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Regiospecific Mno2 Catalyzed Hydration of Phenylmethylene Malononitriles to Cyanophenylacrylamides by Oximes.

Byline: ABDUL RAUF, FAISAL SALEEM AWAN, SAIRA MUMTAZ, AHSAN SHARIF, EJAZ AHMED, MUHAMMAD ARSHAD, FARZANA KAUSAR, GHAZALA YASMIN AND ASHFAQ MAHMOOD QURESHI

Summary: A novel and convenient method for the regiospecific hydration of phenylmethylene malononitriles to cyanoacrylamides was developed; Scope of the method and reaction conditions were optimized extensively, the method was found to be extremely successful in hydration of anti nitrile to phenyl group only in phenylmethylene malononitriles. This regiospecificity is owed mainly to steric factors.

Introduction

Nitriles are converted to amides by the usual means of concentrated sulphuric acid [1], hydrogen peroxide with sodium hydroxide [2] and polyphosphoric acid [3]. All these methods have their inherent problem that acid and base sensitive functionalities are also affected or lost during the harsh reaction condition. Therefore, need for such procedures remain in demand which can selectively hydrolyze nitrile functionality in presence of acid/base sensitive organic moieties. Though the use of TFA/H2SO4 and H2O2/K2CO3/DMSO has been employed to achieve selective hydration of nitrile moiety but still the conditions are reasonably harsh for several organic functionalities [4, 5].

Various metals such as Rh, Pt, Ru, Ir, Mo, and Co showed varying degree of selectivity [6 -11]. Recently, Pd and InCl3 in presence of aldoxime exhibited excellent chemoselectivity for the hydration of nitrile groups [12 -13]. Haefele and Young [14] reported an interesting conversion of alkyl nitriles to alkyl amides using MnO2 as a catalyst, though with aryl nitrile they did not explored extensively just two examples were reported where benzonitriles exhibited very poor yield of the desired amides.

In quest for synthesizing isoxazole via 1,3 dipolar cycloaddittion reaction between benzaldoxime (in situ production of nitrile oxide (dipolar moiety) by the use of MnO2)[15] and dicyanoarylidene (dipolarophile) in presence of MnO2 in DCM at room temperature (Scheme 1).

Cyanoacrylamide was exclusively attained in excellent yield; this result prompted us to explore the scope of this reaction.

Results and Discussion

Previously, there is no reported method involving oximes for regiospecific hydration of malononitriles, few reported methods employing various conditions give mixture of mono and dihydrated products [16-17], the only reported method for monohydration of malononitrile involves harsh conditions of refluxing the substrate in t-BuOH in the presence of KF-H2O-A2lO3, which yielded mono-amide in 57-75 % yield [18]. We thereby claim a rather convenient and high yielding method for the formation of anti monohydrated malononitrile.

In order to optimize reaction conditions we carried out reaction in various solvents amongst which DCM stood out in terms of excellent yields for the desired cyanoacrylamides. Reaction temperature was varied from 0 C-25 C at an increment of 5 degree and raised to refluxing temperature in all solvents but it casts no effect upon time of completion and yield of reaction. The role of MnO2 was evaluated by varying the amount from 10 mol % to 100 mol %; it was observed that 10 mol % was the apt amount to catalyze the reaction to completion. A tentative mechanism is proposed accordingly (Scheme 2).

Interestingly, when benzoinoxime was reacted instead of benzaldoxime it did afford cyanophenylacrylamide in excellent yield along with carbon carbon bond cleavage products (Scheme 3).

Generality of the reaction was determined by the synthesis of 10 - 17, isolated in 75-88% yield (Scheme 4). All are soluble in EtOAc, THF, DCM,propanol, ethanol and DMSO. Characterization techniques employed includes FTIR, 1HNMR, EIMS and X-Ray crystallography. IR showed two ranges for -NH2 from 3200-3372, 3375-3461 cm-1 whereas C=O appeared in the range 1691-1730 cm-1. Mass spectrometry of the synthesized cyanoacrylamides showed molecular ion peaks as base peaks and fragmentation follow a general pattern, a representative fragmentation is provided in scheme 4 for compound (13).

X-Ray Structural Characterization

The crystal structure was determined by single crystal X-ray diffraction method on a Siemens SMART CCD diffractometer with graphite monochromated Mo K(alpha) (l = 0.71073 A) radiation at a temperature of 293 +- 2K. A hemisphere of data was collected using a narrow frame method with a scan width of 0.30deg and an exposure time of 20s/frame. SAINT processing program and SHELXTL crystallographic software package were used to solve the crystal structure [19-21].

