Description:Field of Invention: Nitro substituted azole derivatives have been extensively studied due to their good industrial, agricultural and pharmacological potential. The present invention describes the development of solvent-free and green synthetic protocol for regioselective formation of a series of 2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)-1-arylethanones.
Background: Based on the foregoing research, it can be concluded that pyrazole derivatives with nitrogen containing functional groups at position-4 of the pyrazole ring are of great importance for the scientific community. In particular, Nitroazoles showed a broad spectrum of industrial applications like high energy materials (Molecules. 2020, 25(15), 3475), agricultural applications like plant growth regulators (U.S. Patent 4770692, 1988) and highly useful in medicinal field to treat cancer and bacterial infection like Metronidazole, Tinidazole, Nimorazole etc. (Pharmaceuticals. 2018, 11(2), 54). Furthermore, Nitroazoles possess biological activities like anti-inflammatory (J. Inorg. Biochem. 2020, 206, 111048), anticancer (Environ. Mutagen. 1986, 8, 611-619) , radiosensitizer (Int. J. Radiat. Biol. 1985, 47, 629-643), herbicidal (Angew. Chem., Int. Ed. Engl. 1965, 4(9), 789-790), antiprotozoal (Antimicrob. Chemother. 1985, 16, 589-595), antitubercular (Eur. J. med. Chem. 2004, 39(10), 849-853), coccidiostatic etc. (U.S. Patent No. 3,121,092, 1964). In the reported literature, it has been reported that substitution of phenacyl or naphthacyl groups on azole units can exhibit a broad range of medicinal importance (Bioorg. Med. Chem. Lett. 2010, 20, 4766-4770; Eur. J. Med. Chem. 2012, 57, 275-282; Eur. J. Med. Chem. 2001, 36, 421-433; Bioorg. Med. Chem. Lett. 2008, 18, 141-146). Also, pyrazoles containing 3-, 5- methyl groups have great potential to show antioxidant, anticancer and antibacterial activity (Eur. J. Med. Chem. 2009, 44, 4690-4694; Bioorg. Med. Chem. 2006, 14, 5061-5071). As reported in literature, 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones show anticancer, antibacterial and DNA cleavage activities (Eur. J. Med. Chem. 2014, 81, 267-276). Therefore, in view of the wide range of applications, it is worthwhile to study and explore new and efficient methods for synthesis of such type of pyrazole derivatives with introduction of nitro group at position-4.
Detailed description of the invention:
A major challenge in organic synthesis is to develop a green synthetic protocol devoid of hazardous solvents and harsh operating conditions. Nowadays, green and solvent-free synthetic methods have gained significant attention due to mild reaction conditions, high selectivity, prevention of hazardous solvents and clean reaction profile which make the process economical, eco-friendly and more viable alternative of conventional method of synthesis.
In view of the importance of 4-Nitropyrazole derivatives in various fields, we developed a regioselective and mechanochemical solvent-free method for the synthesis of 2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)-1-arylethanones (3a-s) using grind stone method. To synthesize the target compounds, initially, the key substrates, 3,5-dimethyl-4-nitropyrazole (1) and 2-bromo-1-arylethanones (2a-f) were prepared according to literature procedures (Chem. Heterocycl. Compd. 1988, 24, 353-370; Org. Synth. 1941, 1, 127; Org. Synth. 1929, 1, 20).
General method for the regioseletive synthesis of 2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)-1-arylethanones (3a-s) is outlined in Scheme-1, which was accomplished by a grinding technique using mortar and pestle. Initially, 3,5-dimethyl-4-nitropyrazole (1) and a-bromoketones (2a-f) were prepared using method reported in literature. Then, 3,5-dimethyl-4-nitropyrazole 1 was ground with a-bromoketones (2a-s) in solvent-free conditions in the presence of K2CO3 as a base at an appropriate temperature which leads to formation of 2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)-1-arylethanones (3a-s) regioselectively in good yields ranged from 94-99 %. The structures of the synthesized products were established by analyzing IR, 1H, 13C, 19F NMR and mass spectral data.
In 1H-NMR spectrum of 3c, 3'-and 5'-methyl group protons resonated at d 2.49 and 2.53, respectively. The characteristic singlet signal at d 5.54 due to two protons confirms the presence of CH2 protons which is resonated downfield as it is adjacent with nitrogen at position-1 of the pyrazole ring and carbonyl carbon. The presence of two multiplet bands at around d 7.20 - 7.23 and d 8.02 - 8.05 confirms the presence of four aromatic protons of phenyl ring (3'', 5''), (2'', 6'') respectively. Furthermore, the presence of characteristic signals in 13C-NMR spectrum at 146.60, 131.52, 142.23 due to C-3', C-4', C-5', respectively at pyrazole system supported the formation of 3c. Also, 19F NMR show characteristic signals at d -105.95, -109.99, -99.64 due to substitution of fluorine at position-2, 3, 4 of phenyl ring in 3o, 3l and 3c, respectively. Further, mass spectrum showed a molecular ion peak at m/z = 276 [M-1]+ which supported the formation of 3c exclusively with molecular formula C13H12N3O3F. These observations successfully led to formation of 3c regioselectively in excellent yield. In IR spectrum, characteristics absorption bands for 3c were appeared and observed at 1688 cm-1 due to C=O, 1594 cm-1 due to C=C, 1479 cm-1 due to C=N stretching vibrations, 1350 cm-1 and 1559 cm-1 due to symmetric and asymmetric stretching vibrations of NO2, respectively. Other derivatives were also characterized in similar way.

