N,N,N′,N′-tetramethylmethanediamine - A new reagent for aminomethylation of acetylenes

Article abstract of DOI:10.1134/S1070428008080034

A new procedure has been developed for aminomethylation of terminal acetylenes with N,N,N′,N′-tetramethylmethanediamine in the presence of transition metals and lanthanide complexes and salts. The procedure ensures formation of the corresponding N,N-dimethylprop-2-yn-1-amines with high yield and selectivity.

Full text of DOI:10.1134/S1070428008080034

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 8, pp. 1126–1129. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © M.G. Shaibakova, I.G. Titova, A.G. Ibragimov, U.M. Dzhemilev, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44,
No. 8, pp. 1141–1144.
N,N,N′,N′-Tetramethylmethanediamine—A New Reagent
for Aminomethylation of Acetylenes
M. G. Shaibakova, I. G. Titova, A. G. Ibragimov, and U. M. Dzhemilev
Institute of Petroleum Chemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: ink@anrb.ru
Received October 9, 2007
Abstract—A new procedure has been developed for aminomethylation of terminal acetylenes with N,N,N′,N′-
tetramethylmethanediamine in the presence of transition metals and lanthanide complexes and salts. The proce-
dure ensures formation of the corresponding N,N-dimethylprop-2-yn-1-amines with high yield and selectivity.
DOI: 10.1134/S1070428008080034
Prop-2-yn-1-amines attract interest as monomers in
organic synthesis and as intermediate compounds for
the preparation of biologically active substances [1–8].
A convenient method for the synthesis of prop-2-yn-
amines remains so far classical aminomethylation
of terminal alkynes according to Mannich [9] using
secondary amines and aldehydes in the presence of
copper(I) salts [10–15]. Kabalka et al. [16] recently
proposed an improved procedure for aminomethylation
of acetylenes by reaction of 1-alkynes with paraform-
aldehyde and secondary amines in the presence of
CuI/Al O under microwave irradiation in the absence
ried out under solvent-free conditions. In addition, the
effect of the solvent nature (ethanol, hexane, toluene,
DMSO) on the yield and selectivity of the process was
studied.
In the reaction of oct-1-yne with N,N,N′,N′-tetra-
methylmethanediamine (hereinafter referred to as di-
amine) in the presence of CuCl as catalyst (molar ratio
substrate–diamine–CuCl 1:3:0.05) under argon in 6 h
afforded 81% of N,N-dimethylnon-2-yn-1-amine (Ia).
Analogous reaction in toluene solution gave compound
Ia in 95% yield (Scheme 1; Table 1, run nos. 1, 3).
When the reaction was carried out in air, the product
was hexadeca-7,9-diyne (IIa, yield 39%) which was
formed via oxidative coupling of initial oct-1-yne. All
copper(I) halides showed high catalytic activity and
selectivity in toluene used as solvent. Copper(I) iodide
favored formation of a considerable amount of dimer-
ization product IIa: the yields of Ia and IIa were,
respectively, 63 and 33% under argon and 30 and 66%
in air (Table 1, run nos. 11, 12).
2
3
of a solvent. Prior to our studies, there were no pub-
lished data on catalytic aminomethylation of terminal
alkynes with diamines as synthetic equivalents of
formaldehyde and secondary amines.
Taking into account that the known methods for the
synthesis of prop-2-ynamines are not free from some
disadvantages related to the necessity of using toxic
solvents (such as dioxane, N,N-dimethylformamide,
methylene chloride, acetonitrile, dimethyl sulfoxide,
etc.) and considerable (up to stoichiometric) amounts
of copper(I) salts, as well as to long reaction times
Scheme 1.
Me
Me
R
CH
+
N
N
(
12–72 h), we now propose a new procedure for the
Me
Me
preparation of aminomethyl-substituted acetylenes via
reaction of N,N,N′,N′-tetramethylmethanediamine with
acetylene in the presence of a catalytic amount (up to
Me
N
Me
[
M]
5
mol %) of d-metal and lanthanide salts and com-
R
–
Me NH
2
plexes. We tested a series of Cu, Nb, Pd, Co, Mn, Zr,
Ti, Hf, Ni, V, Fe, and Sm salts and complexes, which
are widely used as catalysts. The reactions were car-
Ia–Id
R = C
6
H
13 (a), C
5
4 9
H11 (b), C H (c), Ph (d).
