DISEÑO CONVENCIONAL DE CONCRETO ARMADO SEGÚN E.060: 9

To an emulsion of chloroacetone (14.1 g, 153 mmol) and water (50 mL), was added NaN3 (9.92 g, 153 mmol). After stirring for 30 min glacial acetic acid (1

mL) was added. After 42 h the reaction mixture was extracted with ether (3 x 30 mL), and the extracts were concentrated in vacuo. In order to complete the reaction water (20 mL) and NaN3 (3.00 g, 46 mmol) were added and after stirring for 30 min glacial acetic acid (0.5 mL)

was added. After 44 h the reaction mixture was extracted with ether (4 x 30 mL), dried (Na2SO4), and filtered. The filtrate was concentrated in vacuo and destillation yielded 6a as a

N₃ O

3-Azidobutan-2-one (6b):

To a solution of NaN3 (19.4 g, 298 mmol) in water (100 mL) was added 3-

chlorobutan-2-one (16.0 g, 150 mmol). After stirring for 30 min glacial acetic acid (2 mL) was added. After stirring for 40 h the organic layer was isolated and the aqueous layer was extracted with ether (4 x 30 mL). The organic layer and extracts were combined, dried (Na2SO4), and filtered. The filtrate was concentrated in vacuo and destillation

yielded 6b as a clear, colourless liquid (13.0 g, 77%); bp. 48 – 49 °C (0.1 mbar).

1_{H NMR (300 MHz, CDCl}

3): δ = 1.44 (d, 3J = 7.1 Hz, 3H, CHCH3), 2.24 (s, 3H, CCH3), 3.94

(q, 3J = 7.1 Hz, 1H, CH).

The spectroscopic data are in accordance with those presented in the literature.30b

2-Azidocyclopentanone (6c):

To a mixture of NaN3 (21.0 g, 322 mmol) methanol (15 mL) was added 2-

chlorocyclopentanone (7.59 g, 64 mmol) at 0 °C. The reaction mixture was allowed to warm to 20 °C and was kept stirring for 3 d. The reaction mixture was filtered, washed with ether, and the filtrate was concentrated in vacuo. Ether was added and the mixture was filtered again. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (silica gel; n-hexane/EtOAc = 10:1) yielding 6c as a colourless liquid (3.91 g, 48%); Rf 0.29 (n-hexane/EtOAc = 10:1).

1_{H NMR (300 MHz, CDCl}

3): δ = 1.68 – 1.94 (m, 2H, CH2), 2.03 – 2.14 (m, 1H, CH2), 2.19 –

2.38 (m, 3H, CH2), 3.82 (t, 3J = 9.1 Hz, 1H, CHN3).

The spectroscopic data are in accordance with those presented in the literature.30c

1-Tosylpropan-2-one (7):

Sodiumtosylate dihydrate (19.1 g, 89.2 mmol) and chloroacetone (8.78 g, 94.9 mmol) were refluxed in ethanol (90 mL) for 6 h. Then the reaction mixture was left stirring for 16 h at 20 °C. Water (200 mL) and ether (300 mL) were added and the organic layer was separated. The aqueous layer was extracted with ether (2 x 100 mL). The organic layers were combined, dried (Na2SO4), and filtered. The filtrate was concentrated in vacuo and the residue

N3 O O N₃ S O O O

5-Azido-4-hydroxy-4-methyl-1-tosylpentan-2-one (9a):

To a THF solution (35 mL) of diisopropylamine (810 mg, 8.0 mmol) was added a 1.6 M solution of nBuLi in hexane (5.0 mL, 8.0 mmol) at 0 °C. After stirring for 30 minutes, the solution was cooled to –78 °C and 1-tosylpropan-2-one 7 (743 mg, 3.5 mmol), dissolved in THF (7 mL), was added and the solution was stirred for 1 h. 1-Azidopropanone 6a (361 mg, 3.6 mmol), dissolved in THF (7 mL), was added at –78 °C and the reaction mixture was warmed to ambient temperature within 15 h and left stirring for 33 h more. Ether (20 mL), CH2Cl2 (20 mL), and a saturated

solution of NH4Cl (50 mL) were added and the organic layer was separated. The aqueous

layer was extracted with ether (2 x 50 mL) and CH2Cl2 (2 x 50 mL). The combined organic

layers were washed with brine, dried (Na2SO4), and filtered. The filtrate was concentrated in

vacuo and the residue was purified by column chromatography (silica gel; petroleum ether/EtOAc = 5:1 → 3:1) to give 9a as a slightly yellow oil (481 mg, 44%); Rf 0.14

