Hydrazoic acid in the Mannich reaction

Article abstract of DOI:10.1007/s11172-009-0296-8

The possibility of the three-component condensation of hydrazoic acid and formaldehyde with primary or secondary amines, as well as with trialkylhydrazines, leading to the corresponding N-azidomethyl derivatives of amines and hydrazides was established.

Full text of DOI:10.1007/s11172-009-0296-8

Russian Chemical Bulletin, International Edition, Vol. 58, No. 10, pp. 2169—2172, October, 2009
2169
Brief Communications
Hydrazoic acid in the Mannich reaction
A. N. Gafarov
Kazan State Technological University
6
8 ul. K. Marksa, 420015 Kazan, Russian Federation.
Fax: +7 (843) 231 4091; +7 (843) 231 4078. Eꢀmail: anavargafarov@mail.ru
The possibility of the threeꢀcomponent condensation of hydrazoic acid and formaldehyde
with primary or secondary amines, as well as with trialkylhydrazines, leading to the correspondꢀ
ing Nꢀazidomethyl derivatives of amines and hydrazides was established.
Key words: hydrazoic acid, aminomethylation, the Mannich reaction, azidomethylamines.
Joint condensation of aldehydes with amines and
Scheme 2
C—Hꢀacids (the Mannich reaction) is widely used in labꢀ
oratory practice and in industry for the synthesis of diverse
amines. On the basis of modern conceptions, a carꢀ
benium—immonium ion formed from aldehyde and amine
in the Mannich reaction couples with the anion of
RNHNO + CH O + HNR´
RN(NO )CH NR´
2 2 2
2
2
2
2
RNHNO + 2 CH O + H NR´
[RN(NO )CH ] NR´
2 2 2
2
2
2
–
a С—Нꢀacid (X ) and gives the final product, a Mannich
base (Scheme 1).
primary nitramines, act as the acid components. The use
of the N—Нꢀacids in the Mannich reaction considerably
extends the synthetic potential of this reaction.
Scheme 1
Hydrazoic acid (hydrogen azide) НN , which possessꢀ
3
es diverse reactivity, is one of the most interesting objects
among N—Нꢀacids. The azide anion N3 is notable for
R NH + OCHR´
R NCH(R´)OH
2
2
–
[
R NCH(R´)]+
R NCH(R´)X
high nucleophilicity and is widely used for the synthesis of
organic azides. Specifically, a possibility of the synthesis
of N,NꢀdialkylꢀNꢀazidomethylamines by the reaction of
N,NꢀdialkylꢀNꢀhalogenomethylamines with sodium azide
in aqueous solution or silver azide in dichloromethane has
been established (Scheme 3).6
2
2
Aminomethylnitramines are formed by the analogous
method in the threeꢀcomponent condensation of formalꢀ
dehyde with nitramines and primary or secondary amines
Scheme 2).1
—5
(
It is considered that the given reaction is one of variꢀ
ants of the Mannich reaction in which N—Hꢀacids, viz.,
N,NꢀDialkylꢀNꢀazidomethylamines undergo hydrolyꢀ
sis giving hydrogen azide and formaldehyde. It can be
6
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2104—2107, October, 2009.
066ꢀ5285/09/5810ꢀ2169 © 2009 Springer Science+Business Media, Inc.
1