Scheme-1: Regioselective synthesis of 2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-arylethanones (3a-s)

Synthesis of 2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)-1-arylethanones (3a-s)
Compound 1 (3,5-dimethyl-4-nitropyrazole) (0.0035 moles, 1 eq), a-bromoketones 2a-s (0.0038 moles, 1.1 eq) and potassium carbonate (0.0070 moles, 2 eq) were ground vigorously in a mortar with pestle on heating at appropriate temperature. The reaction progress was monitored with TLC. After completion of reaction, the product obtained was then washed with water, filtered and dried and then recrystallized from ethanol (Scheme I).

Table-1: Reaction times, percentage yields and melting points of synthesized compounds (3a-s)

S.No. Ar Molecular weight (Calc.) (g/mol) Reaction Time (min.) (approx.) Yield (%)
(crude) Colour Observed Melting Point (°C)
1 C6H5- 259.26 25 98 White 129 - 131
2 4-CH3C6H4- 273.29 35 98 White 143 - 146
3 4-FC6H4- 277.25 30 97 White 125 - 129
4 4-ClC6H4- 293.71 40 98 White 138 - 142
5 4-BrC6H4- 338.16 40 99 White 153 - 158
6 4-OCH3C6H4- 289.29 35 97 White 116 - 119
7 4-C6H5C6H4- 335.4 35 98 White 138 - 142
8 4-CF3C6H4- 327.3 30 94 White 115 - 119
9 4-OCF3C6H4- 343.3 30 95 Yellow 97 - 100
10 4-NO2C6H4- 304.3 35 95 Brown 81 - 83
11 4-CNC6H4- 284.3 25 95 White 183 - 184
12 3-FC6H4- 277.3 25 95 White 148 - 149
13 3-BrC6H4- 338.2 30 99 White 139 - 141
14 3-NO2C6H4- 304.3 35 97 Brown 123 - 126
15 2-FC6H4- 277.3 20 98 White 153 - 155
16 2-OCH3C6H4- 289.3 30 99 White 141 - 143
17 2,4-F2C6H3- 295.2 30 94 White 138 - 140
18 3,4-Cl2C6H3- 328.2 30 98 Brown 90 - 94
19 2-Naphthyl 309.3 35 95 Yellow 157 - 158

Characterisation data of the compounds 3a-s are given below:

