The first general synthesis of 3-lodo-4-R-furazans

Article abstract of DOI:10.1002/hc.20007

The first general synthetic route has been developed for the convenient preparation of iodofurazans. The approach was accomplished by one-pot diazotization-iodation reaction of appropriate aminofurazans. A combination of sodium nitrite and iodine in organic solvent under anhydrous conditions as the reaction conditions allowed to solve problem in iodofurazans preparation. The investigation of the substituent's influence on NMR data of the iodofurazans has been carried out. The X-ray crystal structure of the 3-amino-4-iodofurazan 1d is reported.

Full text of DOI:10.1002/hc.20007

Heteroatom Chemistry
Volume 15, Number 3, 2004
The First General Synthesis of
3-Iodo-4-R-furazans
Aleksei B. Sheremetev,1 Julia L. Shamshina,1 Dmitry E. Dmitriev,1
Denis V. Lyubetskii,2 and Mikhail Yu. Antipin2
1N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47, Leninsky Prosp.,
Moscow 119991, Russia
2A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28
Vavilov Street B-334, Moscow 119991, Russia
Received 19 December 2003; accepted 8 January 2004
replaced by iodine and by many other groups found
ABSTRACT: The first general synthetic route has been
in aqueous diazonium ion reactions.
developed for the convenient preparation of iodofu-
Despite a relatively large number of known fu-
razans. The approach was accomplished by one-pot
razan derivatives, there are only two with iodine at
diazotization-iodation reaction of appropriate amino-
the ring [1]. Thus, the first report of an iodofurazan
furazans. A combination of sodium nitrite and io-
was the synthesis of the parent 3-iodofurazan by re-
dine in organic solvent under anhydrous conditions
duction of 3,4-diiodofuroxan with SO2 in ethanol de-
as the reaction conditions allowed to solve prob-
scribed by Birckenbach and Sennewald in 1931 [2]
lem in iodofurazans preparation. The investigation
As late as 1993, second and final compound, 3-iodo-
of the substituent’s influence on NMR data of the
4-methylfurazan 1a, was prepared by diazotization
iodofurazans has been carried out. The X-ray crys-
of 3-amino-4-methylfurazan 2a with NaNO2/H2SO4
tal structure of the 3-amino-4-iodofurazan 1d is re-
followed by treatment with aqueous solution of
ꢀ
C
ported. 2004 Wiley Periodicals, Inc. Heteroatom Chem
NaI; no iodo product could be obtained when other
aminofurazans were exposed to the same reaction
conditions [3]. A ring-cleavage reaction and triazene
15:199–207, 2004; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20007
formation usually occurred when aminofurazans
were diazotized under ordinary conditions [1,4]. Un-
til now, no general methods for the direct transfor-
mation of the NH2-group at furazan ring to a halogen
have been reported.
Iodofurazans are potential precursors to new
derivatives through the use, for example, of
palladium-catalyzed coupling reaction or halogen-
metal exchange reactions, oxidation, and other
transformations. In the context of developing a syn-
thetic methodology for halofurazans [5], we focused
on iodofurazans 1. Clearly attractive precursors for
the synthesis are available aminofurazans [1]. How-
ever, aminofurazans are weak bases [6]. It is known
that diazotization reactions of weak based aryl and
hetaryl amines are problematic [7].
INTRODUCTION
Iodo heterocycles are building blocks in organic
chemistry due to the reactivity of the iodine sub-
stituent toward different reagents. Among various
methods for the preparation of iodo heterocycles, di-
azotization reaction of corresponding amino deriva-
tives is the most widely used. The amino group can be
Correspondence to: Aleksei B. Sheremetev; e-mail: sab@ioc.
ac.ru.
Contract grant sponsor: Russian Foundation for Basic
Research.
Contract grant number: No 1-03-32944.
c
ꢀ
2004 Wiley Periodicals, Inc.
199

200 Sheremetev et al.
Because aqueous diazotization reaction of
aminofurazans usually gave no desired products, an
alternate route was required. From our viewpoint
the most attractive procedure involves the unaque-
ous diazotization reaction. Relatively little works
have been reported on such processes. Thus, heat-
ing (80–110◦C) of a variety of amines (anilines [8],
aminopyrimidines [9], aminoimidazoles [10]) with
alkyl nitrite in diiodomethane was reported to give
the respective iodo derivatives in moderate yields. In
this process, a free radical is apparently generated
by the homolysis of initially formed diazonium com-
pound, followed by conversion to (het)aryliodide by
iodine abstraction from the solvent. Herein we re-
port a general synthetic partway to iodofurazans re-
sulting from utilization of an optimized unaqueous
diazotization reaction for aminofurazans.
dried and evaporated. Product 1a was isolated by
chromatographic purification. There are difficulties
associated with high volatility of the product. Thus,
in special experiment, a solution of 1a (1 g) in 30 ml
CH2Cl2 was evaporated at room temperature at re-
duced pressure. The only 0.6 g (60%) of starting com-
pound remained in the flask! Additives (ca. 5%) of
alkyl nitrites and alcohols in CH2Cl2 increased the
disappearance of 1a up to 50–80%. When CHCl3 was
employed as a solvent, only 22% of 1a was store.
