Correlation of the product E/Z framework geometry and O/O vs O/N regioselectivity in the dialkylation of hyponitrite

Article abstract of DOI:10.1021/ja994261o

The products from the alkylation of silver hyponitrite with tert-butyl bromide, tert-amyl bromide, p-tert-butyl benzylbromide, and chlorotriethylsilane have been determined. In the reaction of tert-butyl bromide the formation of three new products, namely

Full text of DOI:10.1021/ja994261o

J. Am. Chem. Soc. 2000, 122, 5539-5549
5539
Correlation of the Product E/Z Framework Geometry and O/O vs O/N
Regioselectivity in the Dialkylation of Hyponitrite
Navamoney Arulsamy, D. Scott Bohle,* Jerome A. Imonigie, and Elizabeth S. Sagan
Contribution from the Department of Chemistry, UniVersity of Wyoming, Laramie, Wyoming 82071-3838
ReceiVed December 3, 1999
Abstract: The products from the alkylation of silver hyponitrite with tert-butyl bromide, tert-amyl bromide,
p-tert-butyl benzylbromide, and chlorotriethylsilane have been determined. In the reaction of tert-butyl bromide
the formation of three new products, namely, (Z)-N-tert-butyl-N′-tert-butoxydiazene-N-oxide {(CH3)3CN(O)-
NOC(CH3)3}, 1D, trans-mono-O-tert-butylhyponitrous acid {(CH3)3CONNOH}, 2A, and (Z)-N-tert-butyl-N′-
hydroxydiazene-N-oxide {(CH3)3CN(O)NNOH}, 2D, is observed together with the formation of the known
trans-di-O-tert-butyl hyponitrite {(CH3)3CONNOC(CH3)3}, 1A. The reaction with tert-amyl bromide also yielded
the corresponding tert-amyl derivatives. However, from the reactions of p-tert-butylbenzyl bromide and
chlorotriethylsilane with silver hyponitrite, the corresponding trans-di-O-tert-alkylhyponitrites were obtained
as the only alkylated products. The differential reactivity of the two sets of halides with silver hyponitrite is
explained in terms of the higher stability of the cations generated from the former halides in comparison to
those generated from the latter halides. The thermal decomposition data and UV-visible spectroscopic data
are reported for all of the products. Crystallographic structural data are reported for two of the products, namely,
(Z)-N-tert-butyl-N′-tert-butoxydiazene-N-oxide, 1D, as its hyponitrous acid adduct, (CH3)3CN(O)NOC(CH3)3‚
1/2HONNOH, and trans-di-O-p-tert-butylbenzyl hyponitrite, {p(CH3)3C}C6H4CH2ONNOCH2C6H4-p-{C(CH3)3}.
Theoretical calculations using ab initio density functional theory (B3LYP) are reported for the hyponitrite
dianion, trans-mono-O-methylhyponitrite anion, (Z)-N-methyl-N′-hydroxylatodiazene-N-oxide anion, and for
the methylation transition states. On the basis of the products isolated from the reactions of tert-butyl bromide
and tert-amyl bromide and the theoretical calculations, a pathway is proposed to account for the observed
product distributions where O/O-dialkylation is found in the trans(E) products and O/N-dialkylation is found
in the cis(Z) products.
Several oxyanions of nitrogen are ambidentate nucleophiles
which undergo either N- or O-alkylation reactions depending
upon the incipient electrophile and the reaction conditions.
Although this reactivity pattern is well-established for hydroxy-
lamine1,2 and nitrite,3-5 it has not been well-demonstrated for
the hyponitrite, peroxynitrite, or other oxy-anions of nitrogen.
In the case of hyponitrite, there is only one report where the
ambident nucleophilic nature of silver hyponitrite toward organic
halide has been observed.6 Bis-O-alkylation of hyponitrite is a
well-known reaction, and the resulting trans-dialkylesters are
commonly employed as polymerization initiators.7-11
The most widely employed synthetic route to the alkyl esters
of hyponitrous acid involves the reaction of the appropriate alkyl
halides with silver hyponitrite.8,12-17 It has long been known
that the reaction of tert-butyl- and tert-amyl halides with silver
hyponitrite produces trans-di-O-tert-butyl15,17 and trans-di-O-
tert-amyl hyponitrites,16,18 respectively. However, in principle,
the reactions could produce no less than six isomers as shown
in Figure 1, if hyponitrite’s ambidentate nucleophilic behavior
is coupled to facile E/Z isomerization.
The low yields that are commonly observed for the reactions
of alkyl halides with silver hyponitrite have been attributed to
possible competing elimination reactions and/or side reactions,
whereas the possibility of the formation of other isomers is not
addressed in detail.6,18 Recently, we reported the synthesis and
characterization of alkylammonium and base-stabilized hyponi-
trous acid salts which are stable at ambient temperature and
soluble in a variety of organic solvents.19 As part of our research
into the oxy-anions of nitrogen, we were interested in the
chemical reactivity of the hyponitrite anion. As will be described
below, we have isolated trans-di-O-tert-butyl hyponitrite (1A),
(Z)-N-tert-butyl-N′-tert-butoxydiazene-N-oxide (1D),20 trans-
mono-O-tert-butyl-hyponitrous acid (2A), and (Z)-N-tert-butyl-
(1) Harger, M. J. P. J. Chem. Soc., Perkin Trans. 1 1981, 3284-3288.
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(11) Dulog, L.; Klein, P. Chem. Ber. 1971, 104, 895-901.
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317-340.
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(14) Ho, S. K.; de Sousa, J. B. J. Chem. Soc. 1961, 1788-1797.
(15) Kiefer, H.; Traylor, T. G. Tetrahedron Lett. 1966, 6163-8.
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2058.
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V.; Cornilsen, B. C. J. Am. Chem. Soc. 1982, 104, 5114-5119.
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Mendenhall, G. D. J. Org. Chem. 1983, 48, 3728-3733.
(19) Arulsamy, N.; Bohle, D. S.; Imonigie, J. A.; Sagan, E. S. Inorg.
Chem. 1999, 38, 2716-2725.
(4) Kornblum, N.; Smiley, R. A.; Blackwood, R. K.; Iffland, D. C. J.
Am. Chem. Soc. 1955, 77, 6269-6280.
(5) Kornblum, N. The Synthesis of Aliphatic and Alicyclic Nitro
Compounds. Org. React. 1962, 12, 101-156.
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Org. Chem. 1989, 54, 2769-2771.
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(9) Ray, N. H. J. Chem. Soc. 1960, 4023-8.
(10) Harris, I.; Marshall, I.; Jarrett, K. B. Nature [London] 1947, 159,
843.
10.1021/ja994261o CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/24/2000

5540 J. Am. Chem. Soc., Vol. 122, No. 23, 2000
Arulsamy et al.
lation of MeONNO-. Taken together, these results demonstrate
and lay the framework for understanding the ambiphilic
character of hyponitrite alkylation.
Experimental Section
Materials and Methods. All chemicals and solvents were of reagent
grade. The solvents were purified by standard techniques.29 All of the
organic halides were used without further purification except tert-butyl
bromide, which was dried over molecular sieves and K2CO3 for 24 h
and distilled. Sodium and silver hyponitrites were prepared by literature
methods.19 Silver hyponitrite was thoroughly dried at room temperature
in a vacuum oven. IR spectra were recorded on a MIDAC FTIR
instrument as potassium bromide pellets or as neat samples between
KBr plates. Raman spectra were recorded on a Detection Limit Inc.,
Solution 633 Raman Laser System. UV-vis data were measured in
methanol solvent at room temperature on a Hewlett-Packard 8452 diode-
array spectrometer with quartz cuvettes. 1H and 13C NMR spectra were
recorded on a Bruker 400 MHz instrument at room temperature using
CDCl3 with TMS (0.05% v/v) as internal reference. Elemental analyses
were performed by either Atlantic Microlab, Norcross, GA or Galbraith
Laboratories, Inc., Knoxville, TN.
Figure 1. Six possible isomers for alkylation of Ag2N2O2 with alkyl
halides.
