Synthesis of symmetric 1,4-diamino-2-butynes via a Cu(I)-catalyzed one-pot A3-coupling/decarboxylative coupling of a propiolic acid, an aldehyde, and an amine

Article abstract of DOI:10.1021/jo300562j

A novel microwave-assisted approach for the one-pot Cu(I)-catalyzed A ³-coupling/decarboxylative coupling (PA²-coupling) of a propiolic acid, an aldehyde, and an amine, resulting in the formation of diversely substituted 1,4-diamino-2-butynes,is described. It is noteworthy that this new multicomponent coupling provides an efficient access to introduce alkyl and aryl group at the 1,4-position of the 1,4-diamino-2-butynes.

Full text of DOI:10.1021/jo300562j

Note
pubs.acs.org/joc
Synthesis of Symmetric 1,4-Diamino-2-Butynes via a Cu(I)-Catalyzed
One-Pot A3-Coupling/Decarboxylative Coupling of a Propiolic Acid,
an Aldehyde, and an Amine
Huangdi Feng,†,‡ Denis S. Ermolat’ev,*,† Gonghua Song,‡ and Erik V. Van der Eycken*,†
†Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC), Department of Chemistry, Katholieke Universiteit Leuven,
Celestijnenlaan 200F, B-3001 Leuven, Belgium
‡Shanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, 130 Meilong Road,
Shanghai 200237, China
S
* Supporting Information
ABSTRACT: A novel microwave-assisted approach for the one-
pot Cu(I)-catalyzed A3-coupling/decarboxylative coupling (PA2-
coupling) of a propiolic acid, an aldehyde, and an amine, resulting
in the formation of diversely substituted 1,4-diamino-2-butynes,
is described. It is noteworthy that this new multicomponent
coupling provides an efficient access to introduce alkyl and aryl
group at the 1,4-position of the 1,4-diamino-2-butynes.
1,4-Diamino-2-butynes, containing the propargylamine struc-
tural motif, are effective antioxidants and valuable intermediates
for the preparation of many biologically active compounds
and natural products.1 Conventionally, 1,4-diamino-2-butynes
are synthesized by nucleophilic substitution reaction of 2-butyne
1,4-dihalides with amines.2 Recently, Knochel reported a
copper-catalyzed addition of trimethylsilylacetylene to
enamines (Scheme 1, a),3 and Vogel described a (t-BuO)2 oxi-
dative C−C cross-coupling of tertiary amines with triethyl-
silylacetylene catalyzed by FeCl2 (Scheme 1, b),4 but only one
example is provided in each case. Then Nakamura discovered
an alternative approach to symmetric 1,4-diamino-2-butynes in-
volving deacetylenative self-coupling of propargylamines
(Scheme 1, c).5 Although these approaches disclose elegant
progresses to 1,4-diamino-2-butynes, they are still accessed in
multiple steps requiring relatively long synthetic procedures.
Thus, there is a need for the development of an environ-
mentally friendly, economical and diverse method having a high
functional group tolerance.
Over the past decade, transition-metal-catalyzed decarbox-
ylative coupling reactions have gained particular interest be-
cause of their inherent advantage that the in situ generated
organometallic species from simple carboxylic acids are applied
to replace relatively expensive, toxic, or highly sensitive organo-
metallic reagents to undergo cross-coupling reaction.6 Such
reactions typically involve the formation of carbon−carbon
bonds7−9 and carbon−heteroatom bonds10 for the synthesis of
pharmaceuticals and biologically active natural products.
Sequential decarboxylative coupling reactions of propiolic acid
have recently been achieved for the synthesis of diarylalkynes11
and 1,4-diaryl-substituted 1,3-diynes.12 However, to the best
of our knowledge, the application of propiolic acid in a de-
carboxylative process to access 1,4-diamino-2-butynes has not
yet been performed.
In our previous investigations, we have successfully applied
multicomponent decarboxylative coupling reactions for the
generation of propargylamines and oxazolidinones.13 Herein,
we report a novel Cu(I)-catalyzed one-pot decarboxylative coup-
ling of propiolic acid, an aldehyde, and an amine (PA2 coupling)
under microwave irradiation which provides a broad spectrum of
functional groups at 1,4-position of the 1,4-diamino-2-butynes
that can be introduced (Scheme 1, d).
