Alkynylation of aryl bromides with propargylamines catalyzed by a palladium-tetraphosphine complex

Article abstract of DOI:10.1055/s-2005-865284

The tetraphosphine all-cis-1,2,3,4-tetrakis(diphenylphosphinomethyl) cyclopentane in combination with [Pd(C₃H₅)Cl]₂ affords a very efficient catalyst for the alkynylation of aryl bromides with propargylamines. Higher reactions rates were observed with N,N- dialkylpropargylamines than with N-methylpropargylamine or propargy lamine. A wide variety of substituents such as alkyl, phenyl, methoxy, dimethylamino, fluoro, trifluoromethyl, acetyl, benzoyl, formyl, carboxylate, nitro, or nitrile, on the aryl bromides are tolerated. High turnover numbers can be obtained with most of these aryl bromides. The coupling reaction of sterically very congested aryl bromides such as 9-bromoanthracene or 2,4,6- triisopropylbromobenzene also proceeds in good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865284

PAPER
1359
Alkynylation of Aryl Bromides with Propargylamines Catalyzed by a
Palladium-Tetraphosphine Complex
Alkynylation of Aryl
B
h
romides
w
it
a
h
P
ropargyl
m
amines ed Lemhadri, Henri Doucet,* Maurice Santelli*
UMR 6180 CNRS and Université d’Aix-Marseille III: ‘Chirotechnologies: catalyse et biocatalyse’,
Laboratoire de Synthèse Organique, Faculté des Sciences de Saint Jérôme, Université d’Aix-Marseille III,
Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Fax +33(4)91983865; E-mail: henri.doucet@univ.u-3mrs.fr; E-mail: m.santelli@univ.u-3mrs.fr
Received 22 November 2004; revised 27 January 2005
described using less reactive aryl bromides.5,6 We found
only one example of the formation of such products using
ligands other than triphenylphosphine; the reaction of N-
propargylaniline with various heteroaryl bromides using
Abstract: The
nylphosphinomethyl)cyclopentane
[Pd(C3H5)Cl]2 affords a very efficient catalyst for the alkynylation
of aryl bromides with propargylamines. Higher reactions rates were
tetraphosphine
all-cis-1,2,3,4-tetrakis(diphe-
in combination with
observed with N,N-dialkylpropargylamines than with N-methylpro- Pd/C and several ligands was described by Lopez-Deber
et al.6 However, to our knowledge, low-catalyst loading
pargylamine or propargylamine. A wide variety of substituents such
as alkyl, phenyl, methoxy, dimethylamino, fluoro, trifluoromethyl,
Sonogashira alkynylation reactions using propargylamine
acetyl, benzoyl, formyl, carboxylate, nitro, or nitrile, on the aryl
derivatives have not been reported.
bromides are tolerated. High turnover numbers can be obtained with
In order to obtain a highly stable palladium catalyst, we
prepared the tetraphosphine ligand, all-cis-1,2,3,4-tet-
rakis(diphenylphosphinomethyl)cyclopentane or tedicyp7
(Figure 1). We have already reported the results obtained
in allylic substitution,7 Suzuki cross-coupling,8 and for the
Heck reaction9 using tedicyp as the ligand. We have also
reported recently the first results obtained for the Sono-
gashira reaction with this palladium catalyst.10 In order to
further expand the successful Sonogashira reaction with
our catalyst, we herein report on the reaction of aryl bro-
mides with propargylamine and N-substituted propargyl-
amines.
most of these aryl bromides. The coupling reaction of sterically very
congested aryl bromides such as 9-bromoanthracene or 2,4,6-triiso-
propylbromobenzene also proceeds in good yields.
Key words: palladium, tetraphosphine, catalysis, alkynylation,
propargylamine, aryl bromide
Substituted aryl propargylic amines bearing various sub-
stituents on the aromatic ring are of great biological inter-
est since their structures display strong inhibitory
activities towards several enzymes.1 The palladium-cata-
lyzed Sonogashira reaction is one of the most powerful
methods for the formation of C–C bonds.2 In recent years,
several thermally stable palladium catalysts have been
successfully used for Sonogashira reactions,3 but most of
these catalysts have not been tested in the synthesis of aryl
propargylic amines by the coupling of aryl halides with
propargylamine derivatives. The most popular ligand for
the reaction of propargyl amine derivatives with aryl ha-
lides is triphenylphosphine. However, the catalyst formed
by association of this ligand with palladium complexes is
not very efficient in terms of substrate/catalyst ratio and
1–10 mol% of catalyst had to be used. Moreover, most of
the results described involved very reactive substrates and
the use of expensive aryl iodides.4 Only a few results were
Ph2P
PPh2
Ph2P
PPh2
Tedicyp
Figure 1
For this study, based on our previous results,10 DMF was
chosen as the solvent and potassium carbonate as the base.
Copper(I) iodide (5 mol%) was added as co-catalyst. The
reactions were performed at 80, 110, or 130 °C, under ar-
gon, in the presence of [Pd(C3H5)Cl]2/tedicyp as catalyst
in a ratio of 1:2.
R2
R2
R3
N
R3
N
[Pd(C3H5)Cl]2 / 0.5 equiv Tedicyp,
CuI, DMF, K2CO3, 80–130 °C
+
H
Br
R1
R1
R1 = H, Me, i-Pr, t-Bu, OMe, F, CF3, MeCO, PhCO, CHO, CO2Me, CN, NO2, NMe2
R2 and R3 = H; R2 and R3 = Et; R2 and R3 = n-Pr; R2 = H and R3 = Me; R2 = CH2Ph and R3 = Me
Scheme 1
SYNTHESIS 2005, No. 8, pp 1359–1367
x
x
.
x
x
.2
0
0
5
Advanced online publication: 23.03.2005
DOI: 10.1055/s-2005-865284; Art ID: Z22104SS
© Georg Thieme Verlag Stuttgart · New York

1360
M. Lemhadri et al.
PAPER
Table 1 Palladium-Catalyzed Coupling Reaction of Aryl Halides
with N,N-Diethylpropargylamine (Scheme 1)a
First, we studied the influence of the para-substituents on
the aryl bromide on the reaction rate for the coupling with
the tertiary amine N,N-diethylpropargylamine (Scheme 1,
Table 1). We observed that in most cases the reactions
performed with N,N-diethylpropargylamine proceed very
smoothly. As expected, electron-withdrawing groups on
the aryl bromide support the reaction, while electron-do-
nating groups are unfavorable. Complete conversions can
be achieved with 0.1 mol% of this catalyst for activated
substrates such as 4-bromoacetophenone, 4-bromobenz-
aldehyde, methyl 4-bromobenzoate, 4-bromobenzonitrile,
and 4-bromonitrobenzene (Table 1, entries 2–9). With de-
activated aryl bromides such as 4-bromoanisole and 4-
dimethylaminobromobenzene lower reaction rates were
observed and TONs of 232 and 92 were obtained, respec-
tively (Table 1, entries 13–17). We also compared the re-
activity of iodo- and bromobenzene and, as expected, we
observed a much slower reaction with bromobenzene than
with iodobenzene (Table 1, entries 1 and 12).
