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Me3SiCl and Et3SiI-promoted one-pot synthesis of 1 4-dihydropyridine derivatives.

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Full Paper
Received: 28 December 2008
Revised: 6 April 2009
Accepted: 6 April 2009
Published online in Wiley Interscience: 20 May 2009
(www.interscience.com) DOI 10.1002/aoc.1509
Me3SiCl and Et3SiI-promoted one-pot synthesis
of 1,4-dihydropyridine derivatives
Maryam Mirza-Aghayana∗ , Mahboubeh Khoshkameh Langrodia ,
Mahshid Rahimifarda and Rabah Boukherroubb
An efficient synthesis of 1,4-dihydropyridine derivatives has been achieved by the one-pot cyclocondensation reaction of
methyl 3-aminocrotonate and a range of aldehydes in the presence of chlorotrimethylsilane as a promoter under solvent-free
conditions. The cyclocondenstion reaction requires a very short time and takes place in good to excellent yields. Furthermore
iodotriethylsilane, generated in situ by the reaction of triethylsilane and methyl iodide in the presence of palladium chloride,
has been investigated for the synthesis of 1,4-dihydropyridine derivatives. This facile and efficient method affords high yields
c 2009 John Wiley &
for the preparation of 1,4-dihydropyridines at room temperature and short reaction times. Copyright Sons, Ltd.
Keywords: 1,4-dihydropyridine derivatives; Hantzsch reaction; solvent-free conditions; chlorotrimethylsilane; iodotriethylsilane
Introduction
Appl. Organometal. Chem. 2009 , 23, 267–271
Results and Discussion
Synthesis of 1,4-Dihydropyridine Derivatives using TMSCl
as a Promoter
The reaction of 1 equiv. of benzaldehyde 1a and 4 equiv.
of methyl 3-aminocrotonate in the presence of 1 equiv. of
chlorotrimethylsilane in the absence of solvent at 80 ◦ C afforded
the corresponding 1,4-dihydropyridine 2a in 75% yield after 2 min
reaction (Scheme 1, method i).
In a similar fashion, various aldehydes reacted smoothly with
methyl 3-aminocrotonate under similar reaction conditions to give
the corresponding 1,4-DHP derivatives after 2–10 min in 75–96%
yield. The results are summarized in Table 1.
It should be noted that the yield in the absence of TMSCl is low
and the reaction time is much longer. For example, the reaction
of 1 equiv. of 4-nitrobenzaldehyde or 3-nitrobenzaldehyde with 4
∗
Correspondence to: Maryam Mirza-Aghayan, Chemistry and Chemical Engineering Research Center of Iran, PO Box 14335-186, Tehran, Iran.
E-mail: m.mirzaaghayan@ccerci.ac.ir
a Chemistry and Chemical Engineering Research Center of Iran (CCERCI), P. Box
14335-186, Tehran, Iran
b Institut de Recherche Interdisciplinaire (IRI, USR 3078) and Institut
d’Electronique, de Microélectronique et de Nanotechnologie (IEMN, UMR 8520),
Cité Scientifique, Avenue Poincaré – B.P 60069, 59652 Villeneuve d’Ascq, France
c 2009 John Wiley & Sons, Ltd.
Copyright 267
Multicomponent one-pot synthetic protocols such as the
Hantzsch[1] reaction and their products 1,4-dihydropyridines
(DHPs) have attracted immense attention from synthetic chemists
due to their pharmacological properties.[2] DHP derivatives display prominent biological activities such as Ca2+ channel blockers
and as drugs for the treatment of cardiovascular diseases and
hypertension.[3] The dihydropyrimidine skeleton is common in
many vasodialator, bronchiodialator, antiatheroscletoric, antitumor, hepatoprotective and antidiabetic agents.[4] They are also
known as neuroprotectants and for the antiplatelet treatment of
aggregators, and are important in Alzheimer’s disease as antiischemic agents.[5] Hantzsch synthesis is commonly carried out in
acetic acid or refluxing alcohol for a long time with low yields.[1] Alternative strategies for their synthesis involving different catalysts
and conditions have been developed.[6] However, many of these
methodologies have been associated with problems, such as long
reaction times, expensive reagents, harsh conditions, low product
yields and occurrence of several side products. Therefore, the development of an efficient and versatile method for the preparation
of 1,4-dihydropyridines provides scope for further improvement
towards milder reaction conditions and higher yields.
