Vol. 26, No. 24 (2014)
Efficient and Green Synthesis of Aminoalkyl, Amidoalkyl and Diarylmethane Derivatives 8381
FT- IR (KBr, νmax, cm-1): 3046, 2975, 2898, 1621, 1478, 1265,
815 cm-1; 1H NMR (300 MHz, CDCl3, δ ppm): 2.65 (br s, 4
H), 3.78 (s, 4 H), 4.15 (s, 2 H), 7.09 (d, J = 8.7 Hz, 1H), 7.25-
7.32 (m, 1H), 7.42-7.47 (m, 1H), 7.68-7.83 (m, 3H).
carried out under solvent-free condition. To our delight, with
0.5 equivalents of anhydrous MgSO4 itself the transformation
was completed within 3 min in 98 % yield (Scheme-I).
O
General procedure for the synthesis of amido-
alkyl naphthol: To a stirred mixture of β-naphthol (1 mmol,
144 mg), anhydrous MgSO4 (2 mmol, 241 mg) and benzamide
(1.5 mmol, 181 mg) in a 5 mL round bottom flask, 1.2 mmol
of aldehyde was added and the mixture was further stirred
and heated in an oil bath at 90 °C for 5 h. After completion of
the reaction, the reaction mixture was quenched with 5 mL of
water, stirred and the aqueous layer was decanted. The gummy
residue was stirred with ethanol:water mixture (1:3 v/v, 20 mL),
filtered, washed with 5 mL of cold ethanol and dried.
R1
N
OH
morpholine
R1 = H
anhyd. MgSO4
OH
6
98% yield
R2
N
3 min, r.t.
R1CHO
R1
R2
5
R22NH
OH
anhyd. MgSO4
r.t. or 60 o
C
up to 97% yield
7-15
up to 3 h
R1 = H, Ph, 4-ClC6H4, 4-OMeC6H4
R22NH = morpholine, Me2NH, Et2NH, piperidine, BnNH2
;
N-[(2-Hydroxynaphthalen-1-yl)(4-nitrophenyl)methyl]-
benzamide (16): Yield = 342 mg (86 %); Yellowish white
crystals; m.p. 236-238 °C (Lit.17 233-235 °C); FT-IR (KBr,
Scheme-I: Anhydrous MgSO4 mediated aminoalkyl naphthol synthesis
With 0.2 equivalents of anhydrous MgSO4, the reaction
took 15 min to complete with a marginal decrease in the product
yield to 95 %. Increasing the quantity of anhydrous MgSO4 to
one equivalent reduced the reaction time to one minute with
98 % yield. Half equivalent of anhydrous MgSO4 was chosen
to carry out further transformations (Scheme-I, Table-1).
The aminoalkyl naphthols 6-8 synthesis in excellent yield
at room temperature could be attributed to the high reactivity
of formaldehyde (Scheme-I, Table-1, Entries 1, 2). With two
equivalents of anhydrous MgSO4, both 7 and 8 were obtained
within 1 h. This reaction was found to be general for aldehydes
with electron withdrawing (Table-1, Entries 3, 8) and electron
donating substituents (Table-1, Entry 9). Aromatic aldehydes
with electron withdrawing substituent gave better yield than
aldehydes with electron donating substituent (Table-1, Entry
8 vs 9). Anhydrous MgSO4 mediated aminoalkyl naphthol
synthesis was screened with various aliphatic cyclic and
acyclic amines (Table-1, Entries 1-9). Secondary amines gave
relatively better yield than that of primary amine (Table-1,
Entry 1-4 vs 5). Both cyclic and acyclic amines gave the
corresponding aminonaphthols in excellent yield (Table-1,
Entry 2, 6). It is of interest to extend this methodology to the
amidoalkyl naphthol and diarylmethane synthesis. After
screening several conditions, it was found that reaction carried
out at 90 °C gave the expected product in good yield (Scheme-
II). Interestingly, reactions carried out in solvents such as
ethanol, toluene and glycerol at 90 °C did not give expected
product.
ν
max, cm-1): 3408, 3260, 1643, 1517, 1347, 1057, 865, 810,
706 ; 1H NMR (300 MHz, DMSO-d6, δ ppm): 7.24 (d, J = 9.0
Hz, 1 H), 7.32 (t, J = 7.2 Hz, 1 H), 7.39 (d, J = 7.8 Hz, 1 H),
7.45-7.58 (m, 6 H), 7.82-7.91 (m, 4 H), 8.06 (d, J = 8.4 Hz, 1
H), 8.16 (d, J = 8.4 Hz, 2 H), 9.08 (d, J = 7.8 Hz, 1 H), 10.41
(br s, 1 H).
General procedure for the synthesis of diaryl-
methanes: To a stirred mixture of β-naphthol (1 mmol, 144
mg), anhydrous MgSO4 (1 mmol, 120 mg) in a 5 mL round
bottom flask, 2 mmol of formaldehyde (37 % soln.) and 1.2
mmol of N,N-dialkylaniline were subsequently added and the
mixture was further stirred at room temperature for 15 min.
After completion, the reaction mixture was quenched with
5 mL of water, stirred and the aqueous layer was decanted. To
the gummy solid, hexane (2 × 5 mL) was added and the product
was filtered and dried.
1-{[4-(Dimethylamino)phenyl]methyl}naphthalen-2-ol
(17): Yield = 247 mg (89 %); Brown solid; m.p. 129-131 °C
(Lit.18 127-130 °C); 1H NMR (300 MHz, CDCl3, δ ppm): 2.87
(s, 6 H), 4.34 (s, 2 H), 5.10 (br s, 1 H), 6.64 (d, J = 9.0 Hz,
2H), 7.06-7.25 (m, 3H), 7.29-7.35 (m, 1H), 7.41-7.47 (m, 1H),
7.68 (d, J = 8.7 Hz, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.96 (d, J =
8.4 Hz, 1H).
RESULTS AND DISCUSSION
Initially, anhydrous MgSO4 mediated representative
1-(morpholin-4-ylmethyl)naphthalen-2-ol 6 synthesis was
TABLE-1
ANHYDROUS MgSO4 MEDIATED AMINOALKYL NAPHTHOL SYNTHESISa
Entry
R1
H
R22NH
Et2NH
Product
Temp (oC)
Time (h)
Yieldb (%)
m.p. (oC)
-
Reported m.p. (oC)
-
1c
2c
3
7
r.t.
r.t.
60
60
r.t.
60
60
60
60
3
3
96
97
H
Me2NH
8
57-59
74-7519
4-ClC6H4
C6H5
Me2NH
9
3
75
128-130
162-164
141-142
174-176
197-199
127-129
124-125
128-1309
161-16220
14321
175-17715b
195-19620
130-13222
12623
4
Me2NH
10
11
12
13
14
15
3
85
66 (51)d
5
C6H5
BnNH2
3
6
C6H5
Morpholine
Piperidine
Morpholine
Morpholine
1.5
1.5
3
91
7
C6H5
85
8
4-ClC6H4
4-MeOC6H4
87
9
3
69
aTo a finely ground mixture of anhydrous MgSO4 (0.5 mmol) and β-naphthol (1 mmol), aldehyde (1.5 mmol) and amine (1.5 mmol) were added
and stirred. In entries 3 and 8, aldehyde was ground along with anhydrous MgSO4 and β-naphthol. bYields are for the isolated products. cWith 2
mmol of anhydrous MgSO4 the reaction completes within 1 h. dReaction was carried out at 60 oC for 3 h