(petroleum ether/EtOAc = 3:1). 1_{H NMR (300 MHz, CDCl} 3): δ = 1.28 (s, 3H, CH2CCH3), 2.47 (s, 3H, ArCH3), 2.88 (d, 2J = 17.3 Hz, 1H, CHAHB), 3.05 (d, 2J = 17.3 Hz, 1H, CHAHB), 3.18 (s, 1H, OH), 3.23 (d, 2J = 12.3 Hz, 1H, CHAHB), 3.32 (d, 2J = 12.3 Hz, 1H, CHAHB), 4.17 (d, 2J = 13.1 Hz, 1H, CHAHBSO2), 4.24 (d, 2J = 13.1 Hz, 1H, CHAHBSO2), 7.39 (d, 3J = 8.0 Hz, 2H, Ar), 7.77 (m,

2H, Ar). 13C NMR (150 MHz, CDCl3): δ = 21.8, 25.3 (CH3), 51.4 (COHCH2CO), 60.0

(CH2N3), 68.2 (CH2SO2), 72.4 (COH), 128.4, 130.2 (CHAr), 135.7, 145.9 (CAr), 199.1 (CO).

IR (neat, cm-1): v~= 3504 (br, s), 2979 (m), 2931 (m), 2106 (s), 1717 (s), 1597 (m), 1455 (m), 1398 (s), 1378 (s), 1320 (s), 1294 (s), 1151 (s), 1087 (s), 1048 (s), 918 (m), 816 (s), 516 (s). MS (CI, isobutane): m/z (%) = 312 ([M + 1]+, 8), 284 (33), 255 (40), 213 (100). HRMS (EI, 70 eV): Calcd for C13H17N3NaO4S ([M + Na]+) 334.08320, found 334.08384. Anal. Calcd for

C13H17N3O4S (311.36): C, 50.15; H, 5.50; N, 13.50; S, 10.30. Found: C, 50.11; H, 5.38; N,

12.97; S, 9.58.

5-Azido-4-hydroxy-4-methyl-1-tosylhexan-2-one (9b):

To a THF solution (40 mL) of diisopropylamine (3.23 g, 32 mmol) was added a 1.6 M solution of nBuLi in hexane (20 mL, S O O O HO S O O O HO N₃

was stirred for 1 h. 3-Azidobutan-2-one 6b (1.61 g, 14.2 mmol), was added at –78 °C and the reaction mixture was warmed to ambient temperature within 14 h. A saturated solution of NH4Cl (50 mL) was added and the organic layer was separated. The aqueous layer was

extracted with CH2Cl2 (4 x 50 mL) and ether (50 mL). The combined organic layers were

washed with brine, dried (Na2SO4), and filtered. The filtrate was concentrated in vacuo and

the residue was purified by column chromatography (silica gel; n-hexane/EtOAc = 7:1 → 5:1) to give 9b as a brown oil (1.32 g, 30%, mixture of diastereomers: dr = 2:1); Rf 0.08 (n-

hexane/EtOAc = 5:1).

1_{H NMR (300 MHz, CDCl}

3): δ = 1.20 (s, 3H, CH3COH, major), 1.22 (s, 3H, CH3COH,

minor), 1.25 (d, 3J = 6.8 Hz, 3H, CHCH3, major), 1.29 (d, 3J = 6.7 Hz, 3H, CHCH3, minor),

2.47 (s, 3H, ArCH3, both), 2.80 (d, 2J = 17.0 Hz, 1H, COHCHAHB, major), 2.84 (d, 2J = 16.3

Hz, 1H, COHCHAHB, minor), 3.01 (d, 2J = 16.3 Hz, 1H, COHCHAHB, minor), 3.05 (s, 1H,

OH, minor), 3.08 (d, 2J = 17.0 Hz, 1H, COHCHAHB, major), 3.25 (s, 1H, OH, major), 3.43 (q, 3_{J = 6.7 Hz, 1H, CHN}

3, minor), 3.53 (q, 3J = 6.8 Hz, 1H, CHN3, major), 4.16 (d, 2J = 13.2 Hz,

1H, CHAHBSO2, both), 4.30 (d, 2J = 13.2 Hz, 1H, CHAHBSO2, both), 7.38 (d, 3J = 8.2 Hz, 2H,

