Intramolecular cyclization of 1,2-bis(N-alkoxy-N-nitrosoamino)alkanes: A unique route to 4,5-dihydro-1,2,3-triazole 2-oxides

Article abstract of DOI:10.1055/s-2000-6399

1,2-Bis(N-alkoxy-N-nitroso)amines 7 obtained by nitrosation of the corresponding 1,2-bisalkoxyamines 4 were smoothly converted into 1-alkoxy- 4,5-dihydro-1,2,3-triazole 2-oxides 8 under reflux in methanol in high yields. 4H-1,2,3-Triazole 2-oxides 9, a novel type of triazole oxides, and 2- hydroxy-2H-1,2,3-triazoles 10 were obtained by the reaction of 1-alkoxy-4,5- dihydro-1,2,3-triazole 2-oxides 8 with sodium methoxide.

Full text of DOI:10.1055/s-2000-6399

PAPER
681
Intramolecular Cyclization of 1,2-Bis(N-alkoxy-N-nitrosoamino)alkanes:
A Unique Route to 4,5-Dihydro-1,2,3-triazole 2-Oxides
Vadim K. Khlestkin,* Dmitrii G. Mazhukin, Alexsei Ya. Tikhonov, Tatyana V. Rybalova, Irina Yu. Bagryanskaya,
Yurii V. Gatilov
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Lavrent’eva prosp., 9, Novosibirsk 630090, Russia
Fax +7(3832)344752; E-mail: vadim@nioch.nsc.ru
Received 18 July 1999; revised 18 December 1999
Dedicated to Prof. Leonid B. Volodarsky, founder of the Laboratory of nitrogenous compounds
yields.2,10 More conveniently N,O-disubstituted hydroxy-
Abstract: 1,2-Bis(N-alkoxy-N-nitroso)amines 7 obtained by nitro-
lamine N-nitroso derivatives can be prepared by nitrosa-
sation of the corresponding 1,2-bisalkoxyamines 4 were smoothly
tion of the corresponding N,O-dialkylhydroxyl-
converted into 1-alkoxy-4,5-dihydro-1,2,3-triazole 2-oxides 8 un-
der reflux in methanol in high yields. 4H-1,2,3-Triazole 2-oxides 9,
amines.1,2,4,6a
a novel type of triazole oxides, and 2-hydroxy-2H-1,2,3-triazoles 10
were obtained by the reaction of 1-alkoxy-4,5-dihydro-1,2,3-triaz-
of cis-1,2-bis(N-methoxy-N-nitrosoamino)cycloalkanes,
ole 2-oxides 8 with sodium methoxide.
In a preliminary communication we reported a synthesis
compounds bearing two N-nitroso-N-alkoxyamine
Key words: 1,2-bisalkoxyamines, 1,2-bis(N-alkoxy-N-ni-
groups, and their thermal transformation into 4,5-dihydro-
troso)amines, 1,2-bis(nitrosohydroxylamines), 1,2,3-triazole 2-ox-
ides, intramolecular cyclization, nitrogen, nitrosation, heterocycles
1,2,3-triazole 2-oxides, a novel class of triazole N-ox-
ides.11 Previously known 1,2,3-triazole 2-oxides repre-
sented condensed 1,2,3-triazoles prepared photochemi-
cally12 or via oxidative cyclization of aromatic nitro- or ni-
trosoamines.13-15 In contrast, there are no data on uncon-
densed 1,2,3-triazole 2-oxides in the literature.
Introduction
N-Nitroso derivatives of N,O-disubstituted hydroxyl-
amines still remain an insufficiently known class of or-
ganic compounds. Despite the fact that they were first
synthesized in the last century,1 their study was limited to
the examination of spectroscopy data2 and E,Z-isomerism
of N-nitroso group.3 Their reduction leads to correspond-
ing alkoxyamines4 whereas reaction with organolithium
compounds and Grignard reagents is known to form
azoxyalkanes.5 In the last decade N-nitroso derivatives of
N,O-disubstituted hydroxylamines have been drawing at-
tention as isosteric biomimetics of unstable carcinogenic
a-hydroxynitrosoamines generated from nitrosoamines in
vivo. In this connection their thermolysis and hydrolysis
have been investigated by Kano and Anselme.6 In addi-
tion, a new deamination of N,O-disubstituted hydroxyl-
amine N-nitroso derivatives, resulting in ethers has been
reported recently.7 There are no examples of the involve-
ment of N-nitrosoalkoxyamines into heterocyclic ring
construction in contrast to the parent N-nitrosohydroxyl-
amines.8
The present study was conducted to establish an influence
of substrate structure features on the discovered cycliza-
tion of 1,2-bis(alkoxynitrosoamines) as well as to ascer-
tain a scope of this reaction.
Preparation of 1,2-Bisalkoxyamines
A series of new 1,2-bisalkoxyamines 4 both with an acy-
clic or alicyclic backbone was synthesized via acyl protec-
tion of hydroxylamino groups of the appropriate 1,2-
bishydroxylamines 1,16,17 and alkylation followed by hy-
drolysis of the resulting cyclic diesters 3. Thus, reflux of
1,2-bishydroxylamines 1 with diethyl oxalate in ethanol
gave the corresponding cyclic bishydroxamic acids 2 in a
80-90% yield. Subsequent alkylation of 2 with methyl io-
dide in the presence of K2CO3 in aqueous methanol led to
the diesters 3a-e. Reaction of compound 2a with allyl
bromide and benzyl chloride, and compound 2d with allyl
bromide led to the corresponding diesters of bishydrox-
amic acids 3f, 3g and 3j under the same conditions. Di-
ester 3h was obtained by alkylation of bishydroxamic acid
2a with ethyl chloroacetate in DMF in the presence of tri-
ethylamine (Scheme 1).
Furthermore N-nitroso derivatives of N,O-disubstituted
hydroxylamine might appear to resemble N-nitrosohy-
droxylamines as donors of nitric oxide (NO), a well-
known multifunctional cell mediator.9 Finally NO libera-
tion has been shown to cause specific DNA cleavage un-
der thermal or photoinduced conditions.8
It was found that the reaction rate and products of the
pyrazine ring opening of diesters 3 depend on the number
of alkyl substituents at C-5 and C-6 of the heterocycle.