2170
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
Gafarov
Scheme 3
Scheme 5
RNH + 2 CH O + 2 HN RN(CH N ) + 2 H O
2 2 3
R NCH R´ + MN
R NCH N + MR´
2
2
3
2
2
3
2
3
2
2
2
R´ = Cl, Br; M = Na, Ag
assumed that hydrolysis of azidomethylamines is an equiꢀ
librium reverse process and the mixture of hydrogen azide,
formadehyde, and dialkylamine should contain the prodꢀ
uct of the threeꢀcomponent condensation, i.e., N,Nꢀdiꢀ
alkylꢀNꢀazidomethylamine (1) (Scheme 4).
The reaction of sodium azide with formaldehyde and
ammonium chloride gives N,N,Nꢀtris(azidomethyl)amine
N(CH N ) (2d, Table 2).
NꢀAlkylꢀN´,N´ꢀdimethylhydrazine reacts with hydrꢀ
azoic acid and formaldehyde to form the corresponding
NꢀalkylꢀNꢀazidomethylꢀN´,N´ꢀdimethylhydrazines (3)
under the same conditions (Scheme 6, Table 3).
2
3 3
Scheme 4
HN + CH O + HN(R)R´
N CH N(R)R´ + H O
Scheme 6
3
2
3
2
2
1
Me NNHR + CH O + HN
Me NN(R)CH N + H O
2 2 3 2
2
2
3
Our investigations showed that the reaction of sodium
azide with formadehyde and dimethylammonium chloꢀ
ride in aqueous medium gives the expected Nꢀazidomethꢀ
ylꢀN,Nꢀdimethylamine (1a) in low yield (Table 1), which
can be explained by the high rate of its hydrolysis. Analoꢀ
gous situation is observed for the reaction of diethylamꢀ
monium chloride with formaldehyde and sodium azide.
But the use of dialkylamines with more complex aliphatic
radicals in the reaction increases the yield of the correꢀ
sponding N,NꢀdialkylꢀNꢀazidomethylamines. This is esꢀ
pecially characteristic for dialkylamines containing cyanoꢀ
ethyl substituents (Table 1).
3
Methylhydrazine reacts with formaldehyde and hyꢀ
drazoic acid to give formaldehyde NꢀazidomethylꢀNꢀmeꢀ
thylhydrazone in 10% yield (Scheme 7).
Scheme 7
MeNHNH2 + 2 CH2O + HN3
CH2=NN(Me)CH2N3 + 2 H2O
The hydrazone is a liquid with b.p. 58—59 °С (14 Torr);
d420 =1.0822; nD =1.4859. IR spectrum (ν/cm ):
20
–1
The reaction of hydrazoic acid with formaldehyde
and monoalkylamines leads to NꢀalkylꢀN,Nꢀbis(azidoꢀ
methyl)amines (2) irrespective of the reactant ratio
2120 (N ); 1589, 3067 (N=CH ).
3
2
The obtained azidomethyl derivatives of amines and
hydrazines are chemically unstable. They hydrolyze to the
(
Scheme 5, Table 2).
Table 1. Characteristics of NꢀazidomethylꢀN,Nꢀdialkinamines R(R')NCH N (1)
3
3
Comꢀ
pound
R
R´
Yield B.p./°С
d420
nD20
Found
Calculated
Molecular IR spectrum,
(%)
–
1
(%)
(p/Torr)
formula
ν/cm
MRD
С
H
N
М
—
N3
CN
—
1
1
1
1
1
1
1
а
b
c
d
e
f
Ме
Et
Ме
Et
10
15
46
48—50
0.9619 1.4380 27.11
27.98
36.46
36.00
8.16 55.10
C H N
2110
C H N 2110
3
8
4
(
105)
44—46
12)
8.00 56.00 100
9.47 42.32
9.37 43.75 128
0.9349 1.4490 36.75
37.22
47.43
46.88
—
—
—
5
12
4
(
Bun
Bun
55—55.5 0.8915 1.4519 55.67
1) 55.67
84—84.5 1.0699 1.4770 36.71
59.37
58.69
11.43 29.41 169 C H20N4 2115
10.87 30.44 184
9
(
Me CH CH CN 63
43.68
43.16
6.80 49.66 130 C H N
5
6.47 50.37 139
2115 2265
2
2
5
9
(
2)
82—83
2)
37.04
Et
CH CH CN 60
1.0417 1.4769 41.50
41.65
47.18
47.06
7.16 45.51 152 C H N 2120 2265
7.19 45.75 153
2
2
6
11
5
(
Pr CH CH CN 60
102—103 1.0131 1.4765 46.53
2) 46.37
91—91.5 0.9967 1.4708 50.74
1) 50.88
50.25
50.30
7.45 42.45 161 C H N 2128 2270
7.78 41.92 167
2
2
7
13
5
(
g
Bui CH CH CN 62
53.55
53.04
8.50 38.44 183 C H N 2125 2265
2
2
8
15
5
(
8.29 38.67 181

