Promoting effect of ethanol on the synthesis of N-(2-methylphenyl)-hydroxylamine from o-nitrotoluene

Availableonlineatwww.sciencedirect.comCHINESEScience DirectCHEMICALLETTERSELSEVIERChinese Chemical Letters 22(2011)221-224www.elsevier.com/locate/ccletPromoting effect of ethanol on the synthesis of N-(2-methylphenyl)hydroxylamine from o-nitrotoluene in Zn/H,o/cO, systemShi Juan Liu Yan Hua Wang, Yuan Ping Hao, Jing Yang JiangCollege of Chemical Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China4g b College of Chemistry, Jilin Normal University, Siping 136000, ChinaReceived 7 May 2010AbstractThe promoting effect of ethanol on the synthesis of N-(2-methylphenyl)hydroxylamine from o-nitrotoluene in Zn/H2O/CO2system was observed By adding appropriate amount of ethanol, the selectivity of N-(2-methylphenyl)hydroxylamine increasedfrom 71%to 90% when the reduction was carried out at 25'C under normal pressure of COC 2010 Published by Elsevier B V. on behalf of Chinese Chemical SocietyKeywords: o-Nitrotoluene: N-(2-Methylphenyl)hydroxylamine; Reduction: Zn: CO/H2ON-(2-Methylphenyl)hydroxylamine(M-PHA)is a useful intermediate in the synthesis of biologically activecompounds [1-4]. For its preparation several methods have been developed, and the selective reduction of onitrotoluene(nt) by Zn is the most conventional one. The reaction is known to occur in less acidic solution [5, 6], andNH,CI is widely used to promote the reaction. The method shows the advantages of mild reaction condition, goodproduct selectivity and low cost. Nevertheless, a large amount of NH4Cl is consumed and a lot of wastewater isformedIn our previous work, a novel protocol using Zn in CO2/H2O system for the selective reduction of nitroarenes to N-arylhydroxylamines has been developed [7]. This new system is fully rid of NH4Cl and thus environmentally benignFor the selective reduction of nitrobenzene, an 88% yield of N-phenylhydroxylamine has been realized under theoptimal condition. In this manuscript, the synthesis of M-PHA from NT in this new system is presented, and theemphasis is focused on the promoting effect of ethanol on the reaction1. ExperimentalNTand zn dust are commercial products and used without further purification. appropriate amount of NT, Zn dustand H2O (or H2O and ethanol)were placed in a flask. The flask was put in preheated water bath with magnetic stirringand then COz was bubbled through the reaction mixture. The progress of the reaction was monitored on tlC and theproduct analysis was performed by HPLC.中国煤化工E-mailaddress:jyjiang@chem.dlut.edu.cn(Y.Jiang).CNMHG1001-8417/smatter C 2010 Published by Elsevier B V. on behalf of Chinese Chemical Socidoi:10.0l6 j cclet.2010.0902S.J. Liu et al /Chinese Chemical Letters 22(2011)221-2242. Results and discussionThe selective reduction of nt to M-PHA in Zn/H2O/CO2 system without ethanol was examined. The reactionresults at different temperature were shown in Fig. l. It was seen from Fig. I that both the conversion of N and theyield of M-PHA reached a maximum at 25C, and dropped to a minimum at 50C. This phenomenon conforms to theresults in our previous research work [7, 8 and the reason results from two aspects. One is the effect of the intrinsicreaction rate, and the other is the acidity of the systemThe reduction results with different Zn/Nt molar ratio were listed in Table 1. After 1 h. the conversion of ntincreased with an increase of the molar ratio of Zn to Nt, but the selectivity of M-PHA fell, because of the furtherreduction of M-PHa to 2-methylaniline(M-AN)From the experiment results, the selectivity of M-PHa is no more than 71% even at low conversion of NT. It isenvisioned that the low solubility of M-PHA in H2o may be the key factor Not readily soluble in H O, M-PHA formedin the process is difficult to desorb from the surface of Zn and the tendency of over reduction to by-product M-ANincreases. To overcome this problem, a protocol using ethanol to increase the solubility of M-PHA in the solution isadopted. The reaction results were listed in Table 2.w- Yield of M-PHAYield of M-ANFig. 1. The effect of reaction temperature on the reduction. Reaction conditions: NT 10 mmol, Zn 30 mmol, H20 20 mL, Pco, 0. 1 MPa, and I h.Table 1The effect of the Zn/NT molar ratio on the selective reduction of ntZ/NT(molar ratio)conv.。(MT(%)Selec.