CCDC-858636contains the supplementary crystallographic data for compound 1. The data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic Data Centre, 12 Union road, Cambridge CB21EZ, UK (fax: (+44)1223-336-033; or e-mail: deposit@ccdc.cam.ac.uk).

The most evident substantiation comes from the X-ray crystallographic data which reveals conveniently that hydration is precisely taking place at anti nitrile group with reference to the phenyl group in 10. (fig. 1).

Table1: Screening of the Solvent.

Entry###Solvents###Compound 14

No###at r.t###% Yield

1.###DMSO###00

2.###MeOH###00

3.###Acetone###00

4.###Ethanol###3

5.###EtOAc###7

6.###CHCl3###10

7.###THF###24

8.###1-Propanol###32

9.###1-Butanol###37

10.###DCM###83

Experimental

General Procedure for the Synthesis of Compounds (10-17)

To a solution of 4-chlorobenzaldoxime (1.55 g, 0.01 mol) in 10 ml of dichloromethane 2- (phenylmethylene) malononitrile (1.54 g, 0.01 mol) and MnO2 (10 mol %) were added respectively and the mixture was stirred at room temperature. The reaction was monitored by TLC, and upon completion MnO2 was filtered, the filtrate was concentrated and products were isolated by column chromatography on silica gel and recrystallization was carried out using ethanol.

2-cyano-3-phenylacrylamide (10)

Yield 80 % as white crystalline solid; m.p. 130degC; IR (KBr, cm-1): 3425, 3307 (NH2), 3161 (=C- H), 2215 (C N), 1730 (C=O), 1600 (C=C); 1H- NMR (300 MHZ, DMSO-d6, d, ppm): 7.56 (3H, m, ArH), 7.76 (2H, broad s, NH2), 7.91 (1H, d, J 3.6, ArH), 7.94 (1H, d, J 1.8, ArH), 8.17 (1H, s, =CH); EIMS (70 e V) m/z (%): ([M+], 202 (100) ), 186 (58), 158 (40), 89 (28), 77 ( 15).

2-cyano-3-(4-methoxyphenyl)acrylamide (11)

Yield 75 % as white crystalline solid; m.p. 205 degC; IR (KBr, cm-1) 3444, 3311 (NH2), 3184 (=C- H), 2204 (C N), 1695 (C=O), 1581 (C=C), 1024 (C-O); 1H-NMR (300 MHZ, DMSO-d6, d, ppm): 3.84 (3H, s, OCH3), 7.12 (2H, d, J 8.7, ArH), 7.76 (2H, broad s, NH2), 7.94 (2H, d, J 9, ArH), 8.09 (1H, s, =CH); EIMS (70 e V) m/z (%): ([M+], 202 (100)), 186 (61), 158 (48), 144 (22), 136 (22), 127 (6), 115 (20), 101 (5), 89 (25), 77 ( 11), 63 (14), 50 (8), 44 (17).

2-cyano-3-(2-methoxyphenyl)acrylamide (12)

Yield 79 % as white crystalline solid; m.p. 188 degC; IR (KBr, cm-1) 3454, 3372 (NH ), 3167 (=C-(C-O); H-NMR (300 MHZ, DMSO-d6, d, ppm):3.88 (3H, s, OCH3), 7.10 (1H, t, J 7.5, ArH), 7.17 (1H, d, J 8.1, ArH), 7.56 (1H, m, ArH), 7.85 (2H, broad s, NH ), 7.97 (1H, dd, J 1.5 and 1.8, ArH), 8.39 (1H, s =CH); EIMS (70 e V) m/z (%) 202 (27), 186 (3), 171 (100), 156 (6), 143 (8), 131 (13), 115 (8), 103 (6), 89 (8), 77 (5), 63 (6), 50 (2.4), 44 (7).

2-cyano-3-(4-hydroxyphenyl)acrylamide (13)

Yield 75 % as white crystalline solid; m.p. 169 degC; IR (KBr, cm-1) 3491 (OH), 3426, 3292 (NH2), 3166 (=C-H), 2207 (C N), 1700 (C=O), 1596 (C=C);1H-NMR (300 MHZ, DMSO-d6, d, ppm): 6.91 (2H, d, J 8.4, ArH), 7.69 (2H, broad s, NH2), 7.58 (1H, broad s, OH), 7.84 (2H, d, J 8.4, ArH), 8.03 (1H, s, =CH); EIMS (70 e V) m/z (%) ([M+], 188), 170 (76), 143 (28), 119 (26), 89 (30), 63 (17), 44 (16).