Thus, reflux of diesters 3a,b (C-5 and C-6, secondary car-
bon atoms) in 6% HCl (water/methanol, 1:5) for 16 hours
or in 10% KOH in methanol for 10-14 hours afforded the
corresponding 1,2-bisalkoxyamines hydrochlorides or the
Two basic approaches to the N-nitrosoalkoxyamines are
known. The first is alkylation of N-nitrosohydroxyl-
amines. However, this reaction gives alkoxydiazene ox-
ides as major products while the unstable N-nitrosohy-
droxylamines could not be isolated in satisfactory
Synthesis 2000, No. 5, 681–690 ISSN 0039-7881 © Thieme Stuttgart · New York

682
V. K. Khlestkin et al.
PAPER
R5Hal, K2CO3
MeOH/H2O, rt
48 h
OR5
OR5
N
OH
N
(COOEt)2
R1
6% aq HCl/MeOH, ∆
or
R1
R1
R1
R1
NHOR5
NHOR5
N
NHOH
O
O
O
O
O
EtOH, ∆
R2
R2
R2
R2
R2
KOH/MeOH, ∆
60-94%
3-4 h
+
R3
R3
R4
R3
R4
R3
R3
R4
71-92%
75-100%
NHOR5
R4
N
NHOH
R4
N
OR5
4
5
OH
1
3
2
NaNO2
HCl, rt
94-100%
OR5
N
OR5
MeONa,
MeOH, ∆
3-48 h
R1
R1
R1
R2
R2
R2
R3
MeOH, ∆
0.5-5.5 h
O
O
N
N
N
N
R2
R2
N
+
N
O
N
O
N
OH
R3
R4
R3
R3
R4
R4=H
65-86%
R1=H
N
N
78-98%
N
OR5
N
N
R4
N
N
R4
R3
O
O
OR5
OR5
10
9
8
6
7
Compound
R1
R2
R3
R4
R5
1-4a, 7a, 8a, 10a
1-4b, 7b, 8b, 10b
1-4c, 5cA
5cB
1-8d
1-4e, 7e, 8eA
8eB
H
H
H
Me
Me
H
(CH2)4
(CH2)5
(CH2)4
(CH2)4
H
H
Me
H
Me
Me
Me
Me
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
Me
9e
Me
(CH2)4
(CH2)4
(CH2)4
(CH2)4
3f, 4f, 7f, 8f
3g, 4g, 7g, 8g
3h, 4h, 7h, 8h
4i
H
H
H
H
Allyl
CH2Ph
CH2COOEt
CH2COOH
Allyl
3j
Me
Me
Me
Scheme 1
OR5
N
free bases 4a,b in excellent yields. It took 5-24 hours to
hydrolyze diesters 3e-h by refluxing in 6% aqueous HCl.
Hydrolysis of hydroxamic ester 3h was accompanied by
hydrolysis of side chain ester groups and resulted in 1,2-
bisalkoxyamines 4h in 26% yield and 4i in 37% yield.
OR5
N
O
R1
R2
R3
R4
R1
R1
NHOR5
NHOR5
O
H+
R2
A
R2
R3
R4
R3
OH
(OH-)
O
NH
OR5
O
R4
N
OR5
B
4a-i
3a-h
Acid hydrolysis of compound 3c (C-5, tertiary; C-6, sec-
ondary carbon atoms) also gave 1,2-bisalkoxyamine 4c.
However, prolonged reflux of diester 3c with alkali led
exclusively to the mixture of N-formyl derivatives 5cA,
5cB. Acid hydrolysis of compound 3d with tertiary C-5
and C-6 carbon atoms led to a mixture of the desired 1,2-
bismethoxyamine 4d and its N-formyl derivative 5d. Ob-
viously, consecutive cleavage of the two C-N bonds in
diesters 3a-h results in bisalkoxyamines 4a-i (Scheme 2,
route A) whereas cleavage of one C-N bond and subse-
quent decarboxylation affords the N-formyl derivatives
5cA, cB, d (Scheme 2, route B). However, formation of
the formyl derivatives 5cA, cB, d via cleavage of C-2 - C-
3 bond can not be excluded (Scheme 2, route C).
C
HO
R1
OR5
OR5
OR5
N
OH
O
OH
R1
R1
N
O
N
O
H+
R2
R2
R2
R3
R4
R3
R4
R3
R4
N
OR5
O
N
OR5
O
NHOR5
5cA, cB, d
Scheme 2
6% aqueous HCl to give 1,2-bis(N-alkoxy-N-nitrosoam-
ines) 7 in quantitative yields. Bisnitroso derivatives 7a, b,
e, f, h represent relatively stable yellow oils with a specif-
ic smell, while compounds 7d and 7g are crystalline.
Compound 7d was produced by nitrosation of a mixture
of 1,2-bismethoxyamine 4d and N-formyl derivative 5d
and separated from N-formyl-N’-nitroso derivative 6d
during workup. X-ray structures have been obtained for
6d and 7d.18
Synthesis and Intramolecular Cyclization of 1,2-
Bis(N-alkoxy-N-nitrosoamino)alkanes
1,2-Bisalkoxyamines 4 are stable colorless oils which can
be converted into crystalline salts when reacted with ac-
ids. In contrast to N,N’-disubstituted 1,2-diamines, 1,2-
bisalkoxyamines 4 can be easily nitrosated by NaNO2 in
Thermolysis of N,O-disubstituted hydroxylamines N-ni-
troso derivatives results in a complex mixture of prod-
Synthesis 2000, No. 5, 681–690 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular Cyclization of 1,2-Bis(N-alkoxy-N-nitrosoamino)alkanes
683
ucts.6b We found that reflux of 1,2-bis(N-alkoxy-N- cate a high inversion barrier of the tetrahedral N-1
nitrosoamines) 7 both in polar or non-polar solvents led to possessing electron withdrawing groups.19 At 60°C no
4,5-dihydro-1,2,3-triazole 2-oxide derivatives 8 - a novel signal broadening was observed.
type of heterocyclic N-oxide - as a result of an intramolec-
ular cyclization. Maximum yields (76-92%) were ob-
tained by use of methanol as a solvent. A mixture of
The Trapping
isomeric 4,5-dihydro-1,2,3-triazoles 8eA and 8eB (ratio
5:7) was obtained under the thermolysis of unsymmetrical To confirm NO-liberation the reaction was carried out in
N,N’-bisnitroso derivative 7e.
the presence of 4-methoxy-5,5-dimethyl-2,4-diphenyl-
4,5-dihydroimidazol-1-yl 3-oxide (12) known as a specif-
ic NO-trap20a that is able to react with NO in situ with
change of ESR spectrum due to the radical 11 formation.20
According to literature data, homolytic cleavage of N-N
bond with liberation of nitric oxide (NO) takes place as
the first step of N-nitrosoalkoxyamines thermolysis.6b The
same process is supposed to occur as the first stage of the
intramolecular cyclization of N,N’-bisnitroso derivatives
7. Next, the intermediate alkoxyaminyl radical RA is
trapped by the nitroso group. Subsequent elimination of
alkoxyl radical from the triazinyloxyl radical RT gives
4,5-dihydro-1,2,3-triazole 2-oxides 8 (Scheme 3).