Entry Aryl bromide
Product Ratio
substrate/
catalyst
Yieldb
1
2
3
4
5
6
7
8
9
Iodobenzene
1
2
3
4
5
6
7
8
9
10000:1 100 (94)
1000:1 100 (92)
1000:1 100 (92)
1000:1 100 (94)
1000:1 100 (90)
1000:1 100 (93)
1000:1 100 (93)
1000:1 100 (89)
1000:1 100 (91)
4-Bromoacetophenone
4-Bromobenzophenone
4-Bromobenzaldehyde
Methyl 4-bromobenzoate
4-Trifluoromethylbromobenzene
4-Bromobenzonitrile
4-Bromonitrobenzene
3,5-Bis(trifluoromethyl)bro-
mobenzene
Then, we studied the influence of the presence of meta-
and ortho-substituents on the aryl bromides on the reac-
tion rate. As expected similar reaction rates were obtained
with the meta-substituted 3-trifluoromethylbromoben-
zene and with the para-substituted 4-trifluoromethylbro-
mobenzene (Table 1, entries 6 and 18). Ortho-substituents
on the aryl bromides have a more important effect on the
reaction rates. We observed that the coupling of 2-tri-
fluoromethylbromobenzene with N,N-diethylpropargyl-
amine also proceeds in the presence of 0.1 mol% of
catalyst, however a low conversion of 46% was observed
(Table 1, entry 25). With the other ortho-substituted aryl
bromides, 2-bromoacetophenone, 2-bromobenzaldehyde,
2-bromobenzonitrile, or 2-bromonitrobenzene a similar
tendency was observed; in all cases, they are less reactive
than the para-substituted substrates (Table 1, entries 21–
28).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
4-Fluorobromobenzene
4-Fluorobromobenzene
Bromobenzene
10
10
1
250:1 100 (90)
1000:1 50
250:1 100 (92)
250:1 100 (90)
1000:1 51
4-Bromotoluene
11
11
12
13
4-Bromotoluene
4-t-Butylbromobenzene
4-Bromoanisole
250:1 100 (95)
250:1 93 (87)
100:1 92 (84)
1000:1 100 (92)
250:1 100 (94)
1000:1 88
4-Bromo-N,N-dimethylaniline 14
3-Trifluoromethylbromobenzene 15
2-Bromo-6-methoxynaphthalene 16
2-Bromo-6-methoxynaphthalene 16
Next, we tried to evaluate the difference of reaction rate
between mono- and di-ortho-substituted aryl bromides,
and we observed that even very hindered aryl bromides
could be coupled efficiently with N,N-diethylpropargyl-
amine. For example, with 9-bromoanthracene and 2,4,6-
trimethylbromobenzene the aryl propargylic amines were
obtained with excellent conversion, 100% and 85%, re-
spectively, in the presence of 0.4 mol% and 2 mol% of
catalyst (Table 1, entries 34–36). This coupling reaction
also proceeds in the presence of a very sterically hindered
substrate such as 1-bromo-2,4,6-triisopropylbenzene, but
with this substrate the use of 4 mol% of catalyst was nec-
essary (Table 1, entries 37 and 38). After this we investi-
gated this reaction with 2- and 3-bromopyridines. The
expected adducts were obtained in good yields in the pres-
ence of 0.4 mol% catalyst (Table 1, entries 39 and 40). Fi-
nally, the reactivity of two aryl chlorides was studied, 4-
chloroacetophenone and 4-chlorobenzonitrile with N,N-
diethylpropargylamine and 1 mol% catalyst led to the aryl
propargylic amines in satisfactory yields (Table 1, entries
41 and 42).
2-Bromoacetophenone
2-Bromoacetophenone
2-Bromobenzaldehyde
17
17
18
250:1 100 (90)
1000:1 29
1000:1 100 (88)
250:1 100 (93)
1000:1 46
2-Trifluoromethylbromobenzene 19
2-Trifluoromethylbromobenzene 19
2-Bromobenzonitrile
2-Bromobenzonitrile
2-Bromonitrobenzene
2-Fluorobromobenzene
2-Fluorobromobenzene
1-Bromonaphthalene
2-Bromoanisole
20
20
21
22
22
23
24
25
26
250:1 100 (89)
1000:1 62
250:1 100 (88)
250:1 100 (93)
1000:1 47
250:1 100 (94)
250:1 100 (90)
100:1 100 (91)
250:1 100 (87)
2,6-Difluorobromobenzene
9-Bromoanthracene
Synthesis 2005, No. 8, 1359–1367 © Thieme Stuttgart · New York

PAPER
Alkynylation of Aryl Bromides with Propargylamines
1361
Table 1 Palladium-Catalyzed Coupling Reaction of Aryl Halides
with N,N-Diethylpropargylamine (Scheme 1)a (continued)
coupling reaction of propargylamine derivatives with sub-
stituted aryl bromides. The complex seems to possess a
fine balance between steric and electronic properties
which generally allows for fast catalytic processes. As ex-
pected, both the steric hindrance and the electronic prop-
erties of the aryl bromides have an effect on the reaction
rate. Electron-poor aryl bromides can be reacted at higher
substrate/catalyst ratios than electron-rich aryl bromides.
The presence of ortho-substituents generally led to lower
TONs than the reactions performed in the presence of
para-substituted aryl bromides. Di-ortho-substituted aryl
bromides also gave the coupling products, but a low TON
was observed with the sterically very congested 2,4,6-tri-
isopropylbromobenzene. The substituents on the nitrogen
atom of the propargylamine derivatives also have an im-
portant influence on the reaction rates. N,N-Dialkylprop-
argylamines such as N,N-diethylpropargylamine are more
reactive than N-methylpropargylamine. The lowest TONs
were observed in the presence of propargylamine, with
this substrate, 5 mol% catalyst had to be used. For many
substrates, with N,N-dialkylpropargylamines the reaction
can be performed with as little as 0.1 mol% catalyst with-
out further optimization of the reaction conditions. We be-
lieve that this system compares favorably with the other
catalysts that have been reported for this process. Due to
the high cost of palladium, the practical advantage of such
low catalyst loading reactions is becoming increasingly
important for industrial processes.
Entry Aryl bromide
Product Ratio
substrate/
Yieldb
catalyst
35
36
37
38
39
40
41
42
2,4,6-Trimethylbromobenzene 27
50:1
85 (80)
50
2,4,6-Trimethylbromobenzene 27
2,4,6-Triisopropylbromobenzene 28
2,4,6-Triisopropylbromobenzene 28
100:1
25:1
84 (78)
25
100:1
250:1
250:1
100:1
100:1
2-Bromopyridine
29
30
2
100 (89)
100 (92)
61c
3-Bromopyridine
4-Chloroacetophenone
4-Chlorobenzonitrile
7
85c
a Conditions: [ClPd(C3H5)]2/tedicyp (1:2), aryl halide (1 mmol), N,N-
diethylpropargylamine (2 mmol), K2CO3 (2 mmol), CuI (0.05 mmol),
DMF, 110 °C, 20 h, argon.
b Yields determined by GC and NMR; figures in parentheses are iso-
lated yields.
c Reactions performed without CuI.