Synthesis of (CH3)3CN(O)NOC(CH3)3‚1/2HONNOH {1D‚1/2HON-
NOH}. This compound was prepared according to Kiefer and Tray-
lor’s15 method except that the filtrate was evaporated at high vacuum
to give X-ray quality crystals of N′-tert-butoxy-N-tert-butyl-N-diazene-
oxide with a solvated hyponitrous acid molecule. The volatile products
including the major product, trans-di-O-tert-butyl hyponitrite, were
collected in the liquid nitrogen trap and left behind colorless crystals
of 1D‚1/2HONNOH in the flask. Anal. Calcd for C16H38N6O6: C, 46.81;
H, 9.33; N, 20.47%. Found: C, 46.74; H, 9.27; N, 20.75%. IR (KBr):
3207 b, 3061 m, 2987 m, 2947 w, 2826 w, 1485 s, 1397 m, 1375s,
1274 s, 1252 s, 11185 s, 1067 s, 1020 sh, 1004 vs, 991 vs, 929 sh, 844
s, 809 w, 693 b, 615 w, 571 m, 492 w, 467 m, 448 m cm-1. 1H NMR
(CDCl3) δ 9.55 (s, 1H, HON), 1.57 (s, 9H, (CH3)3-C-N), 1.41 (s,
9H, (CH3)3-C-O); 13C NMR (CDCl3) δ 82.5, 73.5, 27.56, 27.49.The
free ester, 1D, was obtained as a colorless oil by passing the methylene
chloride solution of the hyponitrous acid adduct through either a neutral
preparative TLC plate or neutral alumina column using methylene
chloride as eluent. Anal. Calcd for C8H18N2O2: C, 55.14; H, 10.41; N,
16.08%. Found: C, 55.17; H, 10.50; N, 16.01%. IR (neat): 2992 vs,
2938 s, 2880 sh, 1485 s, 1414 sh, 1391 m, 1368 vs, 1271 s, 1248 sh,
1184 s, 1061 s, 1038 sh, 1013 sh, 991 vs, 924 sh, 901 w, 849 vs, 808
w, 743 m, 571 vs, 554 sh, 488 m, 474 sh, 442 m, 424 w cm-1. UV-
N′-hydroxydiazene-N-oxide (2D) from the reaction of tert-butyl
bromide with silver hyponitrite by the slightly modified
procedure of Kiefer et al.15 Although a number of (Z)-N-alkyl-
N-alkoxydiazene-N-oxides, RN(O)NOR with different organic
groups21-28 have been synthesized by other methods, there is
only one instance in which an N-alkyl-N-alkoxydiazene-N-oxide
has been isolated from the alkylation of silver hyponitrite.6 In
addition, there is no literature data on mono-alkyl hyponitrites
resulting from the reaction of alkyl halides with silver hyponi-
trite. In view of these results, and given the current interest in
this class of compounds, we decided to investigate the reactions
of tert-butyl-, tert-amyl-, p-tert-butylbenzyl bromides, and chloro
triethylsilane with silver hyponitrite more thoroughly to see if
they exhibit ambident alkylation reactivity similar to nitrite.
While the reactions of tert-butyl-15 and tert-amyl16,18 halides
with silver hyponitrite have been reported to yield the corre-
sponding trans-di-O-alkyl esters, those of p-tert-butylbenzyl
bromide and chlorotriethylsilane with silver hyponitrite were
heretofore unreported.
In this paper, we report (i) the synthesis, isolation, and
characterization of four isomers of tert-butyl and tert-amyl
hyponitrites; (ii) the synthesis and structural characterization
of p-tert-butylbenzyl hyponitrite, trans-bis-O-triethylsilyl hy-
ponitrite, and thallium hyponitrite; (iii) the thermal decomposi-
tion (DSC) and UV-vis spectroscopic studies of these com-
pounds, and (iv) ab initio calculations for the ground states and
vibrational frequencies for the dimethyl and methyl homologues
for these compounds, and transition states for the O/N methy-
vis (MeOH, λmax, nm (ꢀ)): 234 (7200 ( 80) M-1 cm-1 1H NMR
.
(CDCl3) δ 1.56 (s, 9H, (CH3)3-C-N), 1.41 (s, 9H, (CH3)3-C-O);
13C NMR (CDCl3) δ 82.3, 73.6, 27.79, 27.75. Yields obtained from
the above syntheses and from those described below are listed in
Table 4.
Synthesis of trans-Di-O-tert-butyl Hyponitrite (1A) trans-Mono-
O-tert-Butyl Hyponitrite (2A) and (Z)-N-tert-Butyl-N′-hydroxydia-
zene-N-oxide (2D). The crude product mixture was obtained from the
reaction of silver hyponitrite and tert-butyl bromide in diethyl ether
solvent as described by Kiefer and Traylor15 except that the solvent
was evaporated under a steady flow of nitrogen gas at room temperature.
The isomers were separated either by column chromatography or on
preparative silica gel TLC plate. First elution with hexane yielded
exclusively the trans-di-O-tert-butyl hyponitrite, 1A. The IR and NMR
spectral features of the product are consistent with those reported in
the literature.15,17,30 Subsequent elution with methylene chloride sepa-
rated the remaining products into three fractions. The first fraction
contained trans-mono-O-tert-butyl hyponitrite (2A), the second fraction
contained (Z)-N-tert-butyl-N′-tert-butoxydiazene-N-oxide (1D), and the
third fraction contained a mixture of (Z)-N-tert-butyl-N′-hydroxydia-
zene-N-oxide (2D) and tert-butyl alcohol. Note: When preparative basic
alumina TLC plate was used, 2A decomposed completely to tert-butyl
alcohol.
(20) In this manuscript the commonly used trans(E) and cis(Z) terms
will be used to describe the stereochemistry of hyponitrite and its esters
but for the alkylated diazenium diolates, which result from N-alkylation,
the stereochemistry will be solely denoted as Z or E around NdN.
(21) Freeman, J. P. J. Org. Chem. 1963, 28, 2508-2511.
(22) Freeman, J. P.; Lillwitz, L. D. J. Org. Chem. 1970, 35, 3107-3110.
(23) Cherepinskii-Malov, V. D.; Marchenko, G. A.; Makhametzyanov;
Buzykin, B. I. Bull. Acad. Sci. USSR, DiV. Chem. Sci. 1985, 34, 871.
(24) Marchenko, G. A.; Chertanova, L. F.; Antipin, M. Y.; Struchkov,
Y. T.; Punegova, L. N. Dokl. Phys. Chem. (Engl. Transl.) 1987, 294, 583-
586.
(25) Atovmyan, L. O.; Golovinam, N. I.; Zyuzin, I. N. Bull. Acad. Sci.
USSR, DiV. Chem. Sci. 1987, 36, 1205-1208.
(26) Bohle, D. S.; Imonigie, J. A. J. Org. Chem. Manuscript sub-
mitted.
(27) George, M. V.; Kierstead, R. W.; Wright, G. F. Can. J. Chem. 1959,
37, 679-699.
(28) Hickmann, E.; Hadicke, E.; Reuter, W. Tetrahedron Lett. 1979,
2457-2460.
(29) Perrin, D. D.; Armargo, W. L. Purification of Laboratory Chemicals,
3rd ed.; Pergamon Press: Oxford, U.K., 1988.
(30) Chen, H.-T. E.; Mendenhall, G. D. J. Am. Chem. Soc. 1984, 106,
6375-6378.

Dialkylation of Hyponitrite
J. Am. Chem. Soc., Vol. 122, No. 23, 2000 5541
(CH3)3CONNOH (2A). This compound is unstable at ambient
temperature, and was spectroscopically characterized. IR (neat): 3418
b, 2986 s, 2938 m, 2878 sh, 1566 w, 1477 m, 1462 sh, 1393 sh, 1372
s, 1267 m, 1190 s, 1082 w, 1030 sh, 988 vs, 926 w, 881 m, 760 s, 633
w, 530 w 469 w cm-1. UV-vis (MeOH, λmax, nm (ꢀ)): 224 (7172 (
5.23 (s, 4H), 7.31(d, 4H, J ) 8.36 Hz), 7.39(d, 4H, J ) 8.36 Hz); 13
NMR (CDCl3) δ131.5, 34.8, 75.6, 125. 7, 128. 8, 132.9, 151.8.
C
Synthesis of (C2H5)3SiONNOSi(C2H5)3 (6A). This compound was
prepared by the method in 6A above by the slow addition of 4.00 g of
dried silver hyponitrite to 2 mL of chlorotriethylsilane solution in
anhydrous ether with constant stirring at 0 °C. (Yield: 1.38 g, 40.7%).
