7526 J. Am. Chem. Soc., Vol. 122, No. 31, 2000
Konya et al.
spectrophotometer. Elemental analyses were carried out using a Perkin-
Elmer 240C elemental analyzer.
Materials. Reagents were of analytical grade, and solvents were
dried over 4 Å molecular sieves. Silver hyponitrite was synthesized
by reaction of silver nitrate with sodium hyponitrite29 and was stored
in the dark at -20 °C.
phase was then acidified at 0 °C with concentrated HCl to pH 2-3.
The white precipitate was filtered off, washed several times with cold
methanol, and dried over P2O5 at -20 °C: yield 0.95 g (92%); mp
1
sintering up to 215 °C with no obvious gas evolution; H NMR (600
MHz, Na phosphate buffer in D2O (pD 7.6), 278 K) δ 7.99-7.86 (m,
4H, ArH), 7.47-7.43 (m, 4H, ArH), 5.35 (s, 4H, CH2OR); 13C NMR
(150 MHz, Na phosphate buffer in D2O (pD 7.6), 278 K) δ 176.3 (Cd
O), 139.5 (CArCO2R), 137.1 (CArCH2OR), 130.0, 129.3 (CArH), 75.7
General Procedure for the Synthesis of Hyponitrites. Silver
hyponitrite was added in small portions to a stirred solution of the
benzylic bromide in a dry solvent in the dark at 0 °C. After all the
silver hyponitrite had been added the reaction mixture was allowed to
warm to room temperature, and when the bromide had completely
reacted (as determined by frequent GC analysis) the silver bromide
was removed by filtration. If the reaction was not complete within 8 h,
the reaction mixture was stored in the refrigerator at 4 °C overnight
and stirred again at room temperature the following day until all the
bromide was consumed. The crude product was obtained from the
filtrate by evaporation of the solvent under reduced pressure without
heating. After purification (vide infra) the organic hyponitrites were
stored at -78 °C since they decompose slowly at -20 °C.
Synthesis of SOTS-1. (i) r-Bromotoluic Acid Chloride. A mixture
of R-bromotoluic acid (Aldrich, 10.0 g, 0.046 mol) and thionyl chloride
(Aldrich, 25 mL, 0.31 mol) was heated to reflux for 3 h and then
allowed to cool to room temperature, which caused the acid chloride
to crystallize. The excess thionyl chloride was removed by distillation
under vacuum. The acid chloride was used without further purifica-
tion: white solid, yield 10.1 g (93%); mp 53-55 °C; 1H NMR (CDCl3)
δ 8.12-8.06 (m, 2H, ArH), 7.56-7.50 (m, 2H, ArH), 4.51 (s, 2H,
CH2); 13C NMR (CDCl3) δ 167.7 (CdO), 145.2 (CArCOCl), 132.8 (CAr-
CH2Br), 131.8, 129.5 (CArH), 31.3 (CH2Br); IR (KBr) νmax 3100, 3035,
2978, 1792, 1211, 851 cm-1. Anal. Calcd for C8H6BrClO: C, 41.15;
H, 2.59; Br, 34.22; Cl, 15.18. Found; C, 41.01; H, 2.57; Br, 33.93; Cl,
15.05.
(CH2OR); IR (KBr) νmax 2950, 1689, 1291 cm-1
.
Syntheses of Et-SOTS. (v) Ethyl r-Bromotoluate. A mixture of
R-bromotoluic acid chloride (3.0 g, 0.012 mol), ethanol (30 mL, 0.52
mol), and sodium bicarbonate (3.4 g, 0.04 mol) was stirred at room
temperature for 4 h and then filtered, and the filtrate was evaporated
under vacuum. The crude product was recrystallized from diethyl ether/
pentane (1:2) as white crystals: yield 2.4 g (88%); mp 35-36 °C; 1H
NMR (CDCl3) δ 8.04-7.99 (m, 2H, ArH), 7.47-7.43 (m, 2H, ArH),
4.49 (s, 2H, CH2Br) 4.38 (q, J ) 7.0 Hz, 2H, OCH2), 1.39 (t, J ) 7.0
Hz, 3H, CH3); 13C NMR (CDCl3) δ 165.9 (CdO), 142.4 (CArCO2R),
130.3 (CArCH2Br), 129.9, 128.9 (CArH), 61.0 (OCH2), 32.2 (CH2Br),
14.2 (CH3); IR (KBr) νmax 3102, 3038, 2982, 2963, 1720, 1275, 861
cm-1; EI MS m/e (relative intensity) 244 [M+ + 2] (4), 242 [M+] (4),
199 (10), 197 (10), 163 (100), 135 (23). Anal. Calcd for C10H11BrO2:
C, 49.41; H, 4.56; Br, 32.87. Found; C, 48.24; H, 4.53; Br, 33.12.