1
126

N,N,N′,N′-TETRAMETHYLMETHANEDIAMINE—A NEW REAGENT
1127
Table 1. Aminomethylation of oct-1-yne with N,N,N′,N′-tetramethylmethanediamine (molar ratio diamine–oct-1-yne–catalyst
3
:1:0.05, 80°C, argon atmosphere for copper salts)
Time, h
Time, h
(solvent)
Run no. Catalyst
Yield of Ia/IIa, % Run no.
Catalyst
Yield of Ia/IIa, %
(
solvent)
0
0
0
0
0
0
0
0
0
1
1
1
2
3
4
5
6
7
8
9
0
1
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuCl
CuI
4 (toluene)
95
26/39
81
13
14
15
16
17
18
19
20
21
22
23
24
CuBr
CuBr
4
61/27
94
a
6
4 (toluene)
4 (toluene)
6
6
PdCl
2
79
2
2
2
2
2
2
4 (toluene)
98
Fe(acac)
3
03
6
98
CoCl
CoCl
CoCl
CoCl
2
2
2
2
4 (DMSO)
6
15/12
19
a
6
90/80
14/60
92/60
53/48
96
4 (EtOH)
4 (DMSO)
4 (hexane)
4 (toluene)
6
4 (hexane)
4 (EtOH)
4 (toluene)
4
46
52/10
82
Sm(NO
Sm(NO
3
)
)
2
2
·5H
·5H
2
O
O
3
2
21
CuI
63/33
30/66
VO(acac)
VO(acac)
2
6
23
a
1
2
CuI
4
2
4 (toluene)
95
a
The reaction was carried out on exposure to air.
In the aminomethylation of oct-1-yne under argon
pounds and isolated the corresponding prop-2-yn-
amines in more than 90% yield. Aminomethylation of
phenylacetylene gave N,N-dimethyl-3-phenylprop-2-
yn-1-amine (Id) whose yield reached ~98% in the
presence of VO(acac) and Sm(NO ) ·5H O as cata-
in the presence of CuCl (molar ratio 1-octyne–di-
2
amine–CuCl 1:3:0.05; 80°C, 6 h), the yield of Ia
2
increased to 98%. When the reaction was carried out
on exposure to air, the yield of Ia was 90%, and up to
2
3 2
2
8
% of IIa was obtained (Table 1, run no. 6).
lyst. Copper(II) chloride showed a lower catalytic ac-
tivity in the aminomethylation of phenylacetylene: the
The use of toluene as solvent almost did not change
the reaction direction, and compound Ia was obtained
in 98% yield in 4 h. In DMSO, the yield of amine Ia
was 92%, and the reaction was accompanied by forma-
tion of dimeric product IIa (6%). The reaction in
diethyl ether was characterized by reduced conversion
of the initial acetylene (20%), the yield of amine Ia
was as poor as 14%, and 6% of by-product IIa was
formed (Table 1, run nos. 7, 8). The complexes
Cu(acac) , NbCl , SnCl , SnCl , MnCl , ZrCl ,
Table 2. Aminomethylation of phenylacetypene with
N,N,N′,N′-tetramethylmethanediamine (molar ratio diamine–
phenylacetylene–catalyst 3:1:0.05, 80°C, argon atmosphere
for copper salts, 4 h)
Run
no.
Catalyst
Solvent Yield of Id/IId, %
0
0
0
0
0
0
0
0
1
2
3
4
5
6
7
8
VO(acac)
Sm(NO
VO(acac)
CuCl
2
Toluene
None
98
98
82
82/10
72
61
51
38
17
12
05
–
2
5
2
4
2
4
3 2 2
) ·5H O
Hf(acac) , Pd(acac) –PPh , Ni(acac) –PPh , Cp ZrCl ,
4
2
3
2
3
2
2
2
None
Cp TiCl , and Fe(acac) showed no appreciable cata-
2
2
3
2
None
lytic activity. No aminomethylation occurred in the
absence of catalyst.
Cp
Cp
2
2
ZrCl
TiCl
2
None
2
None
Our further study revealed high catalytic activity
and selectivity in the aminomethylation of oct-1-yne
in the presence of VO(acac) and Sm(NO ) ·5H O.
CoCl
MnCl
SnCl
NbCl
ZrCl
Cu(acac)
PdCl
Fe(acac)
2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
3
2
3 2
2
These catalysts (5 mol %) ensured formation of the
aminomethylation product in 95 and 82%, respectively,
in toluene at 80°C in 4 h (Table 1, run nos. 21, 24).