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-phenylethanone (3a):
FTIR (?max): 1699 (CO str.), 1592 (C = C str.), 1479 (C = N str.); 1356 and 1559 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.49 (s, 3H, 3'-CH3), 2.52 (s, 3H, 5'-CH3), 5.56 (s, 2H, 2-CH2), 7.52-7.55 (m, 2H, 3'', 5''-H), 7.66-7.69 (m, 1H, 4''-H), 7.97-7.99 (d, 2H, 2'', 6''-H, 3JH-H = 10 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.77 (CH3, C-5'), 14.15 (CH3, C-3'), 55.99 (C-2), 128.12 (C-3'', 5''), 129.16 (C-2'', 6''), 131.51 (C-4'), 133.83 (C-4''), 134.67 (C-1''), 142.23 (C-5'), 146.54 (C-3'), 190.56 (C-1); MS (m/z): 260.10 [M+1]+
2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(p-tolyl)ethanone (3b):
FTIR (?max): 1674 (CO str.), 1604 (C = C str.), 1487 (C = N str.); 1358 and 1563 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.45 (s, 3H, 3'-CH3), 2.52 (s, 3H, 5'-CH3), 2.53 (s, 3H, 4''-CH3), 5.51 (s, 2H, 2-CH2), 7.32-7.34 (d, 2H, 3'', 5''-H, 3JH-H = 10 Hz), 7.87-7.88 ( d, 2H, 2'', 6''-H , 3JH-H = 5 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.82 (CH3, C-5'), 14.17 (CH3, C-3'), 21.84 (CH3, C-4''), 55.88 (C-2), 128.24 (C-2'', 6''), 129.85 (C-3'', 5''), 131.57 (C-4'), 131.39 (C-1''), 142.17 (C-5'), 145.87 (C-4''), 146.59 (C-3'), 189.94 (C-1); MS (m/z): 274.12 [M+1]+
2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(4-fluorophenyl)ethanone (3c):
FTIR (?max): 1688 (CO str.), 1594 (C = C str.), 1479 (C = N str.); 1350 and 1559 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.49 (s, 3H, 3'-CH3), 2.53 (s, 3H, 5'-CH3), 5.54 (s, 2H, 2-CH2), 7.20-7.23 (m, 2H, 3'', 5''-H), 8.02-8.05 ( m, 2H, 2'', 6''-H ); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.75 (CH3, C-5'), 14.11 (CH3, C-3'), 55.81 (C-2), 116.45 (d, C-3'', 5'', 2JC-F = 21.8 Hz), 130.33 (d, C-1'', 4JC-F = 2.7 Hz), 130.97 (d, C-2'', 6'', 3JC-F = 9.4 Hz), 131.53 (C-4'), 142.23 (C-5'), 146.60 (C-3'), 166.54 (d, C-4'', 1JC-F = 257.7 Hz) , 189.05 (C-1); 19F NMR (CDCl3, 80MHz): d (ppm) = -99.64 (s, 1F, C-4''); MS (m/z): 276.08 [M-1]+

1-(4-Chlorophenyl)-2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)ethanone (3d):
FTIR (?max): 1682 (CO str.), 1589 (C = C str.), 1487 (C = N str.); 1356 and 1565 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.49 (s, 3H, 3'-CH3), 2.53 (s, 3H, 5'-CH3), 5.51 (s, 2H, 2-CH2), 7.51-7.53 (d, 2H, 3'', 5''-H, 3JH-H = 10 Hz), 7.92-7.95 ( d, 2H, 2'', 6''-H, 3JH-H = 15 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.80 (CH3, C-5'), 14.14 (CH3, C-3'), 55.84 (C-2), 129.55 (C-3'', 5''), 129.57 (C-2'', 6''), 131.61 (C-4'), 132.16 (C-1''), 141.33 (C-4''), 142.18 (C-5'), 146.71 (C-3'), 189.42 (C-1); MS (m/z): 292.05 [M-1]+ and 294.07 [M+1]+ in the ratio showing typical chlorine isotope profile [3:1]