(vi) Bis(4-ethylcarboxybenzyl)hyponitrite. The crude product
obtained by reaction of ethyl R-bromotoluate (1.5 g, 6.2 mmol) with
silver hyponitrite (1.3 g, 4.7 mmol) in dry dichloromethane (15 mL)
was redissolved in dichloromethane (5 mL)/hexane (15 mL) and then
stored at -20 °C to obtain white crystals: yield 0.51 g (42%); mp 68
1
°C (decomposed with vigorous gas evolution); H NMR (CDCl3) δ
8.06-8.01 (m, 4H, ArH), 7.44-7.39 (m, 4H, ArH), 5.31 (s, 4H, CH2-
OR), 4.38 (q, J ) 7.2 Hz, 4H, OCH2CH3), 1.40 (t, J ) 7.2 Hz, 6H,
CH3); 13C NMR (CDCl3) δ 166.2 (CdO), 140.6 (CArCO2R), 129.9,
128.8 (CArH), 126.4 (CArCH2OR), 74.8 (CH2OR), 61.1 (OCH2CH3),
(ii) Benzyl r-Bromotoluate. A mixture of R-bromotoluic acid
chloride (3.0 g, 0.012 mol), benzyl alcohol (10 mL, 0.097 mol), and
sodium bicarbonate (3.0 g, 0.036 mol) was stirred at room temperature
for 5 h and then filtered. The filtrate was purified on a silica gel column
using dichloromethane as eluent (Rf ) 0.56). After evaporation of the
solvent, a colorless oil was obtained, which gave white crystals on
14.3 (CH3); IR (KBr) Vmax 3038, 2982, 2963, 1722, 1273, 761 cm-1
.
Anal. Calcd for C20H22N2O6: C, 62.16; H, 5.75; N, 7.25. Found; C,
62.31; H, 5.67; N, 7.18.
Synthesis of Benzyl tert-Butyl Peroxide. Following a procedure
described by Kharasch and Fono,30 toluene (5 mL), tert-butylhydro-
peroxide (5 mL), and CuCl2 (0.1 g) were stirred at room temperature
for 36 h. The CuCl2 was removed by filtration, and the filtrate was
washed with dilute NaHCO3 (3 × 15 mL) and then with water. After
drying (MgSO4) and removal of the unreacted organic reagents on a
rotary evaporator, the desired peroxide was separated in low yield (ca.
3%) on preparative silica gel TLC plates using CH2Cl2: 1H NMR
(CDCl3) δ 7.4 (m, 5H, ArH), 5.0 (s, 2H, CH2) 1.2 (s, 9H, C(CH3)3).
1
storage at room temperature: yield 3.4 g (86%); mp 63-64 °C; H
NMR (CDCl3) δ 8.07-8.02 (m, 2H, ArH), 7.47-7.34 (m, 7H, ArH),
5.36 (s, 2H, CH2O), 4.48 (s, 2H, CH2Br); 13C NMR (CDCl3) δ 165.8
(CdO), 142.5 (CArCO2R), 135.9 (CArCH2OR), 131.0 (CArCH2Br), 130.2,
129.0, 128.6, 128.3, 128.2 (CArH), 66.8 (OCH2), 32.2 (CH2Br); IR (KBr)