Additionally, an attempt to improve the separation,
using a high-boiling solvent, such as nitrobenzene,
and evaporation of volatile product (GLPC yield was
47%) failed to yield the expected iodo derivative 1a
since the compound decomposed at heating.
Because the increased volatility had been ob-
served for iodo derivative 1a especially in the pres-
ence of alkyl nitrites and corresponding alcohols,
attention was turned toward the diazotization by a
reagent free of an organic fragment.
We found that amine 2a underwent smooth
diazotization-iodation reaction with a mixture of io-
dine and NaNO2 in acetonitrile to give iodofurazan
1a (Scheme 2). The reaction was initially performed
by addition of solid 2a and NaNO2 to the I2 solution
in MeCN at ca. 5◦C; however for ease of the reaction,
addition of the solid NaNO2 to a slurry of 2a and I2
in MeCN/CH2Cl2 mixture at room temperature was
preferred. The product was isolated by chromato-
graphic purification.
RESULTS AND DISCUSSION
Synthesis
In our case, however, similar diazotization-iodation
procedure with 3-amino-4-methylfurazan 2a af-
forded only little iodo product 1a (GLPC yield was
18%). The major product was ꢀ-hydroxymino ace-
tonitrile 3 (65%) (Scheme 1). Moreover, properties of
iodofurazan 1a and CH2I2 are resembling each other
and isolation of the product 1a proved to be difficult.
It has been reported in the literature that
iodobenzene can be prepared by reaction of ani-
line with amyl nitrite and iodine at refluxing in ben-
zene or CCl4 [11]. Encouraged by this report, we
chose to examine a synthesis of iodofurazan 1a by
diazotization-iodation of amine 2a with iodine using
a variety of different alkyl nitrites and solvents. Upon
reaction of 2a with iodine (1 equiv) at room temper-
ature using i-Amyl-ONO (1.5 equiv) in MeCN, a 62%
GLPC yield of 1a was obtained. However, separated
yield of 1a was only 22%. Use of i-Pr-ONO provided
1a in 65% GLPC yield and only 26% separated yield.
Changing of the solvent to glyme, with i-Pr-ONO as
diazotization agent, reduced the separated yield to
15%. When i-Pr-ONO in ethyl acetate was employed,
attempts to separate 1a were unsuccessful. All reac-
tions were diluted with CH2Cl2, washed with H2O,
This methodology has been successfully applied
for the synthesis of a number of iodofurazans 1b–g
(Scheme 2). The reaction of aminofurazans 2b–g
with iodine and NaNO2 in MeCN/CH2Cl2 mixture oc-
curred readily at room temperature over a period of
2–3 h. The products yields are shown in table.
The transformation is successful in the presence
of a variety of functional groups. It is interesting
R
I
R
NH2
2
1
NaNO2 / I2
N
N
N
N
O
O
2a-f
1a-f
GLPC Yield (%) Separated Yield (%)
Product
R
1a
1b
1c
1d
1e
1f
Me
Et
OMe
NH2
Br
56
52
64
27
51
55
48
35
38
29
21
28
37
35
Me
I
Me
NH2
Me
CN
NOH
i
+
N
N
N
N
O
O
I
2a
1a
3
1g
Ph
SCHEME 1 Reagents and conditions: i , i-Amil-ONO/CH2I2,
80◦C, 1 h.
SCHEME 2

The First General Synthesis of 3-Iodo-4-R-furazans 201
to note that the only an amino group of 3,4-
diaminofurazan 2d was transformed to iodine group
to give 3-amino-4-iodofurazan 1d. However, pure
3-amino-4-iodofurazan 1d subjected to the reac-
tion was readily converted to 3,4-diiodofurazan
1f. This suggests that some species formed in
the diazotization-iodation of diamine 2d inhib-
ited reaction of compound 1d. However, at-
tempted diazotization-iodation of aminofurazans
bearing strong electron-withdrawing substituents
(3-amino-4-nitrofurazan, 3-amino-4-cyanofurazan,
4,4ꢁ-diaminoazo-, and azoxyfurazans) under these
conditions failed to give the corresponding iodofu-
razans. This clearly illustrated the importance of the
electronic properties of the substituent at furazan
ring in the diazotization process.
Cl
I
NHAc
I
N
Cl
N
N
O
N
N
O
5
6
CCl4
AlCl3
AcCl
85%
67%
I
N
I
NH2
MeO
OMe
O
N
N
N
N
32%
O
O
A byproduct, corresponding 1,3-bis(3-R-furazan-
4-yl) triazene 4, was observed at preparation of
the iodofurazans bearing electron donating sub-
stituents; triazenes formation is a well documented
side-reaction for aminofurazans diazotization [1].
The solubility of these triazenes in nonpolar solvent
is quite limited; simple filtration of a solution of the
reaction products through a short SiO2 pad is effec-
tive to separate the byproduct.