Ar, both), 7.77 (m, 2H, Ar, both). 13_{C NMR (75 MHz, CDCl}

3): δ = 13.1, 13.4 (CHCH3), 21.4, 21.4, 22.9, 23.1 (CCH3), 49.9, 51.1 (COHCH2), 63.9, 64.3 (CHN3), 67.7, 67.8 (CH2SO2), 74.08, 74.13 (COH), 127.9. 128.0, 129.8, 129.8 (CHAr), 135.45, 135.47, 145.31, 145.34 (CAr), 198.6, 199.1 (CO). IR (neat, cm-1): v~= 3508 (br, s), 2983 (s), 2937 (m), 2097 (br, s), 1716 (s), 1597 (m), 1454 (m), 1379 (s), 1321 (s), 1293 (s), 1261 (s), 1151 (s), 1086 (s), 816 (m), 516 (s). MS (CI, isobutane): m/z (%) = 326 ([M + 1]+, 4), 280 (44), 255 (48), 213 (100). HRMS (CI, isobutane): Calcd for C14H20N3O4S ([M + 1]+) 326.11690, found 326.11791.

3-(2-Azido-1-hydroxycyclopentyl)-1-tosylpropan-2-one (9c):

To a THF solution (100 mL) of diisopropylamine (3.68 g, 36.4 mmol) was added a 1.6 M solution of nBuLi in hexane (22.8 mL, 36.5 mmol) at 0 °C. After stirring for 20 minutes, 1- tosylpropan-2-one 7 (2.89 g, 13.6 mmol) was added and the solution was stirred for 1 h at 0 °C. 2-Azidocyclopentanone 6c (1.70 g, 13.6 mmol) was added at –78 °C and the reaction mixture was warmed to ambient

S O O O

HO

chromatography (silica gel; n-hexane/EtOAc = 3:1) to give 9c as a brownish, slightly turbid oil (1.06 g, 23%, mixture of diastereomers: dr = 10:1); Rf 0.13 (n-hexane/EtOAc = 3:1). 1_{H NMR (300 MHz, CDCl}

3): δ = 1.50 – 1.75 (m, 2H, CH2), 1.75 – 2.10 (m, 4H, CH2), 2.46 (s,

3H, CH3), 2.83 (d, 2J = 16.4 Hz, 1H, COHCHAHBCO), 2.91 (s, 1H, OH), 3.14 (d, 2J = 16.4

Hz, 1H, COHCHAHBCO), 3.37 (dd, 3J1 = 3J2 = 8.4 Hz, 1H, CHN3), 4.17 (d, 2J = 13.1 Hz, 1H,

CHAHBSO2), 4.31 (d, 2J = 13.1 Hz, 1H, CHAHBSO2), 7.38 (d, 3J = 8.2 Hz, 2H, Ar), 7.76 (d,

3_{J = 8.2 Hz, 2H, Ar).} 13_{C NMR (150 MHz, CDCl}

3): δ = 19.2 (CH2), 21.6 (CH3), 27.0, 35.9

(CH2), 51.4 (COHCH2CO), 67.7 (CHN3), 68.0 (CH2SO2), 79.8 (COH), 128.2, 130.0 (CHAr),

135.5, 145.6 (CAr), 198.5 (CO). IR (KBr, cm-1): v~= 3498 (s), 2988 (m), 2936 (m), 2101 (s),

1694 (m), 1312 (s), 1254 (m), 1152 (s), 1128 (m), 535 (m), 518 (m). MS (CI, isobutane): m/z (%) = 338 ([M + 1]+, 0.7), 310 (100). HRMS (CI neg., isobutane): Calcd for C15H18N3O4S

([M – 1]–) 336.38667, found 336.10125. Anal. Calcd for C15H19N3O4S (337.39): C, 53.40; H,

5.68; N, 12.45; S, 9.50. Found: C, 53.64; H, 5.61; N, 11.83; S, 8.84.

4-(2-Azido-1-hydroxycyclopentyl)-3-oxobutyronitrile (9d):

To a THF solution (35 mL) of diisopropylamine (965 mg, 9.5 mmol) was added a 1.6 M solution of nBuLi in hexane (6.0 mL, 9.6 mmol) at 0 °C. After stirring for 15 minutes, the solution was cooled to –20 °C and 5-methylisoxazole 8 (332 mg, 4.0 mmol), dissolved in THF (5 mL), was added and the solution was stirred for 2 h at –20 °C. 2-Azidocyclopentanone 6c (455 mg, 3.6 mmol), dissolved in THF (5 mL), was added at –78 °C and the reaction mixture was warmed to ambient temperature within 15 h and left stirring for 25 h more. A saturated solution of NH4Cl (50 mL) was added and the organic layer was separated. The aqueous layer

was extracted with Et2O (2 x 70 mL) and CH2Cl2 (3 x 50 mL). The combined organic layers

were washed with brine, dried (Na2SO4), and filtered. The filtrate was concentrated in vacuo

and the residue was purified by column chromatography (silica gel; petroleum ether/EtOAc = 3:1) to give 9d as a slightly brown oil (53 mg, 7%, mixture of diastereomers: dr ≥ 5:1); Rf

0.14 (petroleum ether/EtOAc = 3:1).