1-(4-Bromophenyl)-2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)ethanone (3e):
FTIR (?max): 1680 (CO str.), 1582 (C = C str.), 1483 (C = N str.); 1352 and 1561 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.50 (s, 3H, 3'-CH3), 2.53 (s, 3H, 5'-CH3), 5.51 (s, 2H, 2-CH2), 7.67-7.69 (d, 2H, 3'', 5''-H, 3JH-H = 10 Hz), 7.84-7.86 ( d, 2H, 2'', 6''-H, 3JH-H = 10 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.78 (CH3, C-5'), 14.15 (CH3, C-3'), 55.83 (C-2), 129.58 (C-3'', 5''), 130.09 (C-2'', 6''), 131.57 (C-4'), 132.55 (C-1''), 132.32 (C-4'') 142.21 (C-5'), 146.68 (C-3'), 189.70 (C-1); MS (m/z): 336.00 [M-1]+ and 338.02 [M+1]+ in the ratio showing typical bromine isotope profile [1:1]

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(4-methoxyphenyl)ethanone (3f):
FTIR (?max): 1684 (CO str.), 1603 (C = C str.), 1485 (C = N str.); 1364 and 1567 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.49 (s, 3H, 3'-CH3), 2.52 (s, 3H, 5'-CH3), 3.90 (s, 3H, 4''-OCH3), 5.50 (s, 2H, 2-CH2), 6.98-7.00 (d, 2H, 3'', 5''-H, 3JH-H = 10 Hz), 7.94-7.96 ( d, 2H, 2'', 6''-H, 3JH-H = 10 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.79 (CH3, C-5'), 14.15 (CH3, C-3'), 55.65 (C-2, OCH3-C-4''), 114.35 (C-3'', 5''), 126.78 (C-1''), 130.51 (C-2'', 6''), 131.46 (C-4'), 142.25 (C-5'), 146.46 (C-3'), 164.67 (C-4''), 188.83 (C-1); MS (m/z): 288.10 [M-1]+

1-([1,1'-Biphenyl]-4-yl)-2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)ethanone (3g):
FTIR (?max): 1695 (CO str.), 1598 (C = C str.), 1487 (C = N str.); 1356 and 1563 (NO str.) cm-1;
1H NMR (CDCl3, 400 MHz): d (ppm) = 2.57 (s, 3H, 3'-CH3), 2.59 (s, 3H, 5'-CH3), 5.59 (s, 2H, 2-CH2), 7.78-7.80 (d, 2H, 3'', 5''-H, 3JH-H = 8 Hz), 8.08-8.10 ( d, 2H, 2'', 6''-H, 3JH-H = 8 Hz), 7.66-7.68 (d, 2H, 2''', 6'''-H, 3JH-H = 10 Hz), 7.44-7.54 ( m, 3H, 3''', 4''', 5'''-H ); 13C NMR (CDCl3, 400 MHz): d (ppm) = 11.88 (CH3, C-5'), 14.21 (CH3, C-3'), 55.98 (C-2), 127.33 (C-3'', 5''), 127.76 (C-2''', 6'''), 128.74 (C-3''', 5'''), 128.78 (C-2'', 6''), 129.12 (C-4'''), 131.64 (C-4'), 132.48 (C-1'', 1'''), 142.20 (C-5'), 146.70 (C-3'), 147.41 (C-4''), 189.95 (C-1); MS (m/z): 335.1 [M]+

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(4-(trifluoromethyl)phenyl)ethanone (3h):
FTIR (?max): 1704 (CO str.), 1631 (C = C str.), 1479 (C = N str.); 1360 and 1566 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.53 (s, 3H, 3'-CH3), 2.56 (s, 3H, 5'-CH3), 5.56 (s, 2H, 2-CH2), 8.11-8.12 (d, 2H, 3'', 5''-H, 3JH-H = 5 Hz), 7.82-7.83 (d, 2H, 2'', 6''-H, 3JH-H = 5 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.79 (CH3, C-5'), 14.13 (CH3, C-3'), 56.05 (C-2), 126.28 (dd, C-3'', 5'', 3JC-F = 7.5, 3.5 Hz), 128.60 (C-2'', 6''), 131.72 (C-4'), 136.49 (C-1''), 142.11 (C-5'), 146.86 (C-3'), 135.89 (d, C-4'', 2JC-F = 33 Hz), 189.78 (C-1), 123.26 (d, CF3-C-4'', 1JC-F = 272.5 Hz); 19F NMR (CDCl3, 80MHz): d (ppm) = -60.05 (s, 3F, CF3-C-4''”); MS (m/z): 328.09 [M+1]+

