Synthesis of derivatives of 2, 3, 5, 6-tetrachloromethylbenzene

Abstract Synthesis of derivatives of 2, 3, 5, 6 - tetrachloro- methylbenzene with electron withdrawing groups was studied. Chlorination could not occur when there were two electron withdrawing groups in the para positions of benzene under designed condition. But if one of them was electron donating group such as methyl, high yield of chlorinated products could be gained in carbon tetrachloride and chlorosulphonic acid at a temperature from 50ºC to 55ºC, and catalyzed by iodine. The products were 2, 3, 5, 6-tetrachloro-4-methylbenzonitrile with yield of 96.3%, 2, 3, 5, 6 - tetrachloro-4- nitrotoluene with yield of 85.5%, 2, 3, 4, 5, 6-pentachloromethylbenzene with yield of 84.2%, and methyl 2, 3, 5, 6-tetrachloro-4-methylbenzoate with yield of 62.1%.
Keywords tetrachloromethylbenzene , chlorination, synthesis

1 INTRODUCTION
Derivatives with electron withdrawing groups of 2, 3, 5, 6 - tetrachloromethylbenzene are important intermediates of pesticides with fluorine^[1,2]. They are also used widely in synthesises of liquid crystal materials, medicines, dyes and other industries^[3-5]. There are several main methods reported for chlorination of benzene ring: (1) Pratt method with oleum as solvent and iodine as catalyst ^[6]; (2) chlorosulphonic acid as solvent and iodine monochloride as catalyst^[7]; (3) iodine and ferric as catalysts in oleum^[8]; (4) Lewis acid such as ferric chloride and aluminum chloride as catalyst in carbon tetrachloride^[9,10]; (5) chlorosulphonic acid and carbon tetrachloride as medium catalyzed by iodine^[11]. Method (1), (2) and (3) were used to synthesize compounds with two electron withdrawing groups in the ortho positions of benzene rings. But there were defects of high reaction temperature and easy erosion to equipments. Method (4) was used mainly to synthesize compounds with electron donating groups in the benzene rings. Method (5) was used to synthesize compounds with two electron withdrawing groups in the para positions of benzenes under moderate conditions. But in our works, the reactions would not occur for terephthalonitrile, terephthalic acid, terephthalyl chloride and terephthalyl amide which had two electron withdrawing groups in para positions by method (5), even by method (1), (2) and (3) in oleum under the high temperature of 180ºC .When one of the electron withdrawing groups was replaced by methyl, high yields were gained by method (5) under low temperature 50-55ºC. The products were 2, 3, 5, 6 - tetrachloro - 4 - methylbenzonitrile with yield of 96.3%, 2, 3, 5, 6 - tetrachloro - 4 - nitrotoluene with yield of 85.5%, 2, 3, 4, 5, 6 - pentachloromethylbenzene with yield of 84.2%, and methyl 2, 3, 5, 6 - tetrachloro - 4 - methylbenzoate with yield of 62.1%.The reactions were shown in Scheme 1.

