NITRATION

Abstract

A process for preparing a nitrated compound, including the step of reacting a compound (A) including at least one substituted or unsubstituted aromatic or heteroaromatic ring, wherein the heteroaromatic ring includes at least one heteroatom selected from the group consisting of oxygen, sulfur, phosphor, selenium and nitrogen, with a compound of formula (I)

##STR00001##

wherein Y is selected from the group consisting of hydrogen and nitro.

Claims

1. A process for preparing a nitrated compound, comprising the step of reacting a compound (A) comprising at least one substituted or unsubstituted aromatic or heteroaromatic ring, wherein the heteroaromatic ring comprises at least one heteroatom selected from the group consisting of oxygen, sulfur, phosphor, selenium and nitrogen, with a compound of formula (I) ##STR00258## wherein Y is selected from the group consisting of hydrogen and nitro.

2. The process according to claim 1, wherein compound (A) comprises at least one acid-sensitive residue, and wherein the acid-sensitive residue is selected from the group consisting of difluoromethoxy, trifluoromethoxy, difluoromethylthio, trifluoromethylthio, chloro, iodo, methoxy, ethoxy, propoxy, butoxy, amino, methylamino, dimethylamino, formyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, acyl chlorides, acid anhydrides, carboxylate esters, sulfonate esters, alkyl esters, carboxy, ketals, acetals, hydrazones carboxy and 4,4,5,5-tetramethyl-1,3,2-dioxaborolanyl.

3. The process according to claim 1, wherein the aromatic ring or the heteroaromatic ring of compound (A) comprises at least one electron donating group as residue, the electron donating group being selected from the group consisting of amino, carbamoyl, alkylaminocarbonyl, carboxamido, mercapto, alkylthio, hydroxy, alkoxy, alkyl, acyloxy, aryl, heteroaryl, alkenyl and alkynyl.

4. The process according to claim 1, wherein the aromatic ring or the heteroaromatic ring of compound A comprises at least one electron withdrawing group as residue, the electron withdrawing group being selected from the group consisting of fluoro, chloro, bromo, iodo, acyl, carboxy, benzoyl, carbonyl, aldehyde, arylsulfonyl, haloalkyl, cyano and 2,5-dioxopyrrolidinyl.

5. The process according to claim 1, wherein the compound (A) comprises or consists of a 5- or 6-membered substituted or unsubstituted aromatic or heteroaromatic ring.

6. The process according to claim 1, wherein the compound (A) comprises or consists of a fused aromatic or heteroaromatic ring system comprising 2 to 5 aromatic or heteroaromatic rings which may be substituted or not.

7. The process according to claim 1 wherein the heteroaromatic ring or ring system is selected from the group consisting of pyrrole, thiophene, furan, imidazole, thiazole, pyrimidine, pyridine, pyrazine, pyridazine, isoxazole, oxazole, indole, isoindole, indolizine, quinoline, isoquinoline, purine, carbazole, dibenzofuran, acridine, purine, guanine, xanthine, uric acid, benzothiophen, benzofuran, dibenzothiophen, thianthren, xanthen, phenoxatiin, isochinoline, phthalazine, 1,8-naphthydrine, quinazoline, quinoxaline, cinnoline, pteridine, perimidine, 1,7-phenanthroline, phenazine, phosphindole, phthalimide, furazan and phosphinoline.

8. The process according to claim 1, wherein the aromatic ring or ring system is selected from the group consisting of benzene, pentalene, indene, indan, naphthalene, 1,1′-binaphthalene, azulene, heptalene, biphenylene, as-indacene, s-indacene, acenaphthylene, fluorene phenalene, phenanthrene, anthracene, fluoranthene acephenanthrylene, aceanthrylenetriphenylene, pyrene chrysene, naphthacene, pleiadene, picene and perylene.

9. The process according to claim 1, wherein the compound of formula (I) is the compound of formula (Ia) ##STR00259##

10. The process according to claim 1, wherein the compound of formula (I) is the compound of formula (Ib) ##STR00260##

11. The process according to claim 1, wherein the reaction is carried out in a solvent selected from the group consisting of hexafluoroisopropanol, acetonitrile, nitromethane, methylenechloride, trifluoroethanol, tetrahydrofuran, hexane, benzene and toluene or mixtures thereof.

12. The process according to claim 1, wherein the reaction is carried out in the presence of a catalyst.

13. The process according to claim 12, wherein the proton donating acid is selected from the group consisting of acetic acid, trimethylacetic acid, trichloroacetic acid, trifluoroacetic acid, benzoic acid, and mixtures thereof.

14. The process according to claim 13, wherein the Lewis acid is selected from the group consisting of iron (II) triflate, iron (III) triflate, magnesium (II) triflate, zinc (II) triflate, cupper (II) triflate, iron (II) bromide, iron (III) bromide and magnesium perchlorate, preferably magnesium perchlorate.

15. A method comprising applying a compound of formula (I) ##STR00261## wherein Y is selected from the group consisting of hydrogen and nitro, as nitrating agent of a compound (A) comprising an aromatic or heteroaromatic ring.

Description

EXPERIMENTS

Synthesis of Compound of Formula (Ia)

[0109] ##STR00095##

[0110] Representative procedure for synthesis of reagent 1: In a 250 mL three necked round bottom flask equipped with dropping funnel, air outlet and stirring bar was placed N-saccharin (10.0 g, 54.64 mmol) in acetic anhydride (25.7 mL, 0.27 mol). The solution was cooled to 0-5° C. with ice-bath and concentrated nitric acid (25.1 mL, 0.61 mol) was added dropwise to the solution during 30 minutes, while dry air being bubbled through the solution rapidly in order to remove excess of nitrogen oxides. N-saccharin was completely dissolved once all nitric acid was added. The cooling bath was removed, and the reaction mixture was stirred at room temperate during at least 4 hours with continuous bubbling of air through the liquid. The precipitate which had formed during the reaction was collected on a sintered glass filter and dried under high vacuum until dryness (11.8 g, 95% yield). The material can be recrystallized from hot chloroform or acetonitrile and is a white crystalline compound. Decomposition temperature: 180-182° C. (mass loss-50%, determined by termogravimetric analysis, TGA); .sup.1H-NMR (300 MHz, CD.sub.3CN): δ=8.05 (dt, J=7.4, 1.5 Hz, 1H), 8.14 (dt, J=6.1, 1.4 Hz, 1H), 8.16-8.23 (m, 2H); .sup.13C-NMR (75 MHz): δ=121.7, 123.1, 126.5, 134.4, 135.9, 137.6, 151.7; IR (ATR, neat): 3097, 1781, 1717, 1601, 1463, 1292, 1176, 1068, 1007, 891, 758, 662, 582, 500; HRMS (EI) m/z calc'd for C.sub.7H.sub.4N.sub.2O.sub.5S: [M.sup.+] 227.9836, found 227.9842; Anal. calcd. for C.sub.7H.sub.4N.sub.2O.sub.5S: C 36.85, H 1.77, N 12.28 found: C 36.88, H 1.87, N 12.41.

[0111] Colorless crystals of reagent 1 were obtained by slow evaporation from a saturated solution in chloroform/acetonitrile 1:1.

Synthesis of Compound of Formula (Ib)

[0112] ##STR00096##

[0113] Representative procedure for synthesis of reagent 2: In a 250 mL three necked round bottom flask equipped with dropping funnel, air outlet and stirring bar was placed 6-nitrosaccharin (10.0 g, 36.63 mmol) in acetic anhydride (28.2 mL, 0.30 mol). The solution was cooled 5-10° C. with ice-bath and concentrated nitric acid (28.2 mL, 0.67 mol) was added dropwise to the solution during 30 minutes, while dry air being bubbled through the solution rapidly in order to remove excess of nitrogen oxides.

[0114] 6-Nitrosaccharin was completely dissolved once all nitric acid was added. The reaction mixture was stirred at 5-10° C. during 4 hours with constant bubbling of dry air through the liquid. The reaction mixture was placed to freezer for 10 hours to complete precipitation of the product. The precipitate was collected on a sintered glass filter, washed with cold chloroform and dried under high vacuum until dryness (9.6 g, 96% yield). The product is a light-yellow (almost white) powder/crystalline compound. Decomposition temperature: 174-176° C. (mass loss˜50%, determined by termogravimetric analysis, TGA); .sup.1H-NMR (500 MHz, CD.sub.3CN): δ=9.07 (d, J=2.1 Hz, 1H), 8.76 (dd, J=8.5, 2.0 Hz, 1H), 8.43 (d, J=8.4 Hz, 1H); .sup.13C-NMR (125 MHz, CD.sub.3CN): δ=118.3, 127.8, 128.5, 130.6, 135.4, 150.3, 152.9; IR (ATR, neat): 3073, 1732, 1601, 1529, 1424, 1347, 1180, 1064, 1024, 786, 737, 649, 490; Anal. calcd. for C.sub.7H.sub.3N.sub.3O.sub.7S C 30.78, H 1.11, N 15.38 found: C 30.81, H 1.19, N 15.50.

[0115] Colorless crystals of reagent 2 were obtained by slow evaporation from a saturated solution in chloroform/acetonitrile 1:1.

[0116] Nitration of Arenes and Heteroarenes Using Reagent 1

[0117] Representative general procedure 1 for nitration of compound A: A 25 mL vessel was charged with reagent 1 (1.3 equiv., 0.65 mmol) and sealed under nitrogen atmosphere. Arene (1.0 equiv., 0.5 mmol) and HFIP (1 mL) were added and the reaction mixture was heated at 55-60° C. for 3 hours. After cooling to room temperature, the solvent was removed in vacuum, and the product was purified by flash column chromatography (SiO.sub.2, ethyl acetate/n-hexane gradient).