In our previous studies, we have investigated the system
Et3 SiH–palladium catalyst for various chemical transformations
under mild conditions. It was successfully applied for the
conversion of organic halides to the corresponding alkanes,[7] and
for the conversion of alcohols to their corresponding halides and
alkanes,[8] and also for the hydrogenation of 1-alkenes under mild
conditions.[9] The versatility of the system Et3 SiH–PdCl2 was also
demonstrated for the reduction of olefins and aromatic carbonyl
compounds to the corresponding alkanes,[10,11] conversion of
alcohols to their corresponding silyl ethers and cleavage of
triethylsilyl ethers to the parent alcohols,[12] and for the efficient
isomerization of 1-alkenes to 2- and 3-alkenes.[13]
In continuation of our investigations in organic reactions in
solvent-less systems[14] and the Biginelli condensation,[15] we
report a novel and efficient one-pot method for the synthesis
of 1,4-dihydropyridines using chlorotrimethylsilane (TMSCl) as a
promoter under mild and solvent-free conditions. The second
aspect of this work consists on extension of our previous
work on the exploitation of Et3 SiH–PdCl2 system for chemical
transformations. We have investigated the Et3 SiH–PdCl2 –CH3 I
system for the in situ generation of iodotriethylsilane (Et3 SiI)
and tested its efficiency for promoting the synthesis of 1,4dihydropyridine derivatives under mild conditions at room
temperature.
M. Mirza-Aghayan et al.
Scheme 1. TMSCl and Et3 SiI-promoted synthesis of 1,4-dihydropyridine derivatives.
Table 1. Synthesis of 1,4-dihydropyridine derivatives
m.p. (◦ C)
Entry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
R
Producta
Time (min)
Yield (%)b,c
Found
Reported
C6 H5
4-NO2 C6 H4
3-NO2 C6 H4
4-OMeC6 H4
3-OMeC6 H4
4-OHC6 H4
3-OHC6 H4
4-ClC6 H4
4-BrC6 H4
4-MeC6 H4
2-C4 H3 S
2-C4 H3 O
(CH3 )2 CHCH2
n-C7 H15
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2
2
10
2
2
2
2
2
5
5
2
2
10
10
75 (84)
86 (80)
95 (70)
83 (78)
80 (82)
82 (80)
87 (65)
75 (80)
76 (81)
75 (92)
96 (95)
93 (90)
93 (90)
90 (83)
196–198
198–200
210–212
186–188
173–175
225–227
230–232
196–198
200–202
174–176
195–197
191–193
124–126
80–82
196–198[6k,16]
198–200[6k,17]
210–212[6k,18]
186–188[6k,19]
168–170[19]
230–232[6k]
–
196–198[6k,20]
–
174–176[6k,21]
–
192–194[6k]
122–124[6k]
–
a
All products were characterized by 1 H NMR and mass spectrometry.
Isolated yields using TMSCl as a promoter, under mild and solvent-free conditions at 80 ◦ C; aldehyde–methyl 3-aminocrotonate (1 : 4 mmol).
c The number in parentheses shows the isolated yield using CH I–Et SiH–PdCl system after 2 h at room temperature; aldehyde–methyl
3
3
2
3-aminocrotonate (1 : 2 mmol).
b
268
equiv. of methyl 3-aminocrotonate at 80 ◦ C yielded 55% and 70% of
2b and 2c after 30 and 45 min, respectively. Increasing the amount
of TMSCl in the reaction mixture increases the conversion yield.
For example, the reaction of 1 equiv. of 4-nitrobenzaldehyde,
3-nitrobenzaldehyde or thiophene-2-carbaldehyde in the presence of 4 equiv. of methyl 3-aminocrotonate with 0.5 equiv. of
TMSCl at 80 ◦ C yielded 70, 65 and 75% of 2b, 2c and 2k after 2, 2 and
10 min, respectively. Good yields were obtained when 1 equiv. of
TMSCl was added to the reaction mixture. Under these experimental conditions, the reaction of 4 equiv. of methyl 3-aminocrotonate
with 1 equiv. of 4-nitrobenzaldehyde, 3-nitrobenzaldehyde or
thiophene-2-carbaldehyde and 1 equiv. of TMSCl yielded 86, 95
and 96% of 2b, 2c and 2k after 2, 10 and 2 min, respectively.
The addition of TMSCl accelerated the reaction and gave good
results. When the reaction of 1 equiv. of 4-nitrobenzaldehyde
1b was carried out with 4 equiv. of methyl-3-aminocrotonate
in the presence of 0.1 equiv. of TMSCl, the yield was low. The
product 2b was obtained in 50% after 10 min reaction at 80 ◦ C, as
compared with 86% obtained with 1 equiv. of TMSCl after 2 min.