Anal. Calcd for C12H30Si2N2O2: C, 49.61; H, 10.41%. Found: C, 49.97;
H, 10.44. IR (neat): 2959 vs, 2914 s, 2882 s, 1461 m, 1412 m, 1379
w, 1239 m, 1072 m, 1016 sh, 990 vs, 779 s, 742 vs, 681 sh, 579 w,
459 m cm-1. UV-vis (MeOH, λmax, nm (ꢀ)): 222 (2522 ( 100) M-1
cm-1. 1H NMR (CDCl3) δ 1.00 (t, 6H, J ) 7.82 Hz), 0.79 (q, 4H, J )
7.91 Hz), 13C NMR (CDCl3) δ 7.00, 6.56.
1
50) M-1 cm-1. H NMR (CDCl3) δ 1.38 (s, 9H), 8.31 (s, 1H); 13C
NMR (CDCl3) δ 82.1, 27.89.
(CH3)3CN(O)NOH (2D). This compound is isolated in trace
quantities from the reaction of tert-butyl bromide and silver hyponitrite.
Its spectroscopic properties are identical to those of an authentic sample
of N-tert-butyl-N′-hydroxydiazene-N-oxide prepared as described below.
To a solution of N-tert-butylhydroxylamine acetate (1.49 g, 0.01
mol) in aqueous acetic acid (0.1 M, 5 mL) cooled to 0 °C was added
a saturated aqueous solution of sodium nitrite (0.695 g, 0.01 mol). The
colorless solution was stirred at 0 °C for 2 h, and was allowed to warm
to room temperature with stirring overnight. The product formed as
yellow globules was extracted with methylene chloride. The methylene
chloride solution was dried with anhydrous sodium sulfate. The solvent
was removed in a rotary evaporator at room temperature and the product
was obtained as yellow liquid. Yield: 0.980 g (83%). Anal. Calcd For
C4H10N2O2: C, 40.67; H, 8.53; 23.71. Found: C, 40.36; H, 8.38; N,
23.87. IR (cm-1): 2988 s; 2945 m; 1755 w; 1718 w; 1481 s; 1459 s;
1415 s; 1371 vs; 1343 sh; 1248 s; 1187 s; 1071 vs; 1031 m; 946 s; 810
w; 719 s; 674 m; 577 m; 505 w; 426 m. UV-vis (MeOH, λmax, nm
Synthesis of Tl2N2O2 (7A). Thallium (I) carbonate was suspended
in methanol and cooled in an ice bath. Excess HClO4 was added
dropwise until effervescence stopped. The white precipitate of TlClO4
was filtered and dried. Well-dried TlClO4 (1.31 g) was dissolved in
water and filtered to remove any insoluble materials. Dried sodium
hyponitrite (0.87 g) dissolved in water was added dropwise with
constant stirring. The deep yellow precipitate formed was filtered and
dried in a vacuum oven at room temperature. Yield: 0.87 g, 47.2%.
Anal. Calcd for Tl2N2O2: Tl, 87.2; N, 5.97%. Found: Tl, 87.2; N,
5.91%. IR (KBr): 1106 w, 951 vs, 515 w, 499 w, 472 w cm-1. UV-
vis (0.1 M NaOH, λmax, nm (ꢀ)): 246 (6950 ( 60) M-1 cm-1
.
Kinetics. The kinetics of the decomposition of tert-BuONNOH were
performed using a Hewlett-Packard 8452 Diode-Array Spectrometer
with quartz cuvettes. The reaction temperature was maintained at 25
°C by means of external circulating baths. The reaction was monitored
at 242 nm, and the observed first-order rate constant represents the
average of four replicate runs.
1
(ꢀ)): 228 (4710 ( 20) M-1 cm-1. H NMR (CDCl3) δ 11.9, N2O2H;
1.60, C(CH3)3; 13C NMR (CDCl3) δ 72.3, C(CH3)3; δ 27.3, C(CH3)3.
Synthesis of tert-Amylhyponitrite Isomers. These isomers were
prepared and separated by the method described above for the tert-
butyl hyponitrite isomers. trans-Di-O-tert-amylhyponitrite (3A) isolated
from these isomers has characteristics similar to those reported in the
literature.16,18
Thermal Analysis. Thermal analysis measurements were carried
out on a TA Instruments DSC 2010 Differential Scanning Calorimeter
equipped with a liquid nitrogen cooling accessory and calibrated with
indium reference samples. About 2-5 mg of sample was loaded into
an aluminum sample cup for each run. The thermal cycle was performed
using 10 °C/min heating rate under an argon atmosphere from 25 to
500 °C. The heat exchanger installed on the DSC cell allows for the
measurements of the thermal properties during heating and cooling.
Ab Initio Calculations. The calculations described here were
performed using Gaussian 98 implemented on a Silicon Graphics Iris
Indigo workstation.31 Full optimizations were initially performed at the
restricted Hartree-Fock(HF) level using the polarized split valence
6-31G* basis sets before the final optimizations which were performed
by density functional theory using Becke’s 3 parameter functional and
triple split valence basis sets, 6-311++G**.
Crystallographic Structure Determinations. X-ray diffraction data
were collected for single crystals of compounds (CH3)3CN(O)NOC-
(CH3)3‚1/2HONNOH (1D‚1/2HONNOH), and p-(CH3)3CC6H4CH2-
ONNOCH2C6H4-p-C(CH3)3 (5A) on a Siemens P4 Diffractometer
equipped with a molybdenum tube [λ(KR1) ) 0.70926 Å; λ(KR2) )
0.71354 Å] and a graphite monochromator at -100 °C. The crystals
were mounted on a glass fiber using epoxy adhesive resin and were
coated with Paratone N oil. The intensities of three standard reflections
were monitored every 100 reflections during the respective data
collections indicated negligible crystal decomposition. The structures
were solved by direct methods and refined by full-matrix least-squares
techniques on F2 using structure solution programs from the SHELXTL
system.32 Important crystallographic parameters are collected in Table
(Z)-C2H5(CH3)2CN(O)NOC(CH3)2C2H5 (3D). Anal. Calcd for
C10H22N2O2: C, 59.37; H, 10.96; N, 13.85%. Found: C, 59.86; H,
10.93; N, 13.56%. IR (Neat): 2978 s, 2940 s, 2884 m, 1481 s, 1467
sh, 1386 m, 1369 m, 1302 w, 1266 w, 1247 w, 1203 w, 1174 m, 1153
sh, 1069 m, 1030 m, 987 vs, 928 w, 841 m, 806 w, 743 w, 740 w, 615
w, 593 w, 563 w cm-1. UV-vis (MeOH, λmax, nm (ꢀ)): 234 (6998 (
1
60) M-1 cm-1. H NMR (CDCl3) δ 1.87 (q, 4H, (CH3CH2-C-N), J
) 7.43 Hz), 1.73 (q, 4H, (CH3CH2-C-O), J ) 7.54 Hz), 1.51 (s, 12H,
(CH3)2-C-N), 1.36 (s, 12H, (CH3)2-C-O), 0.91 (t, 6H, (CH3CH2-
C-N), J ) 7.54 Hz), 0.85 (t, 6H, (CH3CH2-C-O), J ) 7.48 Hz); 13
NMR (CDCl3) δ 84.7, 76.7, 25.41, 25.40, 33.2, 33.1, 8.51, 8.43.
C
trans-C2H5(CH3)2CONNOH (4A). This compound is unstable at
ambient temperature and was spectroscopically characterized. IR
(neat): 3430 b, 2978 s, 2938 m, 2885 sh, 1561 w, 1462 m, 1372 s,
1301 w, 1248 w, 1210 w, 1174 m, 1152 m, 1083 sh, 1057 m, 989 vs,
932 sh, 874 m, 785 w, 748 w, 631 w, 577 w, 523 w cm-1. UV-vis
(MeOH, λmax, nm (ꢀ)): 224 (6980 ( 100) M-1 cm-1. 1H NMR (CDCl3)
δ 8.03 (s, 1H), 1.34 (s, 6H), 1.70 (q, 2H, J ) 7.53 Hz), 0.91(t, 3H, J
) 7.52 Hz); 13C NMR (CDCl3) δ 84.4, 25.5, 33.2, 8.36.
C2H5(CH3)2CN(O)NOH (4D). This compound was isolated in trace
quantities and was spectroscopically identified as N-tert-amyl-N′-
1
hydroxydiazene-N-oxide. H NMR (CDCl3) δ 12.0 (s, 1H), 1.55 (s,
6H), 1.91 (q, 2H), 0.92 (t, 3H); 13C NMR (CDCl3) δ 75.64, 32.96,
24.74, 8.27.