[0118] Representative general procedure 2 for nitration of compound A: A 25 mL vessel was charged with reagent 1 (1.3 equiv., 0.65 mmol), Mg(ClO.sub.4).sub.2 (0.05 mmol) and sealed under nitrogen atmosphere. Arene (1.0 equiv., 0.5 mmol) and CH.sub.3CN (1 mL) were added and the reaction mixture was heated at 85° C. for 5 hours. After cooling to room temperature, the solvent was removed in vacuum, and the product was purified by flash column chromatography (SiO.sub.2, ethyl acetate/n-hexane gradient).

TABLE-US-00003 TABLE 1 refers to compounds 101 to 146 and indicates the Isolated yield of said compound using general procedure 1 or general procedure 2 (total yield of isomers) and the ratio of isomers. Isolated Isolated yield in yield in %.sup.[b] using %.sup.[b] using general general Compound procedure procedure Ratio of No. Chemical structure.sup.[a] 1 2 isomers.sup.[c] 101 [00097] >99% >99% 102 [00098] 96% p:o (1.5:1) 103 [00099] 94% p:o (9:1) 104 [00100] 94% p:o (1.85:1) 105 [00101] 95% p:o (1.1:1) 106 [00102] 92% p:o (1.5:1) 107 [00103] 86% (19 h) 97% p:o (1.2:1) 108 [00104] 93% p:o (2.1:1) 109 [00105] 96% p:o (1.5:1) 110 [00106] 91% p:o (1.5:1) 111 [00107] 97% p:o (2.1:1) 112 [00108] 99% o:p (1.5:1) 113 [00109] 87% m:o (4:1) 114 [00110] 81% (19 h) 92% 115 [00111] 72% (19 h) 87% m:o (4.8:1) 116 [00112] 75% (19 h) 84% 117 [00113] 92% (19 h) 97% (1:0.6) 118 [00114] 37% (19 h) 72% 119 [00115] 87% (19 h) 94% (2.5:1) 120 [00116] 93% 121 [00117] 96% 122 [00118] 86% (19 h) 97% (19 h) p:o (4.6:1) 123 [00119] 81% m:o (1:0.9) 124 [00120] 98% (19 h) o:m.p (0.8:1:0.6) 125 [00121] 86% 126 [00122] 82% 127 [00123] 76% 128 [00124] 77% 129 [00125] 86% 130 [00126] 94% 97% p:o (1:1.1) 131 [00127] 74% (19 h) 132 [00128] 64% 133 [00129] 94% 134 [00130] 93% 135 [00131] 92% 136 [00132] 72% 137 [00133] 79% (19 h) 138 [00134] 91% (6:1) 139 [00135] 91% 140 [00136] 85% 141 [00137] 89% (19 h) (2.5:1) 142 [00138] 71% (19 h) 143 [00139] 90% 144 [00140] 75% 145 [00141] 88% (19 h) (15:1) 146 [00142] 98% 147 [00143] 71% 148 [00144] 65.7% 149 [00145] 19.2% 150 [00146] 9.4% 151 [00147] 33% 152 [00148] 45.3% 153 [00149] 39.6% 154 [00150] 38.4% 155 [00151] 12.2% 156 [00152] 36.8 157 [00153] 14.8% (19h) 158 [00154] 41% (19h) 159 [00155] 42.7% (19h) 160 [00156] 38.4% 161 [00157] 36.4% 162 [00158] 24.5% (19h) 163 [00159] 34.5% (19h) 164 [00160] 24.9% (19h) 165 [00161] 32.7% (19h) 166 [00162] 30% (19h) 167 [00163] 17.4% 168 [00164] 13% 169 [00165] 5.5% (19 h) 170 [00166] 88% 171 [00167] 93% 172 [00168] 84% (19 H) 173 [00169] 98% [00170] 174 [00171] 76.1% 175 [00172] 44% 176 [00173] 83% 177 [00174] 91% (19 h) 178 [00175] 74% 179 [00176] 94% 180 [00177] 51% .sup.[a]Major isomer is shown; .sup.[b]The time is extended for some substrates to 19 h in order to complete the reaction. The separated yield of isomers is summarized as a total yield; .sup.[c]The ratio of isomers is shown only for the procedure (1 or 2), which gives the highest yield.

[0119] Spectroscopic Data

Nitrobenzene (Compound of Formula 101)

[0120] ##STR00178##

[0121] Yield 99% (using the general procedure 1); yield 99% (using the general procedure 2); yellowish oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.16 (d, J=7.6 Hz, 2H), 7.68 (t, J=7.6 Hz, 1H), 7.52 (m, 2H); .sup.13C NMR (101 MHz, Chloroform-d) δ 147.88, 134.51, 129.11, 123.24.

1-Fluoro-4-nitrobenzene (Compound of Formula 102)

[0122] ##STR00179##

[0123] Yield 76.8% (using the general procedure 1); light yellow solid; mp 109-112° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.55-8.08 (m, 2H), 7.64-6.86 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 166.30 (d, J=257.9 Hz), 144.43, 126.35 (d, J=10.0 Hz), 116.44 (d, J=23.7 Hz); .sup.19F NMR (282 MHz, Chloroform-d) δ −102.00.

1-(Tert-butyl)-4-nitrobenzene (Compound of Formula 103)

[0124] ##STR00180##

[0125] Yield 84.6% (using the general procedure 1); light yellow solid; mp 99-102° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.50-7.99 (m, 2H), 7.86-7.34 (m, 2H), 1.36 (s, 9H); .sup.13C NMR (75 MHz, Chloroform-d) δ 158.88, 145.96, 126.26, 123.37, 35.43, 31.08.

1-Methoxy-4-nitrobenzene (Compound of Formula 104)

[0126] ##STR00181##

[0127] Yield 61% (using the general procedure 1); light yellow solid; mp 52-54° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.51-8.08 (m, 2H), 7.21-6.80 (m, 2H), 3.98 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 164.64, 141.61, 125.94, 114.05, 56.00.

1-Methyl-4-nitrobenzene (Compound of Formula 105)

[0128] ##STR00182##

[0129] Yield 49.7% (using the general procedure 1); light yellow solid; mp 51-53° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.09 (d, J=8.6 Hz, 2H), 7.31 (d, J=7.4 Hz, 2H), 2.45 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 146.19, 145.99, 129.83, 123.53, 21.62.

1-Bromo-4-nitrobenzene (Compound of Formula 106)

[0130] ##STR00183##

[0131] Yield 55.2% (using the general procedure 1); yellow solid; mp 123-125° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.10 (d, J=9.0 Hz, 2H), 7.69 (d, J=9.0 Hz, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 147.09, 132.66, 130.00, 125.04.

(4-Nitrophenyl)(trifluoromethyl)sulfane (Compound of Formula 107)

[0132] ##STR00184##

[0133] Yield 45% (using the general procedure 1, 19 hours); yield 52.9% (using the general procedure 2); yellowish oil; .sup.1H NMR (400 MHz, Chloroform-d) δ 8.40-8.12 (m, 2H), 7.83 (d, J=8.7 Hz, 2H); .sup.13C NMR (101 MHz, Chloroform-d) δ 149.15, 136.08, 132.56 (q, J=2.0 Hz), 128.94 (q, J=308.8 Hz), 124.35; .sup.19F NMR (376 MHz, Chloroform-d) δ −41.34.

1-Iodo-4-nitrobenzene (Compound of Formula 108)

[0134] ##STR00185##

[0135] Yield 63% (using the general procedure 1); yellow solid; mp 53-55° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.93 (d, J=9.0 Hz, 2H), 7.92 (d, J=9.0 Hz, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 147.83, 138.71, 124.88, 102.68.

1-Chloro-4-nitrobenzene (Compound of Formula 109)

[0136] ##STR00186##

[0137] Yield 57.6% (using the general procedure 1); yellowish solid; mp 82-84° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.19 (d, J=9.0 Hz, 2H), 7.52 (d, J=9.0 Hz, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 146.60, 141.42, 129.62, 124.97.

N,N-Dimethyl-4-nitroaniline (Compound of Formula 110)

[0138] ##STR00187##

[0139] Yield 54.6% (using the general procedure 1); yellow solid; mp 162-164° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.10 (d, J=9.4 Hz, 2H), 6.59 (d, J=9.4 Hz, 2H), 3.10 (s, 6H); .sup.13C NMR (75 MHz, Chloroform-d) δ 154.26, 136.97, 126.12, 110.26, 40.28.

1-Cyclopropyl-2-nitrobenzene (Compound of Formula 111)

[0140] ##STR00188##

[0141] Yield 31.3% (using the general procedure 1); white solid, mp 33-34° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.87 (d, J=8.1 Hz, 1H), 7.54 (t, J=7.6 Hz, 1H), 7.43-7.29 (m, 1H), 7.23 (d, J=7.8 Hz, 1H), 2.46 (ddd, J=13.9, 8.5, 5.4 Hz, 1H), 1.23-1.01 (m, 2H), 0.83-0.70 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 151.25, 138.05, 132.57, 127.96, 126.41, 124.08, 12.51, 8.08.

2-Nitro-1,1′-biphenyl (Compound of Formula 112)

[0142] ##STR00189##

[0143] Yield 59.4% (using the general procedure 1); yellow solid; mp 36-38° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.86 (d, J=8.0 Hz, 1H), 7.62 (td, J=7.5, 1.1 Hz, 1H), 7.55-7.38 (m, 5H), 7.38-7.29 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 149.39, 137.44, 136.40, 132.29, 132.00, 128.72, 128.27, 128.19, 127.94, 124.10.

Methyl 3-nitrobenzoate (Compound of Formula 113)

[0144] ##STR00190##

[0145] Yield 69.6% (using the general procedure 2); yellow crystalline compound; mp 77-79° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.86 (t, J=2.0 Hz, 1H), 8.39 (ddt, J=14.1, 7.8, 1.3 Hz, 2H), 7.65 (t, J=8.0 Hz, 1H), 3.99 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 164.99, 148.34, 135.29, 131.93, 129.66, 127.42, 124.65, 52.83.