As depicted in Table 1, the investigations were initiated
with 3-methylbutanal (1a), N-methylbenzylamine (2a), and
propiolic acid (3) as model substrates to find the optimal
conditions. Our first attempts were focused on the evaluation of
the efficiency of various solvents under microwave irradiation in
the presence of 20 mol % of CuI (Table 1, entries 1−5).
Gratifyingly, 61% yield of the desired product 4a was obtained
when toluene was employed at 100 °C (Table 1, entry 1).
Encouraged by this result, we subsequently examined various
catalysts. Among the copper salts tested, CuI seemed to be the
most active catalyst for this decarboxylative coupling reaction
(Table 1, entries 1 and 6−11). The use of other catalysts, such
as CuBr, CuOTf, and Cu(OTf)2 led to a lower yield of the
desired 1,4-diamino-2-butyne (Table 1, entries 6, 8, and 10).
Varying the concentration of CuI resulted in changes in both
the yield of 4a, and the amount of propargylamine and
unknown byproduct (Table 1, entries 1 and 12−14). We found
that 30% CuI gave a higher yield compared to the use of 10%
CuI, 20% CuI, or 40% CuI. Further screening revealed that a
lower or higher reaction temperature proved to be inferior in
conversions to the desired 1,4-diamino-2-butynes (Table 1,
entries 15 and 16), while increasing the irradiation time to
Received: March 18, 2012
Published: May 7, 2012
© 2012 American Chemical Society
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Note
Scheme 1. Approaches for the Synthesis of 1,4-Diamino-2-butynes
a
Table 1. Optimization of the Reaction Conditions
With the optimized reaction conditions established (Table 1,
entry 13), we next evaluated the substrate scope of the aldehydes
and the amines (Table 2). In general, good yields were obtained
when using aliphatic aldehydes (Table 2, entries 1−8). However,
benzaldehyde afforded the desired compound in only 28% yield
(Table 2, entry 9). Reactions with secondary amines, such as
N-substituted benzylamines, seemed to be working quite well
(Table 2, entries 10−12). Furthermore, dienyne-based com-
pounds, which are very useful substrates for the construction
of double-ringed systems,14 were successfully formed employ-
ing this protocol (Table 2, entries 13−15). The reaction also
worked efficiently with cyclic (Table 2, entry 16) and aliphatic
amines (Table 2, entries 17 and 18), affording the desired
compounds in 74−89% yield. On the contrary, the use of
primary amine resulted in only trace amount of 4t together
with several unidentified byproducts (Table 2, entry 20). To
expand the scope of this approach, various combinations of
aldehydes and amines were evaluated. All reactions provided
good yields (Table 2, entries 20−24). The final products
appear as a mixture of two diastereomers, which are
inseparable by chromatography and spectroscopically.
b
temp
(°C)
yield
(%)
entry
Cu catalyst (equiv)
solvent
time
1
2
3
4
5
6
7
8
9
CuI (0.2)
CuI (0.2)
CuI (0.2)
CuI (0.2)
CuI (0.2)
CuBr (0.2)
CuCl (0.2)
CuOTf (0.2)
toluene
dioxane
THF
100
100
100
100
100
100
100
100
100
100
100
100
100
100
90
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
30 min
45 min
21 h
61
35
55
42
38
47
49
18
25
13
52
74
82
43
59
78
77
ethanol
DCE
toluene
toluene
toluene
Cu(MeCN)4PF6 (0.2) toluene
10 Cu(OTf)2 (0.2)
11 CuCl2 (0.2)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
12 CuI (0.4)
13 CuI (0.3)
14 CuI (0.1)
15 CuI (0.3)
16 CuI (0.3)
17 CuI (0.3)
18 CuI (0.3)
A plausible reaction mechanism is proposed in Scheme 2.
The reaction is initiated by cation exchange between propiolic
acid 3 and the copper salt affording copper species A. Sub-
sequently, the process would involve two possible pathways.
The first pathway is Cu(I)-catalyzed decarboxylation of A
to alkynylcopper B followed by coupling reaction with in situ
formed iminium salt C affording propargylamine copper
complex E (path a). Another pathway involves Cu(I)-catalyzed
coupling of A and C resulting in the formation of intermediate
D, followed by decarboxylation to provide E (path b). This
common intermediate E undergoes further coupling yielding
the desired 1,4-diamino-2-butyne 4 with the concomitant
regeneration of the Cu(I) catalyst.
