Sector Mujer y Poblaciones Vulnerables

1-(4-Isobutylphenyl)propan-1-one 29b

The product 29b was synthesised using a known procedure.[9]To a suspension of AlCl3 (1.29 g, 9.68 mmol) in dry CH2Cl2 under N2, propionyl chloride (910 µL, 10.4 mmol) was slowly added at 0 °C. After stirring for 20 minutes, iso-butylbenzene (1.17 mL, 7.45 mmol) was added dropwise and the resulting solution was stirred at room temperature for 2 h. The mixture was poured into a solution of crunched ice and concentrated HCl (2.5 mL) and left to warm up to room temperature. The reaction mixture was extracted with CH2Cl2 (2 x 30 mL), washed with sat. aq. NaHCO3 solution (20 mL), water (30 mL), dried over MgSO4 and concentrated under vacuum. The pure product was obtained after purification by column chromatography (0 to 10% EtOAc in hexane) as a colourless oil (74% yield, 1.05 g, 5.52 mmol).

The spectroscopic data are in agreement with literature.[9] Colourless oil; 1_{H NMR}

(400 MHz, CDCl3): δ = 7.89 – 7.87 (m, 2H, H-Ar), 7.23 – 7.21 (m, 2H, H-Ar), 2.99 (q,

J = 7.3 Hz, 2H, CH2CH3), 2.52 (d, J = 7.2 Hz, 2H, CH2CH(CH3)2), 1.93 – 1.84 (m, 1H,

CH2CH(CH3)2), 1.22 (t, J = 7.3 Hz, 3H, CH2CH3), 0.90 (d, J = 6.6 Hz, 6H,

CH2CH(CH3)2) ppm; 13C NMR (125 MHz, CDCl3): δ = 200.7 (C=O), 147.4 (CAr), 134.9

(CAr), 129.4 (2 CArH), 128.1 (2 CArH), 45.5 (CH2CH(CH3)2), 31.8 (CH2CH3), 30.2 (CH2CH(CH3)2), 22.5 (CH2CH(CH3)2), 8.5 (CH2CH3) ppm; IR (neat): 2955, 1682, 1607, 1460, 1225, 1180, 951, 783 cm-1; HRMS (NSI): [M+H]+ calc. 191.1430, found 191.1426 [C13H19O]+.

158 1-(2-Bromophenyl)propan-1-ol 183

The product 183 was synthesised using a known procedure.[10] To a solution of 2-bromobenzaldehyde 182 (234 µL, 2.00 mmol) in dry Et2O (10 mL) at -10 °C, a solution of ethyl magnesium bromide in Et2O (3.34 mL, 3 M, 10.0 mmol) was added. The resulting solution was stirred at -10 °C for 3 h, then quenched with sat. aq. NH4Cl solution (20 mL) and the organic phase was extracted with EtOAc (3 x 30 mL), dried over MgSO4 and concentrated under vacuum. 1-(2-Bromophenyl)propan-1-ol 183 was obtained as a colourless oil and used without further purification (77% yield, 332 mg, 1.54 mmol). The spectroscopic data are in agreement with literature.[11]1_{H NMR (300 MHz, CDCl}

3):

δ = 7.56 – 7.50 (m, 2H, H-Ar), 7.33 (td, J = 7.6, 0.9 Hz, 1H, H-Ar), 7.12 (td, J = 7.7, 1.7 Hz, 1H, H-Ar), 5.03 – 5.00 (m, 1H, CHOH), 2.01 (bs, 1H, OH), 1.88 – 1.66 (m, 2H, CHCH2CH3), 1.01 (t, J = 7.4 Hz, 3H, CHCH2CH3) ppm.

1-(2-Bromophenyl)propan-1-one 29h

The product 29h was synthesised using a known procedure.[10] To a suspension of pyridinium chlorochromate (PCC; 500 mg, 2.32 mmol) and silica gel (500 mg) in dry CH2Cl2 (2 mL), a solution of 1-(2-bromophenyl)propan-1-ol 183 (332 mg, 1.54 mmol) in dry CH2Cl2 (3 mL) was added dropwise. After 3 h at room temperature, the reaction mixture was filtered through a silica plug, washing the silica with CH2Cl2 (200 mL). The solvent was removed under vacuum and the desired product was obtained as a pale yellow oil which was used without further purification (96% yield, 316 mg, 1.48 mmol).