3-Nitrobenzonitrile (Compound of Formula 114)

[0146] ##STR00191##

[0147] Yield 81% (using the general procedure 1, 19 hours); yield 92% (using the general procedure 2); yellow solid; 115-117° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.53 (t, J=1.9 Hz, 1H), 8.48 (ddd, J=8.3, 2.4, 1.2 Hz, 1H), 8.00 (dt, J=7.7, 1.4 Hz, 1H), 7.74 (t, J=8.0 Hz, 1H); .sup.13C NMR (75 MHz, Chloroform-d) δ 148.30, 137.64, 130.72, 127.57, 127.27, 116.57, 114.19.

1-Nitro-3-(trifluoromethyl)benzene (Compound of Formula 115)

[0148] ##STR00192##

[0149] Yield 59.8% (using the general procedure 1, 19 hours); yellow oil; yield 72% (using the general procedure 2); .sup.1H NMR (300 MHz, Chloroform-d) δ 8.50 (d, J=1.9 Hz, 1H), 8.44 (dd, J=8.3, 2.2 Hz, 1H), 7.98 (d, J=7.8 Hz, 1H), 7.74 (t, J=8.0 Hz, 1H); .sup.13C NMR (75 MHz, Chloroform-d) δ 148.33, 132.36 (q, J=34.1 Hz), 131.15 (q, J=3.5 Hz), 130.37, 126.69 (d, J=0.75 Hz), 122.73 (q, J=270.7 Hz), 120.87 (q, J=3.9 Hz); .sup.19F NMR (282 MHz, Chloroform-d) δ −62.95.

2-Fluoro-5-nitrobenzaldehyde (Compound of Formula 116)

[0150] ##STR00193##

[0151] Yield 75% (using the general procedure 1, 19 hours); yield 84% (using the general procedure 2); pale-orange solid; mp 58-60° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 10.37 (s, 1H), 8.74 (dd, J=5.9, 2.9 Hz, 1H), 8.49 (ddd, J=9.0, 4.4, 2.9 Hz, 1H), 7.40 (t, J=9.0 Hz, 1H); .sup.13C NMR (75 MHz, Chloroform-d) δ 184.84 (d, J=5.9 Hz), 167.30 (d, J=268.4 Hz), 144.86, 131.05 (d, J=11.0 Hz), 124.95 (d, J=4.1 Hz), 124.63 (d, J=10.5 Hz), 118.33 (d, J=23.2 Hz); .sup.19F NMR (282 MHz, Chloroform-d) δ −111.19 (dt, J=9.9, 5.2 Hz); IR (ATR, neat): 3076, 2899, 1693, 1619, 1523, 1470, 1346, 1226, 1070, 934, 744, 547.

4-Chloro-2-nitro-1-(trifluoromethoxy)benzene (Compound of Formula 117)

[0152] ##STR00194##

[0153] Yield 57.5% (using the general procedure 1, 19 hours); colorless oil; yield 60.6% (using the general procedure 2); .sup.1H NMR (500 MHz, Chloroform-d) δ 7.99 (d, J=2.5 Hz, 1H), 7.64 (dd, J=8.9, 2.6 Hz, 1H), 7.42 (dq, J=8.8, 1.4 Hz, 1H); .sup.13C NMR (126 MHz, Chloroform-d) δ 142.96, 139.83, 134.22, 133.38, 126.06, 124.50, 120.08 (q, J=261.4 Hz); .sup.19F NMR (471 MHz, Chloroform-d) 5-57.75.

1,3-Dichloro-2,4-dinitrobenzene (Compound of Formula 118)

[0154] ##STR00195##

[0155] Yield 37% (using the general procedure 1, 19 hours); yield 79% (using the general procedure 2); yellow solid; mp 70-72° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 8.03 (dd, J=8.9, 1.0 Hz, 1H), 7.65 (dd, J=8.9, 1.0 Hz, 1H); .sup.13C NMR (101 MHz, Chloroform-d) δ 149.49, 146.68, 130.94, 129.54, 126.75, 121.51.

Methyl 4-(tert-butyl)-3-nitrobenzoate (Compound of Formula 119)

[0156] ##STR00196##

[0157] Yield 62.1% (using the general procedure 1, 19 hours); yellow oil; yield 67.2% (using the general procedure 2); .sup.1H NMR (400 MHz, Chloroform-d) δ 8.07 (dd, J=8.4, 1.9 Hz, 1H), 7.97 (d, J=1.9 Hz, 1H), 7.64 (d, J=8.4 Hz, 1H), 3.93 (s, 3H), 1.42 (s, 9H); .sup.13C NMR (101 MHz, Chloroform-d) δ 164.91, 151.09, 146.21, 131.36, 129.13, 129.02, 125.06, 52.55, 36.12, 30.51.

1,3,5-Trimethoxy-2-nitrobenzene (Compound of Formula 120)

[0158] ##STR00197##

[0159] Yield 93% (using the general procedure 1); yellow crystalline compound; mp 151-153° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 6.11 (s, 2H), 3.85 (s, 6H), 3.83 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 162.21, 153.36, 126.56, 90.82, 56.44, 55.75.

2-Bromo-1,3,5-trimethyl-4-nitrobenzene (Compound of Formula 121)

[0160] ##STR00198##

[0161] Yield 96% (using the general procedure 1); yellow solid; mp 58-62° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.10 (s, 1H), 2.49 (s, 3H), 2.43 (s, 3H), 2.29 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 150.66, 140.61, 130.35, 129.62, 127.67, 125.47, 24.04, 18.95, 17.03.

1-Nitro-4-(trifluoromethoxy)benzene (Compound of Formula 122)

[0162] ##STR00199##

[0163] Yield 71.2% (using the general procedure 1, 19 hours); yellowish oil; yield 79.7% (using the general procedure 2, 19 hours); .sup.1H NMR (300 MHz, Chloroform-d) δ 8.59-8.02 (m, 2H), 7.64-7.27 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 153.67 (q, J=1.6 Hz), 146.02, 125.85, 121.00, 120.20 (q, J=258.7 Hz); .sup.19F NMR (282 MHz, Chloroform-d) 5-57.81.

4,4,5,5-Tetramethyl-2-(3-nitrophenyl)-1,3,2-dioxaborolane (Compound of Formula 123)

[0164] ##STR00200##

[0165] Yield 42.6% (using the general procedure 1); yellow solid; mp 73-74° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.73-8.55 (m, 1H), 8.33-8.24 (m, 1H), 8.09 (d, J=7.3 Hz, 1H), 7.53 (t, J=7.8 Hz, 1H), 1.36 (s, 12H); .sup.13C NMR (75 MHz, Chloroform-d) δ 147.90, 140.67, 129.43, 128.76, 125.87, 84.63, 24.91.

(3-Nitrophenyl)(phenyl)methanone (Compound of Formula 124)

[0166] ##STR00201##

[0167] Yield 40.8% (using the general procedure 1, 19 hours); light yellow solid; mp 94-96° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 8.62 (t, J=1.8 Hz, 1H), 8.45 (ddd, J=8.2, 2.2, 1.0 Hz, 1H), 8.14 (dt, J=7.6, 1.2 Hz, 1H), 7.87-7.76 (m, 2H), 7.71 (t, J=7.9 Hz, 1H), 7.66 (t, J=7.4 Hz, 1H), 7.53 (t, J=7.7 Hz, 2H), .sup.13C NMR (101 MHz, Chloroform-d) δ 194.16, 148.09, 139.07, 136.26, 135.44, 133.37, 130.01, 129.64, 128.74, 126.72, 124.72.

2,6-Dichloro-3-nitropyridine (Compound of Formula 125)

[0168] ##STR00202##

[0169] Yield 86% (using the general procedure 2); yellow solid; mp 53-55° C.; .sup.1H NMR (300 MHz, Acetonitrile-d.sub.3) δ 8.36 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.5 Hz, 1H); .sup.13C NMR (75 MHz, Acetonitrile-d.sub.3) δ 152.38, 143.54, 142.06, 137.28, 124.26, 116.91.

2,6-Dimethyl-3-nitropyridine (Compound of Formula 126)

[0170] ##STR00203##

[0171] Yield 82% (using the general procedure 2); yellow solid; mp 36-38° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.15 (d, J=8.3 Hz, 1H), 7.14 (d, J=8.3 Hz, 1H), 2.80 (s, 3H), 2.59 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 163.02, 153.32, 143.69, 132.87, 121.42, 24.71, 24.06.

2,4-Dichloro-5-nitropyrimidine (Compound of Formula 127)

[0172] ##STR00204##

[0173] Yield 76% (using the general procedure 2); yellow solid; 30-32° C.; .sup.1H NMR (400 MHz, Acetonitrile-d.sub.3) δ 9.25 (s, 1H); .sup.13C NMR (101 MHz, Acetonitrile-d.sub.3) δ 161.68, 157.53, 155.17, 142.15.

2,4-Dichloro-6-methyl-5-nitropyrimidine (Compound of Formula 128)

[0174] ##STR00205##

[0175] Yield 77% (using the general procedure 2); yellow solid; mp 50-52° C.; .sup.1H NMR (300 MHz, Acetonitrile-d.sub.3) δ 2.59 (d, J=1.0 Hz, 3H), .sup.13C NMR (75 MHz, Acetonitrile-d.sub.3) δ 164.68, 158.52, 152.68, 143.23.

2-Methyl-5-nitroisoindoline-1,3-dione (Compound of Formula 129)

[0176] ##STR00206##

[0177] Yield 86% (using the general procedure 2); yellow solid; mp 179-180° C.; .sup.1H NMR (300 MHz, Acetonitrile-d.sub.3) δ 8.58 (dd, J=8.1, 1.9 Hz, 1H), 8.53 (d, J=2.0 Hz, 1H), 8.03 (d, J=8.1 Hz, 1H), 3.15 (s, 3H); .sup.13C NMR (75 MHz, Acetonitrile-d.sub.3) b δ 166.24, 165.99, 151.50, 136.59, 133.41, 129.01, 123.78, 117.58, 23.44.