115
100
100
c
81
a
Reactions were performed using 3-methylbutanal (2.2 mmol), N-
methylbenzylamine (2.5 mmol), propiolic acid (1.0 mmol), and
solvent (1 mL) under microwave irradiation at 100 °C and 80 W
maximum power. Isolated yields based on propiolic acid. Conven-
tional heating.
b
c
45 min also resulted in a decreased yield of 77% (Table 1,
entry 17). A control experiment showed that the desired
product 4a was obtained in a yield of 83% after an extended
reaction time of 21 h under conventional heating condition
(Table 1, entry 18).
In summary, we have developed the first Cu(I)-catalyzed A3-
coupling/decarboxylative coupling protocol applying propiolic
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Note
a
Table 2. Scope and Limitations of the Protocol
a
A mixture of aldehyde 1 (2.2 mmol), amine 2 (2.5 mmol), propiolic acid 3 (1.0 mmol), CuI (0.3 equiv) and toluene (1 mL) was irradiated at a
b
ceiling temperature of 100 °C and a maximum power of 80 W for 30 min. Isolated yields.
Scheme 2. Proposed Reaction Pathways
EXPERIMENTAL SECTION
■
General Information. All solvents and reagents were purchased
from commercial sources and were used without prior purification. All
microwave irradiation experiments were carried out in a dedicated
CEM-Discover monomode microwave apparatus, operating at a
frequency of 2.45 GHz with continuous irradiation power from 0 to
300 W. The reactions were carried out in 10 mL glass tubes, sealed
with Teflon septum and placed in the microwave cavity. The reac-
tion mixture was irradiated at a required ceiling temperature using
maximum power for the stipulated time, and the reaction mixture
temperatures were measured by the external IR sensor. The reaction
tube was cooled to ambient temperature with air jet cooling. TLC
analysis was performed on aluminum backed plates SIL G/UV254.
The products were purified by silica gel (200−300 mesh) column
1
chromatography. H NMR spectra were recorded at 300 MHz, 13C
NMR spectra at 75 MHz correspondingly with tetramethylsilane or
solvent (CDCl3) as internal standard. Chemical shifts are reported in
values δ (ppm) and coupling constants given in hertz (Hz). Splitting
patterns are designated as s (singlet), d (doublet), t (triplet) and m
(multiplet). High-resolution mass spectra were recorded by using ion
source temperature 150−250 °C as required and the double-focusing
acid, an aldehyde, and an amine (PA2-coupling) for the
construction of symmetric 1,4-diamino-2-butynes in high
yields. This efficient, fast, and economical one-pot approach
is applicable to a broad scope of aldehydes and amines under
microwave irradiation.
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Note
magnetic sector analyzer. High-resolution EI-mass spectra were
performed with a resolution of 10000.
N4,N7-Dibenzyl-3,8-diethyl-N4,N7-dimethyldec-5-yne-4,7-di-
1
amine (4d): light yellow oil; H NMR (300 MHz, CDCl3) δ 0.81 (t,
J = 7.25 Hz, 6H), 0.89 (t, J = 7.34 Hz, 6H), 1.40−1.51 (m, 4H), 1.53−
1.64 (m, 2H), 1.66−1.80 (m, 4H), 2.20 (s, 6H), 3.25 (d, J = 10.17 Hz,
2H), 3.53 (d, J = 13.38 Hz, 2H), 3.70 (d, J = 13.17 Hz, 2H), 7.23 (t,
J = 6.98 Hz, 2H), 7.28−7.37 (m, 8H); 13C NMR (75.5 MHz, CDCl3)
δ 9.6, 10.6, 20.4, 22.3, 37.7, 37.8, 42.3, 42.4, 58.9, 59.8, 82.7, 126.8,
128.2, 128.9, 139.8; HRMS (EI) m/z calcd for C30H44N2 [M]+
432.3504, found 432.3488.
Synthesis of N-(2-Bromobenzyl)butan-1-amine 2l. A solution
of 2-bromobenzaldehyde (10 mmol) and butan-1-amine (10 mmol) in
toluene (50 mL) was refluxed in a Dean−Stark apparatus for 3 h. After
removal of toluene in vacuo, the corresponding imine derivative
was used directly in the next step without further purification. NaBH4
(20 mmol) was added portionwise to a solution of the previously
obtained imine in MeOH (60 mL) at room temperature. The mixture
was stirred for 2 h, and then saturated aqueous NH4Cl solution
(20 mL) was added. After the mixture was stirred for 30 min, the
solvent was removed under vacuum. The crude mixture was dissolved
in CH2Cl2 (40 mL) and washed with water (20 mL) and brine (30 mL).