R=CN, NO₂, COOH (Cl), COOCH₃, CH_3;
Scheme 1

2.EXPERIMENTAL
2.1 Materials and Instruments
WRS-1 digital melt point appratus; ¹H NMR were detected on a Varian 500MHz spectrometer (CDCl₃ ,TMS); EQUINOX 55 spectrometer for IR(KBr); and CHN-O-RAPID element analyse instrument.
Chlorine gas and methyl i-methylbenzoate were synthesized in our lab. The other reagents were analytical or chemical grade.
2.2 Preparation of Derivatives of 2, 3, 5, 6 - tetrachloromethylbenzene
2.2.1 Preparation of 2, 3, 5, 6 - tetrachloro - 4 - methylbenzonitrile
In a 250 milliliter three-necked flask provided with a thermometer, stirrer, condenser, and a chlorine introduction tube, 20 g (0.17 mol) of 4 - methylbenzonitril, 70 ml of carbon tetrachloride，60 ml of chlorosulphonic acid and 0.5 g of iodine were placed. Chlorine was passed into this mixture at 40ºC. The chlorination was maintained at 50 - 55ºC until no more chlorine could be absorbed. The mixture was cooled to room temperature and poured into ice water. The organic phase was collected until the iodine was removed by sodium bisulphate. The aqueous phase was washed twice with carbon tetrachloride. After the organic layers were combined and the solvent was removed, 46.5 g of crude products were obtained. Recrystallization in chloroform gave 42.0 g of 2, 3, 5, 6 - tetrachloro - 4 - methylbenzonitrile with an yield of 96.3％ and melting point of 260-262ºC. IR: 2926.28cm^-1, 2854.69cm^-1 (C-H of CH₃), 1566.89cm^-1, 1518.91cm^-1, 1439.30cm^-1 (C-C of benzene), 1133.07cm^-1（C-Cl）; ¹H NMR: d 2.666 (s, 3H, CH₃); elemental analysis: C: 37.68%（theoretic value 37.65%）; H: 1.17%（theoretic value 1.18 %）; N: 5.48%（theoretic value 5.49%）; Cl: 55.63%（theoretic value 55.6%）.
2.2.2 Preparation of 2, 3, 5, 6 - tetrachloro - 4 - nitrotoluene
51.2 g white crystals of 2, 3, 5, 6 - tetrachloro - 4 - nitrotoluene with an yield of 85％ and melting point of 146 ~148oC were gained from 30 g (0.219 mol ) of i - methylbenzonitrile by the same procedures mentioned above. IR: 2928.61cm^-1, 2852.45cm^-1 (CH₃), 1550.80cm^-1, 1350.61cm^-1 (stretching of NO₂), 1121.88cm^-1（C-Cl）, 842.39cm^-1; ¹H NMR: d2.624（s, 3H, CH₃）; elemental analysis: C：30.49%（theoretic value 30.54%）; H: 1.09%（theoretic value 1.88 %）; N: 5.08%（theoretic value 5.09%）; C: 51.69%（theoretic value 51.69%）.
2.2.3 Preparation of 2, 3, 4, 5, 6 - pentachloromethylbenzene
28.89 g white crystals of 2, 3, 4, 5, 6 - pentachloromethylbenzene with an yield of 84.2% and melting point of 232~233ºC (lit.^[12]217-218ºC) were gained from 20 g (0.14 mol ) of i - methylbenzoic acid by the same procedures mentioned above. IR: 2998.01cm^-1 (CH₃), 1183.48cm^-1（C-Cl） ¹H NMR: d1.555（s,3H, CH₃）; elemental analysis: C: 36.49%（theoretic value 36.52%）; H: 1.68 %（theoretic value 1.74%）; Cl: 61.71%（theoretic value 61.74%）.
2.2.4 Preparation of methyl 2, 3, 5, 6 - tetrachloro - i - methylbenzoate
34 g white crystals of 2, 3, 5, 6 - tetrachloro - i -methylbenzoate with an yield of 62.1% and melting point of 226-228ºC were gained from 20 g (0.14 mol ) of 2, 3, 5, 6 - tetrachloro - i - methylbenzoate by the same procedures mentioned above. IR：1702.27cm^-1（C=O），1176.11cm^-1（C-Cl）; ¹H NMR: d2.585（s, 3H, CH₃）, d1.529（s, 3H, COCH₃）; elemental analysis: C: 37.58%（theoretic value 37.5%）; H: 2.07%（theoretic value 2.08 %）; Cl: 49.36%（theoretic value 49.31%）.
2.2.5 Preparation of 2, 3, 5, 6 - tetrachloro - i - xylene
4.6 g white crystals of 2, 3, 5, 6 - tetrachloro - i - xylene with an yield of 23.0％ and melting point of 212-214ºC ( lit.^[13]220ºC ) were gained from 8.6 g (0.081 mol ) of i - xylene by the same procedures mentioned above. IR: 2929.56cm^-1, 2855.45cm^-1（CH₃）, 1130.74cm^-1（C-Cl）; ¹H NMR: d2.666 (s, 6H, CH₃); elemental analysis: C: 39.39%（theoretic value 39.34%）; H: 2.48%（theoretic value 2.46 %）; Cl: 58.19%（theoretic value 58.20%）.