The 1H NMR spectrum is in agreement with literature.[12]1_{H NMR (400 MHz, CDCl} 3):

δ = 7.61 – 7.59 (m, 1H, H-Ar), 7.37 – 7.35 (m, 2H, H-Ar), 7.30 – 7.27 (m, 1H, H-Ar), 2.93 (q, J = 7.3 Hz, 2H, CH2), 1.21 (t, J = 7.2 Hz, 3H, CH3) ppm; 13_{C NMR (125 MHz,}

159 CDCl3): δ = 205.1 (C=O), 142.2 (CAr), 133.7 (CArH), 131.4 (CArH), 128.3 (CArH), 127.5

(CArH), 118.7 (CAr), 36.2 (CH2), 8.2 (CH3) ppm; IR (neat): 2978, 1699, 1587, 1427, 1213, 748 cm-1; HRMS (NSI): [M+H]+ calc. 212.9910, found 212.9912 [C9H10OBr]+.

1-(3-Nitrophenyl)propan-1-one 29i

The product 29i was synthesised using a known procedure.[13] Fuming nitric acid (9.7 mL) was added at -45 °C to propiophenone (1.00 mL, 7.45 mmol) and the resulting solution was stirred for 1 h at -45 °C. Crunched ice was added and the resulting green mixture was left to warm up to room temperature. The organic phase was extracted with Et2O (2 x 30 mL), washed with water (20 mL), aq. 2 N NaOH solution (30 mL), brine, dried over MgSO4 and concentrated under vacuum. EtOH (4 mL) was added to the crude solid and the solution was kept at -15 °C for 1 h. The pure product was obtained, after filtration, as pale yellow crystals (52% yield, 700 mg, 3.91 mmol).

m.p. = 95 - 97 °C; 1_{H NMR (400 MHz, CDCl}

3): δ = 8.77 (t, J = 1.9 Hz, 1H, H-Ar), 8.41

(ddd, J = 8.2, 2.2, 1.0 Hz, 1H, H-Ar), 8.32 – 8.27 (m, 1H, H-Ar), 7.68 (t, J = 8.0 Hz, 1H, H-Ar), 3.07 (q, J = 7.2 Hz, 2H, CH2), 1.26 (t, J = 7.2 Hz, 3H, CH3) ppm; 13_{C NMR}

(125 MHz, CDCl3): δ = 198.5 (C=O), 148.7 (CAr), 138.3 (CAr), 133.6 (CArH), 130.0

(CArH), 127.3 (CArH), 123.0 (CArH), 32.3 (CH2), 8.1 (CH3) ppm; IR (neat): 2988, 1687, 1526, 1346, 1213, 1096, 732, 675 cm-1_{; HRMS (NSI): [M+H]}+ _{calc. 180.0655, found} 180.0655 [C9H10O3N]+_.

1-(6-Methoxynaphthalen-2-yl)propan-1-one 29j

To a solution of propionyl chloride (1.20 mL, 13.6 mmol) and AlCl3 (1.88 g, 14.0 mmol) in dry CH2Cl2 (4 mL), a solution of 2-methoxynaphthalene (2.37 g, 15.0 mmol) in dry CH2Cl2 (6 mL) was added via syringe pump (6 mL/h) at room temperature. The resulting

160 mixture was stirred for 20 h, then quenched with crunched ice. The organic phase was extracted with CH2Cl2 (3 x 25 mL), dried over MgSO4 and concentrated under vacuum. After column chromatography (0 to 10% EtOAc in hexane), the desired product was obtained as a white solid (79% yield, 2.55 g, 11.9 mmol).

The spectroscopic data are in agreement with literature.[9] _{m.p. = 105 - 107 °C (lit.}[9] 109 °C); 1_{H NMR (400 MHz, CDCl}

3): δ = 8.40 (s, 1H, H-Ar), 8.01 (dd, J = 8.6, 1.7 Hz,

1H, H-Ar), 7.84 (d, J = 9.0 Hz, 1H, H-Ar), 7.76 (d, J = 8.7 Hz, 1H, H-Ar), 7.20 (dd,

J = 8.9, 2.5 Hz, 1H, H-Ar), 7.14 (d, J = 2.4 Hz, 1H, H-Ar), 3.94 (s, 3H, OCH3), 3.11 (q,

J = 7.3 Hz, 2H, CH2), 1.27 (t, J = 7.3 Hz, 3H, CH3) ppm; 13_{C NMR (125 MHz, CDCl3):}

δ = 200.6 (C=O), 159.8 (CAr – OMe), 137.3 (CAr), 132.5 (CAr), 131.2 (CArH), 129.5 (CArH), 128.0 (CAr), 127.2 (CArH), 124.8 (CArH), 119.8 (CArH), 105.9 (CArH), 55.5 (OCH3), 31.8 (CH), 8.6 (CH3) ppm; IR (neat): 1678, 1620, 1481, 1350, 1265, 1022, 821 cm-1; HRMS (ESI): [M+H]+ calc. 215.1067, found 215.1065 [C14H15O]+.