The organic solution was dried (Na2SO4), filtered, and concentrated in
vacuum. The crude oily amines were purified by flash column chro-
matography with ethyl acetate−heptanes (80:20) as eluent.15
Synthesis of N-Benzyl-2,3-dimethylbut-2-en-1-amine (2m).
A solution of N-benzyl-2,2,2-trifluoroacetamide (47.12 mmol, 9.37 g)
in dry THF (50 mL) was added dropwise to a mixture of NaH (60 wt %
disp) (1.5 equiv, 2.83 g) and NaI (10 mol %) in THF (50 mL) at rt
under argon. Upon completion of addition, the mixture was allowed to
stir for 1 h. Then 2-(bromomethyl)-3-methylbut-2-ene16 (1.2 equiv,
9.22 g) was added dropwise, and the mixture was brought to reflux.
After overnight reflux, the reaction was cooled to rt, quenched with
H2O, and extracted with Et2O. The organic layer was concentrated
under reduced pressure. The residue was dissolved in a mixture of
MeOH (50 mL), H2O (30 mL), and KOH (4.67 g). The resulting
solution was refluxed for 2 h, concentrated under reduced pressure
down to 20−30 mL, and extracted with Et2O. The organic layer was
washed with brine and dried (Na2SO4). Distillation under reduced
pressure from CaH2 afforded pure 2m.17
9
6
9
N6,N -Dibenzyl-N ,N -dimethyltetradec-7-yne-6,9-diamine
(4e): light yellow oil; 1H NMR (300 MHz, CDCl3) δ: 0.90 (t, J = 6.68
Hz, 6H), 1.29−1.34 (m, 8H), 1.44−1.53 (m, 4H), 1.64−1.72 (m, 4H),
2.25 (s, 6H), 3.45 (t, J = 7.44 Hz, 2H), 3.51 (d, J = 13.20 Hz, 2H),
3.70 (d, J = 13.02 Hz, 2H), 7.23 (t, J = 6.98 Hz, 2H), 7.29−7.37 (m,
8H); 13C NMR (75.5 MHz, CDCl3) δ 14.1, 22.7, 26.4, 31.6, 34.4, 34.5,
37.9, 55.6, 59.3, 82.7, 126.8, 128.2, 129.0, 139.5; HRMS (EI) m/z
calcd for C30H44N2 [M]+ 432.3504, found 432.3495.
N1,N4-Dibenzyl-1,4-dicyclohexyl-N1,N4-dimethylbut-2-yne-
1
1,4-diamine (4f): light yellow oil; H NMR (300 MHz, CDCl3) δ
0.85−1.00 (m, 4H), 1.12−1.30 (m, 6H), 1.52−1.57 (m, 2H), 1.64−
1.76 (m, 6H), 2.09−2.16 (m, 4H), 2.21 (s, 6H), 3.10 (d, J = 9.96 Hz,
2H), 3.52 (d, J = 13.38 Hz, 2H), 3.69 (d, J = 13.35 Hz, 2H), 7.22 (t,
J = 6.87 Hz, 2H), 7.27−7.37 (m, 8H); 13C NMR (75.5 MHz, CDCl3)
δ 26.0, 26.2, 26.8, 30.3, 31.5, 37.8, 40.3, 40.4, 59.5, 61.5, 82.5, 126.8,
128.2, 128.8, 139.8; HRMS (EI) m/z calcd for C32H44N2 [M]+
456.3504, found 456.3502.
N11,N14-Dibenzyl-N11,N14-dimethyltetracosa-1,23-dien-12-
yne-11,14-diamine (4g): light yellow oil; 1H NMR (300 MHz,
CDCl3) δ 1.29−1.39 (m, 24H), 1.64−1.69 (m, 4H), 1.97−2.06 (m,
4H), 2.24 (s, 6H), 3.44 (t, J = 7.44 Hz, 2H), 3.51 (d, J = 13.17 Hz,
2H), 3.70 (d, J = 12.99 Hz, 2H), 4.93 (d, J = 13.38 Hz, 2H), 4.97 (d,
J = 13.38 Hz, 2H), 5.73−5.86 (m, 2H), 7.23 (t, J = 6.98 Hz, 2H),
7.28−7.37 (m, 8H); 13C NMR (75.5 MHz, CDCl3) δ 22.0, 26.7, 28.9,
28.9, 29.0, 29.1, 29.3, 29.5, 29.6, 29.7, 33.8, 34.4, 34.4, 37.8, 43.9, 55.5,
59.3, 82.7, 114.1, 126.9, 128.2, 129.0, 139.1, 139.5; HRMS (EI) m/z
calcd for C40H60N2 [M]+ 568.4756, found 568.4773.