7
1d
NaNO2 / H2SO4
NaN3
I
N3
79%
DBI
65%
N
N
O
I
I
N
N
N
8
N
N
N
R
R
H
N
O
O
N
9
N
N
N
N
N
O
O
SCHEME 3
4
give compound 8 [3]. No characterizable product
could be obtained when the amine 1d was exposed
to oxidation with KMnO4 under acidic reaction con-
ditions [1]. In sharp contrast to this result, the amine
1d reacted with the dibromoisocyanurate (DBI) [14]
in an organic solvent to give the desired azofurazan
9 (Scheme 3).
This diazotization-iodation procedure does not
require harsh reaction conditions or difficult to han-
dle reagents and can be easily scaled up to the prepa-
ration of gram quantities of the iodofurazans.
Compounds 1a–f are usually solids at room tem-
perature or slight cooling, but they are volatile liq-
uids after melting point. The purification can be
achieved by sublimation. The iodofurazans are light-
sensitive; at light they decompose with the release of
I2. The iodofurazans are soluble in common organic
solvents and they are stable to solvolysis by MeOD
in DMSO-d6 at room temperature over a period of 3
days.
Scheme 3 demonstrates some of the synthetic
potential of amine 1d for preparation of various
iodofurazans. It reacted smoothly with acetyl chlo-
ride at room temperature to give the amide 5, with
carbon tetrachloride under AlCl3 promotion to give
dichloroimine 6 [12]. The synthesis of pyrrole 7 was
achieved by Clauson-Kaas reaction [13].
MS Data
The electron impact mass spectra showed, for all iod-
ofurazans, molecular ion peak (rel intens 20–35%),
diagnostic fragment corresponding to the loss of io-
dine, giving rise to signals with m/z values for (M-
127) (65–75%) and a strong iodine ion peak at m/z
127 (100%). In the case of the compounds 1a–d, the
spectra also revealed others diagnostic peaks corre-
sponding to the loss of NO [15], affording signals
with m/z value for (M-30) and (M-127-30).
NMR Investigation
Diazotization of amine 1d could easily be accom-
plished by nitrosylsulfuric acid followed by treat-
ment with an aqueous solution of sodium azide to
The structure of the iodofurazans was confirmed on
the basis of a detailed NMR analysis. Assignments

202 Sheremetev et al.
TABLE 1 Chemical Shifts δ NMR 13C and SCS Values for Iodofurazans in CDCl3
C(2)
C(1)
Compound
R
δ (ppm)
SCSia
δ (ppm)
SCSao
R [δ (ppm)]
1a
1b
1c
1db
1e
1f
1g
5b
6
Me
Et
OMe
NH2
Br
155.3
159.4
167.1
159.8
141.0
114.3
156.8
155.1
158.4
154.4
9.2
15.6
31.4
18.2
−6.8
−34.1
13.1
9.5
105.5
104.5
95.7
102.1
108.4
114.3
102.5
106.7
100.3
95.6
0.7
−0.5
−14.4
−13.4
3.2
9.4
11.7 (Me), 18.1 (CH2)
59.6
–
–
–
I
8.9
Ph
NHAc
N=CCl2
−1.1
−8.1
–
−8.3
124.7 (i ), 128.7, 129.0 (o, m-), 131.1 (p-)
22.9 (Me), 169.0 (C O)
140.9 (CCl2)
15.7c
11.9
7
112.5 (b), 120.3 (a)
8
9
N3
158.0
162.8
12.0
97.2
99.0
−9.1
–
21.0c
–
99.0, 162.8
10 [16]
NO2
162.3
19.5
95.1
−4.9
–
aThe values of the substituent constants are from Ewing review [17].
bIn DMSO-d6.
cSCSi values are calculated by [Eq. (2)].
of 1H signals were made using considerations of
splitting patterns and additivity of chemical shifts.
The 13C NMR spectra were assigned by intensity,
peak multiplicity under off-resonance decoupling,
and substituent chemical shifts (SCS) considerations
(Table 1). The 1H and 13C chemical shifts of the com-
pounds are considered to be accurate to 0.02 and
0.05 ppm, respectively.
Recently, we reported [13,19,20] the range of suc-
cessful correlations established on this basis for 13C
chemical shifts in the furazan series. The Lynch cor-
relation of 13C chemical shifts for carbon atom of the
furazan ring bearing variable substituent R in iod-
ofurazans 1 has a slope b of 0.84, indicating that the
substituent effect significantly diminished in iodofu-
razans compared to monosubstituted benzenes.
Correlation of 13C chemical shifts of carbon
atoms of the furazan ring in iodofurazans with the
SCS values of corresponding monosubstituted ben-
zenes (Fig. 1) were performed using Lynch [18]
equation [Eq. (1)]
δ(C2)(R) = a + b × SCS(R)
a = 145.2 0.8
(2)
b = 0.84 0.04
Shiftx(Y) = a + b × SCSx(H)
(1)
(r = 0.990, n = 10)
The correlation of 13C chemical shifts in 1,4-
disubstituted benzenes [Shiftx(Y)] with the SCS val-
ues of monosubstituted benzenes [SCSx(H)] showed
that the fixed substituent (Y in 11) has an effect on
its carbon of attachment [17]. This is measured by
the slope b of the Lynch equation [Eq. (1)]
The above result agrees well with our previous
correlations that showed the absence of significant
polarization of the furazan ring under substituent
influence. Analysis of 13C chemical shifts for carbon
of the furazan ring bearing iodo group (C1) do not
afford good Lynch correlation.
