CC BY
9
54
AZ9RBAYCAN KIMYA JURNALI № 1 2017
UDC 547.789.13
THE REACTIONS OF a-METHOXYAMIDES WITH MALONONITRILE IN THE
PRESENCE OF TiCU AS A CATALYST
K.E.Hajiyeva, A.I.Ismiyev, A.M.Maharramov
Baku State University kushvar. haciyeva@mail. ru Поступила в редакцию 04.04.2016
By using Asinger reaction 2,5-dihydro-1,3-thiazoles obtained in high yields. Treating these heterocyclic imines with acid chlorides followed by methanolysis of formed N-acyliminium chlorides led to a large number of a-methoxyamides. It was determined that the nucleophilic substitution of methoxy group in these a-methoxyamides by malononitrile in the presence of AlCl3, ZnCl2 as well as in the absence of catalyst did not proceed. The reaction proceeds by using TiCl4 as a catalyst. Yields were: 42-47%. Obtained products were purified by column chromatography.
Keywords: 2,5-dihydro-1,3-thiazoles, a-methoxyamide, malononitrile, titan(IV) chloride.
Introduction
2,5-Dihydro-1,3-thiazoles and the related compounds are important part of heterocyclic chemistry as much from the point of view of the research as from the practical aspect. Since the publication of Asinger's first studies on the synthesis of thiazolines [1], the chemistry of these compounds is increasing rapidly. Among the most efficient possibilities to take advantage of the reactive imine bond of the 2,5-dihydro-1,3-thiazoles is the addition of an acyl chloride. In 1987, Martens [2, 3] began to study the addition of acid chlorides to 2,5-dihydro-1,3-thiazoles. Synthetic attractiveness of this reaction is the insertion of active chlorine atom to the hetero-cyclic ring that allows nucleophilic substitution with various functions. Investigations carried out in this area have been published in the following papers [4-6].
In addition to the above stated, especially worth of mentioning is the identified properties of these heterocyclic systems. Some of these compounds have drawn much attention due to their herbicide, pesticide and insecticides activities [7]. Discovery of such activities increased the interest to the chemistry of these compounds. Therefore methods that allow building new synthetic modifications have been developed [8-11].
Results and discussions
We have developed a method for the preparation of new derivatives, based on the reaction of a-methoxyamides with malononitrile in the presence of TiCl4. The starting a-methoxyamides were prepared by known methods [12] and can be represented below by the following scheme:
hc
HC
R-CH3, C^H^
CH
CH2C12
HC
HC
HC
CH3OH; NEt3
CH2C12, -Et3NHC1
HC
HC
Studies have shown that the reaction of when using triethylamine and aliminium these compounds with malononitrile in the chloride as catalysts the reaction does not absence of catalysts is not going at all. Also, proceed. In order to develop a new method of
O
O
R
R
the insertion of malononitrile (III) to the 2-(3-R-2,2,5,5-tetramethylthiazolidin-4-yl)malo-
synthesized a-methoxyamides (I, II) the reac- nonitriles (IV,V) were obtained respectively.
tions were carried out in the presence of equi- Yields were 42-47%: molecular amount of TiCl4 as a catalyst and
HC
HC
TiCl4, CH2Cl2
I, II
® / Cl3Ti—O
HC
CH
HC
Cl= + H2C
CN
/ +Et3N
\
CN
III
N
N
9
CH3
IV, V
I, IV R=CH3
II, V r=c6h5
In the at course of reaction formed pitched its role is in the increasing of nucleophilicity of products was purified by column chromatography malononitrile.
by using solvents methylene chloride and methyl
The structure of 2-(3-acetyl-2,2,5,5-tetra-
tert-butylether in 1:1 ratio. The catalytic action of methylthiazolidin-4-yl)malononitrile was proved TiCl4 is not fully revealed, but we can assume that by NMR 1H and IR spectral methods.
Fig. 1. NMR 1H spectra of 2-(3-acetyl -2,2,5,5-tetramethylthiazolidin-4-yl)malononitrile.
R
R
O
R
R
CH3OTiCl3
-1-1-1-1-1-1—
3500 3000 2500 2000 1500 1000
Wavenumber cm-1
Fig. 2. IR spectra of 2-(3-acetyl-2,2,5,5-tetramethylthiazolidin-4-yl)malononitrile.