1-(2-Nitrophenyl)pyrrolidine-2,5-dione (Compound of Formula 130)

[0178] ##STR00207##

[0179] Yield 51.3% (using the general procedure 1, 19 hours); yield 51% (using the general procedure 2); yellow solid; mp 157-158° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.18 (d, J=8.2 Hz, 1H), 7.76 (t, J=7.7 Hz, 1H), 7.61 (t, J=7.9 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 2.98 (d, J=15 Hz, 2H), 2.92 (d, J=15 Hz, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 175.42, 145.29, 134.45, 130.57, 130.23, 126.17, 126.02, 28.90.

1-(5-Nitrofuran-2-yl)ethan-1-one (Compound of Formula 131)

[0180] ##STR00208##

[0181] Yield 77% (using the general procedure 1); yellow solid; mp 78-79° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.30 (d, J=3.8 Hz, 1H), 7.20 (d, J=3.8 Hz, 1H), 2.54 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 186.76, 151.95, 151.55, 116.75, 111.93, 26.32.

(R)-2,2′-dimethoxy-3-nitro-1,1′-binaphthalene (Compound of Formula 132)

[0182] ##STR00209##

[0183] Yield 64% (using the general procedure 1); yellow solid; mp 189-191° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.77 (d, J=2.3 Hz, 1H), 8.10 (d, J=9.1 Hz, 1H), 7.94 (d, J=9.1 Hz, 1H), 7.87 (dd, J=9.4, 2.3 Hz, 1H), 7.82 (d, J=8.2 Hz, 1H), 7.52 (d, J=9.0 Hz, 1H), 7.39 (d, J=9.0 Hz, 1H), 7.27 (ddd, J=8.1, 6.8, 1.3 Hz, 1H), 7.19-7.09 (m, 2H), 6.95 (d, J=8.5 Hz, 1H), 3.75 (s, 3H), 3.70 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 158.16, 154.95, 143.78, 136.94, 133.68, 131.87, 130.12, 129.23, 128.21, 127.25, 126.78, 126.74, 125.18, 124.65, 123.77, 120.13, 119.75, 117.95, 115.53, 113.89, 56.75, 56.64; IR (ATR, neat): 3062, 2934, 1616, 1509, 1462, 1334, 1265, 1149, 1060, 828, 743, 595; HRMS (ESI+) calcd (m/z) for C.sub.22H.sub.18NO.sub.4: [M.sup.+] 360.1225; found 360.1230.

12-Nitro-1,4(1,4)-dibenzenacyclohexaphane (Compound of Formula 133)

[0184] ##STR00210##

[0185] Yield 94% (using the general procedure 2); yellow solid; mp 155-157° C. .sup.1H NMR (500 MHz, Chloroform-d) δ 7.22 (d, J=1.9 Hz, 1H), 6.79 (dd, J=7.8, 1.9 Hz, 1H), 6.66-6.60 (m, 2H), 6.57 (qd, J=7.9, 1.9 Hz, 2H), 6.51-6.45 (m, 1H), 4.03 (ddd, J=13.3, 9.5, 2.0 Hz, 1H), 3.19 (tdt, J=12.8, 7.2, 3.1 Hz, 4H), 3.12-3.02 (m, 2H), 2.90 (ddd, J=13.3, 10.0, 7.1 Hz, 1H); .sup.13C NMR (126 MHz, Chloroform-d) δ 149.32, 142.08, 139.80, 139.32, 137.77, 137.35, 136.48, 133.20, 133.13, 132.42, 129.99, 129.57, 36.03, 35.01, 34.83, 34.47; IR (ATR, neat): 2924, 1602, 1516, 1482, 1330, 1180, 1094, 903, 804, 634, 507.

[0186] Colorless crystals of 1.sup.2-nitro-1,4(1,4)-dibenzenacyclohexaphane were obtained by slow evaporation from a saturated solution in ethyl acetate/hexane 1:1.

##STR00211##

[0187] Crystal data and structure refinement of 1.sup.2-nitro-1,4(1,4)-dibenzenacyclohexaphane:

TABLE-US-00004 Empirical formula C.sub.16H.sub.15NO.sub.2 Formula weight 253.29 Temperature/K 100.0 Crystal system Monoclinic Space group IT number 9 Space group name C 1 c 1 a/Å 14.308 (3) b/Å 7.3956 (16) c/Å 11.575 (2) α/° 90.0 β/° 91.230 (3) γ/° 90.0 Volume/Å.sup.3 1224.6 (4) Z 4 ρ.sub.calcg/cm.sup.3 1.374 μ/mm.sup.−1 0.091 F(000) 536.0 Crystal size/mm.sup.3 0.18 × 0.28 × 0.42 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 2.848 to 26.989 Index ranges −9 ≤ h ≤ 9, −14 ≤ k ≤ 14, −17 ≤ l ≤ 18 Reflections collected 6274 Independent reflections 2612 Data/restraints/parameters 173/0/2612 Goodness-of-fit on F.sup.2 1.056 Final R indexes [I >= 2σ (I)] R.sub.1 = 0.0659, wR.sub.2 = 0.1308 Final R indexes [all data] R.sub.1 = 0.0504, wR.sub.2 = 0.1450 Largest diff. peak/hole/e Å.sup.−3 0.418/−0.231

1-Nitronaphthalene (Compound of Formula 134)

[0188] ##STR00212##

[0189] Yield 94% (using the general procedure 1); light yellow solid, mp 56-59° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.57 (d, J=8.7 Hz, 1H), 8.24 (d, J=7.6 Hz, 1H), 8.12 (d, J=8.2 Hz, 1H), 7.96 (d, J=8.2 Hz, 1H), 7.73 (ddd, J=8.6, 6.9, 1.5 Hz, 1H), 7.63 (t, J=7.5 Hz, 1H), 7.55 (t, J=7.9 Hz, 1H); .sup.13C NMR (75 MHz, Chloroform-d) δ 134.68, 134.40, 129.49, 128.64, 127.39, 125.19, 124.18, 124.03, 123.18.

9-Nitroanthracene (Compound of Formula 135)

[0190] ##STR00213##

[0191] Yield 92% (using the general procedure 1); yellow solid, mp 145-147° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.55 (s, 1H), 8.02 (d, J=8.4 Hz, 2H), 7.93 (dd, J=8.8, 1.1 Hz, 2H), 7.62 (ddd, J=8.7, 6.7, 1.3 Hz, 2H), 7.52 (ddd, J=8.0, 6.7, 1.1 Hz, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 144.30, 130.80, 130.39, 128.89, 128.41, 126.21, 122.68, 121.40.

1-Chloro-4-((4-chlorophenyl)sulfonyl)-2-nitrobenzene (Compound of Formula 136)

[0192] ##STR00214##

[0193] Yield 72% (using the general procedure 2); white solid; mp 59-61° C.; .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.68 (d, J=2.2 Hz, 1H), 8.26 (dd, J=8.5, 2.3 Hz, 1H), 8.10-8.00 (m, 3H), 7.78-7.71 (m, 2H); .sup.13C NMR (101 MHz, DMSO-d.sub.6) δ 148.39, 141.05, 140.20, 138.79, 134.06, 132.62, 131.42, 130.61, 130.37, 125.39.

5,6-Dimethoxy-7-nitro-2,3-dihydro-1H-inden-1-one (Compound of Formula 137)

[0194] ##STR00215##

[0195] Yield 79% (using the general procedure 1, 19 hours); yellow solid; mp 146-148° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 7.03 (s, 1H), 4.00 (s, 3H), 3.90 (s, 3H), 3.29-2.96 (m, 2H), 2.90-2.56 (m, 2H); .sup.13C NMR (101 MHz, Chloroform-d) δ 200.25, 159.33, 152.87, 140.46, 139.90, 120.46, 110.20, 62.50, 56.88, 36.81, 25.90.

(13S)-3-Methoxy-13-methyl-4-nitro-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one (Compound of Formula 138)

[0196] ##STR00216##

[0197] Yield 78% (using the general procedure 1); yellow solid; mp 150-152° C.; .sup.1H NMR (500 MHz, Chloroform-d) δ 7.34 (d, J=8.8 Hz, 1H), 6.85 (d, J=8.8 Hz, 1H), 3.86 (s, 3H), 2.86-2.69 (m, 2H), 2.51 (dd, J=19.1, 8.8 Hz, 1H), 2.42-2.35 (m, 1H), 2.30-2.21 (m, 1H), 2.15 (dt, J=18.6, 8.9 Hz, 1H), 2.09-2.00 (m, 2H), 1.97 (dd, J=9.1, 2.6 Hz, 1H), 1.68-1.36 (m, 6H), 0.91 (s, 3H); .sup.13C NMR (126 MHz, Chloroform-d) δ 148.55, 141.67, 133.20, 128.86, 127.63, 109.91, 56.32, 50.16, 47.83, 43.83, 37.52, 35.80, 31.44, 25.96, 25.44, 23.92, 21.52, 13.81; IR (ATR, neat): 2929, 1729, 1619, 1514, 1450, 1267, 1014, 755; HRMS (ESI+) calcd (m/z) for C.sub.19H.sub.23NO.sub.4: [M−Na.sup.+] 352.1515; found 352.1519.

3,4-Dimethoxy-5-nitrobenzaldehyde (Compound of Formula 139)

[0198] ##STR00217##

[0199] Yield 91% (using the general procedure 1); light yellow solid; mp 61-62° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 10.46 (s, 1H), 7.62 (s, 1H), 7.43 (s, 1H), 4.04 (s, 3H), 4.03 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 187.81, 153.39, 152.58, 144.05, 125.72, 109.95, 107.35, 56.95, 56.89; HRMS (EI) calcd (m/z) for C.sub.9H.sub.9NO.sub.5: [M.sup.+] 211.04752; found 211.04744.