These results prompted us to investigate the arylation of a
few other propargylamine derivatives and propargyl-
amine (Table 2). As expected, with the two tertiary
amines N,N-dipropylpropargylamine and N,N-benzyl-
methylpropargylamine very similar results to those with
N,N-diethylpropargylamine were obtained (Table 2, en-
tries 1–12). For example, the reaction of N,N-dipropylpro-
pargylamine in the presence of 0.1 mol% catalyst with
activated aryl bromides such as 4-bromoacetophenone led
to the complete conversion to the expected adduct in
(Table 2, entry 2). Sterically hindered 9-bromoanthracene
and N,N-benzylmethylpropargylamine with 0.4 mol%
catalyst gave 100% conversion to the expected product 40
(Table 2, entry 12). The secondary amine N-methylprop-
argylamine was found to be less reactive than the tertiary
amines by a factor of ten (Table 2, entries 13–18), for ex-
ample, a low TON of 32 was obtained for the reaction of
4-bromoanisole with N-methylpropargylamine (Table 2,
entries 16 and 17). A TON of 232 had been obtained for
the reaction of 4-bromoanisole with N,N-diethylpropar-
gylamine (Table 1, entry 16), this lower reactivity results
from the reaction being carried out at a lower temperature
(80 °C). However, the reaction performed at the same
temperature (80 °C) with the primary amine propargyl-
amine gave even lower TONs of 14–18 (Table 2, entries
19–21). These results suggest that with secondary and es-
pecially primary propargylamines a possible interaction
between the nitrogen atom and the palladium complex has
a decelerating effect on the reaction rate. It should be not-
ed that with these two propargyl amines no amination
product was detected.
DMF analytical grade (99.8%) was not distilled before use. Potassi-
um carbonate 99+ was used. All reactions were run under argon us-
ing vacuum lines in Schlenk tubes in oven-dried glassware. The
reactions were followed by GC and NMR for high boiling point
1
substrates and by GC for low boiling point substrates. H (300
MHz) and 13C (75 MHz) spectra were recorded in CDCl3 solutions.
Chemical shifts (d) are reported in ppm relative to CDCl3. Flash
chromatography was performed on silica gel (230–400 mesh).
Preparation of the Pd-Tedicyp Catalyst7
An oven-dried 40-mL Schlenk tube equipped with a magnetic stir-
ring bar, under argon atmosphere, was charged with [Pd-h3-
C3H5)Cl]2 (4.2 mg, 11.6 mmol) and Tedicyp (20 mg, 23.2 mmol).
Anhyd DMF (2.5 mL) was added, then the solution was stirred at
r.t. for 10 min.
Palladium Calatalyzed Coupling Reaction; General Procedure
Aryl halide (1 mmol), alkyne (2 mmol), K2CO3 (0.276 g, 2 mmol),
CuI (0.01 g, 0.05mmol), anhyd DMF (2 mL), and cis,cis,cis-1,2,3,4-
tetrakis(diphenylphosphinomethyl)cyclopentane/0.5[PdCl(C3H5)]2
complex under argon was heated at 80, 110, or 130 °C (see Tables 1
and 2). After this, H2O (10 mL) was added and the product was ex-
tracted with Et2O (1, 6, 9–12, 19, 31) or CH2Cl2 (2–5, 7, 8, 13–18,
20–30, 32–47) (20 mL), the organic phase was dried (MgSO4), and
the solvent was evaporated. Chromatography on silica gel (1–40:
Et2O, then Et2O–CH2Cl2; 41–47: CH2Cl2, then CH2Cl2–MeOH)
gave the desired coupled product.
3-(Diethylamino)-1-phenylpropyne (1)4h
The reaction of iodobenzene (0.204 g, 1 mmol) and N,N-diethylpro-
pargylamine (0.222 g, 2 mmol) afforded 1 in 94% (0.176 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.38 (m, 2 H), 7.24 (m, 3 H), 3.60
(s, 2 H), 2.59 (q, 4 H, J = 7.2 Hz), 1.08 (t, 6 H, J = 7.2 Hz).
The use of the tetradentate ligand tedicyp associated to a
palladium complex provides a convenient catalyst for the
Synthesis 2005, No. 8, 1359–1367 © Thieme Stuttgart · New York

1362
M. Lemhadri et al.
PAPER
Table 2 Palladium-Catalyzed Coupling Reaction of Aryl Halides with Propargylamine Derivatives (Scheme 1)a
Entry
Aryl bromide
Alkyne
Product
Ratio
Yieldb
substrate/catalyst
1
2
Iodobenzene
N,N-Dipropylpropargylamine
N,N-Dipropylpropargylamine
N,N-Dipropylpropargylamine
N,N-Dipropylpropargylamine
N,N-Dipropylpropargylamine
N,N-Dipropylpropargylamine
N,N-Benzylmethylpropargylamine
N,N-Benzylmethylpropargylamine
N,N-Benzylmethylpropargylamine
N,N-Benzylmethylpropargylamine
N,N-Benzylmethylpropargylamine
N,N-Benzylmethylpropargylamine
N-Methylpropargylamine
N-Methylpropargylamine
N-Methylpropargylamine
N-Methylpropargylamine
N-Methylpropargylamine
N-Methylpropargylamine
Propargylamine
31
32
33
34
34
35
36
37
38
38
39
40
41
41
42
43
43
44
45
46
47
10000:1
1000:1
250:1
250:1
1000:1
1000:1
10000:1
1000:1
250:1
1000:1
250:1
250:1
250:1
1000:1
100:1
25:1
100 (90)
100 (94)
100 (94)
100 (91)
82
4-Bromoacetophenone
4-t-Butylbromobenzene
1-Bromonaphthalene
1-Bromonaphthalene
3-Trifluoromethylbromobenzene
Iodobenzene
3
4
5
6
100 (92)
100 (88)
100 (86)
100 (89)
84
7
8
4-Trifluoromethylbromobenzene
4-t-Butylbromobenzene
4-t-Butylbromobenzene
4-Bromoanisole
9
10
11
12
13
14
15
16
17
18
19
20
21
100 (90)
100 (84)
100 (82)c
83 c
9-Bromoanthracene
Iodobenzene
Iodobenzene
4-t-Butylbromobenzene
4-Bromoanisole
100 (84)c
100 (80)c
32c
4-Bromoanisole
100:1
250:1
20:1
1-Bromonaphthalene
Iodobenzene
100 (82)c
88 (74)c
72 (64)c
86 (67)c
4-Bromotoluene
Propargylamine
20:1
1-Bromonaphthalene
Propargylamine
20:1
a Conditions: [ClPd(C3H5)]2/tedicyp (1:2), aryl halide (1 mmol), alkyne (2 mmol), K2CO3 (2 mmol), CuI (0.05 mmol), DMF, 130 °C, 20 h, ar-
gon.
b Yields determined by GC and NMR; figures in parentheses are isolated yields.
c Reaction temperature: 80 °C.
1-(4-Acetylphenyl)-3-(diethylamino)propyne (2)
The reaction of 4-bromoacetophenone (0.199 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 2 in 92% (0.211
g) yield.