Synthesis of 1-Propionylnaphthalene and 2-Propionylnaphthalene

To a solution of propionyl chloride (2.46 mL, 28.1 mmol) and AlCl3 (3.85 g, 28.9 mmol) in dry CH2Cl2 (8 mL), a solution of naphthalene (3.95 g, 30.8 mmol) in dry CH2Cl2 (8 mL) was added via syringe pump (0.2 mL/min) at 35 °C. The resulting mixture was stirred for an additional hour. The reaction was quenched at 0 °C with 3 N HCl (30 mL). The organic phase was extracted with CH2Cl2 (3 x 50 mL), dried over MgSO4 and concentrated under vacuum. Crude 1H NMR showed full conversion into the two products with a ratio of 91:9 (1-naphthyl: 2-naphthyl). After column chromatography (100% hexane), the two propionylnaphthalenes could not be fully separated but some pure fractions were isolated. 2-Propionylnaphthalene 171

The spectroscopic data are in agreement with literature.[14]White solid; m.p. = 62 - 64 °C (Lit.[15] 64 - 65 °C); 1_{H NMR (400 MHz, CDCl3): δ = 8.48 (s, 1H, H-Ar), 8.05 (dd,}

J = 8.2, 1.7 Hz, 1H, H-Ar), 7.97 (d, J = 8.0 Hz, 1H, H-Ar), 7.89 (t, J = 8.4 Hz, 2H, H-Ar),

161 ppm; 13_{C NMR (125 MHz, CDCl}

3): δ = 200.9 (C=O), 135.7 (CAr), 134.5 (CAr), 132.8

(CArH), 129.7 (CArH), 129.6 (CArH), 128.5 (CArH), 128.4 (CArH), 127.9 (CArH), 126.9 (CArH), 124.1 (CArH), 32.0 (CH2), 8.6 (CH3) ppm; IR (neat): 2974, 1678, 1373, 1276, 1188, 1126, 798 cm-1; HRMS (ESI): [M+H]+ calc. 185.0961, found 185.0961 [C13H13O]+_.

1-Propionylnaphthalene 172

The spectroscopic data are in agreement with literature.[16] Pale yellow oil; 1_{H NMR}

(400 MHz, CDCl3): δ = 8.56 (d, J = 8.5 Hz, 1H, H-Ar), 7.98 (d, J = 8.2 Hz, 1H, H-Ar),

7.87 – 7.84 (m, 2H, H-Ar), 7.61 – 7.48 (m, 3H, H-Ar), 3.09 (q, J = 7.3 Hz, 2H, CH2), 1.29 (t, J = 7.3 Hz, 3H, CH3) ppm; 13_{C NMR (125 MHz, CDCl}

3): δ = 205.4 (C=O), 136.5

(CAr), 134.1 (CAr), 132.4 (CArH), 130.3 (CAr), 128.5 (CArH), 127.9 (CArH), 127.2 (CArH), 126.5 (CArH), 126.0 (CArH), 124.5 (CArH), 35.6 (CH2), 8.8 (CH3) ppm; IR (neat): 2974, 2934, 1678, 1508, 1230, 1176, 1111, 794 cm-1; HRMS (ESI): [M+H]+ calc. 185.0961, found 185.0958 [C13H13O]+.

1-(Pyridin-2-yl)propan-1-one 189

The product 189 was synthesised using a known procedure.[17] To a solution of 2-cyanopyridine (0.92 mL, 9.6 mmol) in dry Et2O (15 mL) at -20 °C, a solution of ethyl magnesium bromide (3.84 mL, 3 M, 11.5 mmol) was slowly added. After the addition, the reaction mixture was stirred at that temperature for 1 h and then gradually warmed up to room temperature over 3 h. The reaction was quenched with 2 N HCl (5 mL) and stirred for additional 15 minutes. The two layers were separated, the aqueous phase was neutralised to pH = 8 using 2 N NaOH. The organic phase was extracted with CH2Cl2 (3 x 10 mL), washed with water, brine, dried over MgSO4 and concentrated under

162 vacuum. The pure product was obtained after distillation (0.1 mbar, 80 °C) as a colourless oil (97% yield, 1.25 g, 9.26 mmol).