(1r,1′s,4R,4′R)-4-(3,4-Difluoro-2-nitrophenyl)-4′-propyl-1,1′-bi(cyclohexane) (Compound of Formula 140)

[0200] ##STR00218##

[0201] Yield 90% (using the general procedure 1); yellow solid; mp 67-69° C. .sup.1H NMR (300 MHz, Chloroform-d) δ 7.66 (dd, J=9.6, 7.3 Hz, 1H), 7.24 (dd, J=11.3, 7.6 Hz, 1H), 3.03 (t, J=11.8 Hz, 1H), 1.97-1.68 (m, 9H), 1.47-0.78 (m, 20H); .sup.13C NMR (75 MHz, Chloroform-d) δ 152.76 (dd, J=256.7, 12.4 Hz), 147.48 (dd, J=252.0, 14.1 Hz), 145.42-144.20 (m), 140.15 (dd, J=6.2, 4.1 Hz), 116.76 (d, J=19.1 Hz), 114.27 (dd, J=21.3, 1.9 Hz), 43.28, 42.88, 39.82, 38.95, 37.64, 34.15, 33.57, 30.10, 29.99, 20.08, 14.45; .sup.19F NMR (282 MHz, Chloroform-d) δ −128.75-−128.94 (m), −137.26 (ddd, J=21.7, 9.7, 7.7 Hz); IR (ATR, neat): 2916, 2847, 1600, 1529, 1508, 1445, 1356, 1298, 1186, 882, 804, 633; HRMS (EI) calcd (m/z) for C.sub.21H.sub.28NOF.sub.2: [M.sup.+] 348.21335; found 348.21286.

Methyl 2-(4-isobutyl-3-nitrophenyl)propanoate and methyl 2-(4-isobutyl-2-nitrophenyl)propanoate (Compound of Formula 141)

[0202] ##STR00219##

[0203] Total yield of two compounds 89% (using the general procedure 1, 19 hours); yellow oil; .sup.1H NMR (400 MHz, Chloroform-d) δ 7.80 (d, J=1.9 Hz, 2.5H), 7.70 (s, 1H), 7.44 (dd, J=8.0, 2.0 Hz, 2.5H), 7.36 (d, J=1.1 Hz, 2H), 7.25 (d, J=7.9 Hz, 2.5H), 4.28 (q, J=7.2 Hz, 1H), 3.77 (q, J=7.2 Hz, 2.5H), 3.68 (s, 7.5H), 3.66 (s, 3H), 2.75 (d, J=7.1 Hz, 5H), 2.53 (d, J=7.2 Hz, 2H), 1.89 (dt, J=13.5, 6.8 Hz, 3.5H), 1.58 (d, J=7.2 Hz, 3H), 1.53 (d, J=7.3 Hz, 7.5H), 0.91 (dd, J=6.6, 4.7 Hz, 21H); .sup.13C NMR (101 MHz, Chloroform-d) δ 174.13, 173.93, 149.91, 148.89, 142.40, 139.78, 135.29, 134.15, 133.05, 132.54, 131.60, 129.48, 125.22, 123.83, 52.42, 52.34, 44.75, 44.58, 41.52, 41.02, 30.08, 29.58, 22.57, 22.36, 18.47, 18.05. IR (ATR, neat): 2956, 1735, 1527, 1347, 1192, 1166, 1066, 854, 818, 678; HRMS (ESI+) calcd (m/z) for C.sub.14H.sub.19NNaO.sub.4: [M−Na.sup.+] 288.1200; found 288.1206.

(S)-2-(6-Methoxy-5-nitronaphthalen-2-Yl)propanoic acid (Compound of Formula 143)

[0204] ##STR00220##

[0205] Yield 90% (using the general procedure 1); yellow solid; mp 132-134° C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 12.42 (s, 1H), 8.22 (d, J=9.2 Hz, 1H), 7.95 (d, J=1.7 Hz, 1H), 7.69 (d, J=9.2 Hz, 1H), 7.64 (dd, J=8.8, 1.8 Hz, 1H), 7.56 (d, J=8.8 Hz, 1H), 4.04 (s, 3H), 3.88 (q, J=7.1 Hz, 1H), 1.47 (d, J=7.1 Hz, 3H); .sup.13C NMR (101 MHz, DMSO-d.sub.6) δ 175.50, 148.61, 138.64, 135.26, 132.94, 130.14, 128.15, 126.80, 124.04, 120.23, 114.82, 57.69, 44.88, 18.65; IR (ATR, neat): 2945, 1722, 1608, 1518, 1359, 1281, 1214, 1163, 1076, 903, 818, 641; HRMS (ESI+) calcd (m/z) for C.sub.14H.sub.14NO.sub.5: [M.sup.+] 276.0868; found 276.0866.

(R)-6-Methoxy-2,8-dimethyl-7-nitro-2-((4R,8R)-4,8,12-trimethyltridecyl)chromane (Compound of Formula 144)

[0206] ##STR00221##

[0207] Yield 75% (using the general procedure 1); yellow oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 6.71 (s, 1H), 3.82 (s, 3H), 2.68 (t, J=6.9 Hz, 2H), 2.19 (s, 3H), 1.77 (h, J=7.0 Hz, 2H), 1.56-1.11 (m, 24H), 0.88-0.85 (m, 12H); .sup.13C NMR (75 MHz, Chloroform-d) δ 145.45, 143.29, 138.88, 129.66, 113.65, 113.16, 75.93, 56.75, 39.46, 39.11, 37.17, 37.14, 37.09, 37.02, 32.53, 32.41, 29.87, 27.71, 24.53, 24.18, 23.60, 22.45, 22.35, 20.64, 19.48, 19.35, 18.07, 16.34; IR (ATR, neat): 2924, 1529, 1476, 1375, 1239, 1102, 1016, 911, 809; HRMS (ESI+) calcd (m/z) for C.sub.28H.sub.47NO.sub.4: [M.sup.+] 461.3500; found 461.3500.

2-Nitro-1-(4-nitrophenoxy)-4-(trifluoromethyl)benzene (Fluorodifen) (Compound of Formula 145)

[0208] ##STR00222##

[0209] Yield 82.5% (using the general procedure 1, 19 hours); yellow solid; mp 94-96° C. .sup.1H NMR (300 MHz, Chloroform-d) δ 8.39-8.23 (m, 3H), 7.89 (dd, J=8.8, 2.2 Hz, 1H), 7.30 (d, J=8.7 Hz, 1H), 7.20-7.08 (m, 2H); .sup.13C NMR (126 MHz, Chloroform-d) δ 160.62, 151.06, 144.53, 141.82, 133.97-130.25 (m), 128.06 (q, J=34.8 Hz), 126.44, 124.11 (q, J=3.7 Hz), 123.00, 122.48 (q, J=273.3 Hz), 118.53; .sup.19F NMR (282 MHz, Chloroform-d) 5-62.47; IR (ATR, neat): 2916, 1600, 1586, 1533, 1347, 1322, 1230, 902, 804, 747, 633; HRMS (EI) calcd (m/z) for C.sub.13H.sub.7N.sub.2F.sub.3O.sub.5: [M.sup.+] 328.03016; found 328.03004.

[0210] Colorless crystals of 2-nitro-1-(4-nitrophenoxy)-4-(trifluoromethyl)benzene were obtained by slow evaporation from a saturated solution in ethyl acetate/hexane 1:1.

[0211] Crystal data and structure refinement of 2-Nitro-1-(4-nitrophenoxy)-4-(trifluoromethyl)benzene:

TABLE-US-00005 Empirical formula C.sub.13H.sub.7N.sub.2O.sub.5F.sub.3 Formula weight 328.21 Temperature/K 100.0 Crystal system Monoclinic Space group IT number 15 Space group name P 1 21/c 1 a/Å 21.4056 (18) b/Å 12.0113 (10) c/Å 10.2695 (9) α/° 90.0 β/° 91.143 (2) γ/° 90.0 Volume/Å.sup.3 2639.9 (4) Z 8 ρ.sub.calcg/cm.sup.3 1.652 μ/mm.sup.−1 0.155 F(000) 1328.0 Crystal size/mm.sup.3 0.1 × 0.28 × 0.49 Radiation MoKα (λ = 0.71073) 2Θ range for data collection/° 0.951 to 27.995 Index ranges −13 ≤ h ≤ 13, −15 ≤ k ≤ 15, −28 ≤ l ≤ 28 Reflections collected 38576 Independent reflections 6295 Data/restraints/parameters 415/0/6295 Goodness-of-fit on F.sup.2 1.101 Final R indexes [I >= 2σ (I)] R.sub.1 = 0.0962, wR.sub.2 = 0.1182 Final R indexes [all data] R.sub.1 = 0.0491, wR.sub.2 = 0.1630 Largest diff. peak/hole/e Å.sup.−3 0.258/−0.354

Ethyl 2-(4-chloro-2-nitrophenoxy)-2-methylpropanoate (Compound of Formula 146)

[0212] ##STR00223##

[0213] Yield 98% (using the general procedure 1); light yellow oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.74 (d, J=2.5 Hz, 1H), 7.39 (dd, J=9.0, 2.5 Hz, 1H), 6.95 (d, J=9.0 Hz, 1H), 4.24 (q, J=7.1 Hz, 2H), 1.64 (s, 6H), 1.26 (t, J=7.1 Hz, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 173.22, 147.58, 143.27, 132.82, 127.16, 125.16, 121.43, 82.10, 61.94, 25.09, 14.09; IR (ATR, neat): 2988, 1735, 1604, 1531, 1478, 1384, 1354, 1281, 1176, 1100, 1019, 882, 843, 655; HRMS (ESI+) calcd (m/z) for C.sub.12H.sub.14NO.sub.5ClNa: [M−Na.sup.+] 310.0449; found 310.0453.