O
Ph
N
Ph
N
Ph
N
O
O
O
N
N
N
+NO
-NO2
7a
Ph
Ph
Ph
rt
.
.
O
.
HNO3
O
OH
13
12
11
OR5
N
OR5
N
OR5
Scheme 4
R1
R1
R1
O
O
N
R2
R2
R2
N
∆
N
O
R3
R4
R3
R4
R3
R4
N
N
- NO
N
OR5
However, more than two equivalents of nitronylnitroxide
12 were found to react with the bisnitroso derivative 7a. A
preparative experiment showed 1,2-bis(methoxyni-
trosoamine) 7a to react with nitronylnitroxide 12 even at
room temperature to give only trace amounts of 4,5-dihy-
dro-1,2,3-triazole 8a, whereas nitronylnitroxide 12 was
transformed into 1-hydroxy-2-imidazoline nitrate 13 in a
29% yield (Scheme 4).
N
N
O
OR5
OR5
RT
RA
7
OR5
R1
R1
N
N
N
R2
R2
N
O
R3
R4
N
O
+
R3
R4
-R5O
N
OR5
8
Since compound 12 did not work as a passive NO-trap,
the reaction was carried out under continuous bubbling of
argon through the boiling acetonitrile solution of 7a. The
stream of argon containing the NO formed was introduced
into a separate acetonitrile solution of nitronylnitroxide
12. ESR spectra recorded at intervals showed a progres-
Scheme 3
Cyclization rates for acyclic bisnitroso compounds are
significantly higher than those for alicyclic ones. This fact
may be explained by higher conformational flexibility of
acyclic bisnitroso derivatives. Time for complete conver-
sion decreases in the series R5O = MeO >CH2=CHCH2O
@ PhCH2O >EtO2CCH2O (see Table 3). Thermolysis of
compound 7g produced 4,5-dihydrotriazole 2-oxide 8g
(81% yield) as well as benzhydroxamic acid (60% yield).
The latter is supposed to be formed via reaction of the NO∑
with benzyloxyl radical (PhCH2O∑) and products of its
transformation.
sive
(aN1 = aN3 = 7.1 G) into iminonitroxide 11 (aN1 = 7.5 G,
N3 = 4.0 G) confirming NO formation during the cycliza-
transformation
of
nitronylnitroxide
12
a
tion reaction.
We failed to detect an intermediate radical RT (Scheme 3)
when carrying out the reaction in an ESR spectrometer vi-
al. Data on the NO∑ and H3CO∑ radical fixation have been
given previously.11
It should be noted that crystalline bisnitroso derivative 7g
completely decomposes at room temperature in a few
weeks while 7a, b, d, e, f are stable for months. No 4,5-
dihydrotriazole 8g was observed in the decomposition
products of 7g.
Synthesis and Structures of 2H- and 4H-1,2,3-Triaz-
oles
Treatment of 4,5-dihydro-1,2,3-triazole 2-oxides 8a,b
with sodium methoxide in methanol solution afforded ar-
omatic 2-hydroxy-2H-1,2,3-triazoles 10a,b in high yields.
Under the same conditions the mixture of 2-oxides 8eA
and 8eB gave 4H-1,2,3-triazole 2-oxide 9e by elimination
of methanol from 8eA. In contrast 8eB remained un-
changed (Scheme 1).
4,5-Dihydro-1,2,3-triazole 2-oxides 8 are colorless low-
melting and volatile crystals (8a, b, d, g) or oils (8eA, eB,
f, h). The observed broadening of the C-5 methyl group
signals in the 1H NMR spectra and the absence of C-5 sig-
nal in 13C NMR spectra of compounds 8eA and 8d indi-
Synthesis 2000, No. 5, 681–690 ISSN 0039-7881 © Thieme Stuttgart · New York

684
V. K. Khlestkin et al.
PAPER
Table 1 Selected Bond Lengths [Å] of Compounds 9e and 10a
The X-ray structures of 4H-1,2,3-triazole 2-oxide 9e and
2-hydroxy-2H-1,2,3-triazole 10a are illustrated in Figures
1 and 2. Selected bond lengths and other crystallographic
data are presented in Tables 1 and 2. Compound 9e fea-
tures a marked lengthening of N1-N2 bond [1.458(3) Å]
as compared to the N1-N2 bond of 5-amino- and 5-di-
methylamino-4,4-diphenyl-4H-1,2,3-triazole21 [1.423(3)
and 1.401(4) Å] and calculated N(sp2)-N(sp2) bond
length [1.401(8) Å].22 Such N-N bond lengthening has
been reported earlier for 4,5-dihydrotriazole 2-oxide de-
rivatives.11 The 4H-triazole ring of is planar within 0.011
Å. In compound 10a normal triazole ring bond lengths23
were found and the 2H-triazole ring is planar within
0.003 Å. The cyclohexane ring adopts half chair form.
Atoms
9e
10a
N1-N2
N2-N3
N3-C4
C4-C5
C5-N1
N2-O1
1.458(3)
1.264(3)
1.463(3)
1.488(4)
1.278(3)
1.241(3)
1.317(3)
1.319(3)
1.344(3)
1.380(3)
1.343(3)
1.356(2)
Table 2 Crystallographic Data and Summary of Data Collection
and Refinement
Data
9e
10a
empirical formula
formula weight
color
crystal size, mm
crystal system
space group
a, Å
C5H9N3O
127.15
colorless
C6H9N3O
139.16
colorless
0.45 × 0.38 × 0.20a 0.80 × 0.16 × 0.10
orthorhombic
P212121
6.0490(8)
7.7203(9)
14.687(2)
685.9(2)
4
1.231
0.746
272
orthorhombic
Pbca
6.800(1)
11.332(2)
18.257(4)
1406.8(4)
8
1.314
0.778
592
b, Å
c, Å
V, Å3
Z
ρcalc, g cm-3
m (CuKa), mm-1
F(000)
difractometer
radiation
l, Å
T, K
Syntex P21
CuKa
1.54178
296
Syntex P21
CuKa
1.54178
298
monochromator
2Qmax
reflections collected
graphite
158
932
graphite
120
1046
Figure 1 ORTEP presentation of 4H-1,2,3-triazole 2-oxide 9e.
independent reflections 853
1046
wR2
0.1080
0.0393
1.048
0.1353
0.0454
1.008
R [for I>2s (I)]
goodness-of-fit on F2
a Volatile crystal was placed into polyethylene capillary to prevent
sublimation.