The spectroscopic data are in agreement with literature.[17]1_{H NMR (400 MHz, CDCl} 3):

δ = 8.69 – 8.63 (m, 1H, H-Ar), 8.03 (d, J = 7.9 Hz, 1H, H-Ar), 7.82 (t, J = 7.7 Hz, 1H, H-Ar), 7.48 – 7.41 (m, 1H, H-Ar), 3.23 (q, J = 7.3 Hz, 2H, CH2), 1.21 (t, J = 7.3 Hz, 3H, CH3) ppm; 13_{C NMR (125 MHz, CDCl}

3): δ = 202.7 (C=O), 153.6 (CAr), 149.0 (CArH),

136.9 (CArH), 127.1 (CArH), 121.8 (CArH), 31.2 (CH2), 8.1 (CH3) ppm; IR (neat): 2976, 1697, 1584, 4356, 1223, 995, 760 cm-1_{; HRMS (EI): [M]}+ _{calc. 135.0684, found} 135.0681 [C8H9NO]+.

2-Phenyl-1-(p-tolyl)ethan-1-one 212

To a solution of phenyl acetyl chloride (0.86 mL, 6.5 mmol) and AlCl3 (0.86 g, 6.5 mmol) in dry CH2Cl2 (10 mL), toluene (0.76 mL, 7.1 mmol) was added dropwise at 0 °C. The resulting mixture was stirred at room temperature for 16 h. The reaction was quenched with crunched ice and the organic phase was extracted with CH2Cl2 (3 x 25 mL), dried over MgSO4 and concentrated under vacuum. After column chromatography (0 to 10% EtOAc in hexane), the pure product 212 was obtained as white crystals (75% yield, 1.02 g, 4.78 mmol).

The spectroscopic data are in agreement with literature.[18] _{m.p. = 102 - 105 °C (lit.}[18] 104 - 105 °C); 1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.2 Hz, 2H, H-Ar),

7.34 – 7.30 (m, 2H, H-Ar), 7.27 – 7.24 (m, 5H, H-Ar), 4.26 (s, 2H, CH2), 2.40 (s, 3H, CH3) ppm; 13_{C NMR (125 MHz, CDCl3): δ = 197.4 (C=O), 144.1 (CAr), 135.0 (CAr),}

134.4 (CAr), 129.6 (2 CArH), 129.5 (2 CArH), 128.9 (2 CArH), 128.8 (2 CArH), 127.0 (CArH), 45.6 (CH2), 21.8 (CH3) ppm; IR (neat): 2982, 2904, 1678, 1604, 1334, 1168 cm-1; HRMS (NSI): [M+H]+ calc. 211.1117, found 211.1114 [C15H15O]+.

163 2-Phenyl-1-(p-tolyl)propan-1-one 220

To a suspension of NaH (18 mg, 0.77 mmol) in dry THF (30 mL) at 0 °C, a solution of 2-phenyl-1-(p-tolyl)ethan-1-one 212 (154 mg, 0.734 mmol) in dry THF (30 mL) was added over 30 minutes using a dropping funnel. The reaction was warmed up to room temperature, iodomethane (100 µL, 1.60 mmol) was added and the resulting mixture was stirred for 2 h. After quenching the reaction with water (50 mL), the organic phase was extracted with Et2O (3 x 50 mL), dried over MgSO4 and concentrated under vacuum. After purification by column chromatography (0 to 10% EtOAc in hexane) the pure product 220 was obtained as a colourless oil (80% yield, 132 mg, 0.587 mmol).

The spectroscopic data are in agreement with literature.[19]1_{H NMR (400 MHz, CDCl} 3):

δ = 7.47 – 7.44 (m, 2H, H-Ar), 7.37 – 7.33 (m, 2H, H-Ar), 7.30 – 7.28 (m, 1H, H-Ar), 3.16 (s, 6H, 2 OCH3), 1.91 (q, J = 7.5 Hz, 2H, CH2), 0.59 (t, J = 7.5 Hz, 3H, CH3) ppm;

13_{C NMR (125 MHz, CDCl}

3): δ = 200.1 (C=O), 143.6 (CAr), 141.9 (CAr), 134.2 (CAr),

129.3 (2 CArH), 129.1 (2 CArH), 129.0 (2 CArH), 127.9 (2 CArH), 126.9 (CArH), 47.9 (CH), 21.7 (CH3), 19.6 (CH3) ppm; HRMS (APCI): [M+H]+ _{calc. 225.1274, found 225.1269} [C16H17O]+

.