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(4-(trifluoromethoxy)phenyl)ethanone (3i):
FTIR (?max): 1691 (CO str.), 1598 (C = C str.), 1481 (C = N str.); 1354 and 1564 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.53 (s, 3H, 3'-CH3), 2.55 (s, 3H, 5'-CH3), 5.52 (s, 2H, 2-CH2), 8.05-8.07 (d, 2H, 2'', 6''-H, 3JH-H = 10 Hz), 7.82-7.83 (d, 2H, 3'', 5''-H, 3JH-H = 5 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.80 (CH3, C-5'), 14.14 (CH3, C-3'), 55.85 (C-2), 120.81 (C-3'', 5''), 130.35 (C-2'', 6''), 131.68 (C-4'), 131.91 (C-1''), 142.12 (C-5'), 146.78 (C-3'), 153.71 (d, C-4'', 3JC-F = 1.7 Hz), 189.04 (C-1), 120.23 (d, OCF3-C-4'', 1JC-F = 259.8 Hz); 19F NMR (CDCl3, 80MHz): d (ppm) = -54.78 (s, 3F, OCF3-C-4''); MS (m/z): 344.08 [M+1]+

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(4-nitrophenyl)ethanone (3j):
FTIR (?max): 1691 (CO str.), 1599 (C = C str.), 1485 (C = N str.); 1345 and 1563 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.57 (s, 3H, 3'-CH3), 2.58 (s, 3H, 5'-CH3), 5.62 (s, 2H, 2-CH2), 8.19-8.20 (d, 2H, 2'', 6''-H, 3JH-H = 5 Hz), 8.38-8.40 (d, 2H, 3'', 5''-H, 3JH-H = 10 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.87 (CH3, C-5'), 14.25 (CH3, C-3'), 56.15 (C-2), 124.34 (C-3'', 5''), 129.40 (C-2'', 6''), 131.69 (C-4'), 138.19 (C-1''), 142.25 (C-5'), 146.93 (C-3'), 151.12 (C-4''), 189.51 (C-1); MS (m/z): 305.08 [M+1]+

4-(2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)acetyl)benzonitrile (3k):
FTIR (?max): 1691 (CO str.), 1604 (C = C str.), 1488 (C = N str.); 1354 and 1561 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.52 (s, 3H, 3'-CH3), 2.56 (s, 3H, 5'-CH3), 5.54 (s, 2H, 2-CH2), 8.09-8.11 (d, 2H, 2'', 6''-H, 3JH-H = 10 Hz), 7.85-7.87 (d, 2H, 3'', 5''-H, 3JH-H = 10 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.80 (CH3, C-5'), 14.13 (CH3, C-3'), 55.99 (C-2), 132.99 (C-3'', 5''), 128.65 (C-2'', 6''), 131.75 (C-4'), 136.73 (C-1''), 142.11 (C-5'), 146.93 (C-3'), 117.39 (C-4'', 189.55 (C-1), 117.97 (CN-C-4''); MS (m/z): 285.09 [M+1]+