Hydrogen azide in the Mannich reactions
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
2171
Table 2. Characteristics of N,Nꢀbis(azidomethyl)ꢀNꢀalkylamines RN(CH N ) (2)
2
3 2
Comꢀ
pound
R
Yield
(%)
B.p./°С
(2 Torr)
d420
nD20
Found
Calculated
Molecular
formula
IR spectrum,
νN3/cm
(%)
—
1
MRD
C
H
N
M
2
2
2
2
а
b
c
d
Me
Et
64
68
80
42—43
1.1245 1.4920
1.0950 1.4879
1.0704 1.4836
1.2734 1.5205
36.38
5.97
40.30
0.59
45.14
5.21
43.47
3.96
25.45
25.53
29.76
30.97
35.90
35.50
20.22
19.78
5.11 68.90 140
4.97 69.50 141
5.45 63.52 150
5.81 63.22 155
7.15 57.96 166
6.51 57.99 169
3.51 76.17 178
3.30 76.92 182
C H N
2120
2120
2120
2120
3
7
7
7
3
57.5—58
61.5—62
93—94
C H N
4 9
4
Pr
C H N
5 11
7
4
CH N 64
C H N
3 6
2
3
10
4
starting compound in an aqueous medium. Azidomethylꢀ
amines and azidomethylhydrazines intensively decompose
at 120—130 °С. NꢀAlkylꢀN,Nꢀbis(azidomethyl)amines
have explosive properties, they are sensitive to mechanical
impact. N,N,NꢀTris(azidomethyl)amine has especially
high impact sensitivity.
Scheme 9
МеN(CH N ) + HNO + (MeCO) O
2
3
2
3
2
MeN(NO )CH OCOMe
2
2
The structures of the obtained azidomethylamines and
azidomethylhydrazines were determined by elemental
analysis, molecular weight determination and IR
amino group nitrogen in azidomethylamines, as in amiꢀ
nomethylamines, retains nucleophlic properties and can
react with electrophilic reagents.
Aniline and its derivatives, as well as hydrazine and
nonsymmetrical dimethylhydrazine react with formaldeꢀ
hyde and hydrazoic acid giving the products devoid of the
azido group.
and NMR spectroscopy. NꢀAzidomethylꢀN,Nꢀdimethylꢀ
6
amine was converted to earlier described Nꢀazidomethylꢀ
N,N,Nꢀtrimethylammonium iodide (4) under the action
of methyl iodide (Scheme 8).
Experimental
Scheme 8
NꢀAlkylꢀNꢀ(2ꢀcyanoethyl)amines were obtained by addition
of alkylamines to acrylonitrile. Similarly, N,NꢀdimethylꢀN´ꢀ
+
–
(
CH ) NCH N + CH I
[(CH ) NCH N ] I
8,9
3
2
2
3
3
3
3
2
3
(
2ꢀcyanoethyl)hydrazine was obtained from acrylonitrile and
4
1
0
nonsymmetrical dimethylhydrazine. N,NꢀDimethylꢀN´ꢀproꢀ
pylhydrazine and N,NꢀdimethylꢀN´ꢀbutylhydrazine were obꢀ
tained by the known method by the reaction of formaldehyde
dimethylhydrazone with ethylꢀ and propylmagnesium iodides,
respectively. Quaternization of NꢀazidomethylꢀN,Nꢀdimethylꢀ
amine with methyl iodide was carried out by the known methꢀ
od. IR spectra of the obtained compounds were obtained in
a thin film on a URꢀ20 instrument, the layer thickness was
0.03 mm. NMR spectra were recorded on a VarianꢀT60 specꢀ
N,NꢀBis(azidomethyl)ꢀNꢀmethylamine under the acꢀ
tion of nitric acid — acetic anhydride mixture underwent
nitrolysis to give 1ꢀacetoxyꢀ2ꢀazaꢀ2ꢀnitropropane, which
1
1
7
has earlier been described (Scheme 9).
The obtained results are the evidence of the existence
of the principal similarity between the aminomethylation
reaction of hydrazoic acid and primary nitramines. The
6
Table 3. Characteristics of NꢀazidomethylꢀNꢀalkylꢀN´,N´ꢀdimethylhydrazines (Ме) NN(R)CH N (3)
2
2
3
Comꢀ
pound
R
Yield
(%)
B.p./°С
(2 Torr)
d420
nD20
Found
Calculated
Molecular IR spectrum,
(%)
—
1
formula
νN3/cm
MRD
C
H
N
M
3
3
3
а
b
c
Pr
60
62
65
30—35
41—44
88
0.9485
0.9379
1.0612
1.4569
1.4578
1.4801
45.07 46.13 10.95 44.76 155 C H N
2120
2120
6
15
5
5
6
4
5.81 45.86
9.55 44.59 157
Bu
49.71 49.32 10.09 40.13 174 C H N
7
17
5
0.16 49.12
44.94 42.51
5.60 42.86
9.94 40.94 171
7.33 50.02 171 C H N
7.14 50.00 168
CH CH CN
2120, 2265
2
2
6
12
4