It should be noted that the iodofurazans 1a–f
show the diagnostic chemical shift for quaternary
carbon of the furazan ring bearing iodo group in δ
95–114 ppm region.
o
m
p
i
Y
X
11

The First General Synthesis of 3-Iodo-4-R-furazans 203
FIGURE 1 Plot of chemical shifts (δ) of carbon 2 in iodofurazans vs SCSi values for monosubstituted benzenes.
closest to amino group (an electron donor) is short-
ened to 1.389 A.
X-ray Crystallography
˚
Single crystals of 3-amino-4-iodofurazan 1d (Fig. 2)
were grown by slow evaporation of CHCl3 solution.
Bond angles and bond lengths are given in Table 2.
Molecular geometry for both independent molecules
is as expected, but some features may be noted. Thus
double bond C(1) N(1) at iodine group is slightly
shorter than C(2) N(2) at the amino group, while
the C C single bond is slightly elongated. This may
be attributed to the donor-acceptor nature of the
substituents as well as steric repulsion between the
NH2 group and the iodine atom. In agreement with
earlier reports the length of the N(1) O(1) bond,
proximate to electron-withdrawing substituent, is
Analysis of the crystal packing has revealed that
molecules in crystal are assembled in layers due to
H-bonding and secondary interactions of the iodine
with nitrogen atoms of the furazan rings (Fig. 3).
The H-bonding system is different for two indepen-
dent molecules. For the first molecule, both hydro-
gen atoms of the amino group are strongly bounded
with nitrogen atoms of surrounding furazans (H. . . N
˚
˚
2.27 and 2.28 A, N. . . N 3.11 and 3.23 A, N H. . . N
◦
˚
TABLE 2 Bond Lengths (A) and Angles ( ) for 1d
◦
˚
A
˚
Bond
Angle
equal to 1.399 A, while the length of the N O bonds
I(1) C(1)
2.068(6)
1.334(8)
1.367(9)
1.445(8)
1.284(9)
1.399(7)
1.389(8)
2.079(7)
1.300(9)
1.298(9)
1.432(9)
1.272(9)
1.388(7)
1.398(8)
N(2) C(2) N(3)
N(2) C(2) C(1)
N(3) C(2) C(1)
C(1) N(1) O(1)
N(1) C(1) C(2)
N(1) C(1) I(1)
125.4(6)
107.3(6)
127.3(6)
105.5(6)
110.7(6)
123.4(5)
125.9(5)
110.9(5)
105.5(5)
124.6(7)
107.8(6)
127.6(7)
104.0(5)
111.8(6)
123.6(5)
124.6(5)
111.5(5)
104.9(6)
C(2) N(2)
C(2) N(3)
C(2) C(1)
N(1) C(1)
N(1) O(1)
O(1) N(2)
I(1ꢁ) C(1ꢁ)
C(2ꢁ) N(2ꢁ)
C(2ꢁ) N(3ꢁ)
C(1ꢁ) C(2ꢁ)
N(1ꢁ) C(1ꢁ)
N(1ꢁ) O(1ꢁ)
O(1ꢁ) N(2ꢁ)
C(2) C(1) I(1)
N(2) O(1) N(1)
C(2) N(2) O(1)
N(3ꢁ) C(2ꢁ) N(2ꢁ)
N(2ꢁ) C(2ꢁ) C(1ꢁ)
N(3ꢁ) C(2ꢁ) C(1ꢁ)
C(1ꢁ) N(1ꢁ) O(1ꢁ)
N(1ꢁ) C(1ꢁ) C(2ꢁ)
N(1ꢁ) C(1ꢁ) I(1ꢁ)
C(2ꢁ) C(1ꢁ) I(1ꢁ)
N(1ꢁ) O(1ꢁ) N(2ꢁ)
C(2ꢁ) N(2ꢁ) O(1ꢁ)
FIGURE 2 The general view of 1d.

204 Sheremetev et al.
with nitrogen atoms of furazan in both independent
˚
molecules are almost equal (I. . . N 3.15 and 3.08 A).
Keeping in mind directed character of these con-
tacts, that pointed out by C I. . . N angles 174.8 and
173.3◦, one can conclude that these contacts corre-
spond to lone-pair electron transfer of the nitrogen
atom to the antibonding C I orbital.
The packing also contains I. . . I contacts: the
layer plane contacts (between two independent
◦
˚
molecules, I. . . I 4.08 A, C I. . . I 128.0 ) and weaker
◦
˚
interplanar ones (4.22 A, C I. . . I 107.4 ). The values
of C I. . . I bind angles allow all I. . . I contacts to be
suggested as forced.