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(3-fluorophenyl)ethanone (3l):
FTIR (?max): 1688 (CO str.), 1588 (C = C str.), 1478 (C = N str.); 1349 and 1558 (NO str.) cm-1; 1H NMR (CDCl3, 500 MHz): d (ppm) = 2.52 (s, 3H, 3'-CH3), 2.54 (s, 3H, 5'-CH3), 5.52 (s, 2H, 2-CH2), 7.53-7.57 (m, 1H, 4''-H), 7.77-7.79 (d, 1H, 6''-H , 3JH-H = 10 Hz), 7.37-7.41 ( m, 1H, 5''-H), 7.67-7.69 (d, 1H, 2''-H, 3JH-H = 10 Hz); 13C NMR (CDCl3, 500 MHz): d (ppm) = 11.79 (CH3, C-5'), 14.13 (CH3, C-3'), 55.99 (C-2), 115.01 (d, C-2'', 2JC-F = 22.6 Hz), 131.01 (d, C-5'', 3JC-F = 7.8 Hz), 162.98 (d, C-3'', 1JC-F = 249.8 Hz), 135.50 (C-4'), 123.88 (d, C-6'', 4JC-F = 3.0 Hz), 121.81 (d, C-4'', 2JC-F = 21.5 Hz), 135.79 (d, C-1'', 3JC-F = 6.2 Hz), 142.13 (C-5'), 131.66 (C-3'), 189.43 (d, C-1, 4JC-F = 1.9 Hz); 19F NMR (CDCl3, 80MHz): d (ppm) = -109.99 (s, 1F, C-3''); MS (m/z): 278.09 [M+1]+

1-(3-Bromophenyl)-2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)ethanone (3m):
FTIR (?max): 1707 (CO str.), 1635 (C = C str.), 1471 (C = N str.); 1348 and 1559 (NO str.) cm-1;
1H NMR (CDCl3, 400 MHz): d (ppm) = 2.54 (s, 3H, 3'-CH3), 2.56 (s, 3H, 5'-CH3), 5.53 (s, 2H, 2-CH2), 7.81-7.83 (d, 1H, 4''-H, 3JH-H = 8 Hz), 7.92-7.94 (d, 1H, 6''-H , 3JH-H = 8 Hz), 7.44-7.48 ( t, 1H, 5''-H, 3JH-H = 8Hz), 8.13 (s, 1H, 2''-H); 13C NMR (CDCl3, 400 MHz): d (ppm) = 11.82 (CH3, C-5'), 14.17 (CH3, C-3'), 55.90 (C-2), 130.75 (C-2'', 5''), 131.20 (C-4''), 123.53 (C-3''), 135.50 (C-4'), 126.12 (C-6''), 137.52 (C-1''), 142.12 (C-5'), 146.77 (C-3'), 189.35 (C-1); MS (m/z): 338.32 [M]+

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(3-nitrophenyl)ethanone (3n):
FTIR (?max): 1707 (CO str.), 1612 (C = C str.), 1483 (C = N str.); 1352 and 1564 (NO str.) cm-1;
1H NMR (CDCl3, 400 MHz): d (ppm) = 2.55 (s, 3H, 3'-CH3), 2.60 (s, 3H, 5'-CH3), 5.61 (s, 2H, 2-CH2), 8.55-8.58 (d, 1H, 4''-H , 3JH-H = 12 Hz), 8.35-8.37 (d, 1H, 6''-H , 3JH-H = 8 Hz), 7.80-7.84 ( t, 1H, 5''-H, 3JH-H = 8 Hz), 8.85 (s, 1H, 2''-H); 13C NMR (CDCl3, 400 MHz): d (ppm) = 11.83 (CH3, C-5'), 14.15 (CH3, C-3'), 56.00 (C-2), 123.08 (C-2''), 128.83 (C-4''), 130.65 (C-5''), 131.79 (C-4'), 133.69 (C-6''), 135.05 (C-1''), 142.12 (C-5'), 147.00 (C-3'), 188.88 (C-1), 148.62 (C-3''); MS(m/z): 305.07 [M+1]+