Under the optimal conditions, we performed amino-
methylation of hept-1-yne and hex-1-yne with
N,N,N′,N′-tetramethylmethanediamine in the presence
of the most catalytically active Cu, V, and Sm com-
09
10
2
5
11
4
1
1
1
2
3
4
2
2
–
3
–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

1
128
SHAIBAKOVA et al.
Table 3. Aminomethylation of hepta-1,6-diyne with
N,N,N′,N′-tetramethylmethanediamine (molar ratio diamine–
phenylacetylene–catalyst 3:1:0.05, 80°C, argon atmosphere
for copper salts, 4 h)
corresponding oxidative coupling product (Table 3, run
nos. 6, 7).
Thus we have developed a new procedure for the
aminomethylation of terminal acetylenes with
N,N,N′,N′-tetramethylmethanediamine using transition
d-metal and lanthanide salts and complexes as cata-
lysts, which ensures preparation of the target N,N-di-
methylprop-2-ynamines with high yield (>95%) and
selectivity (~100%).
Run
no.
Catalyst
Sm(NO ·5H
Solvent Yield of IIIa/IVa, %
1
3
)
2
2
O
O
Toluene
Toluene
None
98
96
2
VO(acac)
VO(acac)
2
3
2
88
EXPERIMENTAL
4
CuCl
2
None
77
5
Sm(NO
3
)
2
·5H
2
None
41
The purity of the products was checked by TLC on
Silufol plates using acetone–methanol [9:(2–3)], ace-
tone– chloroform (9:1), and acetone–ethanol (9:1) as
eluents. Initial terminal acetylenes were commercially
available products, and solvents of chemically pure
grade were used. The mass spectra were recorded on
6
CuCl
2
2
EtOH
20/15
08/70
7
CuCl
Hexane
yield of Id was only 82% in 6 h, and ~10% of 1,4-di-
phenylbut-2-yne (IId) was formed (Table 2, run no. 5).
Apart from the above catalysts, Cp ZrCl and Cp TiCl
1
13
a VG-Trio instrument. The H and C NMR spectra
were measured on a Jeol FX-90Q spectrometer at
2
2
2
2
1
3
1
turned out to be fairly active in the aminomethylation
of phenylacetylene (Table 2, run nos. 5, 6).
2
2.5 MHz for C and 90 MHz for H; CDCl was used
3
as solvent, and tetramethylsilane, as internal reference.
The IR spectra were obtained in KBr on a Specord
With a view to extend the scope of the developed
procedure, we examined aminomethylation of terminal
diacetylenic compounds with N,N,N′,N′-tetramethyl-
methanediamine. The reaction of hepta-1,6-diyne with
N,N,N′,N′-tetramethylmethanediamine at a ratio of 1:3
7
5IR spectrometer. The elemental compositions were
determined on a Carlo Erba 1106 analyzer. The UV
spectra were recorded on a Specord M40 spectropho-
tometer. GLC analysis was performed on a Khrom-5
chromatograph equipped with a flame ionization detec-
tor and a 2000×3-mm column (stationary phase SE-
in toluene in the presence of 5 mol % of VO(acac) or
2
Sm(NO ) ·5H O involved both terminal C–H bonds in
3
2
2
3
0); oven temperature programming from 50 to 280°C
the substrate and resulted in selective formation of
N,N,N′,N′-tetramethylnona-2,7-dyine-1,9-diamine
at 8 deg/min; injector temperature 300°C, detector
temperature 250°C.
(
IIIa) in 96 and 98% yield, respectively (Scheme 2;
Table 3, run nos. 1, 2). Likewise, octa-1,7-diyne and
deca-1,9-diyne gave rise to the corresponding bis-
aminomethyl derivatives in more than 95% yield.
Copper halides were less active as catalysts in these
reactions. For example, in the presence of 5 mol % of
General procedure for aminomethylation of
terminal acetylenes with N,N,N′,N′-tetramethyl-
methanediamine. A glass reactor equipped with
a magnetic stirrer was filled with argon and charged
with 0.1 mmol of the corresponding terminal acety-
lene, 0.3 mmol of N,N,N′,N′-tetramethylmethanedi-
amine, and 0.001–0.005 mmol of the catalyst, and the
mixture was stirred for 6 h at 80°C under argon.