3. RESULTS AND DISCUSSION
Chlorination in the benzene ring is an electrophilic substitution reaction, so if there are only electron withdrawing groups in the benzene ring, chlorination would become difficult. A strong condition such as chlorosulphonic acid, sulfinic acid and even oleum as medium is needed to improve the reaction. However, compounds with two electron withdrawing groups in the para positions of benzene ring such as terephthalonitrile, terephthalic acid, terephthalyl chloride and terephthalyl amide would not react even under a high temperature of 180ºC in oleum. But when methyl, a weak electron donating group, replaced one of electron withdrawing groups, the chlorination could proceed easily under a moderate condition. Products of 2, 3, 5, 6- tetrachloromethylbenzene with high yield were gained in the medium of chlorosulphonic acid at 50-55ºC. Decarboxylation occurred in the chlorination of i - methylbenzoic acid, and the product was 2, 3, 4, 5, 6 - pentaachloromethylbenzene. But for i - xylene, the two methyl groups only brought an yield of 23.0%. The rest liquid products were shown to be more than ten kinds of by-products by GC-MS, containing chlorination product of methyl. Maybe the reacting condition was too violent for i - xylene.
    Chlorosulphonic acid should be added slowly into the flask under stirring after the addition of carbon tetrachloride, reactant and catalyst. Otherwise, the discharging heat would raise the temperature up quickly and even overflow the mixture. High reaction temperature would make yield reduction, products gelatiniform and purification difficult. Certainly, the reaction temperature should not be too low. In our result the reaction started above 40ºC, and should be kept at 50- 55ºC for high yield.

REFERENCES
[1] He S Q, Liang T L, Liang J L. Sh. J. Prev. Med. (Shanghai Yufang Yixue Zazhi), 2000, 12 (11): 518 - 519.
[2] Luo W C, Mu L Y. PESTICIDES (Sha chong ji). 1997, 6: 10 - 12.
[3] Zhu S D, Wu Y. Journal of Chemical Industry & Engineering (Huaxue Gongye Yu Gongcheng Jishu). 2000. 01: 33 - 36.
[4] Singh A P, Kumar S B. Applied Catalysis A. 1995, 1: 27 - 38.
[5] Pvutter I, MvacConnell J G. Experimental. 1981, 37: 963 - 964.　
[6] Wang W J, Xu X B. New Materials of Chemical Industry (Huagong Xinxing Cailiao). 2000, 05: 21 - 22.
[7] Boden N, Bushby R J, Cammidge A N et al. Tetrahedron Letters, 1995, 47: 8685 - 8686.
[8] Cao Y Q, Zhang R, Li Z J. Chemical Industry in Jiang Su (Jiangsu Huagong). 1998, 01: 22 - 24.
[9] Steffen K D. Methodofpreparingbis - (chloromethyl) - tetrachl; orobenzenes. US4268698, 1981.
[10] Danovich D, Lazanes G, Michman M et al. An electrochemical aromatic chlorination, comparison with electrophilic reaction. Journal of Electroanalytical Chemistry, 2001, 499: 39-47.
[11] Braden R, Kysela E. Process for the preparation of 2, 3, 5, 6-tetraflourobenzonic acid, and the new compounds 2, 3, 5, 6 - tetrach; oro -4-trifluoromethyl-benzoyl chloride. US4755621, 1988.
[12] Per K, Harry S, Kristin B et al. Syntheses and properties of hexa and heptachlorostyrenes with fully chlorinated aromatic nuclei. Acta Chemica Scandinavica B 1983, 37: 823-831.
[13] Rigger P, Steffen K D. Chlorination of xylenes and secondary products I.Chlorination of the nucleus and side chains of xylenes. (Dynamit Nobel A. G, Trosidarf, Ger.) Chem. -ztg. 1979,103 (1): 1-7.

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