N-oxide form both in crystal or in solution2a (Scheme 5).
Nevertheless in some cases transformations of this com-
pounds propose to proceed via the less stable tautomer.7
Figure 2 ORTEP presentation of 2-hydroxy-2H-1,2,3-triazole 10a.
N
OH
N
O
R
N
R
N
O
OH
Synthesis and Thermolysis of 1,2-Bisnitroso-
hydroxylamines
Scheme 5
To establish an influence of substrate features on intramo-
lecular cyclization reaction, it seemed to be of interest to
synthesize O-unsubstituted derivatives, 1,2-bisnitrosohy-
droxylamines and to study their behaviour under the ther-
mal cyclization conditions. N-Nitrosohydroxylamines
have been shown to exist predominantly as a tautomeric
Nitrosation of 1,2-bishydroxylamines 1a,d by NaNO2 at
pH 2-3 led to 1,2-bis(nitrosohydroxylamines) 14a,d in a
high yield. Temperature, quantity of NaNO2 and pH value
should be strictly controlled to avoid side reactions. N-Ni-
trosohydroxylamines have been previously shown to be
quite capable of deamination reaction.7 Furthermore, an
Synthesis 2000, No. 5, 681–690 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular Cyclization of 1,2-Bis(N-alkoxy-N-nitrosoamino)alkanes
685
oxidation process known for N-nitrosohydroxylamines9
may take place under an excess of HNO2. In fact, reaction
of 1,2-bishydroxylamine 1d with an excess of NaNO2 in
acid media resulted in stable 3,3,4,4-tetramethyl-3,4-di-
hydro-1,2-diazete 1,2-dioxide (15).24 The same com-
pound was obtained by oxidation of 1,2-
bis(nitrosohydroxylamine) 14d by MnO2 (Scheme 6). 1,2-
Bis(nitrosohydroxylamines) 14a,d are stable crystalline
solids that could be stored at least for several months at
room temperature in contrast to mononitrosohydroxyl-
amines usually stabilized as salts.
The X-ray structures was solved using direct methods (SHELXS-
86).26 The non-hydrogen atoms were refined anisotropically on F2
with full matrix least squares procedure (SHELXL-93);27 H-atoms
positions were found from D-synthesis and refined isotropically.28
Bishydroxamic Acids 2a-e; General Procedure
A solution of 1a-e (0.15 mol) and diethyl oxalate (24.4 mL, 0.18
mol) in EtOH (200 mL) was refluxed for 2-4 h. The mixture was
concentrated in vacuo, the residue was treated with acetone. The
precipitate was filtered and washed with Me2CO (20 mL) to give
2a-c,e. Compound 2d29 failed to solidify and was used in the fur-
ther reaction without purification.
cis-1,4-Dimethoxydecahydro-2,3-quinoxalinedione (3a); Typi-
cal Procedure
excess
NaNO2
or MnO2
OH
N
2NaNO2
HCl, 3°C
pH 2-3
Solid K2CO3 (32.29 g, 0.23 mol) and bishydroxamic acid 2a (26 g,
0.13 mol) were successively dissolved in H2O (110 mL) and the so-
lution was diluted with MeOH (250 mL). After addition of MeI
(48.6 mL, 0.78 mol), the mixture was allowed to stand for 1-3 d
with occasional shaking. MeOH was evaporated, the aqueous solu-
tion was extracted with CHCl3 (4 × 50 mL) and organic layer was
dried (MgSO4) and concentrated in vacuo. The white solid residue
was treated with hexane (50 mL) and filtered to give 99% of 3a.
R1
R1
O
O
NHOH
NHOH
R2
N
N
R2
R3
R4
R3
R4
for 14d
59-66%
N
OH
14a,d
1a,d
∆
R1
R2
O
N
N
Compounds 3 b-e, f, g, j
N
O
Ethers 3b-e, f, g, j were synthesized according to the typical proce-
dure described above (with allyl bromide instead of MeI for 3f, j
and with benzyl chloride for 3g). In the case of diether 3d the resi-
due obtained after evaporation of CHCl3 was subjected to chroma-
tography (silica gel, CHCl3/MeOH, 30:1) to provide 3d. In the case
of diether 3g the precipitate formed in the reaction mixture was fil-
tered, triturated with H2O, washed with cold aq 50% EtOH and
dried to give 3g.
R3
R4
N
O
N
OH
16
15
Scheme 6
Thermolysis of 1,2-bis(nitrosohydroxylamines) 14a,d un-
der the intramolecular cyclization reaction conditions
failed to give corresponding 1-hydroxy-4,5-dihydrotriaz-
oles 16 and led to a complex mixture of products. For in-
stance, 1,2-cyclohexanedione dioxime was isolated in the
case of 14a thermolysis.
cis-1,4-Bis(ethoxycarbonylmethoxy)decahydro-2,3-quinoxa-
linedione (3h)
A solution of 2a (0.45 g, 2.25 mmol), Et3N (1.25 mL, 9 mmol) and
ClCH2CO2Et (0.96 mL, 9 mmol) in anhyd DMF (12 mL) was al-
lowed to stand for 24 h. The solvent was removed in a current of air
stream and H2O (10 mL) was added. White precipitate was filtered,
washed with H2O (5 mL) and dried in the air; yield: 0.77 g (92%).
In conclusion, we have demonstrated that 1,2-bis-
alkoxyamines 4 of any structure both with alicyclic frag-
ments or opened chain compounds efficiently give
corresponding N,N’-bisnitroso derivatives 7 which under-
go an intramolecular cyclization under the mild ther-
molytical conditions to form 4,5-dihydro-1,2,3-triazole 2-
oxide derivatives 8. The aforementioned reaction of in-
tramolecular cyclization is considered to be a general
method for preparation of this type of heterocyclic N-ox-
ides.
cis-N,N’-Dimethoxy-1,2-cyclohexanediamine (4a); Typical Pro-
cedure
A solution of 3a (22.38g, 98.2 mmol) in a solution of 6% HCl in
MeOH (250 mL) was refluxed for 11 h, then cooled and concentrat-
ed in vacuo. The residue was dissolved in H2O (100 mL) and pH
was adjusted to 8 with aq 30% NaOH. The solution was extracted
with CHCl3 (4 × 50 mL) and the organic layer was dried (MgSO4)
and evaporated to give 4a (colorless oil) in 85% yield. Compounds
4b,c,e,f were synthesized by the similar method (for the refluxing
time see Table 3).