2172
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 10, October, 2009
Gafarov
trometer, the solvent was CCl , SiMe was used as the internal
solved in ether. The ethereal solution was dried with Na SO ,
4
4
2
4
standard. The signals for the (CH ) N (δ 2.14) and NCH N
3
and concentrated in vacuo; the residue was distilled under reꢀ
duced pressure. NꢀAzidomethylꢀNꢀ(2ꢀcyanoethyl)ꢀNꢀmethylꢀ
amine was obtained (8.8 g, 63%) .
3
2
2
(
δ 4.06) groups were observed in the NMR spectrum for comꢀ
pound 1а, the ratio of the peak intensities was 3 : 1. The analoꢀ
gous spectrum for compound 2а contains signals for the CH N
NꢀAzidomethylꢀN,N,Nꢀtrimethylammonium iodide (4).
NꢀAzidomethylꢀN,Nꢀdimethylamine (0.5 g, 0.005 mol) and meꢀ
thyl iodide (0.84 g, 0.006 mol) were mixed under iceꢀbath coolꢀ
ing. The crystal product that formed was recrystallized from
ethanol. NꢀAzidomethylꢀN,N,Nꢀtrimethylammonium iodide
was obtained (0.9 g, 74%). M.p. 133—134 °С (decomp.)
3
(
δ 2.18) and NCH N3 (δ 4.10) groups, the ratio of the peak
2
intensities was 3 : 4. Molecular weight for compounds was deterꢀ
mined by cryoscopy in benzene.
Synthesis of N,NꢀdialkylꢀNꢀazidomethylamines 1, Nꢀalkylꢀ
N,Nꢀbis(azidomethyl)amines 2 and NꢀalkylꢀNꢀazidomethylꢀ
N´,N´ꢀdimethylhydrazines 3 (general procedure). Amines, trialkyꢀ
lhydrazines, formaldehyde, and hydrogen azide were introduced
in the reaction in the equimolar amounts. Hydrazoic acid was
obtained in situ as the result of the reaction of sodium azide with
hydrogen chloride. Amines or hydrazines (bases) were prelimiꢀ
nary mixed in the equimolar amounts with 35% HCl, then
a solution of the amine or hydrazine salts was added to the mixꢀ
ture of sodium azide and 37% formaldehyde solution. The mixꢀ
ture was stirred for 30 min, the condensation products were disꢀ
solved in diethyl ether. Ethereal solution was separated, dried
with anhydrous Na SO , concentrated in vacuo; the residue was
6
–1
(lit. data : m.p. 134 °С (decomp.)). IR spectrum: νN3 2110 cm
.
References
1
2
. A. P. N. Franchimont, J. Rec. Trav. Chim., 1910. 29, 356
. F. Chapman, P. Y. Owston, D. Woodcock, J. Chem. Soc.,
949, 1638.
1
3
4
5
. S. S. Novikov, A. A. Dudinsakaya, N. V. Makarov, L. I.
Khmel´nitskii, Izv. Akad. Nauk, Ser. Khim., 1967, 1833 [Bull.
Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1967, 16].
. N. V. Makarov, A. A. Dudinskaya, S. S. Novikov, L. I.
Khmel'nitskii, Izv. Akad. Nauk, Ser. Khim., 1967, 1837 [Bull.
Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1967, 16].
. S. S. Novikov, A. A. Dudinsakaya, N. V. Makarov, L. I.
Khmel´nitskii, Izv. Akad. Nauk, Ser. Khim., 1967, 1839 [Bull.
Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 1967, 16].
. H. Böhme, D. Morf, Chem. Ber., 1958. 91, 660
2
4
distilled under reduced pressure. The characteristics of the obꢀ
tained compounds are presented in Tables 1—3. Synthesis of
compounds 1а,d and 4 is described below.
NꢀAzidomethylꢀN,Nꢀdimethylamine (1а). Dimethylammoniꢀ
um chloride (15.9 g, 0.2 mol) was added with stirring to a mixꢀ
ture of sodium azide (13 g, 0.2 mol) and 37% formadehyde soluꢀ
tion (16 mL). The mixture was stirred for 30 min, saturated with
sodium chloride and extracted with ether. The ethereal layer
was dried with Na SO , and concentrated in vacuo; the residue
6
7
∨
. J. Denkstein, V. Kaderábek, Colleсt. Czechosl. Chem. Comꢀ
mun., 1960, 25, 2334.
2
4
8
9
. D. Tarbell, N. Shakespeare, C. Claus, J. Bahnet. J. Am.
Chem. Soc., 1946, 68, 1217.
. D. Tarbell, D. Fukushima, J. Am. Chem. Soc., 1946, 68, 2499.
was distilled under reduced pressure. Compound 1а was obꢀ
tained (2 g, 10%).
NꢀAzidomethylꢀNꢀ(2ꢀcyanoethyl)ꢀNꢀmethylamine (1d). Hyꢀ
drochloric acid (35%, 9 mL) was added dropwise to Nꢀ(2ꢀcyanoꢀ
ethyl)ꢀNꢀmethylamine (8.4 g, 0.1 mol) in water (5 mL) at
1
1
0. R. Z. Hinman, J. Robere. J. Org. Chem.1956. 21, 1539.
1. B. V. Ioffe, L. E. Porshin, Zh. Obshch. Khim., 1959, 29, 3154
[
J. Gen. Chem. USSR (Engl. Transl.), 1959, 29].
2
0—25 °С. The solution that obtained was added to a mixture of
sodium azide (6.5 g, 0.1 mol) and 37% formadehyde solution
8 mL, 0.1 mol). The reaction mixture was intensively stirred for
0 min, then it was kept until oily condensation product sediꢀ
mented as a separate layer. The condensation product was disꢀ
(
3
Received June 19, 2009,
in revised form September 11, 2009