Experimental part General remarks
Preparative column chromatography was carried out using Grace SiO2 (0:035-0:070 mm, type KG 60) with methylene chloride and me-thyl-tert-butylether as eluents. TLC was performed on Merck SiO2 F254 plates on aluminum sheets. The NMR spectra were recorded on a BRUKER AMX R 500 spectrometer. All measurements were carried out with 5 mm NMR sample tubes. Chemical shifts, 5, are represented in part per million (ppm) and coupling constants, J, in hertz (Hz) from tetramethylsilane (TMS) as the internal standard in deuterated solvent such as CDCl3. IR spectra were recorded on a Bruker Tensor 27 spectrometer equipped with a "Golden Gate" diamond Attenuated Total Reflection in the range of 400-4000 cm-1. General experimental procedure Typical procedure for the synthesis of 2-(3 -R-2,2,5,5 -tetramethylthiazolidin-4-yl)malono-nitriles: under argon atmosphere, 1.1 equivalent of TiCl4 were dissolved in 10 ml anhydrous CH2Cl2 and one equivalent of the respective a-methoxyamide, dissolved in anhydrous CH2Cl2 (3 ml per mmol a-methoxyamide) was added drop-wise at 0-50C. After stirring for 30 minutes at
room temperature, a solution of CH2(CN)2 (1.5 equivalent) and anhydrous Et3N (1.75 equivalent) in anhydrous CH2Cl2 (2 ml per mmol a-methoxyamide) was added dropwise at 0-50C. After stirring overnight at room temperature, the solution was poured into ice-water (25 ml per mmol a-methoxyamide). It was stirred for 30 minutes. The phases were separated and the aqueous phase was extracted with CH2Cl2 (2x25 ml per mmol a-methoxyamide). The combined organic phases were dried with MgSO4. The solvent was removed on a rotary evaporator. The crude product was purified by column chromatography.
Physical data of compounds isolated
IV. Yellow solid: mp. - 78-800C; Rf = 0.8. NMR 1H (300 MHz, CDCl3): 1.47 s (3H, CH3), 1.72 s (3H, CH3), 1. 82 s (3H, CH3), 2.02 s (3H, CH3), 2.32 s (3H, NCOCH3), 4.40-4.44 d (H, CH), 4.54-4.58 d (H, CH). IR (KBr, cm-1): 1656 (CO-N), 2889, 2998, 2917, 2938 (C-H).
V. Yellow solid: mp. - 82-850C; Rf= 0.6. NMR 1H (300 MHZ, CDCl3), 1.35 s (3H, CH3), 1.62 s (3H, CH3), 1.82 s (3H, CH3), 2.02 s (3H, CH3), 7.70-8.05 m (5H, NCOC6H5), 4.40-4.44 d (H, CH), 4.54-4.58 d (H, CH). IR (KBr, cm-1): 1656 (CO-N), 2889, 2998, 2917, 2938 (C-H).
References
1. Asinger F. Über die gemeinsame Einwirkung von Schwefel und Ammoniak auf Ketone // Angew. Chem. 1956. V. 68. No 12. P. 413.
2. Schwarze W., Drauz K., Martens J. Umsetzung von 3-Thiazolinen mit Carbonsäurechloriden // J. Chem. Ztg. 1987. V.111. P. 149-153.
3. Martens J., Janknecht H.H. N-Acyl-4-thiazoline aus 3-Thiazolinen // Phosphorus, Sulfur, Silicon. 1991. V. 61. P. 173-176.
4. Johannes K., Martens J.Synthesis of different types of valerolactame starting from 2,5-dihydro-oxazoles // Tetrahedron. 2010. V. 66. P. 242-250.
5. Johannes K., Watzke M., Martens J. Synthesis of a, ß-unsaturated caprolactams starting from heterocyclic imines // J. Heterocyclic Chem. 2010. V. 47. Issue 3. P. 697-702.
6. Watzke M., Schulz K., Johannes K., Ullrich P., Martens J. First Synthesis of Bi- and Tricyclic and alpha; and beta; -Unsaturated and delta: Oxa-caprolactams from Cyclic Imines via Ring-Closing Metathesis // Eur. J. Org. Chem. 2008. V. 22. P. 3859-3867.