IR spectra were recorded on UR-20 and Specord M-80. UV spectra
were recorded on a Specord UV/vis spectrometer. 1H NMR spectra:
Bruker AM-400 (400.13 MHz), Bruker WP-200SY (200.2 MHz)
and Bruker AC-200 (200.2 MHz). 13C NMR spectra: Bruker AM-
400 (100.2 MHz), Bruker AC-200 (50.3 MHz). Mp’s were mea-
sured on Kofler plate (uncorrected). Analytical and preparative
TLC was performed on Silufol UV254 plates (Cavalier, CSFR) and
silica gel (Lachema, CSFR), respectively. 1,2-Bishydroxylamines
1a-e were prepared according to literature procedures.16,17 All spec-
tral and physical data of the synthesized compounds are presented
in the Table 3. For the spectral data of compounds 2a-c, 3a-c, 4a-
c, see: Ref. 25; for 7a,b, 8a,b, 10a,b, see: Ref. 11.
cis-N,N’-Bis(benzyloxy)-1,2-cyclohexanediamine Dihydrochlo-
ride (4g•2HCl)
A suspension of 3g (3.29 g, 8.66 mmol) in solution of concd HCl
(6.5 mL) in MeOH (33 mL) was refluxed for 24 h. The precipitate
was filtered, washed with EtOH (2 × 10 mL) and dried to give 2.92
g of the salt 4g•2HCl. The filtrate was concentrated and residue was
treated with CHCl3 (10 mL) to provide additionally 0.22 g of
4g•2HCl; total yield: 3.14 g (91%).
Free Base 4g
Free base of 4g was prepared by stirring of 4g•2HCl in aq 50%
MeOH followed by slow addition of aq 20% NaOH solution (up to
pH 8). Evaporation and extraction of residue with CHCl3, drying
(MgSO4) and removing of the solvent gave 4g as colorless oil.
Synthesis 2000, No. 5, 681–690 ISSN 0039-7881 © Thieme Stuttgart · New York

686
V. K. Khlestkin et al.
PAPER
Table 3 Physical Data, Conditions for Reactions and Yields of the New Compounds Prepared
Prod- Time, Yield mp (oC)a IR
UV, lmax
(log ε)b
1H NMR, d, J (Hz)
13C NMR,c d
uct
Temp. (%)
n (cm-1
)
2e
4 h,
78°C
80
78
179-
183
1690d
231 (3.90) 1.22 (d, 3 H, J = 7, 6-CH3), 1.24 (s, 3 H, 5- 13.32 (+, CH3), 21.25 (+, CH3),
CH3), 1.34 (s, 3 H, 5-CH3), 3.74 (q, 1 H, J = 24.15 (+, CH3), 60.86 [-,
7, CH), 10.14 (br s, 1 H, OH)e
C(CH3)2], 62.84 (+, CH), 153.39
(-, CO), 154.28 (-, CO)e
3d
3e
2 d,
20°C
123-
2820, 1700, 232 (3.87) 1.33 (s, 12 H, CH3), 3.77 (s, 6 H, OCH3)e
1680d
19.96 (+, CH3), 63.12 (+, OCH3),
66.14 [-, C(CH3)2], 154.46 (-,
CO)e
125
2 d,
20°C
90
85
63
2822, 1696d 228 (4.00) 1.35 (d, 3 H, J = 6.5, CH3), 1.37 (s, 3 H,
CH3), 1.45 (s, 3 H, CH3), 3.66 (q, 1H, J =
6.5, CH), 3.80 (s, 3 H, OCH3), 3.83 (s, 3 H,
OCH3)f
–
3f
2 d,
20°C
59-
60
1690, 1700d 230 (3.97) 0.24-0.72, 0.72-2.1 [2 m, 8 H, (CH2)4],
21.50 (-, CH2), 26.49 (-, CH2),
3.89 (m, 2 H, CH), 4.49 (dt, 4 H, J = 6.5, 1.2, 57.54 (+, CH), 75.8 (-, OCH2),
OCH2), 5.27 (ddd, 2 H, J = 10, 0.7, 0.7,
121.01 (-, CH2, allyl), 131.4 (+,
CHa=CHbHc), 5.32 (dd, 2 H, J = 17.5, 1.5, CH, allyl), 155.54 (-, CO)f
CHa=CHbHc), 5.95 (ddt, J = 17.5, 10, 6.5, 2
H CHa=CHbHc)f
3g
3h
3j
3 d,
20°C
100 158-
1715d
233 sh
(3.75)
1.25-1.60, 1.65-1.95 [2 m, 8 H, (CH2)4], 21.13 (-, CH2), 25.95 (-, CH2),
159
4.05-4.15 (m, 2 H, CH), 4.98, 5.01 (AB-
56.15 (+, CH), 75.68 (-, OCH2),
system, 4 H, J = 10, OCH2), 7.3-7.6 (m, 10 128.33 (+, Ph, Co), 128.64 (+, Ph,
H, C6H5)e
Cp), 129.23 (+, Ph, Cm), 134.73 (-
, Ph, Ci), 154.72 (-, C=O)e
1 d,
20°C
92
43
84-
1756, 1731, 228 (3.90) 1.20 (t, 6 H, J = 7, CH3), 1.3-1.6, 1.7-2.1 [2 13.83 (+, CH3), 21.52 (-, CH2,
86
1700d
m, 8 H, (CH2)4], 4.13 (q, 4 H, J = 7, CH2), ring), 26.38 (-, CH2, ring), 58.54
4.26 (m, 2 H, CH), 4.47 (d, 2 H, J = 16.5, (+, CH), 61.13 (-, OCH2), 71.33
OCHaHx), 4.75 (d, 2 H, J = 16.5, 2OCHaHx)f (-, OCH2), 155.46 (-, CO),
168.21 (-, CO2)f
2 d,
20°C
80-
1685d