1H NMR (300 MHz, CDCl3): d = 7.78 (d, 2 H, J = 8.3 Hz), 7.48 (d,
2 H, J = 8.3 Hz), 3.67 (s, 2 H), 2.63 (q, 4 H, J = 7.2 Hz), 2.58 (s, 3
H), 1.12 (t, 6 H, J = 7.2 Hz).
1H NMR (300 MHz, CDCl3): d = 7.75 (m, 4 H), 7.59 (t, 1 H, J = 7.4
Hz), 7.51 (d, 2 H, J = 8.1 Hz), 7.47 (t, 2 H, J = 7.2 Hz), 3.68 (s, 2
H), 2.65 (q, 4 H, J = 7.2 Hz), 1.13 (t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 195.6, 137.2, 136.4, 132.3, 131.3,
129.8, 129.7, 128.1, 127.4, 87.6, 84.3, 47.2, 41.4, 12.4.
Anal. Calcd for C20H21NO: C, 82.44; H, 7.26. Found: C, 82.21; H,
7.10.
13C NMR (75 MHz, CDCl3): d = 197.1, 135.9, 131.6, 128.1, 128.0,
88.0, 84.3, 47.2, 41.4, 26.4, 12.4.
3-(Diethylamino)-1-(4-formylphenyl)propyne (4)
The reaction of 4-bromobenzaldehyde (0.185 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 4 in 94% (0.202
g) yield.
Anal. Calcd for C15H19NO: C, 78.56; H, 8.35. Found: C, 78.37; H,
8.19.
1-(4-Benzoylphenyl)-3-(diethylamino)propyne (3)
The reaction of 4-bromobenzophenone (0.261 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 3 in 92% (0.268
g) yield.
1H NMR (300 MHz, CDCl3): d = 9.99 (s, 1 H), 7.80 (d, 2 H, J = 8.2
Hz), 7.55 (d, 2 H, J = 8.2 Hz), 3.66 (s, 2 H), 2.62 (q, 4 H, J = 7.2
Hz), 1.11 (t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 191.2, 135.1, 132.1, 129.5, 129.3,
88.9, 84.2, 47.3, 41.5, 12.4.
Synthesis 2005, No. 8, 1359–1367 © Thieme Stuttgart · New York

PAPER
Alkynylation of Aryl Bromides with Propargylamines
1363
Anal. Calcd for C14H17NO: C, 78.10; H, 7.96. Found: C, 77.99; H,
7.82.
3-(Diethylamino)-1-(4-fluorophenyl)propyne (10)
The reaction of 4-fluorobromobenzene (0.175 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 10 in 90%
(0.185 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.37 (dd, 2 H, J = 8.7, 5.5 Hz),
6.96 (t, 2 H, J = 8.7 Hz), 3.60 (s, 2 H), 2.60 (q, 4 H, J = 7.2 Hz), 1.09
(t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 162.2 (d, J = 248.6 Hz), 133.5 (d,
J = 8.3 Hz), 119.4 (d, J = 3.3 Hz), 115.4 (d, J = 21.9 Hz), 84.1, 83.8,
47.3, 41.4, 12.9.
4-[3-(Diethylamino)prop-1-ynyl]benzoic Acid Methyl Ester (5)
The reaction of methyl 4-bromobenzoate (0.215 g, 1 mmol) and
N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 5 in 90%
(0.221 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.92 (d, 2 H, J = 8.2 Hz), 7.42 (d,
2 H, J = 8.2 Hz), 3.86 (s, 3 H), 3.61 (s, 2 H), 2.58 (q, 4 H, J = 7.2
Hz), 1.07 (t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 166.4, 131.5, 129.3, 129.1, 128.0,
87.8, 84.2, 52.0, 47.2, 41.4, 12.5.
Anal. Calcd for C13H16FN: C, 76.06; H, 7.86. Found: C, 75.87; H,
7.99.
Anal. Calcd for C15H19NO2: C, 73.44; H, 7.81. Found: C, 73.57; H,
7.97.
3-(Diethylamino)-1-(p-tolyl)propyne (11)11
The reaction of 4-bromotoluene (0.171 g, 1 mmol) and N,N-dieth-
ylpropargylamine (0.222 g, 2 mmol) afforded 11 in 90% (0.181 g)
yield.
1H NMR (300 MHz, CDCl3): d = 7.29 (d, 2 H, J = 8.1 Hz), 7.08 (d,
2 H, J = 8.1 Hz), 3.60 (s, 2 H), 2.60 (q, 4 H, J = 7.2 Hz), 2.31 (s, 3
H), 1.09 (t, 6 H, J = 7.2 Hz).
3-(Diethylamino)-1-(4-trifluoromethylphenyl)propyne (6)
The reaction of 4-trifluoromethylbromobenzene (0.225 g, 1 mmol)
and N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 6 in
93% (0.237 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.52 (d, 2 H, J = 8.7 Hz), 7.47 (d,
2 H, J = 8.7 Hz), 3.62 (s, 2 H), 2.59 (q, 4 H, J = 7.2 Hz), 1.08 (t, 6
H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 131.8, 129.4 (q, J = 32.4 Hz),
127.0, 125.0 (q, J = 3.9 Hz), 123.8 (q, J = 272.2 Hz), 87.1, 83.7,
47.3, 41.4, 12.4.
1-(4-t-Butylphenyl)-3-(diethylamino)propyne (12)
The reaction of 4-t-butylbromobenzene (0.213 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 12 in 95%
(0.231 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.34 (d, 2 H, J = 8.3 Hz), 6.31 (d,
2 H, J = 8.3 Hz), 3.62 (s, 2 H), 2.61 (q, 4 H, J = 7.2 Hz), 1.29 (s, 9
H), 1.10 (t, 6 H, J = 7.2 Hz).
Anal. Calcd for C14H16F3N: C, 65.87; H, 6.32. Found: C, 65.74; H,
6.43.
1-(4-Cyanophenyl)-3-(diethylamino)propyne (7)
The reaction of 4-bromobenzonitrile (0.182 g, 1 mmol) and N,N-di-
ethylpropargylamine (0.222 g, 2 mmol) afforded 7 in 93% (0.197 g)
yield.
1H NMR (300 MHz, CDCl3): d = 7.55 (d, 2 H, J = 8.4 Hz), 7.46 (d,
2 H, J = 8.4 Hz), 3.64 (s, 2 H), 2.60 (q, 4 H, J = 7.2 Hz), 1.09 (t, 6
H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 151.0, 131.3, 125.1, 120.1, 85.0,
83.2, 47.2, 41.3, 31.3, 31.0, 12.4.
Anal. Calcd for C17H25N: C, 83.89; H, 10.35. Found: C, 83.74; H,
10.21.
1-(p-Anisyl)-3-(diethylamino)propyne (13)11
The reaction of 4-bromoanisole (0.187 g, 1 mmol) and N,N-diethyl-
propargylamine (0.222 g, 2 mmol) afforded 13 in 87% (0.189 g)
yield.