νmax 3087, 3037, 2957, 1716, 1278, 861 cm-1; EI MS m/e (relative
intensity) 306 [M+ + 2] (19), 304 [M+] (19), 225 (27), 199 (54), 197
(54), 91 (100). Anal. Calcd for C15H13BrO2: C, 59.04; H, 4.29; Br,
26.18. Found; C, 59.22; H, 4.20; Br, 26.28.
Synthesis of Dibenzyl Peroxide. Following a published procedure,31
to KO2 (0.355 g, 5.0 mmol) in dry benzene (15 mL) in a dry flask
were added benzyl bromide (0.855 g, 0.6 mL, 5.0 mmol) and
18-crown-6 ether (1.82 g, 5 mmol), and the mixture was stirred
vigorously for 5 h at room temperature. Following that, the mixture
was poured onto a saturated solution of NaCl and extracted with CH2-
Cl2. The product was isolated in small portions using preparative TLC
(iii) Bis(4-benzylcarboxybenzyl)hyponitrite. The crude product
obtained by reaction of benzyl R-bromotoluate (2.15 g, 7.0 mmol) with
silver hyponitrite (2.0 g, 7.3 mmol) in dry dichloromethane (20 mL)
was purified by recrystallization from THF/methanol at -78 °C to give
white crystals: yield 0.42 g (23%); mp 83-85 °C (decomposed with
vigorous gas evolution); 1H NMR (CDCl3) δ 8.09-8.04 (m, 4H, ArH),
7.43-7.35 (m, 14H, ArH), 5.36 (s, 4H, PhCH2O), 5.30 (s, 4H, CH2-
OR); 13C NMR (CDCl3) δ 166.0 (CdO), 140.7 (CArCO2R), 135.9 (CAr-
CH2ONdR), 130.2, 129.9, 129.5, 128.5, 128.2, 128.1 (CArH), 74.8
(CH2ONdR), 66.7 (CH2OR); IR (KBr) νmax 3057, 3041, 2982, 2931,
1
plates and eluting with hexane/CH2Cl2, 1:1 v/v: H NMR (CDCl3) δ
7.3 (s, 1OH, ArH), 4.6 (s, 4H, CH2).
Synthesis of Perdeuteriodibenzylhyponitrite. Benzyl-d7 chloride
(d7, >98%; Cambridge Isotope, MA; 1.00 g, 7.5 mmol) was reacted
with LiBr (3.0 g, 35 mmol) in 10 mL of acetone/methanol (95:5)
containing a drop of water at room temperature. The reaction was
followed by GC/MS analysis and was stopped after reaching equilib-
rium. The two benzyl halides were extracted into ether and dried over
MgSO4. Evaporation yielded a crude product which was treated with
LiBr a second time. The same workup yielded crude benzyl-d7 bromide
(90% bromide by GC/MS), which was reacted without further purifica-
tion in dry CH2Cl2 (15 mL) with silver hyponitrite (2.0 g, 7.3 mmol).
The crude perdeuteriodibenzylhyponitite was recrystallized from CH2-
Cl2/pentane (1:3) as white crystals: yield 101 mg (10%); mp 39-41
1699, 1295, 848 cm-1
.
(iv) Bis(4-carboxybenzyl)hyponitrite (SOTS-1). A potassium
hydroxide solution (3.0 g of KOH in 20 mL of methanol and 10 mL
of water) was added dropwise to a solution of bis(4-benzylcarboxy-
benzyl)hyponitrite (1.60 g, 3.1 mmol) in 15 mL of anhydrous THF at
0 °C. The resulting yellow solution was stirred for 3 h at 0 °C and was
then allowed to warm to room temperature. If precipitation occurred
during this time, THF or water was added to redissolve the precipitate.
After 1 h at room temperature, the solution was diluted with 40 mL of
cold water and extracted with diethyl ether (30 mL × 3). The aqueous
2
°C (decomposed with gas evolution); H NMR (CHCl3) δ 7.38 (s, br,
10 D, ArD), 5.21 (s, 4D, CD2).
(29) Ogle, C. A.; Martin, S. W.; Dziobak, M. P.; Urban, M. W.;
Mendenhall, G. D. J. Org. Chem. 1983, 48, 3728-3733. Quinga, E. M.
Y.; Bieker, T.; Dziobak, M. P.; Mendenhall, G. D. J. Org. Chem. 1989,
54, 2769-2771.
(30) Kharasch, M. S.; Fono, A. J. Org. Chem. 1959, 24, 72-78.
(31) Johnson, R. A.; Nidy, E. G. J. Org. Chem. 1975, 40, 1680-1681.