R. L. Pennington et al. / Bioorg. Med. Chem. Lett. 15 (2005) 2331–2334
2333
treatment for heart failure.15 These results describe a new
functional group (N-hydroxy sulfonimamides) as an
alternative HNO donor that may be useful in distin-
guishing the effects of NO from HNO in some systems.
combined, dried (MgSO4), concentrated, and purified by
flash chromatography to give the protected N-hydroxy-
sulfonimidamides (6, 7, 11, 12) in 41–67% yield.
Compound 6: Rf 0.69 (50:50 pentane–ether); mp 68–
69 ꢁC; 1H NMR (500 MHz, CDCl3): d 7.51–7.20 (m,
9H, ArH), 7.02–7.00 (t, 1H, J = 7.20 Hz, ArH), 6.86
(br s, 1H, NH), 4.87–4.80 (m, 2H, CH2OPh), 3.37–
3.32 (m, 2H, a-CH2), 1.91–1.86 (m, 2H, b-CH2), 1.52–
1.47 (sext., 2H, J = 7.51 Hz, v-CH2), 0.99–0.96 (t, 3H,
J = 7.40 Hz, CH3); 13C NMR (75.5 MHz, CDCl3): d
145.5, 129.7, 129.3, 129.0, 128.8, 124.1, 122.8, 79.2,
51.4, 23.3, 21.8, 13.9; LRMS (ESI) m/z 319 (MH+).
3. N-Phenylbutane sulfinamide (4)
N-Butyllithium (5.74 mL of a 2.5 M solution in hexanes,
1.44 · 10À2 mol wasadded to a stirred solution of N-thion-
ylaniline (0.81 mL, 7.2 · 10À3 mol) in THF (5 mL) at
À78 ꢁC (acetone–dry ice bath). The reaction mixture
wasmonitored by TLC and after 30 min. wascarefully
worked up by the addition of water, diluted with ether
and extracted with 1 M HCl, NaHCO3 (satd) and water.
The organic layerswere combined, dried (MgSO 4), con-
centrated, and purified by flash chromatography (silica
gel, 50:50 pentane–ether, Rf 0.23) to give 1.20 g
(84.5%) of 4 asa white powder: mp 73–74 ꢁC; 1H
NMR (300 MHz, CDCl3): d 7.32–7.26 (m, 2H, ArH),
7.08–7.04 (m, 3H, ArH), 5.85 (br s, 1H, NH), 2.97–
2.91 (m, 2H, a-CH2), 1.81–1.71 (p, 2H, J = 7.59 Hz, b-
CH2), 1.56–1.46 (m, 2H, v-CH2), 1.00–0.95 (t, 3H,
J = 7.31 Hz, CH3); 13C NMR (75.5 MHz, CDCl3): d
141.0, 129.5, 123.4, 118.8, 56.0, 25.0, 21.8, 13.7; LRMS
(ESI) m/z 198 (MH+).
Compound 7: 0.75 (50:50 pentane–ether); mp 100–
103 ꢁC; 1H NMR (300 MHz, CDCl3): d 8.17–8.15
(m, 2H, ArH), 7.64–7.53 (m, 3H, ArH), 7.35–7.29 (m,
7H, ArH), 7.25–7.20 (m, 2H, ArH), 7.08–7.05 (m, 1H,
ArH), 6.91 (br s, 1H, NH), 4.79–4.78 (m, 2H, CH2OPh),
13C NMR (75.5 MHz, CDCl3): d 143.4, 137.6, 136.0,
133.6, 129.5, 129.3, 128.9, 128.8, 128.8, 124.4, 123.1,
79.0; LRMS (ESI) m/z 339 (MH+).
Compound 11: Rf 0.53 (50:50 pentane–ether); mp 78–
81 ꢁC; 1H NMR (300 MHz, CDCl3): d 7.23–7.20 (t,
2H, J = 7.75 Hz, ArH), 7.15–7.13 (d, 2H, J = 7.80 Hz,
ArH), 6.96 (t, 1H, J = 7.79 Hz), 6.43 (br s, 1H, NH),
3.36–3.34 (m, 2H, a-CH2), 1.94–1.91 (p, 2H,
J = 7.64 Hz, b-CH2), 1.54–1.53 (m, 2H, v-CH2), 1.02–
0.99 (t, 3H, J = 7.57 Hz, CH3), 0.93 (s, 9H, SiC(CH3)3),
0.17 (s, 3H, SiCH3), 0.08 (s, 3H, SiCH3); 13C NMR
(75.5 MHz, CDCl3): d 143.5, 129.0, 123.8, 122.3, 50.0,
26.1, 25.2, 21.7, 18.2, 13.7; LRMS (ESI) m/z 343 (MH+).