Dimers IIa, IId, and IVa formed as by-products from
initial acetylenes were identified by comparing with
samples synthesized according to the procedure de-
scribed in [17].
CuCl under solvent-free conditions, the yield of IIIa
2
was 77%, and it decreased to 20 and 8% in going to
ethanol and hexane as solvent, respectively; in addi-
tion, the reaction was accompanied by formation of the
Scheme 2.
Me
Me
HC
CH
N
N
N,N-Dimethylnon-2-yn-1-amine (Ia). bp 75–76°C
+
(
)
–1 1
n
Me
Me
(3 mm). IR spectrum: ν 1255 cm . H NMR spectrum,
δ, ppm: 0.89 t (3H, J = 6.09 Hz), 1.2–1.97 m (8H),
[M]
Me
Me
N
N
1.98 t ( 2H, J = 6.69 Hz), 2.19 s (6H), 3.21 s (2H).
–
Me NH
13
2
( )
Me
C NMR spectrum, δ , ppm: 13.70, 18.84, 22.26,
C
Me
n
2
8.25, 28.38, 31.09, 43.72, 48.18, 75.66, 84.90. Mass
IIIa–IIIc
+
spectrum, m/z (I , %): [M] 167 (26.47), 166 (100),
rel
n = 3, 4, 6.
152 (14.7), 138 (11.76), 110 (35.8), 108 (14.6), 96
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008

N,N,N′,N′-TETRAMETHYLMETHANEDIAMINE—A NEW REAGENT
1129
(
35.29), 94 (41.18), 82 (91.18), 58 (32.35). Found, %:
trum, δ, ppm: 1.07–1.67 m (8H), 2.02 t (4H, J =
6.68 Hz), 2.18 s (12H), 2.96 s (4H). C NMR spec-
1
3
C 78.90; H 12.78; N 7.46. C H N. Calculated, %:
11
21
C 79.04; H 12.57; N 8.39.
trum, δ , ppm: 18.58, 28.10, 28.36, 42.75, 48.65,
C
7
5.67, 84.35. Found, %: C 76.98; H 11.31; N 10.95.
N,N-Dimethyloct-2-yn-1-amine (Ib). bp 61–62°C
3 mm). H NMR spectrum, δ, ppm: 0.95–1.4 m (6H),
1
C H N . Calculated, %: C 77.44; H 11.27; N 11.29.
(
16 28
2
2
.12 t (2H, J = 6.87 Hz), 2.20 s (6H), 3.14 s (2H).
1
3
REFERENCES
C NMR spectrum, δ , ppm: 13.82, 18.35, 22.38,
C
2
8.21, 31.08, 43.71, 48.02, 75.10, 84.90. Found, %:
1
. Bieber, L.W. and da Silva, M.F., Tetrahedron Lett.,
C 77.02; H 12.19; N 9.41. C H N. Calculated, %:
1
0
19
2
004, vol. 45, p. 8281.
C 78.43; H 12.42; N 9.15.
N,N-Dimethylhept-2-yn-1-amine (Ic). bp 49–
0°C (3 mm). UV spectrum: λ 289 nm. IR spec-
2
3
4
. Miura, M., Enna, M., Okuro, K., and Nomura, M.,
J. Org. Chem., 1995, vol. 60, p. 4999.
5
max
. Huffman, M.A., Yasuda, N., DeCamp, A.E., and Gra-
–
1
1
trum: ν 1255 cm . H NMR spectrum, δ, ppm: 0.88
bowski, E.J.J., J. Org. Chem., 1995, vol. 60, p. 1590.
(
3H, J = 6.2 Hz), 1.3–1.7 m (4H), 2.06–2.12 t (2H, J =
. Jenmalm, A., Berts, W., Li, Y.L., Luthman, K.,
Csoregh, I., and Hacksell, U., J. Org. Chem., 1994,
vol. 59, p. 1139.
1
3
6
.68 Hz), 2.20 s (6H), 3.19 s (2H). C NMR spectrum,
δC, ppm: 13.00, 17.80, 20.96, 30.21, 42.9, 47.14,
4.14, 83.93. Found, %: C 76.91; H 12.01; N 9.81.
7
5
6
7
. Hattori, K., Miyata, M., and Yamamoto, H., J. Am.
Calculated, %: C 77.70; H 12.23; N 10.07.
Chem. Soc., 1993, vol. 115, p. 1151.