(E)-N,2-Dimethylbut-2-en-1-amine (20) was prepared according
to ref 18.
N,3-Dimethylbut-2-en-1-amine (2p) was prepared according to
ref 19.
General Procedure for the Synthesis of Propagylamines 4. A
mixture of aldehyde 1 (2.2 mmol), amine 2 (2.5 mmol), and propiolic
acid 3 (1.0 mmol) was dissolved in toluene (1.0 mL) applying a
microwave vial along with a magnetic stir bar, and then copper
bromide (0.3 mmol) was added. The reaction vessel was sealed and
irradiated in the cavity of CEM-Discover microwave reactor at a ceiling
temperature of 100 °C and a maximum power of 80 W for 30 min.
The resulting reaction mixture was loaded on a silica gel column and
flashed with 6−10% EtOAc in heptanes to afford the desired product 4
as light yellow oil.
N3,N6-Dibenzyl-N3,N6-dimethyl-1,8-diphenyloct-4-yne-3,6-
diamine (4h): light yellow oil; 1H NMR (300 MHz, CDCl3) δ 1.94−
2.10 (m, 4H), 2.27 (s, 6H), 2.81 (t, J = 7.64 Hz, 4H), 3.51 (t, J = 7.34
Hz, 2H), 3.53 (d, J = 13.20 Hz, 2H), 3.73 (d, J = 13.20 Hz, 2H), 7.13−
7.33 (m, 16H), 7.37 (d, J = 7.14 Hz, 4H); 13C NMR (75.5 MHz,
CDCl3) δ 32.8, 36.2, 36.2, 37.8, 55.0, 59.3, 82.8, 125.8, 127.0, 128.2,
128.3, 128.5, 128.9, 139.3, 141.8; HRMS (EI) m/z calcd for C36H40N2
[M]+ 500.3191, found 500.3183.
N1,N4-Dibenzyl-N1,N4-dimethyl-1,4-diphenylbut-2-yne-1,4-
diamine (4i): light yellow oil; 1H NMR (300 MHz, CDCl3) δ 2.29 (s,
6H), 3.71 (d, J = 12.99 Hz, 2H), 3.80 (d, J = 12.99 Hz, 2H), 4.94(s,
2H), 7.25−7.40 (m, 12H), 7.44 (d, J = 7.17 Hz, 4H), 7.72 (d, J =
7.35 Hz, 4H); 13C NMR (75.5 MHz, CDCl3) δ 38.1, 59.1, 59.3, 83.2,
127.1, 127.5, 128.1, 128.3, 128.9, 139.2, 139.3; HRMS (EI) m/z calcd
for C32H32N2 [M]+ 444.2565, found 444.2572.
N4,N7-Dibenzyl-N4,N7,2,9-tetramethyldec-5-yne-4,7-diamine
(4a): light yellow oil; 1H NMR (300 MHz, CDCl3) δ 0.90 (d, J = 6.60
Hz, 12H), 1.51−1.65 (m, 4H), 1.86−1.95 (m, 2H), 2.23 (s, 6H), 3.50
(d, J = 13.02 Hz, 2H), 3.54 (t, J = 7.44 Hz, 2H), 3.70 (d, J = 13.02 Hz,
2H), 7.21 (t, J = 7.07 Hz, 2H), 7.27−7.37 (m, 8H); 13C NMR (75.5
MHz, CDCl3) δ 22.7, 25.2, 37.9, 43.5, 43.5, 53.8, 59.5, 82.8, 127.1,
128.3, 129.1, 139.6; HRMS (EI) m/z calcd for C28H40N2 [M]+
404.3191, found 404.3195.