4. N-Phenylbenzenesulfinamide (5)
Phenylmagnesium bromide (3.6 mL of a 3 M solution in
THF, 1.08 · 10À2 mol) was added to a stirred solution
of N-thionylaniline (0.81 mL, 7.18 · 10À3 mol) in THF
(5 mL) at 0 ꢁC. The reaction mixture wastsirred at
0 ꢁC for 1 h, and then at room temperature for 2 h, with
monitoring by TLC until completion. The reaction mix-
ture wasworked up by the addition of water, dilution
with ether, and extraction with 1 M HCl, NaHCO3
(satd) and water. The organic layers were combined,
dried (MgSO4), concentrated and he resultant oil was
purified by flash chromatography (silica gel, 50:50 pen-
tane–ether Rf 0.31), to yield 1.13 g (72.8%) of 5 asa
white solid: mp 108–111 ꢁC; 1H NMR (300 MHz,
CDCl3): d 7.83–7.81 (m, 2H, ArH), 7.56–7.55 (m, 3H,
ArH), 7.32–7.29 (m, 2H, ArH), 7.12–7.07 (m, 3H,
ArH), 6.06 (br s, 1H, NH); 13C NMR (75.5 MHz,
CDCl3): d 131.8, 129.9, 129.5, 125.8, 124.1, 119.4.
LRMS (ESI) m/z 239 (M+Na+).
Compound 12: Rf 0.75 (50:50 pentane–ether); mp 91–
93 ꢁC; 1H NMR (300 MHz, CDCl3): d 8.17–8.15 (m,
2H, ArH), 7.67–7.65 (m, 3H, ArH), 7.30–7.22 (m, 4H,
ArH), 7.06–7.00 (m, 1H, ArH), 6.56 (br s, 1H, NH),
0.89 (s, 9H, SiC(CH3)3), 0.07 (s, 3H, SiCH3), 0.01 (s,
3H, SiCH3); 13C NMR (75.5 MHz, CDCl3): d 143.0,
136.7, 133.4, 129.1, 129.1, 128.9, 124.1, 122.6, 26.0,
18.0; LRMS (ESI) m/z 363 (MH+).
6. N-Phenylbutane sulfonimamide (10)
Prepared in a similar fashion to 6, 7, 11, and 12 with
ammonia being added to give 10: Rf 0.75 (ether); mp
1
125–128 ꢁC; H NMR (300 MHz, CDCl3): d 7.33–7.25
(m, 2H, Ar), 7.18–7.15 (m, 2H, Ar), 7.07–7.02 (t, 1H,
J = 7.25 Hz, Ar), 4.42 (br s, 1H, NH), 3.28–3.23 (m,
2H, a-CH2), 1.97–1.88 (m, 2H, b-CH2), 1.50–1.42 (m,
2H, J = 7.36 Hz, v-CH2), 0.99–0.94 (t, 3H, J =
7.33 Hz, CH3); 13C NMR (75.5 MHz, CDCl3): d 129.6,
123.3, 122.9, 56.0, 26.3, 21.7, 14.0; LRMS (ESI) m/z
213 (MH+), 235 (M+Na+).
5. Protected N-hydroxy sulfonimidamides (6, 7, 11, 12)
t-Butyl hypochlorite (1.2 equiv) in CCl4 (1 mL) was
added dropwise to a solution of the sulfinamide
(1 equiv) in CCl4 (2 mL) and stirred at 0 ꢁC in an alumi-
num foil-covered flask. After stirring for 1.5 h, the mix-
ture was concentrated and the resultant residue was
taken up in CCl4 (2 mL) at room temperature. A solu-
tion of benzyl hydroxylamine or t-butyldimethylsilyl
hydroxylamine (2.4 equiv) in CCl4 wasadded to this
solution dropwise. After stirring overnight, the reaction
mixture wasdiluted with ether and extracted with 1 M
HCl, satd NaHCO3, and water. The organic layerswere
7. Attempted deprotection of 11 and nitrous oxide
detection
A
solution of tetra-n-butyl ammonium fluoride
(4.38 mL, 1 M, 4.37 · 10À3 mol) in THF wasadded