234 (3.66) 1.37 (s, 12 H, CH3), 4.48 (d, 4 H, J = 6.5,
CH2), 5.26 (d, 2 H, J = 10, CHa=CHbHc),
5.33 (d, 2 H, J = 15, CHa=CHbHc), 5.97 (ddt,
2 H, J = 15, 10, 6.5, CHa=CHbHc)f
–
82
4dg 21 h,
65°C
–
oil
oil
3275, 2810h
3260, 2810h
–
1.08 (s, 12 H, CH3), 3.48 (s, 6 H, OCH3),
5.84 (br s, NH)f
–
4e
12 h,
94
–
0.87 (s, 3 H, CH3), 1.02 (s, 3 H, CH3), 1.03 13.73 (q, CH3), 19.29 (q, CH3),
65°C
(d, 3H, J = 6.5, CH3), 3.02 (q, 1 H, J = 6.5, 23.20 (q, CH3), 58.39 (d, CH),
CH), 3.44 (s, 3 H, OCH3), 3.45 (s, 3 H,
59.47 (s, C), 61.76 (q, OCH3),
OCH3), 5.66 (br, NH)f
62.68 (q, OCH3)f
4f
10 h,
65°C
79
oil
2860, 1645i
–
1.2-1.5, 1.5-1.8 [2 m, 8 H, (CH2)4], 3.18 22.22 (-, CH2), 25.96 (-, CH2),
(m, 2 H, CH), 4.17 (ddd, 4 H, J = 6, 3.5, 1.8, 58.36 (+, CH), 75.44 (-, OCH2),
2 CH2), 5.16 (dm, 2 H, J = 14, CHa=CHbHc), 117.29 (-, CH2, allyl), 134.57 (+,
5.23 (ddd, 2 H, J = 17.5, 3.5, 1.8, CHa=CH- CH, allyl)f
bHc), 5.71 (s, 2 H, 2 NH), 5.92 (ddt, J = 17.5,
14, 6, 2 H, CHa=CHbHc)f
4g•
2HCl 65°C
24 h,
91
90
145-
–
–
–
1.40-2.05 [m, 8 H, (CH2)4], 3.75-3.85 (m,
2 H, CH), 4.97 (s, 4 H, OCH2), 7.41 (s, 10 H,
C6H5)j
–
150
4g
oil
3259, 2857h
1.27-1.50, 1.62-1.83 [2 m, 8 H, (CH2)4], 22.20 (-, CH2), 25.98 (-, CH2),
3.25-3.35 (m, 2 H, CH), 4.73 (s, 4 H, 58.36 (+, CH), 76.55 (-, OCH2),
OCH2), 5.55-5.85 (br s, 2 H, NH), 7.36 (s, 127.54 (+, Ph, Cp), 128.15 (+, Ph,
10 H, C6H5)f
Cm(o)), 128.27 (+, Ph, Co(m)),
137.95 (-, Ph, Ci)f
Synthesis 2000, No. 5, 681–690 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular Cyclization of 1,2-Bis(N-alkoxy-N-nitrosoamino)alkanes
687
Table 3 (continued)
Prod- Time, Yield mp (oC)a IR
UV, lmax
(log e)b
1H NMR, d, J (Hz)
13C NMR,c d
uct
Temp. (%)
n (cm-1)
4h
5h,
85°C
27
oil
–
–
1.25 (t, 6 H, J = 7, CH3), 1.2-1.5, 1.5-1.75 14.04 (+, CH3), 22.14 (-, CH2),
[2 m, 8 H, (CH2)4], 3.23 (m, 2 H, CH), 4.18 25.85 (-, CH2), 58.22 (+, CH),
(q, 4 H, J = 7, OCH2CH3), 4.24, 4.25 (AB- 60.53 (-, OCH2), 71.66 (-,
system, 2 H, J = 16, OCHaHbCO2Et), 6.32 OCH2), 170.75 (-, CO)f
(s, 2 H, NH)f
4i
5 h
85°C
37
25
158
-162
1722, 1646d
–
–
1.35-1.48, 1.53-1.77, 1.78-1.90 [3 m, 8 H, 23.32 (-, CH2), 26.46 (-, CH2),
(CH2)4], 3.39 (m, 2 H, 2 CH), 4.31, 4.39
59.46 (+, CH), 71.79
(AB-system, 4 H, J = 16.5, OCH2)j
(-, OCH2), 175.27 (-, CO2H)j
5cA, 50 h,
5cB 65°C
oil
2939, 2860,
1687i
0.75-2.30 [m, 8 H, (CH2)4], 1.06 (s, 3 H,
20.40 (-, CH2), 20.83 (-, CH2),
CH3), 1.10 (s, 3 H, CH3), 3.28-3.35 (m, 1 H, 21.37 (+, CH3), 23.54 (+, CH3),
CH), 3.51 (s, 6 H, OCH3), 3.85 (s, 3 H,
25.44 (-, CH2), 25.94 (-, CH2),
OCH3), 4.12-4.23 (m, 1 H, CH), 5.80-5.90 26.43 (-, CH2), 29.54 (-, CH2),
(br s, 1 H, NH), 5.90-6.00 (br s, 1 H, NH), 30.15 (-, CH2), 33.55 (-, CH2),
7.94 (s, 1 H, CHO), 8.47
60.32 (-, C), 60.57 (-, C), 61.89,
62.59, 63.47, 64.89, 65.53, 66.67
(6 s, +, OCH3 and CH), 154.19 (+,
CHO), 158.37 (+, CHO)f
(s, 1 H, CHO)f
5dk 21h,
65°C
–
–
–
–
–
–
6d
–
34l
92-
95
1670, 1400d 241 (3.86) 1.44 (s, 6 H, CH3), 1.67 (s, 6 H, CH3), 3.80 23.49 (+, CH3), 23.80 (+, CH3),
(s, 3 H, OCH3), 3.81 (s, 3 H, OCH3), 8.15 (s, 64.22, 64.55 (+, OCH3), 67.90 (-
1 H, CHO)f
, C), 73.80 (-, C), 148.33 (+, CO)f
7d
7e
–
–
30l
97
97-
1405d
240 (3.99) 1.62 (s, 12 H, CH3), 3.80 (s, 6 H, OCH3)f
23.49 (+, CH3), 64.47 (+, OCH3),
100
73.22 (-, C)f
oil
1463, 1410i 240 (3.93) 1.44 (d, 3 H, J = 17, CH3), 1.59 (s, 3 H,
365 (2.20) CH3), 1.69 (s, 3 H, CH3), 3.85 (s, 3 H,
OCH3), 3.87 (s, 3 H, OCH3), 5.20 (q, 1 H, J
= 17, CH)f
–
–
7f
–
100 oil
1640, 1450, 240 (4.09)
1410h
363 (2.42)
–
7g
30 min, 81
20°C
71-
72.5
1450, 1430d 238 (3.95) 1.38-1.52, 1.77-1.96, 2.21-2.35 [3 m, 8 H, 22.22 (-, CH2), 26.82 (-, CH2),