The layer planes are situated close enough to
˚
each other (3.27 A), that exhibit the presence of stak-
ing interactions between ꢁ-systems of furazan rings
(Fig. 4).
During the search in the Cambridge Structural
Database (CSD; Allen, 2002), several compounds
containing furazan fragment were found. The anal-
ysis of their geometry has revealed that the values of
bond lengths and angles in furazan ring are similar
to those in 1d. The minor deviations arised mainly
from influence of substituents of various nature.
Thus, mesomeric effect of substituent causes C N
bond elongation due to n-ꢁ (in the case of NH2)
and ꢁ-ꢁ (in the case of Ph) conjugation. This ef-
fect is strongest for phenyl substituent (C N bond
FIGURE 3 The packing scheme of 1d in the crystal.
162.2 and 171.9◦, respectively). For the second in-
dependent molecule, hydrogen atoms form only one
˚
strong H-bond with the iodine atom (H. . . I 2.93 A,
◦
˚
I. . . N 3.85 A, N H. . . I 179.2 ) and one weak con-
˚
˚
tact with oxygen atom (H. . . O 2.50 A, O. . . N 3.06 A,
N H. . . O 121.2◦ ). Secondary interactions of iodine
˚
length equals ∼1.35 A), while in the case of amino
FIGURE 4 The formation of staking interactions in 1d.

The First General Synthesis of 3-Iodo-4-R-furazans 205
group there is almost no conjugation (C N bond
raphy was performed with CH2Cl2/pentane solvent
system using 0.040–0.060 mm silica gel (230–400
mesh) or silica gel 60 (200–400 mesh). All separa-
tions were carried out under above conditions.
˚
length is ∼1.30 A) because the corresponding dis-
tance between C and N at the methyl group is equal
˚
to ∼1.29 A. Despite of the analogous n-ꢁ mesomeric
effects in 1d, the C N bond adjacent to the iodine
˚
atom in this molecule is shorter (∼1.28 A) than that
X-ray Crystallography
at the amino group. This might be explained by the
presence of negative inductive effect of iodine sub-
stitution that competes against the mesomeric one
and its absence in other cases.
Intensities of 5521 reflections were measured with
a Smart 1000 CCD diffractometer (ꢂ(MoKꢀ) =
◦
˚
0.71072 A, ꢃ-scans with 0.3 step in ꢃ 5 s per frame
exposure, 2ꢄ < 60◦) and 1565 independent reflec-
Also, it would be interesting to notice that the
packing in the crystal of methylamine substituted fu-
razan [21] is similar to that in 1d, i.e., two indepen-
dent molecules of the unit cell form planar layers sta-
bilized by intermolecular contacts. However, the hy-
drogens of second independent molecule forms two
strong H-bonds with oxygen and nitrogen atoms in
the furazan rings of adjacent molecules (H. . . O 2.21
tions (R = 0.0337) were used in further refinement.
int
Crystallographic data for 1d: at 170 K C2H2IN3O
(M = 210.97) are monoclinic, space group P21/m;
˚
˚
˚
a = 7.318(2) A, b = 6.548(1) A, c = 10.688(2) A, V =
511.5(2) A , Z = 8 (Z = 2), dcalc = 2.740 g cm−3,
3
ꢁ
˚
µ(MoKꢀ) = 6.136 mm−1, F(000) = 384.
The structure was solved by direct method and
refined by the full-matrix least-squares technique
against F2 in the anisotropic-isotropic approxima-
tion. Hydrogen atoms were located from the Fourier
synthesis and refined in the isotropic approxima-
tion. The refinement converged to wR2 = 0.0873 and
GOF = 1.076 for all independent reflections (R1 =
0.0366 was calculated against F for 1237 observed
reflections with I > 2ꢅ(I)). All calculations were per-
formed using the SHELXTL PLUS 5.10 [22] on IBM
PC AT. Atomic coordinates, bond lengths and angles
and thermal parameters have been deposited at the
Cambridge Crystallographic Data Center (CCDC) as
supplementary publication numbers 228976.
˚
˚
and H. . . N 2.20 A, N. . . O 3.05 and N. . . N 3.08 A,
N H. . . O 161.7 and N H. . . N 170.2◦) whereas sec-
ond independent molecule of 1d has only one strong
N H. . . I contact and weak N H. . . O.
CONCLUSION
In summary, the originally developed method in-
volving the use of NaNO2-I2 has proven to be effec-
tive in transformation of aminofurazans to iodofu-
razans. Simple reaction procedure combined with
easy workup and generally moderate yields make for
an attractive alternative to syntheses of iodo deriva-
tives of other ꢁ-deficient (het)arenes.