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(2-fluorophenyl)ethanone (3o):
FTIR (?max): 1674 (CO str.), 1605 (C = C str.), 1475 (C = N str.); 1348 and 1557 (NO str.) cm-1;
1H NMR (CDCl3, 400 MHz): d (ppm) = 2.56 (s, 3H, 3'-CH3), 2.58 (s, 3H, 5'-CH3), 5.49-5.50 (d, 2H, 2-CH2 , 3JH-H = 4 Hz), 7.25-7.30 (m, 1H, 3''-H), 7.33-7.37 (t, 1H, 5''-H, 3JH-H = 8 Hz), 7.66-7.71 (m, 1H, 4''-H), 7.99-8.03 (m, 1H, 6''-H); 13C NMR (CDCl3, 400 MHz): d (ppm) = 11.77 (CH3, C-5'), 14.20 (CH3, C-3'), 59.55 (C-2, d, 4JC-F = 14.1 Hz), 116.85 (C-3'', d, 2JC-F = 23.5 Hz), 122.17 (C-1'', d, 2JC-F = 13.8 Hz), 125.26 (C-5'', d, 4JC-F = 3.1 Hz), 131.10 (C-6'', d, 3JC-F = 2.6 Hz), 131.65 (C-4'), 136.54 (C-4'', d, 3JC-F = 9.3 Hz), 142.05 (C-5'), 146.65 (C-3'), 162.59 (C-2'', d, 1JC-F = 254.3 Hz), 188.86 (C-1, d, 3JC-F = 5.1 Hz); 19F NMR (CDCl3, 80MHz): d (ppm) = -105.95 (s, 1F, C-3''); MS(m/z): 278.08 [M+1]+

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(2-methoxyphenyl)ethanone (3p):
FTIR (?max): 1667 (CO str.), 1594 (C = C str.), 1473 (C = N str.); 1354 and 1555 (NO str.) cm-1;
1H NMR (CDCl3, 400 MHz): d (ppm) = 2.56 (s, 6H, 3', 5'-CH3), 5.52 (s, 2H, 2-CH2), 4.04 (s, 3H, 2''-OCH3), 7.07-7.13 (m, 2H, 3'', 5''-H), 7.60-7.64 (t, 1H, 4''-H, 3JH-H = 8 Hz), 7.94-7.97 ( d, 1H, 6''-H , 3JH-H = 12 Hz); 13C NMR (CDCl3, 400 MHz): d (ppm) = 11.84 (CH3, C-5'), 14.24 (CH3, C-3'), 55.76 (C-2), 60.38 (OCH3, C-2''), 111.72 (C-3''), 121.38 (C-1''), 123.95 (C-5''), 129.90 (C-6''), 131.41 (C-4'), 135.76 (C-4''), 142.02 (C-5'), 146.41 (C-3'), 159.67 (C-2''), 191.32 (C-1); MS (m/z): 290.11 [M+1]+

1-(2,4-Difluorophenyl)-2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)ethanone (3q):
FTIR (?max): 1679 (CO str.), 1604 (C = C str.), 1488 (C = N str.); 1354 and 1561 (NO str.) cm-1;
1H NMR (CDCl3, 400 MHz): d (ppm) = 2.56 (s, 3H, 3'-CH3), 2.57 (s, 3H, 5'-CH3), 5.45-5.46 (d, 2H, 2-CH2 , 3JH-H = 4 Hz), 6.99-7.04 (m, 1H, 3''-H), 7.07-7.11 ( m, 1H, 5''-H), 8.05-8.11 (m, 1H, 6''-H); 13C NMR (CDCl3, 400 MHz): d (ppm) = 11.77 (CH3, C-5'), 14.19 (CH3, C-3'), 59.32 (C-2, 4JC-F = 14.0 Hz), 105.07,(dd, 2JC-F = 27.5 Hz, 2JC-F = 25.8 Hz, C-3''), 113.32 (dd, 2JC-F = 21.7 Hz, 4JC-F = 3.1 Hz, C-5''), 119.79 (dd, 2JC-f = 16.6 Hz, 4JC-F = 5.2 Hz, C-1'') 133.26 (dd, 3JC-F = 10.9 Hz, 3JC-F = 4.5 Hz, C-6''), 131.60 (C-4'), 142.04 (C-5'), 146.71 (C-3'), 163.39 (d, 1JC-F = 244.1 Hz, C-2''), 167.29 (d, 1JC-F = 214.0 Hz, C-4''), 187.45 (d, 3JC-F = 5.8 Hz, C-1); 19F NMR (CDCl3, 80MHz): d (ppm) = -98.75 (s, 1F, C-4''), -100.67 (s, 1F, C-2''); MS (m/z): 296.08 [M+1]+

