Synthesis of Propargylic Amines and Ethers
J . Org. Chem., Vol. 64, No. 2, 1999 491
Ta ble 5. Rea ction s of
ethers by desilylation of compounds of type 23c and 24
is straightforward and would certainly find many ap-
plications.
(Ben zotr ia zol-1-yl)d ieth oxym eth a n e (22) w ith Sod iu m
Dia lk yn yld ieth yla lu m in a tes (Et2Al(CtCR)2Na ) in th e
P r esen ce of Zin c Iod id e
yield
R
AAA
conditionsa
product
(%)b
Exp er im en ta l Section
Ph
Ph
C5H11
(CH3)3Si
(CH3)3Si
5
5
11
12
12
A
B
A
A
B
23a
21j
23b
23c
24
95
85
89
90
75
Gen er al Com m en ts. Sodium diethyldihydroaluminate (Et2-
AlH2Na) was purchased from Aldrich. Benzotriazole deriva-
tives 13, 16a -j, and 20a -g were obtained by procedures
already described in the literature.7
P r ep a r a tion of Et2Al(CtCP h )2Na (5). Into a 150 mL
flask under nitrogen were introduced at room temperature a
solution of Et2AlH2Na in toluene (1.54 M, 19.4 mL, 30 mmol)
and toluene (33.9 mL). Phenylacetylene (6.7 mL, 61.5 mmol)
was added with vigorous stirring, which was continued for an
additional 3 h, until the evolution of hydrogen ceased. The
solution thus prepared was 0.5 M in alkynide 5.
P r ep a r a tion of Et2Al(CtCH)2Na (9). Into a 150 mL flask
under nitrogen were introduced at room temperature a solu-
tion of Et2AlH2Na in toluene (1.54 M, 19.4 mL, 30 mmol) and
toluene (40.6 mL). The solution was maintained at 0 °C, and
acetylene gas (99% purity) was introduced with vigorous
stirring. The solution was stirred for 40 min under a flow of
acetylene; then the solution was stirred at room temperature
for an additional 1 h. The solution thus prepared was 0.5 M
in alkynide 9.
a
Benzotriazole derivative 22 (2.0 mmol) was reacted for 1 h
with the appropriate aluminate (A, 2.2 mmol, 1.1 equiv; B, 4.0
mmol, 2.0 equiv) in the presence of zinc iodide (A, 2.0 mmol, 1.0
equiv; B, 8.0 mmol, 4.0 equiv) at room temperature (A) or under
b
reflux (B), both in toluene-ether (1:1). Isolated yields.
iodide (84%)3 and comparable to the reaction of 2-phe-
nylsulfonyltetrahydropyran with phenylethynylzinc
(97%).13,14
Gen er a l P r oced u r e for th e P r ep a r a tion of P r op a r gy-
la m in es 14a ,b a n d 17a -j. The alkynylation of 1-(N-methyl-
N-phenylaminomethyl)benzotriazole (13) is representative. To
a solution of aluminate 5 in toluene (0.5 M, 5.5 mmol, 11 mL)
was added a solution of 1-(N-methyl-N-phenylaminomethyl)-
benzotriazole (13) (0.5 M, 5 mmol, 10 mL) in toluene at room
temperature. After 3 h, the reaction mixture was hydrolyzed
with saturated NH4Cl (25 mL) and the product was extracted
with ethyl acetate (25 mL). The ethyl acetate layer was dried
over anhydrous MgSO4 and concentrated under reduced pres-
sure. The crude residue was subjected to column chromatog-
raphy on a silica gel column (eluent: hexanes/EtOAc, 95:5) to
give 1.01 g (91%) of N-methyl-N-phenyl-3-phenylpropyn-2-
ylamine (14a ): 1H NMR (CDCl3) δ 3.05 (s, 3 H), 4.27 (s, 2 H),
6.80-7.50 (m, 10 H); IR (neat) 3061, 2957, 2361, 1599, 1504;
GCMS m/z (relative intensity) (EI, 70 eV) 221 (M+, 95), 77 (16),
104 (14), 115 (100), 116 (11), 144 (20), 220 (88). Anal. Calcd
for C16H15N: C, 86.84; H, 6.83; N, 6.33. Found: C, 86.90; H,
6.92; N, 6.15.