N,N-Dimethyl-3-phenylprop-2-yn-1-amine (Id).
. Nilsson, B., Vargas, H.M., Ringdahl, B., and Hack-
bp 86–87°C (3 mm). UV spectrum: λ
spectrum, ν, cm : 2240 (C≡C), 1250 (N–C), 1590
279 nm. IR
sell, U., J. Med. Chem., 1992, vol. 35, p. 285.
max
–
1
. Sanders, K.B., Thomas, A.J., Pavia, M.R., Davis, R.E.,
Coughenour, L.L., Myers, S.L., Fischer, S., and
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p. 803.
1
(
C–Carom). H NMR spectrum, δ, ppm: 2.06 s (6H),
1
3
3
.17 s (2H), 7.21–7.28 m (5H, Harom). C NMR spec-
trum, δ , ppm: 43.53, 48.02, 84.32, 84.88, 123.04,
C
1
28.18, 128.57, 131.67. Mass spectrum, m/z (I , %):
8. Konishi, M., Ohkuma, H., Tsuno, T., Oki, T., Van-
Duyne, G.D., and Clardy, J., J. Am. Chem. Soc., 1990,
vol. 112, p. 3715.
rel
+
[
(
M] 159 (52.5), 158 (100), 143 (20.6), 144 (6.25), 129
3.12), 115 (100), 89 (28.0), 82 (53.0), 63 (18.6).
Found, %: C 81.84; H 8.43; N 8.54. C H N. Cal-
culated, %: C 83.02; H 8.18; N 8.80.
9. Mannich, C. and Chang, F.T., Chem. Ber., 1933, vol. 66,
11
13
p. 418.
1
0. Youngman, M.A. and Dax, S.L., Tetrahedron Lett.,
N,N,N′,N′-Tetramethylnona-2,7-diyne-1,9-di-
amine (IIIa). bp 79–80°C (3 mm). H NMR spectrum,
1
1997, vol. 38, p. 6347.
11. McNally, J.J. and Youngman, M.A., Tetrahedron Lett.,
δ, ppm: 1.52–1.81 m (2H), 2.10 t (4H, J = 6.77 Hz),
1
3
1998, vol. 39, p. 967.
2
.19 s (12H), 3.23 s (4H). C NMR spectrum, δC,
ppm: 18.28, 23.36, 43.75, 48.42, 75.71, 84.42. Found,
1
2. Chukhadzhyan, E.O., Gevorkyan, A.R., Chukhad-
zhyan, El.O., and Shakhatuni, K.G., Russ. J. Org.
Chem., 2000, vol. 36, p. 1263.
%
%
: C 74.78; H 10.10; N 13.98. C H N . Calculated,
13 22 2
: C 75.73; H 10.68; N 13.59.
N,N,N′,N′-Tetramethyldeca-2,8-diyne-1,10-di-
amine (IIIb). bp 91°C (3 mm). IR spectrum:
1
1
1
3. Youngman, M.A. and Dax, S.L., J. Comb. Chem., 2001,
vol. 3, p. 469.
4. Bieber, L.W. and da Silva, M.F., Tetrahedron Lett.,
–
1 1
ν 1270 cm . H NMR spectrum, δ, ppm: 1.47 t (4H,
J = 6.87 Hz), 2.19 s (12H), 2.2–2.5 m (4H), 3.11 s
2
004, vol. 45, p. 8281.
5. Gevorkyan, A.A., Arakelyan, A.S., Movsisyan, A.A.,
Dzhandzhulyan, Zh.L., and Petrosyan, K.A., Russ. J.
Gen. Chem., 2006, vol. 76, p. 1175.
1
3
(
4
4H). C NMR spectrum, δ , ppm: 18.65, 27.89,
C
3.80, 48.12, 75.66, 84.71. Found, %: C 75.9; H 11.30;
N 11.92. C H N . Calculated, %: C 76.36; H 10.92;
1
4
24
2
1
6. Kabalka, G.W., Zhou, L.-L., Wang, L., and Pagni, R.M.,
N 12.72.
Tetrahedron, 2006, vol. 62, p. 857.
N,N,N′,N′-Tetramethyldodeca-2,10-diyne-1,12-
diamine (IIIc). bp 103–105°C (3 mm). H NMR spec-
17. Brandsma, L., Verkrujsse, H.D., and Walda, B., Synth.
Commun., 1991, vol. 21, p. 137.
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 8 2008