(M-PHA)(%)ield(M-PHA)(%) Yield(M-AN)(%)7134132705131Reaction conditions: NT 10 mmol, Hz0 20 mL, Poo, 0.I MPa, 25"C, and I bb Determined by HPLc.Table 2The effect of different amount of ethanol on the selective reduction of Nt"try H2O/ethanol(mL) t(hcomv:°0NSelec. (M-PHA)(%) Yield(M-PHA)(%) Yield(M-AND)(%)l0/10中国煤化工95/152225/15712929CNMHG4/162248Reaction conditions: NT 10 mmoL, Zn 30 mmol, Pco, 0.1 MPa, and 25'C.Determined by HPLC.S.J. Liu et al. /Chinese Chemical Letters 22(2011)221-224223Table 3The effect of temperature on the selective reduction of NT".Entry T(C) Conv.(NT)(%) Selec. (M-PHA)(%) Yield(M-PHA)(%6)Yield(M-AN)(%)3445675500003658922980443143Reaction conditions: NT 10 mmol, Zn 30 mmol. H20 5 mL +ethanol 15 mL, Pco, 0.1 MPa, and 12 h.Determined by HPLCIndeed, the addition of ethanol increased the reaction selectivity to M- PhA. without ethanol in the reaction system,the conversion of NT was 77% and the selectivity of M-PHA was 65%(Table 2, entry 1). when the mixture of 10 mLH2O and 10 mL ethanol was employed, the selectivity toward M-PHa increased to 80%, but the conversion of NTdecreased to 61%. Further increasing the amount of ethanol(H2O/ethanol =5 mL/15 mL)resulted in a negative effecton the conversion of NT and a positive effect on the selectivity to M-PHA. In the condition, prolonging the reactiontime to 12 h, a 59% conversion of NTand a 92% selectivity of M-PHa were realized. These results demonstrated thatwith the increase of the ethanol portion, the selectivity of M-PHa was improved, meanwhile, the reaction rate becamelow. Ethanol added into the system favors the desorption of M-PHA from the Zn surface, so the selectivity of M-PHAis elevated. On the other hand the dielectric constant of the solution decreases with the addition of ethanol. as it isknown, the dielectric constants of H2O and ethanol are 78.3 and 24.5, respectively. The lower the dielectric constant is,the worse it is for the acidic proton to dissociate from the acid [9]. So the acid strength drops with increasing theamount of ethanol, which leads to the low reaction rate. To balance the conversion and the selectivity of the reaction,the following experiments are carried out with the mixture solvent of 5 mL H2O and 15 mL ethanolThe effect of different reaction parameters on the selective reduction of NT in Zn/H2O/CO2 system with theaddition of ethanol was systematically examined. Firstly the reaction results at different temperature were shown inTable 3Apparently, in the temperature range from0C to 70C, the conversion of nt and the yield of M-Pha reached to aaximum at 25C. The trend is similar to that obtained without ethanol, but over the range of this reactiontemperature, the selectivity of M-PHA is high and the yield of M-AN, the by-product for the full reduction of NT, isThe reaction results with different amount of Zn used and reaction time were illustrated in Fig. 2. With prolongingthe reaction time the conversion of NT increased, but nt was not converted completely during 24 h as the molar ratioof Zn to NT was equal to 2 and 3. with further increase of the molar ratio of Zn to NT (Z/NT= 4 and 5), the yield ofM-PHA was as high as 89%(14 h and 10 h, respectively) and the selectivity of M-Pha was almost constant. Thenfurther prolonging the reaction time led to an obvious increase in the amount of M-AN, so the yield of M-PHA<4z中国煤化工CNMHGt/hFig. 2. The effect of reaction time and amount of Zn on the reduction. Reaction conditions: NT 10 mmol. H205 mL ethanol 15 mL, 25'C,Pco, 0.1 MPa. a, a'(Zn 20 mmol), b, b(Zn 30 mmol), c,e(Zn 40 mmol ) and d, d(Zn 50 mmol)S.J. Liu et al/Chinese Chemical Letters 22(2011)221-224In conclusion, the selective reduction of o-nitrotoluene to N-(2-methylphenyl)hydroxylamine has been investigatedin Zn/H2O/ CO2 system. The promoting effect of ethanol in the system is obvious for high selectivity of N-(2-methylphenyl)hydroxylamine. By adding appropriate amount of ethanol, the selectivity of N-(2-methylphenyl)hydroxylamine increased from 71% to 90% when the reduction was carried out at 25C under normal pressure of CO2AcknowledgmentsThis work was supported by the Doctoral Fund of Ministry of Education of China(No. 20070141046)and the Fundof Education Department of Liaoning Province(No [2006]124).References[] C Hou, Z Li, C. Liu, Nongyao[nl]Pesticides 41(2002)41 (in Chinese).[2]A. Porzelle, M D. Woodrow, N.C. O. Tomkinson, Synlett(2009)798[3]R. Ross Jr, D.V. Nguyen, S.H. Shaber, wO2002046142(2002).4]A Brouillard, N. Reinier, FR2751644 (1998).[S]Z Li,J. Li, w. Liu, Hunan Daxue Xuebao 31(2004)4[6]MK. Das, P. Bose, N. Roy, J. Chem. Eng. Data 29(1984)345[7]S Liu, Y. Wang, J. Jiang, et al. Green Chem. 11(2009)1397.[8] G. Gao, Y. Tao, J. Jiang, Green Chem. 10(2008)4[9] T.S. Chamblee, R.R. Weikel, S.A. Nolen, Green Chem. 6(2004)382.中国煤化工CNMHG