7. Böcker E., Draber W.In Chemie der Pflanzenschutz-und Schädlings-bekämpfungsmittel (Hrsg.: Wegler,
R.) // Springer Verlag, Berlin, Heildelberg, New York. 1970. V. 1 P. 220-240.
8. Stalling T., Brockmeyer F., Kröger D., Schwäblein A., Martens J. 2,5-Dihydro-1,3-thiazoles as Scaffolds in the Synthesis of O,N-Diacyl O,N-Acetals in a one-pot Reaction // Z. Naturforsch. B: Chem. Sci. 2012. V. 67 b. P.1045-1055.
9. Kröger D., Brockmeyer F., Kahrs C. Three-Component Reaction for a Rapid Access to Underexplored 1,3-Thiazine-2-thiones // Org. Biomol. Chem. 2015. V. 13. P. 7223-7229.
10. Kröger D., Schlüter T., Fischer M., Geibel I., Martens J. Three-Component Reaction toward Polyannulated Quinazolinones, Benzoxazinones and Benzothiazinone // ACS Comb. Sci. 2015. V. 17. P. 202-207.
11. Brockmeyer F., Kröger D., Stalling T., Ullrich P., Martens J. A Manifold Three-Step Synthetic Route to Polycyclic Annulated Hydantoines via Cyclic Imines // Helv. Chim. Acta. 2012. V. 95. P. 1857-1870.
12. Martens J., Kramer U., Gertje A., Schütte M. Synthese von neuen monomeren schwefelhaltigen Acrylsäureamid-Derivaten aus 3-Thiazolinen // Makromol. Chem. 1992. V. 194. P. 475-484.
a-METOKSiAMiDLORlN TiCl4 KATALlZATORU i§TRAKINDA MALONONiTRlLLO QARSILIQLI TOSlR REAKSlYALARI
K.E.Haciyeva, A.I.Ismiyev, A-M.Maharramov
Azinger reaksiyasi ila yüksak grnmla 2,5-dihidro-1,3-tiazollar alinmüj, onlann tur§u xloranhidridlari ila qar§iliqli tasirindan N-asetil iminium xloridlar sintez edilmi§, sonuncularin metanoliz reaksiyasindan isa müvafiq a-metok-siamidlarin alinmasi göstarilmiijdir. Müayyan olunmu§dur ki, sintez edilmi§ a-metoksiamidlarda metoksi qrupun malononitrilla nukleofil avaz olunmasi ham katalizatorsuz, ham da AlCl3, ZnCl2 tipli Lyuis katalizatorlari i§tirakinda ba§ vermir. A§kar olunmu§dur ki, bu reaksiya katalizator kimi TiCl4-dan istifada etdikda gedir, reaksiya mahsulu olan 2-(3-asetil-2,2,5,5-tetrametiltiazolidin-4-il)malononitrilin giximi 42-47% ta§kil edir. Reaksiya mahsullarinin tamiz-lanmasi va ayrilmasi kolonkali xromotoqrafiya üsulu ila yerina yetirilmi§dir.
Agar sözlar: 2,5-dihidro-1,3-tiazollar, a-metoksiamid, malononitril, titan(IV) xlorid.
РЕАКЦИЯ а-МЕТОКСИАМИДОВ С МАЛОНОНИТРИЛОМ В ПРИСУСТВИИ TiCl4
В КАЧЕСТВЕ КАТАЛИЗАТОРА
К.Э.Гаджиева, А.И.Исмиев, А.М.Магеррамов
Реакцией Азингера синтезированы 2,5-дигидро-1,3-тиазолы с высокими выходами. В результате обработки этих гетероциклических иминов с хлорангидридами кислот получены ^ацетилиминиумхлориды, с последующим метанолизом которых были синтезированы соответствующие а-метоксиамиды. Выявлено, что, нуклеофильное замещение метоксигруппы в а-метоксиамидах на малононитрильную группу, без участия катализатора, а также в присутствии катализаторов Льюиса - А1С13, 2пС12 не происходит. Осуществить реакцию удалось в случае использования в качестве катализатора ТЮ4. Выходы продуктов реакции - 2-(3-ацетил-2,2,5,5-тетра-метилтиазолидин-4-ил)малононитрилов составили 42-47%. Продукты реакции были выделены и очищены с использованием метода колоночной хроматографии.
Ключевые слова: 2,5-дигидро-1,3-тиазолы, а-метоксиамид, малононитрил, титан(1У)хлорид.