Synthesis of p-(CH3)3CC6H4CH2ONNO-p-CH2C6H4C(CH3)3 (5A).
p-tert-Butylbenzyl bromide, 1 mL, was dissolved in anhydrous ether
and cooled in ice. Excess silver hyponitrite (3 g) was added slowly
and the temperature maintained at 0 °C with constant stirring. After
the mixture stirred for about 1 h, the precipitated AgBr was filtered
off and the solution evaporated under a stream of nitrogen gas. Crystals
suitable for X-ray analysis were obtained by recrystallizing the crude
product from ether at -68 °C. Yield: 0.73 g, 38%. Anal. Calcd for
C22H30N2O2: C, 74.12; H, 9.05; N, 7.86%. Found: C, 74.11; H, 8.68;
N, 7.60%. IR (KBr): 2961 s, 2872 m, 1618 vw, 1516 vw, 1472 w,
1406 vw, 1368 m, 1267 w, 1271 vw, 1113 w, 1013 vs, 936 m, 826 m,
689 w, 565 m cm-1. Raman: 3068 m, 3047 w, 2963 vs, 2954 vs, 2925
m, 2901s, 2863 m, 1611 s, 1508 vw, 1465, w 1441 vw, 1356 w, 1264
vw, 1219 m, 1197 m, 1187 m, 1105 s, 1081s, 1020 vw, 978 vw, 919
(31) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.;
Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A.
D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi,
M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.;
Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick,
D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.;
Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi,
I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M.
W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98; Gaussian Inc.: Pittsburgh,
PA, 1998.
w, 854 m, 829 w, 812 s, 745 w, 680 w, 636 m, 623 vs, 542 w cm-1
UV-vis (MeOH, λmax, nm): 226. H NMR (CDCl3) δ 1.32 (s, 18H),
.
(32) Sheldrick, G. M. SHELXTL Crystallograpic System, version 5.3;
Iris Siemens Analytical X-ray Instruments, Inc.: Madison, WI, 1995.
1

5542 J. Am. Chem. Soc., Vol. 122, No. 23, 2000
Arulsamy et al.
Table 1. Crystallographic Data for 1D‚1/2(HONNOH) and 5A
However, in the reaction of p-tert-butylbenzyl bromide with
silver hyponitrite, trans-di-O-alkylated hyponitrite was isolated
as the sole alkylated product together with small amounts of
p-tert-butylbenzyl alcohol and p-tert-butylbenzyl aldehyde.
Similarly, only the trans-di-O-silyl hyponitrite was isolated in
good yield (Table 3) from the reaction of chlorotriethylsilane
with silver hyponitrite.
Alkylation reactions of Na2N2O2, Tl2N2O2, [HEt2NCH2CH2-
NEt2H][N2O2],19 and [quinuclidinium]2[N2O2]19 were also at-
tempted by treating ethereal solutions of the alkyl halides with
the corresponding hyponitrite salts. However, the reactions did
not yield alkylated products.
During the separation of the constitutional isomers present
in the mixture of products obtained from the reaction of tert-
butyl bromide with silver hyponitrite, trans-mono-O-tert-butyl
hyponitrous acid was found to decompose slowly on silica gel
and rapidly on alumina to tert-butyl alcohol and nitrous oxide.
Although the isomers were separated by chromatographic
techniques, pure trans-di-O-tert-butyl hyponitrite could also be
obtained by re-crystallizing the crude mixture from methanol
at -58 °C as reported in the literature.15 Pure crystals of (Z)-
N-tert-butyl-N′-tert-butoxydiazene-N-oxide, as its hyponitrous
acid adduct, could also be obtained by subjecting the crude
product mixture to high vacuum; the more volatile components
are removed leaving behind only (Z)-N-tert-butyl-N′-tert-
butoxydiazene-N-oxide with solvated hyponitrous acid (1D‚
1/2HONNOH). The remaining two isomers were separated by
column chromatography or by preparative TLC plates as
described in the Experimental Section.
1D‚1/2(HONNOH)
5A
empirical formula
fw
λ, Å
space group
a, Å
b, Å
c, Å
C16H38N6O6
410.52
0.71073
P21/c
7.6869 (6)
17.979 (2)
9.0732 (13)
90
92.464(10)
90
1252.8 (3)
2
0.083
1.088
-100
1.018
0.0384
0.1026
C22H30N2O2
354.48
0.71073
C2/c
13.076 (2)
10.113 (2)
15.780 (2)
90
94.146 (8)
90
2081.3 (5)
4
0.072
1.131
-100
1.049
0.0463
0.1169
R, °
â, °
γ, °
V, Å3
Z
µ, mm-1
F
calcd, g cm-3
T, °C
Sgof
R1a [F > 2σF]
b
wR2
a R1 ) Σ||Fo| - |Fc||/Σ|Fo|. b wR2 ) [Σ{w(Fo -Fc2)2}/Σ{w(Fo )2}]1/2
.
2
2
1. Selected atomic positional parameters, interatomic distances and bond
angles for 1D and 5A are presented in Tables S1-S8 and 2.
(CH3)3CN(O)NOC(CH3)3‚1/2HONNOH (1D‚1/2HONNOH). X-ray
diffraction data were collected for a colorless crystal of dimensions,
0.38 × 0.42 × 0.90 mm. The compound crystallizes in the monoclinic
space group P21/c with 2 (CH3)3CN(O)NOC(CH3)3‚1/2HONNOH in the
unit cell, each lying on an inversion center. A total of 2191 (Rint
)
0.0135) observed independent reflections [F > 4σ(F)] were collected
in the 2θ range, 4.54 to 50°, with the data gathered having -9 e h e
1, -21 e k e 1, -10 e l e 10. The data were not corrected for
absorption. All hydrogen atoms were located in successive Fourier maps
and refined isotropically, whereas the non-hydrogen atoms were refined
anisotropically. The structure was refined by weighted least-squares,
Kinetics. The decomposition of tert-BuONNOH in 1.0 M
NaOH, ionic strength (I ) 1.0 M) at 25 °C, results in the
formation of tert-BuOH and N2O, respectively, according to
the eq 1. The rate law for the decomposition of tert-BuONNOH
is given by eq 2 with a first-order rate constant (k) of (1.08 (
w-1 ) σ2Fo + (0.0262P)2 + 0.08P, where P ) (Fo + 4Fc2)/3. The
maximum and minimum residual intensities remaining were 0.153 eÅ-3
and -0.162 eÅ-3, respectively.
2
2
0.01) × 10-3 s-1
.
p-(CH3)3CC6H4CH2ONNOCH2C6H4-p-C(CH3)3 (5A). X-ray dif-
fraction data were collected for a colorless crystal of dimensions, 0.5
mm × 0.62 mm × 0.74 mm. The compound crystallizes in the
monoclinic space group C2/c with four p-(CH3)3CC6H4CH2ONNO-p-
CH2C6H4C(CH3)3 molecules in the unit cell, each located on a center
of inversion. A total of 1821 (Rint ) 0.0225) observed independent
reflections [F > 4σ(F)] were collected in the 2θ range, 5.10 to 50°,
with the data gathered having -1 e h e 15, -12 e k e 1, -18 e l
e 18. The data were not corrected for absorption. All hydrogen atoms
were located in successive Fourier maps and refined isotropically,
t-BuONNOH + OH- 9k8 t-BuOH + N2Ov
-d[t-BuONNO-]/dt ) k[t-BuONNO-]
(1)
(2)
Spectroscopic Results. The IR spectra of these compounds
were recorded between 4000 and 400 cm-1. The spectra exhibit
a strong peak at ∼1000 cm-1 corresponding to the N-O
asymmetric stretch vibrational mode. In addition, the spectra
of compounds 2A and 3A also exhibit a peak in the 3400 cm-1
region indicating the presence of hydroxyl group together with
another absorption at ca. 1540 cm-1 corresponding to δ(OH)
stretching vibrational mode (Table 4).
whereas the non-hydrogen atoms were refined anisotropically. The
structure was refined by weighted least-squares, w-1 ) σ2Fo
+
2
(0.0763P)2 + 4.54P, where P ) (Fo + 4Fc2)/3. The maximum and
minimum residuals in the electron density difference maps were 0.285
eÅ-3 and -0.217 eÅ-3, respectively.
2
The UV-visible spectra for the compounds were measured
at room temperature in methanol solution. The spectral data are
collected in Table 4. The spectra of compounds 1A, 2A, 3A,
4A, 5A, and 6A exhibit single bands with λmax in the narrow
224-226 nm region while compounds 1D and 3D exhibit a
single band at λmax 234 nm.