1H NMR (300 MHz, CDCl3): d = 7.24 (d, 2 H, J = 8.7 Hz), 6.71 (d,
2 H, J = 8.7 Hz), 3.69 (s, 3 H), 3.51 (s, 2 H), 2.52 (q, 4 H, J = 7.2
Hz), 1.00 (t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 131.8, 131.5, 127.8, 118.0, 110.8,
89.0, 83.3, 47.0, 41.2, 12.1.
Anal. Calcd for C14H16N2: C, 79.21; H, 7.60. Found: C, 79.00; H,
7.68.
3-(Diethylamino)-1-(4-nitrophenyl)propyne (8)1
The reaction of 4-bromonitrobenzene (0.202 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 8 in 89% (0.207
g) yield.
1H NMR (300 MHz, CDCl3): d = 8.14 (d, 2 H, J = 8.5 Hz), 7.52 (d,
2 H, J = 8.5 Hz), 3.66 (s, 2 H), 2.61 (q, 4 H, J = 7.2 Hz), 1.10 (t, 6
H, J = 7.2 Hz).
3-(Diethylamino)-1-(4-dimethylaminophenyl)propyne (14)
The reaction of 4-bromo-N,N-dimethylaniline (0.200 g, 1 mmol)
and N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 14 in
84% (0.194 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.28 (d, 2 H, J = 8.8 Hz), 6.59 (d,
2 H, J = 8.8 Hz), 3.60 (s, 2 H), 2.93 (s, 6 H), 2.61 (q, 4 H, J = 7.2
Hz), 1.09 (t, 6 H, J = 7.2 Hz).
1-[3,5-Bis(trifluoromethyl)phenyl]-3-(diethylamino)propyne
(9)
13C NMR (75 MHz, CDCl3): d = 149.7, 132.4, 111.5, 109.9, 85.7,
80.9, 47.0, 41.3, 40.0, 12.2.
The reaction of 3,5-bis(trifluoromethyl)bromobenzene (0.293 g, 1
mmol) and N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded
9 in 91% (0.294 g) yield.
Anal. Calcd for C15H22N2: C, 78.21; H, 9.63. Found: C, 78.40; H,
9.51.
1H NMR (300 MHz, CDCl3): d = 7.81 (s, 2 H), 7.75 (s, 1 H), 3.64
(s, 2 H), 2.61 (q, 4 H, J = 7.2 Hz), 1.10 (t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 131.6 (q, J = 33.4 Hz), 131.4,
125.5, 122.5 (q, J = 272.8 Hz), 121.1 (m), 88.5, 82.1, 47.3, 41.3,
12.4.
3-(Diethylamino)-1-(3-trifluoromethylphenyl)propyne (15)12
The reaction of 3-trifluoromethylbromobenzene (0.225 g, 1 mmol)
and N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 15 in
92% (0.235 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.66 (s, 1 H), 7.57 (d, 1 H, J = 7.7
Hz), 7.52 (d, 1 H, J = 7.7 Hz), 7.40 (t, 1 H, J = 7.7 Hz), 3.64 (s, 2
H), 2.61 (q, 4 H, J = 7.2 Hz), 1.11 (t, 6 H, J = 7.2 Hz).
Anal. Calcd for C15H15F6N: C, 55.73; H, 4.68. Found: C, 55.91; H,
4.87.
Synthesis 2005, No. 8, 1359–1367 © Thieme Stuttgart · New York

1364
M. Lemhadri et al.
PAPER
3-(Diethylamino)-1-(6-methoxynaphthalen-2-yl)propyne (16)
The reaction of 2-bromo-6-methoxynaphthalene (0.237 g, 1 mmol)
and N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 16 in
94% (0.251 g) yield.
3-(Diethylamino)-1-(2-nitrophenyl)propyne (21)13
The reaction of 2-bromonitrobenzene (0.202 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 21 in 88%
(0.204 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.85 (s, 1 H), 7.65 (d, 1 H, J = 7.3
Hz), 7.63 (d, 1 H, J = 7.3 Hz), 7.43 (dd, 1 H, J = 8.5, 1.5 Hz), 7.13
(dd, 1 H, J = 8.5, 2.4 Hz), 7.06 (d, 1 H, J = 2.4 Hz), 3.88 (s, 3 H),
3.68 (s, 2 H), 2.66 (q, 4 H, J = 7.2 Hz), 1.14 (t, 6 H, J = 7.2 Hz).
1H NMR (300 MHz, CDCl3): d = 7.97 (d, 1 H, J = 8.0 Hz), 7.58 (d,
1 H, J = 7.7 Hz), 7.51 (t, 1 H, J = 7.7 Hz), 7.40 (t, 1 H, J = 7.6 Hz),
3.69 (s, 2 H), 2.63 (q, 4 H, J = 7.2 Hz), 1.09 (t, 6 H, J = 7.2 Hz).
3-(Diethylamino)-1-(2-fluorophenyl)propyne (22)
The reaction of 2-fluorobromobenzene (0.175 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 22 in 93%
(0.191 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.40 (t, 1 H, J = 7.5 Hz), 7.25 (m,
1 H), 7.05 (m, 2 H), 3.68 (s, 2 H), 2.63 (q, 4 H, J = 7.2 Hz), 1.11 (t,
6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 162.4 (d, J = 250.8 Hz), 133.3,
129.3 (d, J = 8.2 Hz), 123.6 (d, J = 3.9 Hz), 115.1 (d, J = 20.8 Hz),
111.5 (d, J = 15.9 Hz), 89.5 (d, J = 3.3 Hz), 78.1, 47.1, 41.3, 12.4.
13C NMR (75 MHz, CDCl3): d = 157.9, 133.6, 130.8, 128.9, 128.8,
128.1, 126.4, 119.0, 117.9, 105.4, 85.2, 83.5, 55.0, 47.0, 41.2, 12.3.
Anal. Calcd for C18H21NO: C, 80.86; H, 7.92. Found: C, 80.97; H,
7.80.
1-(2-Acetylphenyl)-3-(diethylamino)propyne (17)
The reaction of 2-bromoacetophenone (0.199 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 17 in 90%
(0.206 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.64 (d, 1 H, J = 7.8 Hz), 7.50 (d,
1 H, J = 7.8 Hz), 7.45–7.30 (m, 2 H), 3.68 (s, 2 H), 2.61 (q, 4 H,
J = 7.2 Hz), 1.09 (t, 6 H, J = 7.2 Hz).
Anal. Calcd for C13H16FN: C, 76.06; H, 7.86. Found: C, 76.21; H,
8.04.
13C NMR (75 MHz, CDCl3): d = 200.3, 140.8, 134.2, 130.9, 128.2,
3-(Diethylamino)-1-(naphthalen-1-yl)propyne (23)14
The reaction of 1-bromonaphthalene (0.207 g, 1 mmol) and N,N-di-
ethylpropargylamine (0.222 g, 2 mmol) afforded 23 in 94% (0.223
g) yield.
127.8, 121.4, 90.6, 83.8, 47.3, 41.5, 29.7, 12.5.
Anal. Calcd for C15H19NO: C, 78.56; H, 8.35. Found: C, 78.40; H,
8.41.