General Procedure for Preparation of
Iodofurazans
EXPERIMENTAL SECTION
General Information
To a slurry (or a solution) of an aminofurazan 2a–
f (10 mmol) and I2 (20 mmol) in a mixture of
MeCN/CH2Cl2 (1/1, 20 ml) was added solid NaNO2
(20 mmol) by small portions at room temperature
and stirring. After stirring for 2–3 h (until TLC
analysis indicated complete consumption of start-
ing material), a mixture of pentane/CH2Cl2 (2/3, 30
ml) was added and resulting mixture was washed
with H2O (100 ml), 0.1 N solution of Na2S2O3
(2 × 10 ml), and H2O (2 × 20 ml), sequentially. Or-
ganic solution was dried over MgSO4 and passed
through a short SiO2 pad and evaporated to give
product. These compounds 1a–f can be addition-
ally purified by flash chromatography or sublima-
tion onto a Dry Ice cooled cold finger when heated to
35–55◦C/1 mm.
Unless otherwise stated, reactions were performed
with magnetic stirring using dry, distilled solvents.
Solvents for reactions were purified by standard pro-
cedures. All reagents used are commercially avail-
able. Melting points were determined with an open
capillary and are uncorrected. Infrared spectra were
determined on a Perkin-Elmer Model 577 spectrom-
eter in KBr pellets or thin films. Mass-spectra were
recorded on a Varian MAT-311A instrument. UV
spectra were taken in MeOH on a Beckman DU-7
1
spectrophotometer. H NMR spectra were recorded
at 300 MHz and 13C spectra at 75 MHz on a Bruker
AM-300 instrument. Chemical shifts were reported
in δ values relative to the residual solvent peaks in 1H
and 13C NMR (CDCl3). All reactions were monitored
by thin-layer chromatography (TLC) using Merck sil-
ica gel 60 F254 precoated aluminum plates. TLC was
visualized with UV light (254 nm). Flash chromatog-
3-Methyl-4-iodofurazan (1a). A light yellow
1
solid: mp 26–27◦C. H NMR δ 2.38 (Me). MS (EI),

206 Sheremetev et al.
m/z: 210 [M+], 180 [M+ − NO], 83 [M+ − I]. The
substance corresponded in all respects with the com-
pound described earlier [3].
(253.00): C 18.99, H 1.59, N 16.61, I 50.16. Found: C
19.01, H 1.62, N 16.57, I 50.12.
(3-Iodofurazan-4-yl)dichloroimine (6). To a so-
lution of amine 1d (0.42 g, 2 mmol) in CCl4 (10 ml)
at room temperature, AlCl3 (1.88 g, 0.014 mol) was
added in a single portion with stirring under anhy-
drous conditions. The reaction mixture was vigor-
ously stirred at 60–70◦C for about 2.5 h, until the
complete consumption of the starting amine (ac-
cording to TLC). The mixture was cooled to room
temperature and poured with stirring over 20 g of
ice and water. The quenched mixture was extracted
with CH2Cl2 (2 × 20 ml). The combined extracts were
washed with cold water until neutral and dried with
MgSO4. The solution was passed through a short
SiO2 pad and evaporated to give product as clear
liquid (0.36 g, 67%) that slowly crystallized, mp
29◦C. MS, m/z: 295, 293, 291 [M+]. Anal. Calcd for
C3Cl2I1N3O1 (291.86): C 12.35, N 14.40. Found: C
12.29, N 14.34.
3-Ethyl-4-iodofurazan (1b). A light yellow oil,
1
mp −7 to −6◦C. H NMR (CDCl3)δ: 1.37 (3H, Me),
2.74 (2H, CH2). MS, m/z: 224 [M+].
3-Methoxy-4-iodofurazan (1c). A light yellow
solid: mp 27–27.5◦C. IR (ꢆ/cm−1): 2948, 1580, 1476,
1450, 1420, 1384, 1204, 1124, 1000, 848, 712, 700,
664. 1H NMR (CDCl3) δ: 4.12 (OMe). MS, m/z: 226
[M+].
3-Amino-4-iodofurazan (1d). A light yellow
solid: mp 26–27◦C. IR (ꢆ/cm−1): 3472, 3420, 3384,
3336, 3200, 1636, 1620, 1568, 1468, 1404, 1120, 972,
856, 716. 1H NMR (DMSO-d6) δ: 6.22 (NH2). MS, m/z:
211 [M+], 180 [M+ − NO], 127 [I+], 84 [M+ − I], 54
[M+ − I − NO].
3-Bromo-4-iodofurazan (1e). A light yellow oil,
mp −11 to −9◦C. IR (ꢆ/cm−1): 1616, 1488, 1380, 1308,
1280, 1035, 982, 916, 860, 832, 812. MS, m/z: 275
[M+], 195 [M+ − Br], 148 [M+ − I], 127 [I+]. Anal.
Calcd for C2Br1I1N2O1 (274.84): C 8.74, N 10.19.
Found: C 8.77, N 10.15.
3-Iodo-4-(pyrrol-1-yl)furazan (7). A solution of
amine 1d (0.42 g, 2 mmol) in AcOH (3 ml) was
treated with 2,5-dimethoxytetrahydrofuran (0.29 g,
2.2 mmol). The mixture was heated to reflux for 1
h, cooled, and the solvent was evaporated in a ro-
tary evaporator. The residue was taken up in CH2Cl2
(25 ml), washed with 5% aqueous K2CO3 (3 × 5 ml),
water (5 × 3 ml), dried with MgSO4, passed through
a short SiO2 pad and concentrated to give product as
clear liquid (0.17 g, 32.5%). IR (ꢆ/cm−1): 2920, 2848,
1572, 1464, 1376, 1212, 1100, 1012, 908, 884, 728.
