophenone thiosemicarba-zone (II) was investigated in solutions. The studies were carried out at +220C - +950C intervals and depending on time. At NMR in-
vestigation of thiosemicarbazone molecule (II) in DMSO-d6 solution are observed splitting of signals. In the 1H NMR spectra (Figure) of 5% fresh DMSO-d6 solution, we observed one signals for all hydrogen at the 220C as a result
+
S
of fast exchange between the conformers. The protons resulting from rotations around the -
mixture of conformers were not present in this NH-C=S and C-Ar bonds.
solution. But in the 1H spectra obtained after The obtained results confirmed the
one week (5% DMSO-d6 solution at +22+ existence of four conformer in solution of (E)-
+950C), were observed eight singlet signals (4-hydroxy-2-methylacetophenone thiosemicar-
instead of two for the two different CH3 and bazone (II).
four singlet signals instead of one for the NH
ho
ch,
h
n
Г
ch
nh2 ho
ch3
h
n
ch3 ch3
h
^ /n.
n
YS
nh2 ho1
ch3 ch3 ■ 3 ■ 3 h
r
s
9.5 9.0
9.0 7.5 1.0 pp.- 2.3 2.2 ppm
l
9.5 9.0 8.5 8-0 l.b 1.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm
220c
9.5 9.0
7.5 1.0 ppm
„лАаЛ
9.0 В.5 8 . 0 7.5 7.0 6.5 ¿.0 5.5 5.0 4.5 4.0 3.5 5.0 2.5 ppm
1H NMR spectral sections of (I) in 5% DMSO-d6 solution within the temperature interval of +22 ^ + 950C.
3
d
b
a
950c
INVESTIGATION OF (£)-(4-HYDROXY-2-METHYLPHENYL) ACETOPHENONE
15
Conclusion
Our DNMR studies showed the existence of anisotropic reorientation in the acetone-d6 solution for the (£)-(4-hydroxy-2-methylphe-nyl) acetophenone oxime (I).
The NMR investigation results confirmed the presence of -NH-=S and C-Ar rotation in DMSO-d6 solution and the existence of four conformers for the (£)-(4-hydroxy-2-methyl-acetophenone thiosemicarbazone (II).
NMR results have confirmed that relaxation times are very important for studying of molecular mobility in solutions, have theoretical-practical significance and may be applicable at determination of molecular configuration.
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(£)-1-(4-HiDROKSi-2-METiLFENiL)ASETOFENONOKSiM УЭ (£)-4-HiDROKSi-2-METiLASETOFENON TiOSEMiKARBAZON MOHLUL SiSTEMLORlNiN NMR METODU iLO TODQiQi
A-M.Maharramov, A.E.Farz3liyeva, M.R.Bayramov, LQ.Mammadov
Taqdim olunan i§ (£)-1-(4-hidraksi-2-metilfenil)etanon oksim va (£)-4-hidroksi-2-metilasetofenon tiosemikarbazon molekullannin mahlul sistemlarinda ba§ veran dinamik proseslarin NMR metodu ila tadqiqina hasr edilmi§dir.
Agar sözlar: oksim, tiosemikarbazon, hidrogen rabitabri, nüva maqnit resonansi.
ИССЛЕДОВАНИЕ (£)-1-(4-ГИДРОКСИ-2-МЕТИЛФЕНИЛ)АЦЕТОФЕНОНОКСИМА И СЕ>4-ГИДРОКСИ-2-МЕТИЛАЦЕТОФЕНОНТИОСЕМИКАРБАЗОНА В РАСТВОРАХ МЕТОДОМ ЯМР
А.М.Магеррамов, А.Э.Фарзалиева, М.Р.Байрамов, И.Г.Мамедов
Представленная работа посвящена синтезу производных 4-гидрокси-2-метилацетофенона (£)-1-(4-гидрокси-2-метилфенил)этанон оксимa и (£)-4-гидрокси-2-метилацетофенонтиосемикарбазонa и исследование различных растворов полученных веществ методом ЯМР.
Ключевые слова: оксим, тиосемикарбазон, водородные связи, ядерный магнитный резонанс.