(CH2)4], 4.43-4.58 (br s, 2 H, CH), 4.91,
4.97 (AB-system, 4 H, J = 10.4, OCH2),
7.27-7.44 (m, 10 H, C6H5)f
64.09 (+, CH), 77.10 (-, OCH2),
128.45 (+, Ph, Co), 129.01 (+, Ph,
Cp), 129.29 (+, Ph, Cm), 133.93
(-, Ph, Ci)f
7h
8d
–
90
oil
38
1750,1440, 234 (3.77)
1210h
–
–
50 min, 92
65°C
2810, 1560d 219 (4.36) 1.10 (br s, 6 H, CH3), 1.22 (s, 6 H, CH3),
3.90 (s, 3 H, OCH3)f
17.27 (+, br, CH3), 21.02 (+,
CH3), 64.88 (+, OCH3), 67.65
(-, C), 69.43 (-, C)f
8eA 135
min,
oil
–
–
1.00 (br s, 3 H, CH3), 1.25 (d, 3 H, J = 6.9, 11.91 (+, CH3), 13.99 (+, CH3),
CH3), 1.29 (s, 3 H, CH3), 3.75 (q, 1 H, J = 21.09 (+, CH3), 64.52 (+, CH),
65°C
6.9, CH), 3.95 (s, 3 H, OCH3)f
64.95 (+, OCH3), 68.01 (-, C)e,m
98
8eB 135
min,
oil
oil
2810, 1570h 218 (3.82) 1.20 (s, 3 H, CH3), 1.27 (d, 3 H, J = 7, CH3), 10.85 (q, CH3), 19.58 (q, CH3),
1.32 (s, 3 H, CH3), 3.16 (q, 1 H, J = 7, CH), 25.32 (q, CH3), 64.81 (q, OCH3),
65°C
3.98 (s, 3 H, OCH3)f
65.84 (s, C), 67.98 (d, CH)f
8f
90 min, 78
1575i
219 (4.00) 0.9-2.3 [m, 8 H, (CH2)4], 3.5 (br, 1 H, CH), 20.00 (-, CH2), 21.92 (-, CH2),
3.94 (m, 1 H, CH), 4.63 (m, 2 H, OCH2), 23.50 (-, br, CH2), 28.69 (-,
5.23 (dm, 1 H, J = 10.5, CHa=CHbHc), 5.29 CH2), 60.28 (+, CH), 62.27 (+,
65°C
(ddd, 1 H, J = 17.5, 3, 1.5, CHa=CHbHc),
5.93 (ddt, 1 H, J = 17.5, 10.5, 6.5, CHa=
CHbHc)f
CH), 77.50 (-, OCH2), 119.57
(-, CH2allyl), 132.39 (+,
CHallyl)f
Synthesis 2000, No. 5, 681–690 ISSN 0039-7881 © Thieme Stuttgart · New York

688
V. K. Khlestkin et al.
Table 3 (continued)
Prod- Time,
PAPER
Yield mp (oC)a IR
UV, lmax
(log e)b
1H NMR, d, J (Hz)
13C NMR,c d
uct
Temp.
(%)
n (cm-1)
8g
100 min, 81
65°C
92-
94
1565d
210 (4.20) 0.8-2.2 [m, 8 H, (CH2)4], 3.3-3.6 (br s, 1 H, 19.69 (-, CH2), 21.95 (-, CH2),
CH), 3.8-4.0 (m, 1 H, CH), 5.13, 5.23 (AB- 23.53 (-, br, CH2), 26.77 (-,
system, 4 H, J = 11, OCH2), 7.3-7.5 (m, 10 CH2), 60.44 (+, CH), 62.27 (+,
H, C6H5)f
CH), 78.65 (-, OCH2), 128.26
(+, Ph, Co), 128.45 (+, Ph, Cp),
129.44 (+, Ph, Cm), 135.79 (-,
Ph, Ci)f
8h
30 min 78
65°C
oil
1750, 1563h 217 (4.29) 0.9-2.7 [m, 8 H, (CH2)4], 1.27 (t, 3 H, J =
7.5, CH3), 3.4-3.6 (br s, 1 H, CH), 3.95-
4.05 (m, 1 H, CH), ), 4.20 (q, 2 H, J = 7.5,
CH2), 4.73, 4.97 (AB-system, 2 H, J = 18,
NOCH2)j
–
9e
2 d,
20°C
13
29
78-
1630, 1545d 243 (3.60) 1.47 (s, 6 H, 2 CH3), 2.31 (s, 3 H, CH3)f
10.35 (+, CH3), 21.40 (+, CH3),
81
81.43 (-, C), 189.56 (-, C)f
13n
–
116-
119
1610, 1380,
1290d
–
0.73 (s, 3 H, CH3), 1.50 (s, 3 H, CH3), 3.46
(s, 3 H, OCH3), 7.26-7.60 (m, 8 H, C6H5),
8.03 (d, J = 7.5, 2 H, C6H5), 11.04 (s, 1 H,
OH)f
–
14a 1 h,
3°C
66
59
78-
1448, 1430d 232 (4.10) 1.46 (m, 2 H, CH2), 1.6-2.1 [m, 4 H,
21.41 (-, CH2), 26.12 (-, CH2),
22.29 (+, CH3), 78.12 (-, C)e
81
(CH2)2], 2.10-2.40 (m, 2 H, CH2), 4.82 (m, 68.73 (+, CH)e
2 H, 2CH), 12.8 (br, 2 H, OH)e
14d 1 h,
3°C
125-
128
1465, 1245, 232 (4.01) 1.56 (s, 12 H, CH3)e
1125, 1063d
a Analytical samples were purified by recrystallization: 3g, 8g, from EtOH; 7g, from Et2O; 4g◊2HCl, from MeOH; 6d, 7d, 9e, 3h, from hexane/
EtOAc; 8d, from pentane. Free base of 4g was purified by sublimation at 160°C/3 Torr. Satisfactory microanalyses obtained: C 0.5; H 0.2;
N
0.3.
b In EtOH (10–4 mol/L).
c 13C NMR spectra (except for 4e and 8eB) were performed in J-modulation mode.
d As KBr pellet (0.25%).
e In DMSO-d6, standard: DMSO.
f In CDCl3, standard: CHCl3.
g Analyzed as 4d◊HCl.
h Film.
i In CCl4 (3%).
j In CD3OD, standard: CH3OH.
k Isolated as a mixture with 4d.
l Prepared from a mixture of 4d and 5d.
m Spectrum was recorded at 60oC.
n Analyzed as 13◊HNO3.