1H NMR δ 6.49 (ꢇ), 7.48 (ꢀ). MS, m/z: 261 [M+], 134
[M+ − I], 127 [I+], 104 [M+ − I − NO]. Anal. Calcd
for C6H4I1N3O1 (261.02): C 27.61, H 1.54, N 16.10, I
48.62. Found: C 27.57, H 1.51, N 16.03, I 48.69.
3,4-Diiodofurazan (1f). A light yellow solid: mp
64–65◦C. IR (ꢆ/cm−1): 1616, 1436, 1276, 1252, 1016,
980, 868, 860. MS, m/z: 322 [M+], 254 [I2+], 195 [M+
− I], 165 [M+ − I − NO], 127 [I+]. Anal. Calcd for
C2I2N2O1 (321.84): C 7.46, N 8.70, I 78.86. Found: C
7.42, N 8.66, I 78.81.
3-Iodo-4-phenylfurazan (1g). A light yellow
solid: mp 107–108◦C (dec). IR (ꢆ/cm−1): 2920–2875,
1580, 1540, 1488, 1448, 1408, 1352, 1164, 1004, 996,
1
980, 876, 840, 768, 716, 696. H NMR δ 7.57 (3H),
3-Azido-4-iodofurazan (8). Amine 1d (1.05 g, 5
mmol) was added to nitrosylsulfuric acid prepared
by dissolving NaNO2 (0.35 g, 5 mmol) in H2SO4 (4
ml) with efficient stirring in an ice bath. After 30 min
the mixture was diluted with AcOH (5 ml) and a so-
lution of NaN3 (0.6 g, 10 mmol) in H2O (4 ml) was
added slowly from dropping funnel at such a rate
that the temperature was kept between 0 and 5◦C.
After the end of the addition the mixture was stirred
for 2 h at 15◦C. It was diluted with water (50 ml) and
extracted with CH2Cl2 (3 × 15 ml). The combined ex-
tract was washed with 5% aqueous K2CO3 (3 × 5 ml),
water (2 × 7 ml), dried with MgSO4, passed through
a short SiO2 pad, and concentrated. The residue was
crystallized from CCl4 to give product as colorless
crystals (0.65 g, 65%); mp 92–92.6◦C. IR (ꢆ/cm−1):
2324, 1636, 1620, 1568, 1468, 1120, 972, 856. 14N
7.89 (2H). MS, m/z: 272 [M+], 145 [M+ − I], 127
[I+], 115 [M+ − I − NO]. Anal. Calcd for C8H5I1N2O1
(272.05): C 35.32, H 1.85, N 10.30, I 46.65. Found: C
35.30, H 1.89, N 10.25, I 46.69.
3-Acetylamino-4-iodofurazan (5). A mixture of
amine 1d (0.3 g, 1.4 mmol) and acetyl chloride (2 ml)
was stirred at room temperature for 2 h. The precip-
itated crystals were filtered, washed with CCl4 (3 × 5
ml), and dried in a vacuum oven at 40◦C; yield was
0.35 g (90%), mp 150–152◦C. A sample was recrys-
tallized from CCl4; mp 152–153◦C. IR (ꢆ/cm−1): 3212,
3088, 3044, 2328, 1708, 1556, 1332, 1240, 1124, 860,
1
668, 596. H NMR (DMSO-d6) δ 2.12 (Me), 10.67
(NH). MS (EI), m/z: 253 [M+], 211 [M+ − COMe],
127 [I+], 126 [M+ − I]. Anal. Calcd for C4H4I1N3O2

The First General Synthesis of 3-Iodo-4-R-furazans 207
[8] (a) Smith, W. B.; Ho, O. C. J Org Chem 1990, 55,
2543–2546; (b) Cornforth, J.; Kuman, A.; Stuart, A.
S. J Chem Soc, Perkin Trans 1, 1987, 859–866.
[9] (a) Nair, V.; Richardson, S. G. J Org Chem 1980, 45,
3969–3974; (b) Nair, V.; Richardson, S. G. Synthesis
1982, 670–672; (c) Nair, V.; Young, D. A.; DeSilvia, R.
J Org Chem 1987, 52, 1344–1347; (d) Tanji, K.; Kato,
H.; Higashino, T. Chem Pharm Bull 1991, 39, 2793–
2796.
[10] Coad, E. C.; Liu, H.; Rasmussen, P. G. Tetrahedron
1999, 55, 2811–2826.
[11] Paudler, W. W.; Shin, H. G. J Org Chem 1968, 33, 1638.
[12] Sheremetev, A. B.; Aleksandrova, N. S.; Yudin, I. L.
Mendeleev Commun 2003, 1, 30–31.