2-(Diethylamino)-N-(2,6-dimethyl-3-nitrophenyl)acetamide (Compound of Formula 147)

[0214] ##STR00224##

[0215] Yield 71% (using the general procedure 1, 19 hours); yellow oil; .sup.1H NMR (400 MHz, Chloroform-d) δ 9.08 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.20 (d, J=8.4 Hz, 1H), 3.24 (s, 2H), 2.71 (q, J=7.1 Hz, 4H), 2.38 (s, 3H), 2.29 (s, 3H), 1.14 (t, J=7.1 Hz, 6H); .sup.13C NMR (101 MHz, Chloroform-d) δ 170.52, 148.99, 141.23, 135.91, 130.72, 128.15, 123.01, 57.38, 48.97, 19.21, 14.87, 12.58. IR (ATR, neat): 3260, 2969, 1673, 1518, 1485, 1343, 1290, 1203, 1088, 824, 747, 503; HRMS (ESI+) calcd (m/z) for C.sub.14H.sub.22N.sub.3O.sub.3: [M.sup.+] 280.1652; found 280.1656.

1-Cyclopropyl-4-nitrobenzene (Compound of Formula 148)

[0216] ##STR00225##

[0217] Yield 65.7% (using the general procedure 1); light yellow oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.42-7.91 (m, 2H), 7.26-6.96 (m, 2H), 2.24-1.74 (m, 1H), 1.27-1.03 (m, 2H), 0.94-0.69 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 152.64, 145.88, 125.97, 123.67, 15.89, 11.04.

1-Fluoro-2-nitrobenzene (Compound of Formula 149)

[0218] ##STR00226##

[0219] Yield 19.2% (using the general procedure 1); yellowish oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.23-8.05 (m, 1H), 7.76-7.60 (m, 1H), 7.54-7.25 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 155.60 (d, J=264.8 Hz), 137.55, 135.63 (d, J=8.6 Hz), 126.16 (d, J=2.8 Hz), 124.61 (d, J=4.4 Hz), 118.47 (d, J=20.6 Hz); .sup.19F NMR (282 MHz, Chloroform-d) δ −117.65.

1-(tert-Butyl)-2-nitrobenzene (Compound of Formula 150)

[0220] ##STR00227##

[0221] Yield 9.4% (using the general procedure 1); yellowish oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.58-7.44 (m, 1H), 7.36 (ddd, J=8.2, 6.3, 2.4 Hz, 1H), 7.30-7.12 (m, 2H), 1.34 (s, 9H); .sup.13C NMR (75 MHz, Chloroform-d) δ 151.34, 141.30, 130.76, 128.62, 126.87, 123.91, 35.71, 30.72.

1-Methoxy-2-nitrobenzene (Compound of Formula 151)

[0222] ##STR00228##

[0223] Yield 33% (using the general procedure 1); yellowish oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.83 (dd, J=8.1, 1.7 Hz, 1H), 7.54 (ddd, J=8.4, 7.4, 1.7 Hz, 1H), 7.20-6.92 (m, 2H), 3.95 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 153.00, 134.23, 125.70, 120.31, 113.56, 56.52.

1-Methyl-2-nitrobenzene (Compound of Formula 152)

[0224] ##STR00229##

[0225] Yield 45.3% (using the general procedure 1); yellowish oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.95 (d, J=8.2 Hz, 1H), 7.49 (t, J=7.4 Hz, 1H), 7.40-7.27 (m, 2H), 2.59 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 149.32, 133.54, 133.01, 132.77, 126.90, 124.63, 20.39.

4-Nitro-1,1′-biphenyl (Compound of Formula 153)

[0226] ##STR00230##

[0227] Yield 39.6% (using the general procedure 1); yellow solid; mp 113-114° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.30 (d, J=8.8 Hz, 2H), 7.74 (d, J=8.8 Hz, 2H), 7.69-7.58 (m, 2H), 7.58-7.39 (m, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 147.68, 147.15, 138.84, 129.19, 128.95, 127.84, 127.43, 124.15.

4,4,5,5-Tetramethyl-2-(2-nitrophenyl)-1,3,2-dioxaborolane (Compound of Formula 154)

[0228] ##STR00231##

[0229] Yield 38.4% (using the general procedure 1); orange oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.14 (d, J=8.1 Hz, 1H), 7.71-7.60 (m, 1H), 7.60-7.46 (m, 2H), 1.42 (s, 12H); .sup.13C NMR (75 MHz, Chloroform-d) δ 151.01, 133.75, 132.88, 130.08, 123.00, 84.65, 24.77.

1-Nitro-2-(trifluoromethyl)benzene (Compound of Formula 155)

[0230] ##STR00232##

[0231] Yield 12.2% (using the general procedure 1, 19 hours); yellow oil; yield 15% (using the general procedure 2); .sup.1H NMR (300 MHz, Chloroform-d) δ 7.95-7.78 (m, 2H), 7.80-7.67 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 148.26, 133.14, 132.58, 127.97 (q, J=5.2 Hz), 125.00, 123.81 (q, J=33.7 Hz), 122.06 (q, J=271.5 Hz); .sup.19F NMR (282 MHz, Chloroform-d) δ −60.01.

1-Bromo-2-nitrobenzene (Compound of Formula 156)

[0232] ##STR00233##

[0233] Yield 36.8% (using the general procedure 1); yellow solid; mp 42-44° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.84 (dd, J=7.5, 2.3 Hz, 1H), 7.75 (dt, J=8.3, 1.9 Hz, 1H), 7.56-7.37 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 149.94, 135.12, 133.21, 128.27, 125.63, 114.51.

1-Nitro-2-(trifluoromethoxy)benzene (Compound of Formula 157)

[0234] ##STR00234##

[0235] Yield 14.8% (using the general procedure 1, 19 hours); yellowish oil; yield 17.3% (using the general procedure 2, 19 hours); .sup.1H NMR (300 MHz, Chloroform-d) δ 7.99 (dd, J=8.4, 1.7 Hz, 1H), 7.67 (td, J=7.8, 1.7 Hz, 1H), 7.56-7.39 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 142.85, 141.35 (q, J=2.0 Hz), 134.25, 127.61, 125.95, 123.26, 120.24 (q, J=260.6 Hz); .sup.19F NMR (282 MHz, Chloroform-d) δ −57.58.

(2-Nitrophenyl)(trifluoromethyl)sulfane (Compound of Formula 158)

[0236] ##STR00235##

[0237] Yield 41% (using the general procedure 1, 19 hours); yield 44.1% (using the general procedure 2); yellowish oil; .sup.1H NMR (400 MHz, Chloroform-d) δ 8.12 (dd, J=8.2, 1.4 Hz, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.68 (td, J=7.8, 1.4 Hz, 1H), 7.55 (td, J=7.9, 1.2 Hz, 1H); .sup.13C NMR (101 MHz, Chloroform-d) δ 149.29, 133.70, 132.72-131.91 (m), 129.42, 188.66 (q, J=311.0 Hz), 125.70, 124.37-124.06 (m); .sup.19F NMR (376 MHz, Chloroform-d) δ −41.23.

1-(4-Nitrophenyl)pyrrolidine-2,5-dione (Compound of Formula 159)

[0238] ##STR00236##

[0239] Yield 42.7% (using the general procedure 1, 19 hours); yield 46% (using the general procedure 2); yellow solid; mp 208-209° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.41 (d, J=8.9 Hz, 2H), 7.67 (d, J=8.9 Hz, 2H), 3.03 (s, 4H); .sup.13C NMR (75 MHz, Chloroform-d) δ 175.35, 147.16, 137.53, 127.00, 124.54, 28.56.

1-Chloro-2-nitrobenzene (Compound of Formula 160)

[0240] ##STR00237##

[0241] Yield 38.4% (using the general procedure 1); yellowish solid; mp 32-33° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.87 (dd, J=8.0, 1.6 Hz, 1H), 7.63-7.47 (m, 2H), 7.42 (ddd, J=8.7, 6.9, 2.0 Hz, 1H); .sup.13C NMR (75 MHz, Chloroform-d) δ 148.28, 133.16, 131.93, 127.60, 127.13, 125.60.

N,N-Dimethyl-2-nitroaniline (Compound of Formula 161)

[0242] ##STR00238##

[0243] Yield 36.4% (using the general procedure 1); yellow oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.70 (d, J=2.7 Hz, 1H), 8.21 (dd, J=9.5, 2.7 Hz, 1H), 7.01 (d, J=9.4 Hz, 1H), 3.06 (s, 6H); .sup.13C NMR (75 MHz, Chloroform-d) δ 149.16, 136.56, 135.85, 127.80, 124.22, 116.63, 42.45.

(4-Nitrophenyl)(phenyl)methanone (Compound of Formula 162)

[0244] ##STR00239##

[0245] Yield 24.5% (using the general procedure 1, 19 hours); light yellow solid; mp 136-139° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 8.35 (d, J=8.6 Hz, 2H), 7.94 (d, J=8.6 Hz, 2H), 7.80 (d, J=8.3 Hz, 2H), 7.66 (t, J=7.4 Hz, 1H), 7.53 (t, J=7.8 Hz, 2H); .sup.13C NMR (101 MHz, Chloroform-d) δ 194.79, 149.84, 142.89, 136.29, 133.47, 130.70, 130.10, 128.69, 123.55.

1-Chloro-2-nitro-4-(trifluoromethoxy)benzene (Compound of Formula 163)

[0246] ##STR00240##

[0247] Yield 34.5% (using the general procedure 1, 19 hours); colorless oil; yield 36.4% (using the general procedure 2); .sup.1H NMR (500 MHz, Chloroform-d) δ 7.78 (d, J=2.8 Hz, 1H), 7.62 (d, J=8.9 Hz, 1H), 7.41 (ddd, J=8.9, 2.9, 1.0 Hz, 1H); .sup.13C NMR (126 MHz, Chloroform-d) δ 148.13, 147.46 (q, J=2.3 Hz), 133.23, 125.65, 125.52, 120.14 (q, J=260.3 Hz), 118.50; .sup.19F NMR (471 MHz, Chloroform-d) δ −58.30.