N,N’-Dimethoxy-2,3-dimethylbutane-2,3-diamine (4d) and N-
Formyl-N’-methoxy-2,3-dimethylbutane-2,3-diamine (5d)
A solution of 3d (3.5 g, 15.3 mmol) in a 12% solution of HCl in
MeOH (70 mL) was refluxed for 21 h, then cooled and concentrated
in vacuo. The aqueous residue was brought to pH 8 with aq 30%
NaOH and solution was extracted with CHCl3 (3 × 30 mL). Com-
bined organic extracts were dried (MgSO4) and concentrated in vac-
uo to give a mixture of 4d and 5d as colorless oil (2.77g).
ed with Et2O (3 × 10 mL) and the combined organic extracts were
dried (MgSO4) and evaporated in vacuo to give 4h in 27% yield.
Analytical sample was purified by column chromatography (silica
gel, Et2O/hexane, 1:4).
Aqueous solution was concentrated in vacuo, the residue was treat-
ed with EtOH (5 mL) and the precipitate was filtered off. Filtrate
was evaporated up to 1/5 of its initial volume and EtOAc (4 mL)
was added to give the precipitate of 4i (0.76 g, 37%).
cis-N,N’-Bis(ethoxycarbonylmethoxy)-1,2-cyclohexanediamine
(4h) and cis-N,N’-Bis(carboxymethyloxy)-1,2-cyclohexanedi-
amine (4i)
A solution of 3h (2 g, 5.38 mmol) in a solution of concd HCl (4 mL)
in EtOH (20 mL) was refluxed for 5 h, then cooled and concentrated
in vacuo. The residue was dissolved in H2O (10 mL) and the pH was
adjusted to 9 with aq 30% NaOH solution. The mixture was extract-
N-Methoxy-N-(2-methoxyamino-2-methylcyclohexyl)forma-
mide (5cA) and N-Methoxy-N-(2-methoxyamino-1-methylcy-
clohexyl)formamide (5cB)
A solution of KOH (0.30 g, 5.36 mmol) in MeOH (5 mL) was added
to a solution of 3c (0.22 g, 0.92 mmol) MeOH (5 mL) and the mix-
ture was refluxed for 50 h. The solution was brought to pH 9 with
aq 6% HCl and MeOH was evaporated in vacuo. Residue was
Synthesis 2000, No. 5, 681–690 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Intramolecular Cyclization of 1,2-Bis(N-alkoxy-N-nitrosoamino)alkanes
689
mixed with H2O (5 mL) and extracted with CHCl3 (2 × 5 mL). The
organic extract was dried (MgSO4) and concentrated to give color-
less oil which was purified by column chromatography (silica gel,
hexane/Et2O, 2:1) to yield 0.05 g (25%) of the mixture 5cA and 5cB
in ~1:1 ratio.
were dried (MgSO4) and concentrated in vacuo. The residue was fil-
tered to give an additional amount of 10a (0.08 g); total yield: 86%.
10b
Compound 10b was synthesized in a similar manner in a 65% yield.
Nitrosation of 1,2-Bishydroxylamines 1a, d; General Procedure
A solution of 1d (9 mmol) in aq HCl (10 mmol) (pH 2-3), was
cooled to 0∞C and an aqueous solution of NaNO2 (1.24 g, 18 mmol)
was added dropwise with stirring for 40 min (temperature should
not exceed 3∞C, pH should not exceed 4). Then the mixture was al-
lowed to stir for an additional 20 min. The precipitate was filtered,
washed with ice-cold H2O (5 mL) and dried in the air to yield 1.08
g (95%) of 14d. Substance 14a was synthesized in a similar manner.
Nitrosation of 1,2-Bis(alkoxyamines) 4a, b, e-h; General Proce-
dure
A solution of NaNO2 (0.27 g, 4.05 mmol) in H2O (1 mL) was added
dropwise to a stirred mixture of solution of 4a (2 mmol) in 6% HCl
(5 mL) and Et2O (5 mL). After additional 10-30 min of stirring, the
yellow organic layer was separated, and the aqueous layer was ex-
tracted with Et2O. The combined organic extracts were dried
(MgSO4) and concentrated in vacuo to give 7a in quantitative yield.
7b, e-h
Oxidation of 2,3-Bis(N-hydroxy-N-nitroso)-2,3-dimethylbut-
anediamine (14d) with MnO2
Compounds 7b, e-h were synthesized similarly.
A suspension of 14d (0.25 g, 1.23 mmol) and MnO2 (0.42 g, 4.9
mmol) in MeOH (10 mL) was stirred for 2 h, filtered and concen-
trated in vacuo. The residue was treated with Et2O (4 mL) and kept
for 48 h at 0∞C. The precipitate was filtered to give 0.14 g (78%) of
3,4-dihydro-3,3,4,4-tetramethyl-1,2-diazete 1,2-dioxide (15).
N-Formyl-N,N’-dimethoxy-2,3-dimethyl-N’-nitrosobutane-2,3-
diamine (6d) and 2,3-Bis(N-methoxy-N-nitroso)dimethylbut-
ane-2,3-diamine (7d)
A solution of NaNO2 (0.8 g, 11.7 mmol) in H2O (10 mL) was added
dropwise to a stirred solution of mixture of 4d and 5d (1 g) in 6%
HCl (10 mL). After additional 10 min of stirring, the precipitate was
filtered and washed with H2O (5 mL) to furnish 0.42 g (30%) of 6d.
The aqueous solution was extracted with CHCl3 (2 × 20 mL), the
combined organic extracts were dried (MgSO4) and concentrated in
vacuo. Treatment of the residue with Et2O/pentane (5 mL, 1:1) gave
7d in 34% yield.
Acknowledgement
This investigation was supported by Russian Foundation for Basic
Research (project no. 99-03-33113a).
References
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Article Identifier:
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