N4,N7-Bis(3,4-dimethoxybenzyl)-N4,N7,2,9-tetramethyldec-5-
yne-4,7-diamine (4j): light yellow oil; 1H NMR (300 MHz, CDCl3)
δ 0.89−0.92 (m, 12H), 1.53−1.60 (m, 4H), 1.85−1.94 (m, 2H), 2.26
(s, 6H), 3.47 (d, J = 12.96 Hz, 2H), 3.52 (t, J = 7.71 Hz, 2H), 3.65 (d,
J = 12.96 Hz, 2H), 3.86 (s, 6H), 3.88 (s, 6H), 6.81 (d, J = 7.17 Hz,
2H), 6.88 (d, J = 8.28 Hz, 2H), 6.94 (s, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 22.6, 25.0, 37.6, 43.3, 53.0, 55.7, 55.8, 59.2, 82.6, 110.7,
112.0, 121.0, 132.0, 148.0, 148.9; HRMS (EI) m/z calcd for
C32H48N2O4 [M]+ 524.3614, found 524.3620.
N4,N7-Dibenzyl-N4,N7-dimethyldec-5-yne-4,7-diamine (4b):
light yellow oil; 1H NMR (300 MHz, CDCl3) δ 0.93 (t, J =
7.26 Hz, 6H), 1.45−1.56 (m, 4H), 1.64−1.68 (m, 4H), 2.24 (s, 6H),
3.47 (t, J = 7.53 Hz, 2H), 3.51 (d, J = 13.17 Hz, 2H), 3.70 (d, J = 13.17
Hz, 2H), 7.22 (t, J = 6.96 Hz, 2H), 7.28−7.37 (m, 8H); 13C NMR
(75.5 MHz, CDCl3) δ 13.9, 19.9, 36.6, 37.8, 55.3, 59.3, 82.7, 126.9,
128.2, 129.0, 139.5; HRMS (EI) m/z calcd for C26H36N2 [M]+
376.2878, found 376.2865.
N4,N4,N7,N7-Tetrabenzyl-2,9-dimethyldec-5-yne-4,7-diamine
1
(4k): light yellow oil; H NMR (300 MHz, CDCl3) δ 0.73−0.85 (m,
N3,N 6-Dibenzyl-N 3,N 6,2,7-tetramethyloct-4-yne-3,6-di-
12H), 1.45−1.57 (m, 2H), 1.63−1.75 (m, 2H), 1.74−1.95 (m, 2H),
3.35−3.59 (m, 6H), 3.79−3.92 (m, 4H), 7.20−7.44 (m, 20H); 13C
NMR (75.5 MHz, CDCl3) δ 22.3, 23.1, 25.0, 43.6, 50.0, 55.3, 82.8,
127.1, 128.4, 129.1, 140.1; HRMS (EI) m/z calcd for C40H48N2 [M]+
556.3817, found 556.3810.
1
amine (4c): light yellow oil; H NMR (300 MHz, CDCl3) δ 1.04
(d, J = 6.42 Hz, 6H), 1.08 (d, J = 4.71 Hz, 6H), 1.81−1.90 (m, 2H),
2.22 (s, 6H), 2.98 (d, J = 9.96 Hz, 2H), 3.55 (d, J = 13.35 Hz, 2H),
3.71 (d, J = 13.38 Hz, 2H), 7.22 (t, J = 6.96 Hz, 2H), 7.30 (t, J = 7.25
Hz, 4H), 7.37 (d, J = 7.17 Hz, 4H); 13C NMR (75.5 MHz, CDCl3) δ
19.9, 19.9, 21.1, 21.2, 31.3, 31.4, 37.9, 37.9, 59.7, 63.0, 82.7, 126.9,
128.3, 129.0, 139.9; HRMS (EI) m/z calcd for C26H36N2 [M]+
376.2878, found 376.2875.
N4,N7-Bis(2-bromobenzyl)-N4,N7-dibutyl-2,9-dimethyldec-5-
yne-4,7-diamine (4l): light yellow oil; 1H NMR (300 MHz, CDCl3)
δ 0.84−0.91 (m, 18H), 1.25−1.56 (m, 12H), 1.85−1.93 (m, 2H), 2.56
(t, J = 7.07 Hz, 4H), 3.57 (t, J = 7.34 Hz, 2H), 3.70−3.84 (m, 4H),
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7.05 (t, J = 7.55 Hz, 2H), 7.26 (t, J = 7.53 Hz, 2H), 7.50 (d, J =
7.92 Hz, 2H), 7.59 (d, J = 7.53 Hz, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 14.1, 20.7, 22.6, 25.0, 30.5, 43.6, 51.3, 55.5, 82.8, 124.2,
127.0, 127.9, 130.5, 132.4, 139.6; HRMS (EI) m/z calcd for
C34H50Br2N2 [M]+ 644.2341, found 644.2336.