Methyl 4-(tert-butyl)-2-nitrobenzoate (Compound of Formula 164)

[0248] ##STR00241##

[0249] Yield 24.9% (using the general procedure 1, 19 hours); light yellow oil; yield 26.8% (using the general procedure 2); .sup.1H NMR (400 MHz, Chloroform-d) δ 7.86 (d, J=1.7 Hz, 1H), 7.73-7.61 (m, 2H), 3.90 (s, 3H), 1.36 (s, 9H); .sup.13C NMR (101 MHz, Chloroform-d) δ 165.80, 156.50, 148.64, 129.83, 129.67, 124.30, 120.92, 53.11, 35.39, 30.89.

(2-Nitrophenyl)(phenyl)methanone (Compound of Formula 165)

[0250] ##STR00242##

[0251] Yield 32.7% (using the general procedure 1, 19 hours); light yellow solid; mp 104-106° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 8.24 (d, J=8.2 Hz, 1H), 7.76 (dd, J=11.4, 8.0 Hz, 3H), 7.68 (t, J=7.8 Hz, 1H), 7.59 (t, J=7.4 Hz, 1H), 7.54-7.41 (m, 3H); .sup.13C NMR (101 MHz, Chloroform-d) δ 193.43, 146.72, 136.24, 135.92, 134.16, 133.82, 130.52, 129.24, 128.91, 128.78, 124.48.

1-Iodo-2-nitrobenzene (Compound of Formula 166)

[0252] ##STR00243##

[0253] Yield 30% (using the general procedure 1); yellow oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.98 (dd, J=7.9, 1.3 Hz, 1H), 7.79 (dd, J=8.1, 1.5 Hz, 1H), 7.42 (td, J=7.8, 1.3 Hz, 1H), 7.33-7.11 (m, 1H); .sup.13C NMR (75 MHz, Chloroform-d) δ 153.13, 141.95, 133.39, 129.08, 125.46, 86.23.

Methyl 2-nitrobenzoate (Compound of Formula 167)

[0254] ##STR00244##

[0255] Yield 17.4% (using the general procedure 2); yellow oil; .sup.1H NMR (300 MHz, Chloroform-d) δ 7.91 (dd, J=7.4, 1.9 Hz, 1H), 7.83-7.72 (m, 1H), 7.65 (pd, J=7.4, 1.7 Hz, 2H), 3.92 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 165.89, 148.31, 132.92, 131.79, 129.90, 127.64, 123.96, 53.30.

(13S)-3-Methoxy-13-methyl-2-nitro-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one (Compound of Formula 168)

[0256] ##STR00245##

[0257] Yield 13% (using the general procedure 1); yellow solid; mp 244-248° C.; .sup.1H NMR (500 MHz, Chloroform-d) δ 7.84 (s, 1H), 6.80 (s, 1H), 3.94 (s, 3H), 2.97 (p, J=11.4 Hz, 2H), 2.54 (dd, J=19.1, 8.7 Hz, 1H), 2.45-2.38 (m, 1H), 2.32-2.22 (m, 1H), 2.17 (dt, J=18.7, 8.9 Hz, 1H), 2.12-2.05 (m, 2H), 2.01 (d, J=12.3 Hz, 1H), 1.71-1.47 (m, 6H), 0.94 (s, 3H); .sup.13C NMR (126 MHz, Chloroform-d) δ 151.16, 144.39, 137.36, 132.42, 123.12, 113.58, 56.49, 50.26, 47.87, 43.48, 37.86, 35.79, 31.33, 29.81, 26.07, 25.72, 21.54, 13.81; IR (ATR, neat): 2917, 1728, 1526, 1491, 1404, 1377, 1282, 1074, 856, 816, 657; HRMS (ESI+) calcd (m/z) for C.sub.19H.sub.23NO.sub.4: [M−Na.sup.+]352.1515; found 352.1519.

2,4-Dinitro-1-(4-(trifluoromethyl)phenoxy)benzene (Compound of Formula 169)

[0258] ##STR00246##

[0259] Yield 5.5% (using the general procedure 1, 19 hours); white solid; mp 114-116° C. .sup.1H NMR (300 MHz, Chloroform-d) δ 8.91 (d, J=2.7 Hz, 1H), 8.42 (dd, J=9.2, 2.7 Hz, 1H), 7.78 (d, J=8.5 Hz, 2H), 7.31-7.24 (m, 2H), 7.16 (d, J=9.2 Hz, 1H); .sup.13C NMR (75 MHz, Chloroform-d) δ 156.80, 154.79, 142.59, 140.48, 129.08, 128.68 (d, J=33.2 Hz), 128.24 (q, J=3.6 Hz), 123.77 (q, J=270.7 Hz), 122.35, 120.35, 119.92; .sup.19F NMR (282 MHz, Chloroform-d) δ −62.23; IR (ATR, neat): 3095, 1601, 1532, 1508, 1349, 1317, 1270, 1123, 1063, 833, 676, 638; HRMS (EI) calcd (m/z) for C.sub.13H.sub.7N.sub.2F.sub.3O.sub.5: [M.sup.+] 328.03016; found 328.03004.

2,6-Dihydroxy-3-nitrobenzoic acid (Compound of Formula 170)

[0260] ##STR00247##

[0261] Yield 88%, 88 mg (using the general procedure I); yellow solid; mp 215.5-217.0° C.; .sup.1H NMR (400 MHz, Acetone-d.sub.6) δ 14.95 (s, 1H), 8.00 (d, J=9.4 Hz, 1H), 6.24 (d, J=9.4 Hz, 1H), 3.45 (bs, 2H); .sup.13C NMR (101 MHz, Acetone-d.sub.6) δ 176.8, 169.7, 162.7, 131.1, 129.4, 106.6, 104.5; IR (ATR, neat): 3436, 1718, 1595, 1450, 1249, 1145, 922, 824, 755, 590; HRMS (ESI+) calcd (m/z) for C.sub.7H.sub.4NO.sub.6: [M−H] 198.0044; found 198.0049.

4-Chloro-3-nitrophenol [CAS: 610-78-6] (Compound of Formula 171)

[0262] ##STR00248##

[0263] Yield 93%, 81 mg (using the general procedure I); yellow solid; mp 126° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 10.47 (s, 1H), 8.11 (d, J=2.6 Hz, 1H), 7.54 (dd, J=9.0, 2.6 Hz, 1H), 7.14 (d, J=9.0 Hz, 1H); .sup.13C NMR (75 MHz, Chloroform-d) δ 153.7, 137.6, 125.3, 124.4, 121.5.

Cyclopropyl(5-nitrothiophen-2-yl)methanone [CAS: 1330049-33-6] (Compound of Formula 172)

[0264] ##STR00249##

[0265] Yield 84%, 83 mg (using the general procedure I, 19 hours); white solid; mp 104-105° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.52 (d, J=1.4 Hz, 1H), 8.29 (d, J=1.5 Hz, 1H), 2.55 (tt, J=7.7, 4.5 Hz, 1H), 1.35-1.24 (m, 2H), 1.21-1.08 (m, 2H); .sup.13C NMR (75 MHz, Chloroform-d) δ 192.2, 145.4, 132.9, 125.1, 17.9, 12.4.

Phenytoin-NO.SUB.2 .(Compound of Formula 173)

[0266] ##STR00250##

[0267] Total yield of isomers 98%, 145.5 mg (using the general procedure 1); white solid, mp 235-240° C.; .sup.1H NMR of left molecule (500 MHz, DMSO-d.sub.6) δ 11.3 (s, 1H), 9.51 (s, 1H), 8.29 (d, J=10.0 Hz, 2H), 7.67 (d, J=10.0 Hz, 2H); 7.43-7.34 (m, 5H); .sup.1H NMR of middle molecule (500 MHz, DMSO-d.sub.6) δ 11.3 (s, 1H), 9.5 (s, 1H), 8.30-8.24 (m, 2H), 7.88 (d, J=10.0 Hz, 1H), 7.74 (t, 10.0 Hz, 1H), 7.43-7.34 (m, 5H), .sup.1H NMR of right molecule (500 MHz, DMSO-d.sub.6) δ 11.1 (s, 1H), 9.3 (s, 1H), 8.11 (d, J=5.0 Hz, 1H), 7.97 (t, J=5.0 Hz, 1H), 7.98-7.91 (m, J=5.0 Hz, 3H), 7.43-7.34 (m, 5H). .sup.13C NMR of mixture (125 MHz, Chloroform-d) δ 175.3, 174.57, 174.41, 156.44, 156.27, 148.2, 147.6, 147.0, 142.0, 140.4, 135.55, 134.89, 133.8, 130.8, 129.3, 129.2, 128.95, 128.93, 129.91, 128.52, 128.47, 127.0, 126.9, 125.1, 123.2, 123.7, 121.5, 121.4, 70.6, 70.5, 70.1; IR (ATR, neat): 3048, 1771, 1714, 1519, 1347, 1225, 1095, 852, 691; HRMS (ESI+) calcd (m/z) for C.sub.15H.sub.11N.sub.3O.sub.4Na: [M+Na.sup.+] 320.0642; found 320.0642.

Nimesulide-NO.SUB.2 .(Compound of Formula 174)

[0268] ##STR00251##

[0269] Yield of left molecule 76.1%, 134 mg (using the general procedure I); yellow solid, mp 177.2-178.0° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 10.36 (s, 1H), 8.54-8.24 (m, 2H), 8.18 (dd, J=9.1, 2.6 Hz, 1H), 7.96 (d, J=2.6 Hz, 1H), 7.82 (d, J=9.1 Hz, 1H), 7.26 (d, J=9.2 Hz, 2H), 3.18 (s, 3H); .sup.13C NMR (101 MHz, Chloroform-d) δ 166.67, 149.31, 148.33, 148.26, 142.28, 131.20, 126.79, 123.33, 121.74, 46.12; IR (ATR, neat): 3264, 1717, 1586, 1509, 1336, 1226, 1160, 965, 897, 744, 514; HRMS (ESI+) calcd (m/z) for C.sub.13H.sub.1N.sub.3NaO.sub.7S: [M+Na] 376.0212; found 376.0214.