Differential Scanning Calorimetric Data. The thermal
decomposition properties of compounds 1A-7A, 1D, and 3D
were studied by differential scanning calorimetry in the tem-
perature region, 25-500 °C, under a steady stream of argon
gas. Compounds 1A-7A undergo exothermic decomposition,
while compounds 1D and 3D undergo endothermic decomposi-
tion, and the data are presented in Table 5.
Results
Synthesis. The alkylation reactions of silver hyponitrite were
carried out by the procedure of Kiefer et al.15 When silver
hyponitrite was added to a solution of tert-butyl bromide at ∼0
°C, a vigorous effervescence with the evolution of a colorless
gas was observed. The yields for these reactions were generally
low. As shown in the Scheme 1 and Table 3 below, four
products were isolated from the reactions of tert-butyl and tert-
amyl bromide with silver hyponitrite. The ratio of the products
was only slightly altered by the addition of K2CO3 to the reaction
mixture. Together with that of the four isomers the formation
of the corresponding alcohols was also observed. When sub-
stoichiometric amounts of tert-butyl bromide or tert-amyl
bromide were used in the reactions, the trans-mono-O-alkylated
isomer was obtained as the predominant product.
Theoretical Results. Optimized ground-state structures cal-
culated for trans-dimethylhyponitrite, 8, trans-methylhyponi-
trite, 9, (Z)-N-methyl-N′-methoxydiazene-N-oxide, 10, and N-

Dialkylation of Hyponitrite
J. Am. Chem. Soc., Vol. 122, No. 23, 2000 5543
Table 2. Selected Bond Lengths (Å) and Angles (deg) of 1D‚1/2(HONNOH) and 5A
compds
NdN (Å)
N-O (Å)
N-N-O (deg)
other parameters
1D‚1/2(HONNOH) N(1)-N(2) 1.264 (2)
N(1)-O(1) 1.2679 (14) N(1)-N(2)-O(2) 108.66 (10)
C(1)-O(2) 1.483 (2) (Å)
O(1)‚‚‚O(3) 2.696 (2) (Å)
N(2)-O(2) 1.369 (2)
N(2)-N(1)-O(1) 125.47 (11)
N(3)-N(3A) 1.216 (2) N(3)-O(3) 1.382 (2)
N(3)-N(3A)-O(3) 108.22 (14) O(1)-N(1)-C(5) 117.65 (10) (°)
N(2)-O(2)-C(1) 109.67 (10) (°)
O(2)-C(1)-C(2) 109.31 (13) (°)
O(2)-C(1)-C(3) 109.13 (12) (°)
O(2)-C(1)-C(4) 101.83 (13) (°)
5A
N(1)-N(1A) 1.230 (3) N(1)-O(1) 1.361(2)
N(1)-N(1A)-O(1) 107.7 (2)
C(1)-O(1) 1.468 (2) (Å)
N(1)-O(1)-C(1) 108.29 (13) (°)
O(1)-C(1)-C(2) 108.0 (2) (°)
Scheme 1. Reaction of tert-Butyl- or tert-Amyl Bromides with Ag2N2O2
1
2
4
5
3
6
Table 3. Reactions of Alkyl Halides with Silver Hyponitritea
isolated yield (%) ( 1%
RBr to Ag2N2O2 order of addition RONNOR RN(O)NOR RONNOH RN(O)NOH Total
alkyl
group (R)
reaction
conditions
mole ratio of
(CH3)3C
Et2O
Et2O/K2CO3
Et2O
Et2O
Et2O/K2CO3
Et2O
2:1
3:1
1:1
2:1
2:1
1:1
1:2
1:1.5
Ag2N2O2 to RBr
Ag2N2O2 to RBr
RBr to Ag2N2O2
Ag2N2O2 to RBr
Ag2N2O2 to RBr
RBr to Ag2N2O2
Ag2N2O2 to RBr
Ag2N2O2 to RBr
16
12
6
14
11
7
6
6
4
8
5
4
e
e
8
13
18
7
12
16
e
2
2
4
2
1
3
e
e
32d
33d
32d
31d
29d
30d
38d
41d
(CH3)3Cb
(CH3)3Cc
CH3CH2(CH3)2C
bCH3CH2(CH3)2C
cCH3CH2(CH3)2C
p-(CH3)3CC6H4CH2 Et2O
(CH3CH2)3Si Et2O
38
41
e
a All reactions were performed in ∼20 mL ether at -5 to 0 °C for 45 min except the last reaction that performed for about 24 h. b These
reactions were performed in ∼20 mL ether/K2CO3. c A substoichiometric equivalent of the corresponding alkyl halides was added to an ether
1
suspension of excess Ag2N2O2. d The yield was estimated from the H NMR integration ratio and the actual yield. e Products not formed.
methyldiazenenium diolate, 11, at B3LYP/6-311++G** level
of theory are shown in Figure 5. The local minima for all four
structures have a mirror plane of symmetry defined by the
ONNO framework. The trans derivative 8 has inversion and
C2 axial symmetries, which result in a net C2h point group
symmetry. Thus for their respective point groups the vibrations
of 8, Cs, symmetry, are either in plane, A′, or out of plane, A′′,
while for 9, C2h point symmetry, these modes are either gerade
or ungerade with respect to the inversion symmetry. At the
B3LYP/6-311+G* level of theory optimization of the trans-
hyponitrite dianion has N-O and NdN bond lengths of 1.3671
and 1.2645 Å, respectively, and an O-N-N bond angle of
115.421° Comprehensive lists of the vibrational modes, their
energies, and symmetries are collected in Table S9.
Structure of (CH3)3CN(O)NOC(CH3)3‚1/2HONNOH (1D‚
1/2HONNOH). The crystals contain N-tert-butyl-N′-tert-bu-
toxydiazene-N-oxide (1D) cocrystallized with hyponitrous acid
as shown in Figure 2. Whereas the diazene-N-oxide molecule
occupies general positions, the hyponitrous acid molecule lies
on an inversion center. All atoms of the latter molecule are
coplanar, and the molecule possesses trans geometry. Bonding
features associated with the acid molecule are comparable to
those of the molecule also present as solvate in the crystals of
the N, N-N′, N′-tetraethylethylenediammonium salt of hyponi-
trous acid.19
The N2O2 fragment in the diazene-N-oxide exhibits Z
geometry with respect to the orientation of the N-oxide and tert-
butoxy oxygen atoms. The fragment is nearly coplanar with the
maximum deviation from the least mean squares plane being
0.0017 Å and the dihedral angle between the two NNO planes
being 0.6°. The bonding environment of one of the two nitrogen
Structural Data. Compounds 1D‚1/2HONNOH and 5A have
been characterized by single X-ray diffraction data at -100 °C.
Selected bond distances and angles are presented in Table 2.

5544 J. Am. Chem. Soc., Vol. 122, No. 23, 2000
Arulsamy et al.
Table 4. Spectroscopic Results for New Compounds
IR
UV-vis (in MeOH)
ꢀ(max) (M-1 cm-1
)
compound
ν(OH)
δ(OH)
ν(N-O)as
other bandsf
λ(max)
1A
1D
995a
226a
224.6b
226c
234
6200a
7010b
7100c
7200
990b
995c vs
1061 vs
991 s
-
ν(NdN) 1485 s
1D‚1/2(HONNOH)
3207 b
3418 b
1532 m
1067 vs
ν(NdN) 1485 s
1004 vs
991 vs
988 vs
ν(NdN) 1481 s
2A
2D
3A
1566 w
1718 w
224
228
225b
226c
234
224
226d
7172
4710
7000b
7060c
6998
6980
-
1071 vs
990b vs
988c vs
1069 s
989 vs
1013 vs
3D
4A
5A
-
-
ν(NdN) 1481 s
3430 b
-
1561 w
ν(N-N)as (Ram) 1611 s
ν(N-O)s (Ram) 1081 s
ν(N-N-O)s (Ram) 623 vs
6A
7A
-
-
990 vs
951 vs
222
2522
246e
6950e
a Reference 15. b Reference 18. c This work. d Benzyl chromophore overlap prevents quatitative determination of ꢀ. e 0.1 M NaOH. f Raman
active bands denoted (Ram).
Table 5. Differential Scanning Calorimetric Data
Tonset
(°C)
Tmax
(°C)
∆H
(cal/g)
∆H
(kcal/mol)
compound
1A
1A
1A
1D
-
-
82a
-
-
-
-
84.5b
86.5c
86.7
76.5
120
73.4
66.4
73.9
106
81.0
74.7
117
190
91.4c
119
81.2
142
90.8
68.3
92.7
136
93.3
84.1
143
205
-62.3c
+37.4
+34.8
+35.9
-55.4
-7.59
-131
+40.3
-57.3
-198
-150
-51.1
-10.84c
+6.52
+16.72
1D‚1/2(HONNOH)
Figure 3. ORTEP view of (CH3)3CC6H4CH2ONNOCH2C6H4C(CH3)3.