1-(3,4-Dichlorophenyl)-2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)ethanone (3r):
FTIR (?max): 1738 (CO str.), 1688 (C = C str.), 1486 (C = N str.); 1357 and 1564 (NO str.) cm-1;
1H NMR (CDCl3, 400 MHz): d (ppm) = 2.55 (s, 3H, 3'-CH3), 2.57 (s, 3H, 5'-CH3), 5.51 (s, 2H, 2-CH2), 7.65-7.67 (d, 1H, 6''-H, 3JH-H = 8Hz), 7.83-7.85 (dd, 1H, 5''-H, 3JH-H = 8Hz), 8.09-8.10 (d, 1H, 2''-H, 3JH-H = 4Hz); 13C NMR (CDCl3, 400 MHz): d (ppm) = 11.82 (CH3, C-5'), 14.15 (CH3, C-3'), 55.80 (C-2), 127.07 (C-6''), 130.17 (C-5''), 131.37 (C-2''), 131.73 (C-4'), 133.29 (C-3''), 134.16 (C-1''), 139.59 (C-4''), 142.11 (C-5'), 146.89 (C-3'), 188.62 (C-1); MS (m/z): 328.04 [M]+, 330.03 [M+2]+, 332 [M+4]+ in the ratio showing typical chlorine isotope profile [9:6:1]

2-(3,5-Dimethyl-4-nitro-1H-pyrazol-1-yl)-1-(naphthalen-2-yl)ethanone (3s):
FTIR (?max): 1688 (CO str.), 1623 (C = C str.), 1473 (C = N str.); 1350 and 1559 (NO str.) cm-1;
1H NMR (CDCl3, 400 MHz): d (ppm) = 2.57 (s, 3H, 3'-CH3), 2.60 (s, 3H, 5'-CH3), 5.70 (s, 2H, 2-CH2), 7.62-7.72 (m, 2H, Ar), 7.94-8.05 (m, 4H, Ar), 8.55 (s, 1H, Ar); 13C NMR (CDCl3, 400 MHz): d (ppm) = 11.90 (CH3, C-5'), 14.21 (CH3, C-3'), 56.02 (C-2), 123.25 (C-3''), 127.42 (C-5''), 128.00 (C-4''), 129.26 (C-6''), 129.44 (C-7''), 129.69 (C-1''), 130.23 (C-8''), 131.19 (C-4'), 131.65 (C-2''), 132.36 (C-9a''), 136.18 (C-10a''), 142.20 (C-5'), 146.71 (C-3'), 190.31 (C-1); MS (m/z): 310.10 [M+1]+
, Claims:Claims:
I/We claim:
1. The development of a green synthetic protocol for the synthesis of 2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)-1-arylethanones (Formula-I) comprising the step of reacting 3,5-dimethyl-4-nitropyrazole (0.0035 moles, 1 eq), a-bromoketones (0.0038 moles, 1.1 eq) and potassium carbonate (0.0070 moles, 2 eq) at temperature upto 90 °C for 20 – 40 minutes where Ar may -C6H5, 4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-CH3C6H4, 4-OCH3C6H4, 4-C6H5C6H4, 4-CF3C6H4, 4-OCF3C6H4, 4-NO2C6H4, 4-CNC6H4, 3-FC6H4, 3-BrC6H4, 3-NO2C6H4, 2-OCH3C6H4, 2-FC6H4, 3,4-Cl2C6H3, 2,4-F2C6H3, 2-acetonaphthyl.

Formula I
2. The process as claimed in claim 1, wherein 3,5-Dimethyl-4-nitropyrazoles were converted into final products with Formula-I under solvent-free reaction condition by grindstone methodology.
3. The process as claimed in claim 1, wherein the said process provides the desired products regioselectivity.
4. The process as claimed in claim 2, wherein the yield of 94 - 99 % can be achieved.
5. A process as recited in claim 2, wherein the temperature required is 55 °C as minimum to 90 °C as maximum during the whole process.