3-(4-chlorophenyl)-2-cynoacrylamide (14)

Yield 83 % as white crystalline solid; m.p. 190 degC; IR (KBr, cm-1) 3461, 3303 (NH2), 3161 (=C- H), 2214 (C N), 1703 (C=O), 1585 (C=C), 709 (C- Cl); 1H-NMR (300 MHZ, DMSO-d6, d, ppm) 7.64 (2H, d, J 8.4, ArH), 7.72 (2H, broad s, NH2), 7.94 (2H, d, J 8.4, ArH), 8.16 (1H, s, =CH); EIMS (70 e V) m/z (%) 205 ([M+], 100), 190 (20), 162 (23), 136 (33), 127 (22), 111 (7), 100 (9), 75 (20), 50(8).

2-cyano-3-(2-nitrophenyl)acrylamide (15)

Yield 80 % as white crystalline solid; m.p. 165 degC; IR (KBr, cm-1) 3398, 3200 (NH2), 3156 (=C- H), 2237 (C N), 1691 (C=O), 1612 (C=C), 1525, 1384 (NO2);1H-NMR (300 MHZ, DMSO-d6, d, ppm) 7.89 (5H, m, 2H-NH2 and 3H-ArH), 8.27 (1H, dd, J 8.1 and 0.9, ArH), 8.55 (1H, s, =CH); EIMS (70 e V) m/z (%) 217 ([M+], 00), 200 (3), 171 (100), 157 (62), 145 (9), 130 (59), 116 (42), 102 (25), 89 (48), 76 (29), 63 (16), 50 (20), 44 (34).

2-cyano-3-(3-nitrophenyl)acrylamide (16)

Yield 78 % as white crystalline solid; m.p. 136 degC; IR (KBr, cm-1) 3375, 3208 (NH2), 3185 (=C- H), 2229 (C N), 1694 (C=O), 1600 (C=C), 1528, 1376 (NO2); 1H-NMR (300 MHZ, DMSO-d6, d, ppm) 7.59 (1H, d, J 8.4, ArH), 7.85 (1H, t, J 8.1, ArH), 7.98 (2H, broad s, NH2), 8.37 (1H, s, ArH), 8.40 (1H, m, ArH), 8.76 (1H, s, =CH); EIMS (70 e V) m/z (%) 217 ([M+], 74), 200 (81), 170 (100), 157 (14), 147 (18), 142 (16), 127 (46), 116 (27), 101 (26), 89 (16), 75 (18), 63 (7), 50 (14), 44 (22).

3-(3-bromophenyl)-2-cynoacrylamide (17)

Yield 88 % as white crystalline solid; m.p. 145 degC; IR (KBr,cm-1) 3429, 3307 (NH2), 3187 (=C- H), 2216 (C N), 1700 (C=O), 1605 (C=C), 610 (C- Br);1H-NMR (300 MHZ, DMSO-d6, d, ppm) 7.55 (1H, d, J 8.4, ArH), 7.66 (1H, t, J 8.1, ArH), 7.76 (2H, broad s, NH2), 8.39 (1H, s, ArH), 8.42 (1H, m, ArH), 8.80 (1H, s, =CH); EIMS (70 e V) m/z (%) 251 ([M+], 100), 233 (16), 207 (11), 182 (18), 171 (29), 155 (12), 127 (40), 101 (11), 75 (12), 44 (16).

Acknowledgement

One of the authors, A. M. Qureshi is thankful to the grant offered by Bahauddin Zakariya University to carry out this work and HEC Pakistan.

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1Department of Chemistry, Bahauddin Zakariya University, Multan-60800, Pakistan., 2Department of Chemistry, The Islamia University, Bahawalpur-60000, Pakistan., 3Institue of Chemistry, University of the Punjab, Lahore-54590, Pakistan., 4Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad-22060, Pakistan., shamashfaq@yahoo.com
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Author:Rauf, Abdul; Awan, Faisal Saleem; Mumtaz, Saira; Sharif, Ahsan; Ahmed, Ejaz; Arshad, Muhammad; Kausa
Publication:Journal of the Chemical Society of Pakistan
Article Type:Report
Geographic Code:9PAKI
Date:Jun 30, 2012
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