All atoms except hydrogen atoms are labeled.
2A
2D
3A
3D
4A
5A
6A
7A
-6.55
-0.897
-26.46
+8.15
methoxydiazene-N-oxide), and propane-2,2-bis(N′-methoxydia-
zene-N-oxide)25 also exhibit similar structural features.
The diazene-N-oxide and hyponitrous acid molecules are
involved in intermolecular hydrogen bonding. The two sym-
metrically related hydroxy groups of the acid molecule interact
with the N-oxide oxygen atoms of two diazene-N-oxide
molecules with the O‚‚‚O distance of 2.696(2) Å.
-7.52
-71.67
-33.65
-23.93
a Reference 15. b Reference 30. c This work.
Structure of p-(CH3)3CC6H4CH2ONNOCH2C6H4-p-C-
(CH3)3 (5A). The structure consists of trans-p-di-tert-butylben-
zyl hyponitrite molecules, with the NdN bond situated on an
inversion center, Figure 3. The molecule exhibits trans geometry
with respect to the orientation of the two alkoxy groups, and
the N2O2 fragment is planar similar to trans-di-O-tert-butyl
hyponitrite.17 However, the observed N-N, N-O, and O-C
bond distances of 1.230(3) Å, 1.361(2) Å, and 1.468(2) Å,
respectively, are significantly shorter ( ∼0.02 Å) in comparison
to those in trans-di-O-tert-butyl hyponitrite.17
Discussion
A critical observation described here is that the reaction of
tert-butyl- and tert-amyl bromides with Ag2N2O2 leads to
ambiphilic alkylation of Ag2N2O2. Of the oxyanions of nitrogen
the best understood ambiphilic alkylation is for the reaction of
tert-butyl- and tert-amyl halides with silver nitrite which results
in both the nitrito and nitro derivatives.3-5 Although the
ambiphilic alkylation of silver hyponitrite with bromo- and
chlorodiphenylmethane has been outlined,6 this report describes
this reactivity pattern for a wider range of electrophiles.
Curiously, despite the numerous experiments with di-tert-butyl
hyponitrite it is the only reported product from the alkylation
of silver hyponitrite with tert-butylbromide. The most plausible
Figure 2. ORTEP view of (CH3)3CN(O)NOC(CH3)3‚1/2(HONNOH).
All atoms except hydrogen atoms are labeled.
atoms, N(1), is trigonal planar (sum of bond angles ) 360°).
The observed N-N, N-Obutoxy, N-Ooxide bond distances of
1.264(1) Å, 1.369(1) Å, and 1.268(1) Å, respectively, indicate
delocalized π-bonding over the N2O2 fragment. Four other
compounds, namely, N-methyl-N′-methoxydiazene-N-oxide,24
methylene-bis(N′-methoxydiazene-N-oxide),23 ethane-1,1-bis(N′-

Dialkylation of Hyponitrite
J. Am. Chem. Soc., Vol. 122, No. 23, 2000 5545
Figure 4. Frontier molecular orbital diagrams and Mulliken charges for N2O22-, MeONNO-, and MeN(O)NO-.
reason other workers have not observed the formation of the
complete product spectrum in the alkylation of hyponitrite is
due to the routine use of methanol in the final recrystallization
step. This step allows for the isolation and separation of
compound A from all of the other products.15 Unlike trans-di-
O-alkyl hyponitrite, the polar O/N-alkylated products, as well
as the mono-alkylated products, are highly soluble in methanol
and water.
Any discussion of the mechanism of hyponitrite alkylation
is tempered by the heterogeneous nature of these transformations
and the concomitant absence of homogeneous phase kinetic data
(see below). There is also a critical requirement for a Lewis
acid, in our experiments the silver cation, and this poses the
possibility for electron-transfer catalysis in these alkylations.33
Despite these severe limitations, we note that Mendenhall has
concluded that the reactivity of alkyl halides with Ag2N2O2
follows the stability of the incipient carbocation,6 and thus there
is likely to be considerable SN1 character in these transition
states. In his seminal studies of the ambident alkylation of nitrite
Kornblum dissected these alkylations into transition states with
varying SN1/SN2 character.3,4 Many of his conclusions can be
more succinctly stated in terms of frontier molecular orbital
theory,34 and we note that very complicated ambident nucleo-
philicity can be successfully understood in terms of charge vs
orbital control as well by considerations of thermodynamic/
kinetic control.35,36
Initial O-alkylation results in a mono-O-alkyl hyponitrite
intermediate species, RONNO-. As can be seen in Figure 4,
the Mulliken charges of MeONNO- are more biased toward
the nonalkylated oxygen atom, and the HOMO is largely
localized on this same atom. The expectation for either a charge
or orbital controlled reaction, for the SN1 limiting case, is then
for the second alkylation to occur by attack of the incipient
carbocation on the oxygen atom, resulting in the formation of
trans-di-O-alkyl hyponitrite, RONNOR, as the major product,
as found for the entries in Table 3 for R ) Et3Si, p-(CH3)3-
CC6H4CH2, and (CH3)3C. In the first two cases the O/O-
dialkylated product is the only one isolated. Since charge and
orbital localization on the nitrogen atom of the nonalkylated
half of the species is very poor, N-alkylation will be highly
disfavored. In the case of a limiting SN2 mechanism the gas-
phase transition states for the alkylation of MeONNO-, Figure
6, also suggest that the comparatively low barriers to O-
alkylation will favor the formation of MeONNOMe. Therefore,
To help understand the regioselectivity in these alkylation
reactions we have performed ab initio calculations for trans-
hyponitrite, trans-hyponitrous acid, analogues of the most likely
intermediates in these reactions, and representative SN2 transition
states corresponding to O- and N-alkylation. For computational
efficiency we have optimized the geometries and calculated the
frequencies for the mono- and dimethyl analogues of these
species with density functional theory, B3LYP, and large basis
sets, 6-311++G**, Figure 5. The HOMO and LUMO orbitals
for mono-O-alkyl and mono-N-alkyl hyponitrite anions are
shown in Figure 4. The HOMO of the hyponitrite dianion has
Au symmetry and is delocalized over the complete framework.
However, the Mulliken charges and the orbital coefficients
indicate slightly more electron density resides on the oxygens
than the nitrogens, both being critical factors for a limiting SN1
alkylation mechanism. The other limiting case is an SN2
transition state where C-O or C-N bond formation is coupled
to C-X bond cleavage. To help distinguish between oxygen
and nitrogen nucleophilicity in O vs N alkylation we have
calculated the transition states for the addition of methyl chloride
to either atom. The geometries for these transition states, shown
in Figure 6, were initially located by scanning the energies of
Z-matrix representations of the expected transition state with
respect to the Cl-C-H angle as a function of the reaction
coordinate. The resulting initial transition states were subse-
quently completely optimized to give the transition-state
structures in Figure 6. Confirmation that these transition states
connect the reactants, MeONNO- and CH3Cl, with the products,
MeONNOMe or MeONN(O)Me and Cl-, was found by
geometrical optimization of the steps along the internal reaction
coordinate away from the transition-state saddle point. As shown
in Figure 6 alkylation of either oxygen or nitrogen with methyl
chloride gives slightly early transition states characterized by
an O-C-H and an N-C-H angles of 84.53° and 87.88°, and
(33) Kornblum, N. Chemistry of the Amino, Nitroso, and Nitro Functional
Groups; Patai, S., Ed.; Wiley: New York, 1982; Part I, Suppl. F, Chapter
10, pp 361-393.
(34) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley & Sons: London, 1976.
(35) Arndt, A.; Handke, G.; Krause, N. Chem. Ber. 1993, 126, 251-
259.
q
which have ∆Ea of 5.6 and 7.5 kcal mol-1, respectively.
(36) Frederick, M. A.; Hulce, M. Tetrahedron 1997, 53, 10197-10227.

5546 J. Am. Chem. Soc., Vol. 122, No. 23, 2000
Arulsamy et al.
h
Figure 5. Optimized ground-state structures of critical substrates and proposed intermediates in this study. Geometries calculated at B3LYP/
6-311++G** level of theory, distances given in Å and angles given in degrees.
the formation of (Z)-N-alkyl-N′-alkoxydiazene-N-oxide species
D probably does not involve the mono-O-alkylated intermediate.