[13] Sheremetev, A. B.; Konkina, S. M.; Yudin, I. L.;
Dmitriev, D. E.; Averkiev, B. B.; Antipin, M. Yu. Izv
Acad Nauk, Ser Khim 2003, 1337–1342 (in Russian);
Russ Chem Bull, Int Ed (English Translation), 2003,
52, 1413–1418.
[14] Sheremetev, A. B.; Shatunova, E. V.; Averkiev, B.
B.; Dmitriev, D. E.; Petukhov, V. A.; Antipin, M. Yu.
Heteroat Chem 2004, 15, 131–145.
NMR (CDCl3) δ: −145.9, −345.6 (N3). Anal. Calcd
for C2I1N5O1 (236.96): C 10.14, N 29.56. Found: C
10.17, N 29.50.
4,4ꢁ-Diiodoazofurazan (9). To a slurry of DBI
(0.57 g, 2 mmol) in CH2Cl2 (35 ml) was added amine
1d (0.21 g, 1 mmol) in one portion. After stirring for
1.5 h the mixture was passed through a short SiO2
pad and concentrated. The residue was crystallized
from hexane to give product as orange crystals (0.18
g, 85%); mp 158–159◦C. IR (ꢆ/cm−1): 1616, 1576,
1560, 1540, 1504, 1456, 1404, 1352, 1124, 1020, 920,
800, 736. MS, m/z: 418 [M+], 388 [M+ − NO], 358 [M+
− 2NO], 292 [M+ − I], 261 [M+ − NO − I], 127 [I+].
Anal. Calcd for C4I2N6O2 (417.89): C 11.50, N 20.11,
I 60.74. Found: C 11.51, N 20.06, I 60.77.
[15] Paton, R. M. In Comprehensive Heterocyclic Chem-
istry; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.
(Eds.); Pergamon Press: Oxford, 1996; Vol. 4, pp. 229–
265.
[16] Novikova, T. S.; Melnikova, T. M.; Kharitonova, O. V.;
Kulagina, V. O.; Aleksandrova, N. S.; Sheremetev, A.
B.; Pivina, T. S.; Khmelnitskii, L. I.; Novikov, S. S.
Mendeleev Commun 1994, 138–140.
[17] Ewing, D. F. Org Magn Reson 1979, 12, 499–524.
[18] Lynch, B. M. Can J Chem 1977, 55, 541–547.
[19] Dmitriev, D. E. Strelenko, Yu. A.; Sheremetev, A. B. Izv
Acad Nauk, Ser Khim 2002, 2, 277–282; Russ Chem
Bull, Int Ed (English Translation), 2002, 51, 290–
296.
[20] Sheremetev, A. B.; Andrianov, V. A.; Mantseva, E.
V.; Shatunova, E. V.; Aleksandrova, N. S.; Kulag-
ina, V. O.; Melnikova, T. M.; Yudin, I. L.; Dmitriev,
D. E.; Averkiev, B. B.; Antipin, M. Yu. Izv Acad
Nauk, Ser Khim (in press); Russ Chem Bull, Int Ed
(English Translation), (in press).
REFERENCES
[1] Sheremetev, A. B.; Makhova, N. N.; Friedrichsen, W.
Adv Heterocycl Chem 2001, 78, 65–188.
[2] Birckenbach, L.; Sennewald, K. Liebigs Ann Chem
1931, 489, 7–31.
[3] Rakitin, O. A.; Zalesova, O. A.; Kulikov, A. S.;
Makhova, N. N.; Godovikova, T. I.; Khmelnitskii, L.
I. Izv Akad Nauk, Ser Khim 1993, 1949–1953 (in
Russian) [Russian Chem Bull (English Translation)
1993, 42, 1865–1870].
[4] Melnikova, T. M.; Novikova, T. S.; Khmelnitskii, L. I.;
Sheremetev, A. B. Mendeleev Commun 2001, 30–31.
[5] Sheremetev, A. B.; Aleksandrova, N. S.; Mantseva, E.
V.; Dmitriev, D. E. Mendeleev Commun 2000, 67–69.
[6] (a) Tselinskii, I. V.; Melnikova, S. F.; Vergizov, S. N.;
Frolova, G. M. Khim Geterotsikl Soedin 1981, 35–
37 (in Russian) [Chem Heterocycl Compd (English
Translation) 1981, 17, 27–29]; (b) Tselinskii, I. V.; Mel-
nikova, S. F.; Vergizov, S. N. Khim Geterotsikl Soedin
1981, 321–324 (in Russian) [Chem Heterocycl Compd
(English Translation) 1981, 17, 228–231].
[21] Viterbo, D.; Serafino, A. Acta Crystallogr, Sect B:
Struct Crystallogr Cryst Chem 1978, 34, 3444–3446.
[22] Sheldrick G. M. SHELXTL v. 5.10, Structure De-
termination Software Suite, Bruker AXS, Madison,
Wisconsin, USA, 1998a.
[7] Godovikova, T. I.; Rakitin, O. A.; Khmelnitskii, L. I.
Usp Khim 1983, 52, 777–786 (in Russian) [Russ Chem
Rev (English Translation) 1983, 52, 440–445.