Gen er a l P r oced u r e for th e Com p etitive Rea ction w ith
Et2Al(CtCP h )2Na (5). To a 0.5 M solution of aluminate 5
(1.5 mmol, 3 mL) in toluene at room temperature were added
a solution 0.5 M of 1-(N-methyl-N-phenylaminomethyl)ben-
zotriazole (13) and 1,2-decene oxide (18) (1 mmol, 2 mL) in
toluene. After 3 h, the reaction mixture was hydrolyzed with
saturated NH4Cl (5 mL), and ethyl acetate (5 mL) was added.
The organic layer was dried over anhydrous MgSO4. GC
analysis showed the formation of N-methyl-N-phenyl-3-phe-
nylpropyn-2-ylamine (14a ) (100% by GC), while 1,2-decene
oxide (18) remained unreacted.
Gen er a l P r oced u r e for th e P r ep a r a tion of P r op a r gylic
Eth er s 21a -k . The alkynylation of benzotriazolylmethyl octyl
ether (20a ) is representative. To a mixture of toluene (3.6 mL)
and ether (4.0 mL) at room temperature were added zinc iodide
(98% purity, 4.0 mmol, 1.28 g), a 0.5 M solution of Et2Al(Ct
CPh)2Na (2.2 mmol, 4.4 mL) in toluene, and a 0.25 M solution
of benzotriazolylmethyl octyl ether (2.0 mmol, 8.0 mL) in
toluene. After 1 h, the reaction mixture was hydrolyzed with
saturated NH4Cl (25 mL) and the product was extracted with
ethyl acetate (25 mL). The organic layer was dried over
anhydrous MgSO4 and concentrated under reduced pressure.
The crude residue was subjected to column chromatography
on a silica gel column (eluent: hexanes/EtOAc, 99:1) to give
0.472 g (97%) of phenylpropargyl octyl ether (21a ): 1H NMR
(CDCl3) δ 0.85-0.88 (m, 3 H), 1.28-1.64 (m, 12 H), 3.58 (t, 2
H, J ) 6.6 Hz), 4.36 (s, 2 H), 7.30-7.47 (m, 5 H); IR (neat)
3059, 2928, 2235, 1099; GCMS m/z (relative intensity) (EI, 70
An interesting example is represented by the alkyny-
lation of (benzotriazol-1-yl)diethoxymethane (22) with
sodium dialkynyldiethylaluminates 5, 11, and 12 in the
presence of zinc iodide under two different reaction
conditions, marked A and B in Table 5.
(i) Under conditions A, the benzotriazole derivative 22
was treated with 1.1 equiv of the appropriate aluminate
and 1 equiv of zinc iodide at room temperature, to afford
propargylic aldehyde acetals 23a -c as unique com-
pounds (89-95%).
(ii) Under conditions B, the benzotriazole derivative
22 was heated at reflux with 2 equiv of the appropriate
aluminate and 4 equiv of zinc iodide to give derivatives
21j and 24 in 85% and 75% yields, respectively.
In conclusion, the use of sodium dialkynyldiethylalu-
minates as alkynylating reagents in the reaction with
benzotriazole derivatives is a good alternative to the
classical methods and not only displays good yields and
selectivity in the synthesis of propargylic amines and
ethers but also shows an excellent chemoselectivity when
other functional groups such as epoxides, halides, esters,
and nitriles are present. Propargyl aldehyde acetals
23a -c obtained from (benzotriazol-1-yl)diethoxymethane
(22) are useful starting materials for the generation of
R,â-unsaturated ethers, γ-lactones, pyrroles, and func-
tionalized alkynyl ketones via various propargyl ethyl
ether intermediates.15-17 Since this benzotriazole deriva-
tive is readily available, the synthesis of propargylalkyl
(13) Brown, D. S.; Bruno, M.; Davenport, R. J .; Ley, S. V. Tetrahe-
dron 1989, 45, 4293.
(14) Ley, S. V.; Lygo, B.; Sternfeld, F.; Wonnacott, A. Tetrahedron
1986, 42, 4333.
(15) Carlson, R. M.; Isidor, J . L. Tetrahedron Lett. 1973, 14, 4819.
(16) Katritzky, A. R.; Lang, H. J . Org. Chem. 1995, 60, 7612.
(17) Katritzky, A. R.; Feng, D.; Lang, H. J . Org. Chem. 1997, 62,
715.