The formation of (Z)-N-alkyl-N′-alkoxydiazene-N-oxide from
trans- or (E)-hyponitrite can be rationalized as follows. The first
alkylation could occur on one of the two nitrogen atoms resulting
in the formation of a mono-N-alkylhyponitrite or diazenium
diolate species, RN(O)NO-. As can be seen in Figure 4, the
Mulliken charges and the orbital coefficients of the HOMO of
MeN(O)NO- are significantly localized on the second oxygen
atom, suggesting that in an SN1 limiting mechanism O-alkylation
of the terminal oxygen will be more favored over second
N-alkylation.
The experimental observation of the formation of trans-di-
O-alkylhyponitrite and N-alkyl-N′-alkoxydiazene-N-oxide, with
the former being the major product, is consistent with the above
theoretical arguments. The isolation of the two protonated
species of the initial mono-O- and mono-N-alkyl derivatives,
namely, mono-O-tert-butylhyponitrous acid, (CH3)3CONNOH,
and N-tert-butyl-N′-hydroxydiazene-N-oxide, (CH3)3CN(O)-
NOH, also supports the above arguments. However, the
observed Z-geometry for N-tert-butyl-N′-tert-butoxydiazene-N-
oxide remains to be explained.
instructive to consider the sequence of events that might follow
from subsequent trans/cis or E/Z-isomerization after O-alkyla-
tion. If initial O-alkylation forms the trans-mono-O-alkylated
intermediate, isomerization of the trans-O-alkylated intermediate
to the Z form might occur before the second N-alkylation.
However, we have found that the Z form of the O-alkylated
intermediate is electronically unstable; at both the B3LYP and
MP2 levels of theory we are unable to find a stable minimum
which would correspond to cis-O-monomethyl hyponitrite, G
in Figure 7. All attempts to locate such a minimum consistently
optimize to a weakly associated methoxide adduct of nitrous
oxide, Figure 7, as the local minima. Thus, the potential energy
surface which describes the reaction coordinate between the
putative structure G, and the minimum in Figure 6, does not
contain a significant barrier which would result in a saddle point/
transition state. Therefore, trans f cis, or E f Z, isomerization
is expected to spontaneously result in the formation of RO-
and nitrous oxide, and this may account for why cis-dialkylated
hyponitrites are not isolated in these reactions. Also, a second
N-alkylation of the trans-RONNO- is electronically disfavored.
We conclude that the formation of N/O-dialkyl products most
likely occurs via the mono-N-alkylated intermediate species.
A comparison of the ground-state energies of the E and Z forms
of the N/O-dialkyl hyponitrite indicates that the Z form is
marginally more thermodynamically stable, ∼2 kcal/mol, in the
On the basis of the frontier molecular orbital calculations and
model transition states we predict that initial O-alkylation does
not lead to mixed N/O-dialkylated products. It is however

Dialkylation of Hyponitrite
J. Am. Chem. Soc., Vol. 122, No. 23, 2000 5547
intermediate, which would then have to undergo E/Z isomer-
ization to form the comparatively more stable Z form of the
intermediate. This intermediate would then undergo a second
O-alkylation (1D and 3D) or O-protonation (2D and 4D) to give
the observed products. Due to either their inherent instability,
or to the conformational dynamics leading to their formation,
compounds with the structure B, C, E, and F, were not observed
in any of the alkylation reactions studied.
To help understand the origin of protons and protonated
mono-alkylated derivatives in these reactions, a NMR experi-
ment was carried out in dry C6D6 using tert-amyl bromide and
Ag2N2O2. The spectrum exhibits the characteristic peaks at 5.2
(quintet) and 4.8 (singlet) ppm corresponding to the methyne
proton of the 2-methyl-2-butene, and the methylene protons of
2-methyl-1-butene, respectively, together with peaks corre-
sponding to the alkylated products. The two butenes result from
E2 elimination from the alkyl bromide. As shown in Table 3
addition of solid-phase potassium carbonate to the reaction has
little effect on either the product distribution or the yield of the
reaction. Similar elimination reactions have also been reported
for the reaction of cyclohexyl bromide with Ag2N2O2.6 Also,
from these NMR results, the colorless gas observed during the
reaction of tert-butyl bromide with silver hyponitrite may be
ascribed to the formation of 2-methylpropene {CH2dC(CH3)2}
which has a boiling point at -6.9 °C. The observed instability
of trans-mono-O-alkyl hyponitrite in basic conditions is con-
sistent with the reported instability of mono protonated hyponi-
trous acid (HONNO-) in the 8-10 pH range.8 Attempts to
alkylate trans-mono-O-tert-butylhyponitrous acid with diazo-
methane in ether were unsuccessful, as were attempts to isolate
the corresponding silver salt. All of these observations can be
attributed to the ease of elimination of alkoxide (or hydroxide)
from RONNO- with the concomitant formation of nitrous oxide.
This deleterious reaction may also account for the uniformly
low overall yields from these reactions.
Figure 6. Transition-state structures and reaction paths for alkylation
of MeONNO- at the oxygen, filled circles, and the nitrogen, open
circles. Theory and basis set: B3LYP/6-311++G**.
Figure 7. Proposed and optimized ground-state structures for the
putative cis-mono-methyl hyponitrite, MeONNO-. Note that the
minimized structure on the right corresponds to a methoxy adduct of
nitrous oxide rather than to a configurational isomer of 8 in Figure 5.
Sodium nitrite is readily alkylated with alkyl halides at
ambient temperatures in DMSO or DMF.4 However, the
alkylation of [HEt2NCH2CH2NEt2H][N2O2],19 [quinuclidinium]2-
[N2O2],19 Na2N2O2, or Tl2N2O2 in DMSO, DMF, or ether with
tert-butyl bromide or p-tert-butylbenzyl bromide were all
unsuccessful. We concur with Mendenhall’s prior results which
demonstrated that Lewis acids are required to promote these
alkylation reactions,6,37 and that in certain heterogeneous
conditions, for example, ferric chloride or zinc chloride suspen-
sions in ether or pentane, the yield of O/O-dialkylhyponitrite
can be quite high, > 85%. Unfortunately the kinetics of these
reactions are difficult to determine due the heterogeneous condi-
tions, the thermal instability, and general insolubility of most
simple hyponitrite salts. As described above, the markedly more
soluble bis-tetraalkylammonium salts of hyponitrite are not alky-
lated under these conditions either, even in polar organic solvents
such as DMSO, DMA, or DMF. Surprisingly, thallium hyponi-
trite is not alkylated under these conditions either, even though
TlBr and AgBr have similar solubilities. Ultimately, the silver
and other Lewis acids may have the role originally ascribed to
it by Kornblum, that is, the silver ion polarizes the carbon-
halogen bond of the alkyl halides, which consequently stabilizes
the transition state through interaction with the leaving group.4
The structural results for 1D‚1/2HONNOH and 5A not only
confirm the stereochemistry of the product, but they also allow
for considerable insight into the electronic structures for these
species. Of particular note the lattice cocrystallized hyponitrous
acid in 1D‚1/2HONNOH is required for crystallization of 1D;
gas phase and is separated from the E-form by a low barrier of
9 kcal/mol.26 Therefore, the initially formed E isomer can be
expected to undergo isomerization to the Z-form.
In support of the argument that only initial N-alkylation
pathway leads to N/O-dialkylated product, we note that the
alkylation of the silver salt of (Z)-N-tert-butyl-N′-hydroxydia-
zene-N-oxide with tert-butyl bromide yields only the N/O-
dialkylated product, 1D. This suggests that the oxygen site is
the most favored in the second alkylation step, and that the
intermediacy of species such as 2D or 4D result in the formation
of 1D and 3D. If the substrate possesses two sites with unequal
charge localization as in the hyponitrite anion, the nature of
the cation, its size, stability, and charge localization determine
whether the cation will attack one or both of the sites. The
cations generated from p-tert-butylbenzyl bromide and chlo-
rotriethylsilane exclusively attack the more negatively charged
oxygen atoms of the hyponitrite anion, and therefore no
formation of other products is observed.
The mechanism of the alkylation reactions of silver hyponi-
trite with tert-butyl bromide and tert-amyl bromide is sum-
marized in Scheme 2. The first pathway involves the initial
alkylation of one of the two oxygen atoms of hyponitrite dianion
to form the trans-mono-O-alkyl hyponitrite intermediate species,
which may be further alkylated or protonated to form the
corresponding trans-di-O-alkyl hyponitrite (1A and 3A) and
trans-mono-O-alkylated hyponitrite (2A and 4A), respectively.