1_{H NMR (300 MHz, CDCl}

3): δ = 1.40 – 2.15 (m, 6H, CH2), 2.63 (d, 2J = 15.0 Hz, 1H,

CHAHBCO), 2.78 (br, 1H, OH), 2.98 (d, 2J = 15.0 Hz, 1H, CHAHBCO), 3.48 (t, 3J = 7.9 Hz,

1H, CHN3), 3.59 – 3.74 (m, 2H, CHAHBCO). 13C NMR (75 MHz, CDCl3): δ = 19.2 (CH2,

HO

O

N₃ CN

(COHCH2CO, major), 67.9 (CHN3, major), 69.2 (CHN3, minor), 79.7 (COH, major), 81.8

(COH, minor), 113.3 (CN, minor), 113.7 (CN, major), 197.4 (CO, major), 199.5 (CO, minor).

3-Azidocyclohexanone (13):

To a solution of NaN3 (19.5 g, 300 mmol) and cyclohex-2-enone (15.1 g, 157

mmol) in water (100 mL) was added acetic acid (9.94 g, 166 mmol) and the reaction mixture was stirred for 40 h. After separation the aqueous layer was extracted with ether (4 x 40 mL). The organic layers were combined, dried (Na2SO4), and concentrated in vacuo. Destillation yielded 13 as a clear, slightly yellow liquid

(9.75 g, 45%); bp. 83 °C. 1_{H NMR (300 MHz, CDCl} 3): δ = 1.66 – 1.87 (m, 2H, CH2), 2.01 – 2.14 (m, 2H, CH2), 2.35 (m, 2H, CH2), 2.43 (dd, 2J = 14.3 Hz, 3J = 8.6 Hz, 1H, CHN3CHAHBCO), 2.66 (dd, 2J = 14.3 Hz, 3J = 4.6 Hz, 1H, CHN3CHAHBCO), 3.89 (m, 1H, CHN3). 13C NMR (75 MHz, CDCl3): δ = 21.0, 29.3, 40.3, 46.1 (CH2), 59.2 (CH), 207.2 (CO). IR (neat, cm-1): v~= 2951 (s), 2874 (m), 2101 (s), 1717 (s), 1314 (m), 1251 (s), 1222 (s), 1101 (m), 515 (w). MS (GC-EI, 70 eV): m/z (%) = 139 (M+, 30), 82 (19), 69 (27), 68 (30), 56 (54), 55 (80), 54 (33), 42 (86), 41 (100), 39 (39). Anal. Calcd for C6H9N3O (139.16): C, 51.79; H, 6.52; N, 30.20. Found: C, 52.17; H,

6.62; N, 29.93.

Ethyl 4-(3-azido-1-hydroxycyclohex-1-yl)-3-oxo-butyrate (14):

To a THF solution (50 mL) of diisopropylamine (1.35 g, 13.3 mmol) was added a 1.6 M solution of nBuLi in hexane (8.3 mL, 13.3 mmol) at 0 °C. After stirring for 20 minutes, ethyl acetoacetate (0.77 g, 5.9 mmol) was added and the solution was left stirring at 0 °C. After 1 h, the solution was cooled to –78 °C and 3-azidocyclohexanone 13 (0.93 g, 6.7 mmol) was added. The reaction mixture was warmed to ambient temperature within 14 h and was stirred for 4 h more. A saturated solution of NH4Cl (50 mL) was added

and the aqueous layer was extracted with THF (2 x 50 mL) and ether (2 x 50 mL). The THF extracts were concentrated in vacuo to remove the THF. The residue and ether extracts were combined, washed with brine, dried (Na2SO4), and filtered. The filtrate was concentrated in

HO O OEt O N₃ O N₃

1_{H NMR (300 MHz, CDCl}

3): δ = 1.29 (t, 3J = 7.1 Hz, 3H, CH3), 1.35 – 1.97 (m, 8H, CH2),

2.72 (s, 2H, COHCH2CO), 3.52 (s, 2H, CH2COOEt), 3.63 (m, 1H, CHN3), 3.69 (s, 1H, OH),

4.20 (q, 3J = 7.1 Hz, 2H, OCH2). 13C NMR (75 MHz, CDCl3): δ = 13.9 (CH3), 18.4, 29.8,

36.9, 40.9, 50.6, 51.2 (CH2), 57.2 (CHN3), 61.3 (OCH2), 71.1 (COH), 166.9 (COOEt), 203.2

(CO).