5.38−5.44 (m, 2H); 13C NMR (75.5 MHz, CDCl3) δ 21.9, 27.0, 28.9,
29.1, 29.4, 29.5, 31.0, 33.8, 34.0, 34.1, 34.4, 34.6, 46.6, 53.0, 57.9, 83.2,
114.1, 139.1; HRMS (EI) m/z calcd for C36H64N2 [M]+ 524.5070,
found 524.5057.
N3,N3,N6,N6-Tetrabutyl-1,8-diphenyloct-4-yne-3,6-diamine
(4w): light yellow oil; 1H NMR (300 MHz, CDCl3) δ 0.90 (t, J = 7.07
Hz, 12H), 1.26−1.41 (m, 16H), 1.88−1.95 (m, 4H), 2.31−2.40 (m,
4H), 2.49−2.58 (m, 4H), 2.77 (t, J = 7.82 Hz, 4H), 3.47 (t, J = 7.23
Hz, 2H), 7.13−7.29 (m, 10H); 13C NMR (75.5 MHz, CDCl3) δ 14.2,
20.8, 30.9, 33.1, 36.6, 51.5, 53.2, 83.0, 125.8, 128.3, 128.5, 142.2;
HRMS (EI) m/z calcd for C36H56N2 [M]+ 516.4443, found 516.4454.
N11,N14-Bis(2-bromobenzyl)-N11,N14-dibutyltetracosa-1,23-
N4,N4,N7,N7-Tetraallyl-2,9-dimethyldec-5-yne-4,7-diamine
(4m): light yellow oil; 1H NMR (300 MHz, CDCl3) δ 0.90 (t, J = 6.50
Hz, 12H), 1.49 (t, J = 7.25 Hz, 12H), 1.79−1.87 (m, 2H), 2.85−2.92
(m, 4H), 3.25−3.31 (m, 4H), 3.63 (t, J = 7.44 Hz, 2H), 5.11 (d, J =
9.90 Hz, 4H), 5.20 (d, J = 17.13 Hz, 4H), 5.77−5.90 (m, 4H); 13C
NMR (75.5 MHz, CDCl3) δ 22.4, 22.7, 25.1, 43.2, 43.3, 50.6, 54.1,
77.0, 82.7, 116.9, 136.8; HRMS (EI) m/z calcd for C24H40N2 [M]+
356.3191, found 356.3181.
1
dien-12-yne-11,14-diamine (4x): light yellow oil; H NMR (300
N4,N7,2,9-Tetramethyl-N4,N7-bis(2-methylbut-2-en-1-yl)dec-
5-yne-4,7-diamine (4n): light yellow oil; 1H NMR (300 MHz,
CDCl3) δ 0.89−0.92 (m, 12H), 1.47 (t, J = 7.25 Hz, 4H), 1.62
(s, 12H), 1.79−1.88 (m, 2H), 2.12 (s, 6H), 2.84 (d, J = 12.45 Hz, 2H),
2.95 (d, J = 12.42 Hz, 2H), 3.46 (t, J = 7.64 Hz, 2H), 5.39−5.43 (m,
2H); 13C NMR (75.5 MHz, CDCl3) δ 13.3, 14.6, 22.5, 22.7, 25.1, 37.3,
53.2, 63.8, 82.5, 121.7, 133.9; HRMS (EI) m/z calcd for C24H44N2
[M]+ 360.3504, found 360.3490 .
MHz, CDCl3) δ 0.88 (t, J = 7.16 Hz, 6H), 1.26−1.50 (m, 36H), 1.57−
1.70 (m, 4H), 1.99−2.06 (m, 4H), 2.56 (t, J = 6.87 Hz, 4H), 3.47 (t,
J = 7.25 Hz, 2H), 3.70−3.83 (m, 4H), 4.90−5.01 (m, 4H), 5.73−5.86
(m, 2H), 7.06 (t, J = 7.44 Hz, 2H), 7.26 (t, J = 7.44 Hz, 2H), 7.49 (d,
J = 7.92 Hz, 2H), 7.60 (d, J = 7.53 Hz, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 14.2, 20.8, 26.8, 29.0, 29.2, 29.4, 29.5, 29.7, 30.6, 33.9, 34.6,
51.6, 53.4, 55.6, 83.0, 114.2, 124.3, 127.1, 128.0, 128.3, 129.1, 130.5,
132.5, 139.2, 139.8; HRMS (EI) m/z calcd for C46H70Br2N2 [M]+
808.3906, found 808.3898.