1H NMR (300 MHz, CDCl3): d = 8.34 (d, 1 H, J = 8.5 Hz), 7.83 (d,
1 H, J = 7.9 Hz), 7.79 (d, 1 H, J = 8.4 Hz), 7.66 (d, 1 H, J = 8.3 Hz),
7.56 (t, 1 H, J = 7.5 Hz), 7.52 (t, 1 H, J = 7.5 Hz), 7.40 (t, 1 H,
J = 7.4 Hz), 3.83 (s, 2 H), 2.73 (q, 4 H, J = 7.2 Hz), 1.18 (t, 6 H,
J = 7.2 Hz).
3-(Diethylamino)-1-(2-formylphenyl)propyne (18)
The reaction of 2-bromobenzaldehyde (0.185 g, 1 mmol) and N,N-
diethylpropargylamine (0.222 g, 2 mmol) afforded 18 in 88%
(0.190 g) yield.
1H NMR (300 MHz, CDCl3): d = 10.54 (s, 1 H), 7.89 (d, 1 H, J = 7.8
Hz), 7.52 (m, 2 H), 7.40 (m, 1 H), 3.71 (s, 2 H), 2.62 (q, 4 H, J = 7.2
Hz), 1.11 (t, 6 H, J = 7.2 Hz).
1-(o-Anisyl)-3-(diethylamino)propyne (24)
The reaction of 2-bromoanisole (0.187 g, 1 mmol) and N,N-diethyl-
propargylamine (0.222 g, 2 mmol) afforded 24 in 90% (0.196 g)
yield.
13C NMR (75 MHz, CDCl3): d = 191.3, 135.6, 133.5, 133.3, 128.1,
126.7, 126.6, 91.9, 80.4, 47.2, 41.3, 12.4.
1H NMR (300 MHz, CDCl3): d = 7.36 (dd, 1 H, J = 7.4, 1.9 Hz),
7.22 (td, 1 H, J = 7.5, 1.9 Hz), 6.84 (td, 1 H, J = 7.5, 1.9 Hz), 6.82
(d, 1 H, J = 7.5 Hz), 3.83 (s, 3 H), 3.67 (s, 2 H), 2.61 (q, 4 H, J = 7.2
Hz), 1.09 (t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 159.7, 133.2, 129.0, 120.0, 112.2,
110.4, 88.0, 81.0, 55.4, 47.0, 41.4, 12.3.
Anal. Calcd for C14H17NO: C, 78.10; H, 7.96. Found: C, 78.34; H,
7.77.
3-(Diethylamino)-1-(2-trifluoromethylphenyl)propyne (19)
The reaction of 2-trifluoromethylbromobenzene (0.225 g, 1 mmol)
and N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 19 in
93% (0.237 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.62 (d, 1 H, J = 8.0 Hz), 7.55 (d,
1 H, J = 7.8 Hz), 7.45 (t, 1 H, J = 7.6 Hz), 7.36 (t, 1 H, J = 7.6 Hz),
3.69 (s, 2 H), 2.62 (q, 4 H, J = 7.2 Hz), 1.10 (t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 134.1, 131.2, 131.3 (q, J = 30.2
Hz), 127.6, 125.5 (q, J = 4.9 Hz), 123.2 (q, J = 273.4 Hz), 121.3 (q,
J = 2.1 Hz), 90.4, 81.0, 47.2, 41.1, 12.4.
Anal. Calcd for C14H19NO: C, 77.38; H, 8.81. Found: C, 77.21; H,
8.94.
3-(Diethylamino)-1-(2,6-difluorophenyl)propyne (25)
The reaction of 2,6-difluorobromobenzene (0.193 g, 1 mmol) and
N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 25 in 91%
(0.203 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.20 (m, 1 H), 6.86 (m, 2 H), 3.70
(s, 2 H), 2.61 (q, 4 H, J = 7.2 Hz), 1.09 (t, 6 H, J = 7.2 Hz).
Anal. Calcd for C14H16F3N: C, 65.87; H, 6.32. Found: C, 65.61; H,
6.18.
13C NMR (75 MHz, CDCl3): d = 162.6 (d, J = 253.1 Hz), 129.1 (t,
J = 9.8 Hz), 110.0 (d, J = 24.7 Hz), 102.1 (t, J = 19.7 Hz), 94.8 (t,
J = 3.2 Hz), 71.7, 47.2, 41.4, 12.5.
1-(2-Cyanophenyl)-3-(diethylamino)propyne (20)
The reaction of 2-bromobenzonitrile (0.182 g, 1 mmol) and N,N-di-
ethylpropargylamine (0.222 g, 2 mmol) afforded 20 in 89% (0.189
g) yield.
1H NMR (300 MHz, CDCl3): d = 7.51 (d, 1 H, J = 7.5 Hz), 7.42 (m,
2 H), 7.28 (m, 1 H), 3.64 (s, 2 H), 2.58 (q, 4 H, J = 7.2 Hz), 1.02 (t,
6 H, J = 7.2 Hz).
Anal. Calcd for C13H15F2N: C, 69.94; H, 6.77. Found: C, 70.12; H,
6.84.
1-(Anthracen-9-yl)-3-(diethylamino)propyne (26)
The reaction of 9-bromoanthracene (0.257 g, 1 mmol) and N,N-di-
ethylpropargylamine (0.222 g, 2 mmol) afforded 26 in 87% (0.250
g) yield.
13C NMR (75 MHz, CDCl3): d = 132.3, 132.1, 132.1, 127.9, 126.9,
117.4, 115.0, 91.2, 81.2, 47.2, 41.2, 12.4.
1H NMR (300 MHz, CDCl3): d = 8.55 (d, 2 H, J = 8.7 Hz), 8.39 (s,
1 H), 7.99 (d, 2 H, J = 8.7 Hz), 7.55 (t, 2 H, J = 7.0 Hz), 7.50 (t, 2
Anal. Calcd for C14H16N2: C, 79.21; H, 7.60. Found: C, 78.97; H,
7.51.
Synthesis 2005, No. 8, 1359–1367 © Thieme Stuttgart · New York

PAPER
Alkynylation of Aryl Bromides with Propargylamines
1365
H, J = 7.0 Hz), 4.01 (s, 2 H), 2.80 (q, 4 H, J = 7.2 Hz), 1.23 (t, 6 H,
J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 132.7, 131.1, 128.6, 127.2, 126.7,
126.4, 125.5, 117.4, 95.6, 81.5, 47.6, 41.8, 12.8.
1-(4-tert-Butylphenyl)-3-(dipropylamino)propyne (33)
The reaction of 4-tert-butylbromobenzene (0.213 g, 1 mmol) and
N,N-dipropylpropargylamine (0.278 g, 2 mmol) afforded 33 in 94%
(0.255 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.34 (d, 2 H, J = 8.6 Hz), 7.29 (d,
2 H, J = 8.6 Hz), 3.58 (s, 2 H), 2.47 (t, 4 H, J = 7.2 Hz), 1.49 (m, 4
H), 1.27 (s, 9 H), 0.89 (t, 6 H, J = 7.2 Hz).
Anal. Calcd for C21H21N: C, 87.76; H, 7.36. Found: C, 87.56; H,
7.49.