[0270] Yield of right molecule 23%, 40.5 mg (using the general procedure 1); yellow-red solid, mp 173.1-173.6° C.; .sup.1H NMR (300 MHz, Chloroform-d) δ 8.16 (dd, J=8.2, 1.6 Hz, 1H), 8.06 (dd, J=9.0, 2.4 Hz, 1H), 7.85 (d, J=9.0 Hz, 1H), 7.77 (td, J=8.2, 1.6 Hz, 1H), 7.60 (s, 1H), 7.57 (d, J=2.4 Hz, 1H), 7.56-7.46 (m, 1H), 7.33 (dd, J=8.2, 1.1 Hz, 1H), 3.19 (s, 3H); .sup.13C NMR (75 MHz, Chloroform-d) δ 147.1, 145.5, 143.6, 141.3, 135.7, 134.3, 127.1, 126.9, 123.4, 120.5, 117.9, 111.1, 40.5; IR (ATR, neat): 3263, 1599, 1517, 1336, 1267, 1186, 1160, 952, 738, 516; HRMS (ESI+) calcd (m/z) for C.sub.13H.sub.11N.sub.3NaO.sub.7S: [M+Na] 376.0212; found 376.0212.

Secinidazole [CAS: 3366-95-8] (Compound of Formula 175)

[0271] ##STR00252##

[0272] Yield 44%, 41 mg (using the general procedure II, 19 hours); white solid, mp 80.5-81.5° C.; .sup.1H NMR (300 MHz, Acetonitrile-d.sub.3) δ 7.91 (s, 1H), 4.60-4.21 (m, 1H), 4.21-3.90 (m, 2H), 3.26 (s, 1H), 2.46 (s, 3H), 1.23 (d, J=5.9 Hz, 3H); .sup.13C NMR (101 MHz, Acetonitrile-d.sub.3) δ 151.6, 138.6, 132.3, 66.0, 52.4, 19.7, 13.7; IR (ATR, neat): 3503, 3136, 1526, 1447, 1388, 1352, 1181, 1083, 932, 839, 741, 490; HRMS (ESI+) calcd (m/z) for C.sub.7H.sub.12N.sub.3O.sub.3: [M+H] 186.0873; found 186.0877.

Ethyl 1-(4-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate and ethyl 1-(2-nitrophenyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Compound of Formula 176)

[0273] ##STR00253##

[0274] Yield of left molecule 83%, 136.5 mg (using the general procedure II); yellow solid; mp 115.3-116.5° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 8.41 (d, J=9.0 Hz, 2H), 7.75-7.59 (m, 2H), 4.41 (q, J=7.1 Hz, 2H), 1.41 (t, J=7.1 Hz, 3H); .sup.13C NMR (101 MHz, Chloroform-d) δ 160.5, 148.2, 143.9, 143.3, 132.74 (q, J=40.5 Hz), 126.8, 124.6, 118.95 (q, J=271.7 Hz), 117.9 (q, J=1.1 Hz), 61.6, 14.1; .sup.19F NMR (376 MHz, Chloroform-d) δ −54.94; IR (ATR, neat): 1735, 1523, 1345, 1224, 1151, 1018, 970, 855, 756, 704; HRMS (ESI+) calcd (m/z) for C.sub.13H.sub.11F.sub.3N.sub.3O.sub.4: [M+H] 330.0696; found 330.0697.

[0275] Yield of right molecule 10%, 16.5 mg (using the general procedure II); yellow solid; mp 119-120° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 8.23 (dd, J=8.0, 1.7 Hz, 1H), 8.20-8.15 (m, 1H), 7.88-7.71 (m, 2H), 7.56 (dd, J=7.7, 1.6 Hz, 1H), 4.41 (q, J=7.1 Hz, 2H), 1.41 (t, J=7.1 Hz, 3H); .sup.13C NMR (101 MHz, Chloroform-d) δ 160.5 (q, J=1.0 Hz), 144.9, 143.5, 134.3 (q, J=40.3 Hz), 133.9, 132.9, 131.4, 129.7 (q, J=1.0 Hz), 125.7, 118.9 (q, J=271.6 Hz), 116.9 (q, J=1.5 Hz), 61.4, 14.1; .sup.19F NMR (376 MHz, Chloroform-d) δ −56.66; IR (ATR, neat): 2914, 1724, 1565, 1385, 1249, 1145, 1067, 972, 752; HRMS (ESI+) calcd (m/z) for C.sub.13H.sub.10F.sub.3N.sub.3O.sub.4Na: [M+Na]352.0516; found 352.0515.

Procymidone-NO.SUB.2 .(Compound of Formula 177)

[0276] ##STR00254##

[0277] Yield 91%, 150 mg (using the general procedure I, 19 hours); yellow solid; mp 199.3-200.0° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 7.58 (d, J=2.1 Hz, 1H), 7.33 (s, 1H), 1.91 (d, J=4.8 Hz, 1H), 1.48 (s, 6H), 1.22 (d, J=4.8 Hz, 1H); .sup.13C NMR (101 MHz, Chloroform-d) δ 174.7, 144.5, 137.5, 131.1, 129.0, 128.4, 127.1, 32.6, 30.7, 9.9; IR (ATR, neat): 3074, 1780, 1720, 1571, 1442, 1360, 1143, 1143, 1110, 806, 731, 522; HRMS (ESI+) calcd (m/z) for C.sub.13H.sub.10F.sub.3N.sub.3O.sub.4Na: [M+H] 329.009; found 329.0089.

Arbutin Peracetate-NO.SUB.2 .(Compound of Formula 178)

[0278] ##STR00255##

[0279] Yield 74%, 195 mg (using the general procedure II); yellow solid, mp 149.6-150.0° C.; .sup.1H NMR (300 MHz, Acetonitrile-d.sub.3) δ 7.63 (d, J=2.7 Hz, 1H), 7.52-7.34 (m, 2H), 5.42-5.31 (m, 2H), 5.30-5.11 (m, 2H), 4.24 (qd, J=12.4, 3.9 Hz, 2H), 4.15-4.02 (m, 1H), 2.29 (d, J=3.3 Hz, 3H), 2.09-1.93 (m, 15H); .sup.13C NMR (75 MHz, Acetonitrile-d.sub.3) δ 169.9, 169.5, 169.2, 168.9, 168.9, 146.4, 145.2, 140.4, 127.3, 119.2, 118.2, 99.2, 71.8, 71.6, 69.9, 67.6, 61.2, 19.8, 19.6, 19.6, 19.5, 19.5; IR (ATR, neat): 1751, 1533, 1366, 1227, 1185, 1038, 926, 597; HRMS (ESI+) calcd (m/z) for C.sub.22H.sub.25KNO.sub.14: [M+K] 566.0907; found 566.0898.

Nordihydrocapsaicin-NO.SUB.2 .(Compound of Formula 179)

[0280] ##STR00256##

[0281] Yield 94%, 159 mg (using the general procedure I); yellow solid; mp 121.5-122.5° C.; .sup.1H NMR (400 MHz, Chloroform-d) δ 10.72 (s, 1H), 7.57 (d, J=1.9 Hz, 1H), 7.12 (d, J=1.9 Hz, 1H), 5.99 (s, 1H), 4.41 (d, J=6.0 Hz, 2H), 3.94 (s, 3H), 2.26 (t, J=7.6 Hz, 2H), 1.67 (p, J=7.4 Hz, 2H), 1.39-1.21 (m, 11H), 0.88 (t, J=6.8 Hz, 3H); .sup.13C NMR (101 MHz, Chloroform-d) δ 173.3, 150.2, 145.7, 133.4, 130.2, 117.5, 114.2, 56.7, 42.7, 36.7, 31.8, 29.3, 29.1, 25.7, 22.6, 14.1; IR (ATR, neat): 3296, 2920, 2847, 1642, 1532, 1327, 1268, 1220, 1130, 1060, 857, 689; HRMS (ESI+) calcd (m/z) for C.sub.17H.sub.30N.sub.3O.sub.5: [M+NH.sub.4] 356.2180; found 356.2186.

N-Boc-p-nitro-L-phenylalanine [CAS: 33305-77-0] and N-Boc-o-nitro-L-phenylalanine [CAS: 185146-84-3] (Compound of Formula 180)

[0282] ##STR00257##

[0283] Yield of left molecule 51%, 125 mg (using the general procedure 1), yellow solid; mp 111.9-112.6° C.; .sup.1H NMR (300 MHz, DMSO-d.sub.6) δ 12.71 (s, 1H), 8.15 (d, J=8.6 Hz, 2H), 7.53 (d, J=8.4 Hz, 2H), 7.20 (d, J=8.6 Hz, 1H), 4.19 (ddd, J=10.5, 8.5, 4.5 Hz, 1H), 3.18 (dd, J=13.7, 4.6 Hz, 1H), 2.96 (dd, J=13.7, 10.5 Hz, 1H), 1.30 (s, 9H); .sup.13C NMR (75 MHz, DMSO-d.sub.6) δ 173.0, 155.3, 146.4, 146.2, 130.4, 123.1, 78.1, 54.5, 36.2, 28.0.

[0284] Yield of right molecule 13%, 20 mg (using the general procedure 1), yellow solid, mp 129-131° C.; .sup.1H NMR (300 MHz, DMSO-d.sub.6) δ 12.36 (s, 1H), 7.91 (d, J=8.1 Hz, 1H), 7.72 (dt, J=13.8, 6.9 Hz, 3H), 7.50 (t, J=7.5 Hz, 1H), 5.33 (q, J=8.3 Hz, 1H), 2.91-2.54 (m, 2H), 1.31 (s, 9H); .sup.13C NMR (75 MHz, DMSO-d.sub.6) δ 171.2, 154.7, 147.9, 138.3, 128.2, 128.2, 123.9, 78.2, 46.9, 28.1.