N4,N7,2,9-Tetramethyl-N4,N7-bis(3-methylbut-2-en-1-yl)dec-
5-yne-4,7-diamine (4o): light yellow oil; 1H NMR (300 MHz,
CDCl3) δ 0.92 (t, J = 6.50 Hz, 12H), 1.42−1.59 (m, 4H), 1.67 (s, 6H),
1.73 (s, 6H), 1.79−1.88 (m, 2H), 2.20 (s, 6H), 3.02 (d, J = 7.17 Hz,
4H), 3.54 (t, J = 7.53 Hz, 2H), 5.22 (t, J = 7.07 Hz, 2H); 13C NMR
(75.5 MHz, CDCl3) δ 18.0, 22.1, 22.8, 25.2, 25.9, 37.4, 43.4, 52.6, 53.5,
82.7, 122.2, 135.0; HRMS (EI) m/z calcd for C24H44N2 [M]+
360.3504, found 360.3512.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H NMR and 13C NMR spectra for all new com-
pounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
1,1′-(2,9-Dimethyldec-5-yne-4,7-diyl)bis(4-methylpiperi-
dine) (4p): light yellow oil; 1H NMR (300 MHz, CDCl3) δ 0.90−0.95
(m, 18H), 1.16−1.47 (m, 8H), 1.53−1.67 (m, 6H), 1.79−1.87 (m,
2H), 2.17 (t, J = 10.31 Hz, 2H), 2.47 (t, J = 11.21 Hz, 2H), 2.66 (d, J =
11.31 Hz, 2H), 2.76 (d, J = 11.13 Hz, 2H), 3.41 (t, J = 7.53 Hz, 2H);
13C NMR (75.5 MHz, CDCl3) δ 21.9, 23.3, 25.5, 31.0, 34.4, 34.7, 42.9,
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: denis.ermolatev@chem.kuleuven.be, erik.vandereycken@
chem.kuleuven.be.
43.0, 46.5, 53.1, 56.0, 83.1; HRMS (EI) m/z calcd for C24H44N2 [M]+
360.3504, found 360.3508 .
Notes
The authors declare no competing financial interest.
N4,N4,N7,N7-Tetrabutyl-2,9-dimethyldec-5-yne-4,7-diamine
1
(4q): light yellow oil; H NMR (300 MHz, CDCl3) δ 0.88−0.93 (m,
ACKNOWLEDGMENTS
24H), 1.27−1.46 (m, 20H), 1.78−1.87 (m, 2H), 2.27−2.35 (m, 4H),
2.44−2.53 (m, 4H), 3.51 (t, J = 7.35 Hz, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 14.1, 20.8, 22.4, 22.8, 30.9, 43.7, 51.5, 51.7, 82.9; HRMS
(EI) m/z calcd for C28H56N2 [M]+ 420.4443, found 420.4446.
N4,N4,N7,N7-Tetraisobutyl-2,9-dimethyldec-5-yne-4,7-dia-
mine (4r): light yellow oil; 1H NMR (300 MHz, CDCl3) δ 0.76−0.84
(m, 36H), 1.27−1.38 (m, 4H), 1.52−1.61 (m, 4H), 1.76−1.84 (m,
2H), 1.90−1.98 (m, 4H), 2.13−2.19 (m, 4H), 3.36 (t, J = 7.25 Hz,
2H); 13C NMR (75.5 MHz, CDCl3) δ 20.8, 21.1, 22.6, 22.7, 24.8, 26.6,
43.9, 51.5, 60.8, 82.4; HRMS (EI) m/z calcd for C28H56N2 [M]+
420.4443, found 420.4449.
■
We thank the FWO (Fund for Scientific Research-Flanders
(Belgium)) and the Research Fund of the University of Leuven
for financial support to the laboratory. D.S.E. is grateful to the
FWO for a postdoc fellowship. H.F. thanks the China
Scholarship Council for financial support.
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