3-(Diethylamino)-1-(2,4,6-trimethylphenyl)propyne (27)15
The reaction of 2,4,6-trimethylbromobenzene (0.199 g, 1 mmol)
and N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 27 in
80% (0.183 g) yield.
1H NMR (300 MHz, CDCl3): d = 6.83 (s, 2 H), 3.73 (s, 2 H), 2.62
(q, 4 H, J = 7.2 Hz), 2.36 (s, 6 H), 2.25 (s, 3 H), 1.11 (t, 6 H, J = 7.2
Hz).
13C NMR (75 MHz, CDCl3): d = 150.9, 131.3, 125.1, 120.3, 84.9,
83.9, 55.8, 42.7, 31.2, 31.0, 20.6, 11.8.
Anal. Calcd for C19H29N: C, 84.07; H, 10.77. Found: C, 84.27; H,
10.60.
3-(Dipropylamino)-1-(naphthalen-1-yl)propyne (34)
The reaction of 1-bromonaphthalene (0.207 g, 1 mmol) and N,N-
dipropylpropargylamine (0.278 g, 2 mmol) afforded 34 in 91%
(0.242 g) yield.
1H NMR (300 MHz, CDCl3): d = 8.35 (d, 1 H, J = 8.5 Hz,), 7.83 (d,
1 H, J = 7.9 Hz), 7.79 (d, 1 H, J = 8.4 Hz), 7.66 (d, 1 H, J = 8.3 Hz),
7.56 (t, 1 H, J = 7.5 Hz), 7.52 (t, 1 H, J = 7.5 Hz), 7.39 (t, 1 H,
J = 7.4 Hz), 3.78 (s, 2 H), 2.60 (t, 4 H, J = 7.2 Hz), 1.58 (m, 4 H),
0.96 (t, 6 H, J = 7.2 Hz).
3-(Diethylamino)-1-(2,4,6-triisopropylphenyl)propyne (28)
The reaction of 2,4,6-triisopropylbromobenzene (0.283 g, 1 mmol)
and N,N-diethylpropargylamine (0.222 g, 2 mmol) afforded 28 in
78% (0.245 g) yield.
1H NMR (300 MHz, CDCl3): d = 6.95 (s, 2 H), 3.75 (s, 2 H), 3.50
(septet, 2 H, J = 7.0 Hz), 2.85 (septet, 1 H, J = 7.0 Hz), 2.62 (q, 4 H,
J = 7.2 Hz), 1.24 (d, 18 H, J = 7.0 Hz), 1.12 (t, 6 H, J = 7.2 Hz).
13C NMR (75 MHz, CDCl3): d = 133.3, 133.1, 130.3, 128.2, 128.1,
126.5, 126.2, 126.1, 125.1, 121.1, 89.7, 82.9, 56.0, 42.9, 20.8, 11.9.
13C NMR (75 MHz, CDCl3): d = 150.5, 148.6, 120.1, 118.6, 91.4,
81.9, 47.5, 41.3, 34.5, 31.7, 23.9, 23.7, 12.8.
Anal. Calcd for C19H23N: C, 85.99; H, 8.74. Found: C, 86.15; H,
8.86.
Anal. Calcd for C22H35N: C, 84.28; H, 11.25. Found: C, 84.41; H,
11.34.
3-(Dipropylamino)-1-(3-trifluoromethylphenyl)propyne (35)12
The reaction of 3-trifluoromethylbromobenzene (0.225 g, 1 mmol)
and N,N-dipropylpropargylamine (0.278 g, 2 mmol) afforded 35 in
92% (0.261 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.65 (s, 1 H), 7.56 (d, 1 H, J = 7.7
Hz), 7.52 (d, 1 H, J = 7.7 Hz), 7.40 (t, 1 H, J = 7.7 Hz), 3.60 (s, 2
H), 2.47 (t, 4 H, J = 7.2 Hz), 1.50 (m, 4 H), 0.91 (t, 6 H, J = 7.2 Hz).
3-(Diethylamino)-1-(pyridin-2-yl)propyne (29)1
The reaction of 2-bromopyridine (0.158 g, 1 mmol) and N,N-dieth-
ylpropargylamine (0.222 g, 2 mmol) afforded 29 in 89% (0.168 g)
yield.
1H NMR (300 MHz, CDCl3): d = 8.53 (d, 1 H, J = 4.5 Hz), 7.60 (td,
1 H, J = 7.7, 1.7 Hz), 7.37 (d, 1 H, J = 7.8 Hz), 7.18 (dd, 1 H,
J = 7.8, 4.5 Hz), 3.65 (s, 2 H), 2.61 (q, 4 H, J = 7.2 Hz), 1.08 (t, 6
H, J = 7.2 Hz).
3-(Benzylmethylamino)-1-(phenyl)propyne (36)17
The reaction of iodobenzene (0.204 g, 1 mmol) and N,N-benzyl-
methylpropargylamine (0.318 g, 2 mmol) afforded 36 in 88%
(0.207 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.50–7.25 (m, 9 H), 3.63 (s, 2 H),
2.50 (s, 2 H), 2.39 (s, 3 H).
3-(Diethylamino)-1-(pyridin-3-yl)propyne (30)16
The reaction of 3-bromopyridine (0.158 g, 1 mmol) and N,N-dieth-
ylpropargylamine (0.222 g, 2 mmol) afforded 30 in 92% (0.173 g)
yield.
1H NMR (300 MHz, CDCl3): d = 8.66 (m, 1 H), 8.54 (m, 1 H), 7.67
(d, 1 H, J = 7.7 Hz), 7.21 (m, 1 H), 3.62 (s, 2 H), 2.59 (q, 4 H, J = 7.2
Hz), 1.07 (t, 6 H, J = 7.2 Hz).
3-(Benzylmethylamino)-1-(4-trifluoromethylphenyl)propyne
(37)
The reaction of 4-trifluoromethylbromobenzene (0.225 g, 1 mmol)
and N,N-benzylmethylpropargylamine (0.318 g, 2 mmol) afforded
37 in 86% (0.261 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.60 (m, 4 H), 7.45–7.25 (m, 5 H),
3.68 (s, 2 H), 2.57 (s, 2 H), 2.46 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 138.3, 131.9, 129.8 (q, J = 32.4
Hz), 129.1, 128.3, 127.3, 127.1, 125.1 (q, J = 3.9 Hz), 123.9 (q,
J = 271.8 Hz), 87.3, 84.4, 60.3, 45.7, 42.0.
3-(Dipropylamino)-1-phenylpropyne (31)12
The reaction of iodobenzene (0.204 g, 1 mmol) and N,N-dipropyl-
propargylamine (0.278 g, 2 mmol) afforded 31 in 90% (0.194 g)
yield.
1H NMR (300 MHz, CDCl3): d = 7.33 (m, 2 H), 7.56 (m, 3 H), 3.52
(s, 2 H), 2.41 (t, 4 H, J = 7.2 Hz), 1.42 (m, 4 H), 0.83 (t, 6 H, J = 7.2
Hz).
Anal. Calcd for C18H16F3N: C, 71.28; H, 5.32. Found: C, 71.48; H,
5.32.