The second pathway involves the initial alkylation of one of
the two nitrogen atoms to form the unstable (E)-N-alkyl
(37) Mendenhall, G. D. Tetrahedron Lett. 1983, 24, 451-452.

5548 J. Am. Chem. Soc., Vol. 122, No. 23, 2000
Arulsamy et al.
Scheme 2. Proposed Mechanism for O,N-Alkylation of Ag2N2O2
pure 1D is an oily liquid at room temperature. This is only the
second reported instance of a structurally characterized cocrys-
tallized hyponitrous acid, the other being in [HEt2NCH2CH2-
NEt2H][HONNO]2‚HONNOH, 12A.19 In both cases the metric
parameters are similar, NdN 1.226(4) and 1.216(2) Å, N-O
1.363(3) and 1.382(2) Å, N-N-O 109.9(3) and 108.22(14)°,
in 12A and 1D respectively. Theoretically calculated gas-phase
ground-state values for these parameters, B3LYP/6-311++G**,
are in very good agreement with these crystallographic data:
NdN 1.2254, N-O 1.3885 Å, and N-N-O 108.231°. The
hyponitrous acid is of course hydrogen-bonded in both solid-
state structures, resulting in O-O separations of 2.648(3) and
2.696(2) Å in 12A and 1D respectively. Supporting evidence
for this is also found in the IR spectra which have broad ν(O-
H-O) bands at 3177 and 3207 cm-1 in 12A and 1D respec-
tively. In contrast, the theoretically calculated ν(O-H) vibra-
tional bands (B3LYP/6-311++G**) are much higher for gas-
phase hyponitrous acid occurring at 3816.41 and 3813.49 cm-1
for the Ag and Bu modes, respectively.
The diazenium diolate portion of the structure of 1D indicates
that this species adopts a Z geometry with metrical parameters
very similar to those reported for the related compounds
N-methyl-N′-methoxydiazene-N-oxide,24 methylene-bis(N′-meth-
oxydiazene-N-oxide),23 ethane-1,1-bis(N′-methoxydiazene-N-
oxide),25 and propane-2,2-bis(N′-methoxydiazene-N-oxide).25 In
all of these structures the NdN bond lengths are longer than
those found for the hyponitrous acid cocrystallite and for
dialkylhyponitrites. In 1D, the N(1)-O(1) and N(2)-O(2) bond
lengths, 1.369 (2) Å and 1.2679 (14) Å, are both significantly
shorter than the N-O bond lengths in hyponitrous acid and 5A.
These observations are consistent with π-bond delocalization
over the N(1)-N(2)-O(2) framework. These metric parameters
are similar to those calculated for the bis-dimethyl analogue,
N-methyl-N′-methoxydiazene-N-oxide (Figure 5). Together these
experimental and theoretical results suggest that the shortening
of the N(2)-O(2) bond is consistent with multiple bonding or
π-delocalization which in turn is found in azine-N-oxides. From
this perspective a diazenium diolate such as 1D is the N-oxide
of the unknown O-alkylated diazotate, H. The reported products
of the alkylation of diazotates with Meerwein’s reagent or alkyl
iodides are azoxyalkanes, I in eq 3, which correspond to
N-alkylation.38
( )
The observed and calculated vibrational data for the ONNO
frameworks in 1D, 1D‚1/2HONNOH, 2D, and 3D are also in
fair agreement and correlate with strong coupling of the
framework modes. In particular, the strongest IR active band,
1071-1061 cm-1, for the products with a D conformation, Table
4, corresponds to an asymmetric ν(NOR) mode as the primary
component, calculated to be at 1037.1 cm-1 in the gas phase
for (Z)-MeONdN(O)Me, Table S9. A second strong IR active
mode for these compounds is between 1487 and 1481 cm-1
which best correlates with the value calculated for ν24 at 1577.3
cm-1, a mode with primarily ν(NdN) character.
In contrast with the observed structural, spectroscopic, and
theoretical data for the diazenium diolates are the related data
for the hyponitrite framework, such as that found in the structure
of 5A, Table 2 and Figure 3. In 5A the observed N-N bond
distance of 1.230 (3) Å is close to the typical N-N double bond
even though the N(1)-O(1) distance of 1.361 (2) Å is
significantly smaller than that of a typical N-O single bond.
In this respect the trend observed in 5A differs from that for
trans-di-O-tert-butyl-hyponitrite.17 Generally, the observed N-N
double bond and N-O single bond distances are much smaller
than the corresponding bond distances observed for trans-di-
O-tert-butyl-hyponitrite,17 by 0.022 and 0.019 Å, respectively.
(38) Moss, R. A.; Landon, M. J.; Luchter, K. M.; Mamantov, A. J. Am.
Chem. Soc. 1972, 94, 4392-4394.

Dialkylation of Hyponitrite
J. Am. Chem. Soc., Vol. 122, No. 23, 2000 5549
These structural characteristics for 5A are consistent with the
considerably higher ν(N-O)asym stretching vibrational mode
1081 cm-1 in contrast to 1019 cm-1 reported for trans-di-O-
tert-butyl-hyponitrite17 but both are lower than the value 1093.9
cm-1 calculated for trans-dimethylhyponitrite, Table S9. In
contrast with these somewhat variable results the Raman active
ν(NN)sym band for 5A is at 1611 cm-1, and is calculated to be
at 1614.9 cm-1 in dimethylhyponitrite, Table S9.
in the protonated forms, namely, trans-mono-O-alkyl hyponi-
trous acid and (Z)-N-alkyl-N′-alkoxydiazene-N-oxide. Theoreti-
cal calculations suggest the presence of negative charge
localization over both the oxygen and nitrogen atoms of the
hyponitrite dianion, with more charge being localized over the
oxygen atom. Thus, the mono-O-alkyl intermediate is clearly
preferred over the N-alkyl intermediate. The isolation of the
trans-di-O-alkyl product as the major product in each of the
alkylation reactions is consistent with the theoretical results.
A comparison of the available structures of trans-di-O-alkyl
hyponitrites with the structure of trans-di-O-p-tert-butylbenzyl
hyponitrite reveals partial double bond character for the two
N-O bonds in the latter molecule. The lower thermal stability
of trans-di-O-p-tert-butylbenzyl hyponitrite in comparison to
those of the analogous tert-butyl and tert-amyl derivatives is
attributed to the presence of R-methylene protons and higher
N-O bond order in the former compound.
Interestingly, de Sousa39 has observed a decrease in the rate
of decomposition with methyl substituents and an increase in
the rate of decomposition with halide substituents in the phenyl
ring relative to unsubstituted dibenzyl hyponitrite. On the basis
of these observations, Sousa et al. have proposed that electron-
releasing substituents increase the N-O bond order and electron-
withdrawing substituents decrease the N-O bond order. The
observed N-O double bond character in 5A is in good agree-
ment with what has been predicted by de Sousa.39 Also sup-
porting this conclusion is the higher thermal stability of com-
pound 5A (dec 86 °C) relative to the unsubstituted dibenzyl
hyponitrite (dec 48 °C).13
p-tert-Butylbenzaldehyde is a side product, e14% yield, of
the reaction of silver hyponitrite with p-tert-butylbenzyl bro-
mide. The formation of the aldehyde most likely results from
the partial decomposition and oxidation of the intermediate
trans-O-p-tert-butylbenzyl hyponitrite, during the reaction.
Acknowledgment. We gratefully acknowledge support from
the NIH (GM-53828), and the Air Force Office of Scientific
Research. (Grants F49620-96-1-0417 and 98-1-0461).
Supporting Information Available: Tables S1-S8 of
positional parameters, bond distances and angles, anisotropic
displacement parameters, and hydrogen atom coordinates, for
complexes 1D‚1/2(HONNOH) and 5A, Table S9, listing the
calculated vibrational modes for compounds discussed in the
theoretical section, and Table S10, a table with complete
spectroscopic data for new compounds (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
Conclusions
Alkylation reactions of silver hyponitrite with tert-butyl
bromide and tert-amyl bromide yield both, O/O- and N/O-
dialkylated products, clearly demonstrating the ambidentate
nucleophilic behavior of the hyponitrite dianion. The interme-
diacy of mono-O- and mono-N-alkyl species in the alkylation
reactions is well established by the isolation of the two species
JA994261O
(39) de Sousa, J. B. Nature 1963, 199, 64-65.