1-(4-Acetylphenyl)-3-(dipropylamino)propyne (32)
The reaction of 4-bromoacetophenone (0.199 g, 1 mmol) and N,N-
dipropylpropargylamine (0.278 g, 2 mmol) afforded 32 in 94%
(0.242 g) yield.
1H NMR (300 MHz, CDCl3): dEt2O= 7.83 (d, 2 H, J = 8.3 Hz), 7.44
(d, 2 H, J = 8.3 Hz), 3.58 (s, 2 H), 2.53 (s, 3 H), 2.44 (t, 4 H, J = 7.2
Hz), 1.46 (m, 4 H), 0.87 (t, 6 H, J = 7.2 Hz).
3-(Benzylmethylamino)-1-(4-tert-butylphenyl)propyne (38)
The reaction of 4-t-butylbromobenzene (0.213 g, 1 mmol) and N,N-
benzylmethylpropargylamine (0.318 g, 2 mmol) afforded 38 in 89%
(0.259 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.45–7.22 (m, 9 H), 3.64 (s, 2 H),
3.51 (s, 2 H), 2.40 (s, 3 H), 1.32 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 197.1, 135.8, 131.7, 128.3, 128.0,
88.7, 84.2, 55.8, 42.7, 26.4, 20.6, 11.8.
13C NMR (75 MHz, CDCl3): d = 151.2, 138.5, 131.4, 129.3, 128.3,
127.2, 125.3, 120.3, 85.7, 83.6, 60.2, 45.7, 41.9, 34.7, 31.2.
Anal. Calcd for C17H23NO: C, 79.33; H, 9.01. Found: C, 79.09; H,
8.87.
Synthesis 2005, No. 8, 1359–1367 © Thieme Stuttgart · New York

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M. Lemhadri et al.
PAPER
Anal. Calcd for C21H25N: C, 86.55; H, 8.65. Found: C, 86.40; H,
8.52.
7.55 (t, 1 H, J = 7.5 Hz), 7.49 (t, 1 H, J = 7.5 Hz), 7.40 (t, 1 H,
J = 7.4 Hz), 3.77 (s, 2 H), 2.62 (s, 3 H), 2.15 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 133.2, 133.1, 130.3, 128.4, 128.2,
1-(p-Anisyl)-3-(benzylmethylamino)propyne (39)
The reaction of 4-bromoanisole (0.187 g, 1 mmol) and N,N-benzyl-
methylpropargylamine (0.318 g, 2 mmol) afforded 39 in 90%
(0.239 g) yield.
126.6, 126.3, 126.1, 125.1, 120.8, 86.7, 81.3, 41.0, 35.4.
Anal. Calcd for C14H13N: C, 86.12; H, 6.71. Found: C, 86.33; H,
6.57.
1H NMR (300 MHz, CDCl3): d = 7.35–7.10 (m, 7 H), 6.73 (d, 2 H,
J = 8.5 Hz), 3.68 (s, 3 H), 3.53 (s, 2 H), 3.40 (s, 2 H), 2.29 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 159.3, 138.5, 133.0, 129.2, 128.2,
127.1, 115.4, 113.8, 85.4, 82.8, 60.2, 55.2, 45.8, 41.9.
3-Phenylprop-2-ynylamine (45)18
The reaction of iodobenzene (0.204 g, 1 mmol) and propargylamine
(0.110 g, 2 mmol) afforded 45 in 74% (0.097 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.28 (m, 2 H), 7.17 (m, 3 H), 3.52
(s, 2 H).
Anal. Calcd for C18H19NO: C, 81.47; H, 7.22. Found: C, 81.21; H,
7.01.
3-(p-Tolyl)prop-2-ynylamine (46)19
1-(Anthracen-9-yl)-3-(benzylmethylamino)propyne (40)
The reaction of 9-bromoanthracene (0.257 g, 1 mmol) and N,N-ben-
zylmethylpropargylamine (0.318 g, 2 mmol) afforded 40 in 84%
(0.282 g) yield.
1H NMR (300 MHz, CDCl3): d = 8.62 (d, 2 H, J = 8.6 Hz), 8.42 (s,
1 H), 8.01 (d, 2 H, J = 8.6 Hz), 7.70–7.20 (m, 9 H), 3.89 (s, 2 H),
3.84 (s, 2 H), 2.61 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 138.5, 132.7, 131.1, 129.3, 128.6,
128.4, 127.3, 127.2, 126.7, 126.5, 125.6, 117.5, 95.9, 82.3, 60.3,
46.3, 42.3.
The reaction of 4-bromotoluene (0.171 g, 1 mmol) and propargyl-
amine (0.110 g, 2 mmol) afforded 46 in 64% (0.093 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.27 (d, 2 H, J = 8.0 Hz), 7.07 (d,
2 H, J = 8.0 Hz), 3.60 (s, 2 H), 2.31 (s, 3 H).
3-(Naphthalen-1-yl)prop-2-ynylamine (47)
The reaction of 1-bromonaphthalene (0.207 g, 1 mmol) and propar-
gylamine (0.110 g, 2 mmol) afforded 47 in 67% (0.122 g) yield.
1H NMR (300 MHz, CDCl3): d = 8.31 (d, 1 H, J = 8.5 Hz), 7.82 (d,
1 H, J = 7.9 Hz), 7.78 (d, 1 H, J = 8.4 Hz), 7.63 (d, 1 H, J = 8.3 Hz),
7.55 (t, 1 H, J = 7.5 Hz), 7.49 (t, 1 H, J = 7.5 Hz), 7.39 (t, 1 H,
J = 7.4 Hz), 3.78 (s, 2 H), 1.68 (s, 2 H).
Anal. Calcd for C25H21N: C, 89.51; H, 6.31. Found: C, 89.71; H,
6.14.
13C NMR (75 MHz, CDCl3): d = 133.2, 133.1, 130.2, 128.4, 128.2,
126.6, 126.3, 126.0, 125.1, 120.8, 95.1, 80.4, 32.4.
3-(Methylamino)-1-(phenyl)propyne (41)4d
The reaction of iodobenzene (0.204 g, 1 mmol) and N-methylprop-
argylamine (0.138 g, 2 mmol) afforded 41 in 82% (0.119 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.30 (m, 2 H), 7.18 (m, 3 H), 3.49
(s, 2 H), 2.42 (s, 3 H).
Anal. Calcd for C13H11N: C, 86.15; H, 6.12. Found: C, 86.42; H,
5.97.
Acknowledgment
1-(4-tert-Butylphenyl)-3-(methylamino)propyne (42)
The reaction of 4-tert-butylbromobenzene (0.213 g, 1 mmol) and N-
methylpropargylamine (0.138 g, 2 mmol) afforded 42 in 84%
(0.169 g) yield.
1H NMR (300 MHz, CDCl3): d = 7.36 (d, 2 H, J = 8.5 Hz), 7.34 (d,
2 H, J = 8.5 Hz), 3.65 (s, 2 H), 2.56 (s, 3 H), 2.39 (s, 1 H), 1.29 (s,
9 H).
We thank the CNRS for providing financial support.
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