On the other hand, we performed the reaction of 1 equiv. of
4-nitrobenzaldehyde 1b and 4 equiv. of methy 3-aminocrotonate
in the presence of 1 equiv. of methoxytrimethylsilane (Me3 SiOMe).
After 2 min reaction at 80 ◦ C, the product 2b was obtained in 47%
www.interscience.wiley.com/journal/aoc
while under similar conditions the use of 1 equiv. of TMSCl led to
the formation of 2b in 86%.
Synthesis of 1,4-Dihydropyridines using Et3 SiH–CH3 I–PdCl2
System
In earlier studies on the reduction of alkyl bromides and iodides
with Et3 SiH–PdCl2 , we observed the formation of small amounts
of Et3 SiCl and molecular hydrogen along with bromotriethylsilane
and iodotriethylsilane, respectively.[7] Based on this observation,
we investigated palladium dichloride –Et3 SiH–CH3 I system for the
in situ generation of Et3 SiI and the latter was used for the synthesis
of 1,4-dihydropyridine derivatives under mild conditions at room
temperature.
The addition of 1 equiv. of the aldehyde 1a–n and 2 equiv.
of methyl 3-aminocrotonate in the reaction mixture containing
methyliodide –Et3 SiH–PdCl2 in 1 : 1.2 : 10% ratio in acetonitrile
as solvent at room temperature afforded the corresponding
1,4-dihydropyridine derivatives 2a–n in 65–95% yield after 2 h
reaction at room temperature (Scheme 1, method ii). The results
are summarized in Table 1. The obtained results clearly indicate
that the reaction of both electron-rich and electron-deficient
aldehydes as well as heterocyclic ones such as thiophene-2-
c 2009 John Wiley & Sons, Ltd.
Copyright Appl. Organometal. Chem. 2009, 23, 267–271
Me3 SiCl and Et3 SiI-promoted one-pot synthesis of 1,4-dihydropyridine derivatives
carboxaldehyde and furfural takes place in high yields. Similarly,
the Hantzsch reaction can be effectively performed with aliphatic
aldehydes in high yields with the promotion of Me3 SiCl or Et3 SiI
(entries 13 and 14).
Although the role of TMSCl and Et3 SiI promoters is not
completely understood, two plausible scenarios may account
for the reaction mechanism: (i) activation of the carbonyl group;
and (ii) generation of HX (X = Cl, I) upon hydrolysis. It is well
documented that both protic and Lewis acids promote the onepot cyclocondensation of methy 3-aminocrotonate with various
aldehydes. In this respect, halogenosilanes display a strong Lewis
acid character, which may activate the carbonyl group[22] and
would explain the low efficiency of Me3 SiOMe to promote the
cyclocondensation reaction. On the other hand, the mechanism
of the Hantzsch dihydropyridine synthesis can be visualized as
proceeding through a Knoevenagel condensation product as a
key intermediate. In this situation, water molecules are generated.
The latter will react with Me3 SiCl or Et3 SiI to generate HCl or HI,
respectively known to promote the reaction effectively.
In conclusion, we have developed a novel method using TMSCl,
a cheap and easily available promoter for the synthesis of several
1,4-dihydropyridine derivatives. This protocol is advantageous:
the reaction is carried out at 80 ◦ C in high yields under solvent-free
conditions and very short reaction times. It should be noted that
the absence of solvent in these reactions is beneficial from an
environmental point of view. We have also shown that the in situ
generation of Et3 SiI using the CH3 I–Et3 SiH–PdCl2 system can
also serve as very efficient reagent for the synthesis of several
1,4-dihydropyridine derivatives at room temperature in high
yields and short reaction times. The present method has many
obvious advantages as compared with many previous reports,
including the simplicity, the generality of the methodology and
the avoidance of discharging harmful organic solvents. Further
investigations to elucidate the reaction mechanism are currently
in progress.
Experimental
Melting points were determined in evacuated capillaries with
a Buchi B-545 apparatus.1 H NMR spectra were recorded on
a Bruker 80 or 500 MHz in CDCl3 or CDCl3 –DMSO-d6 using
tetramethylsilane as internal standard. 13 C NMR spectra were
recorded on a Bruker 125 MHz in CDCl3 or CDCl3 –DMSO-d6 . Mass
spectra were obtained on a Fisons GC 8000/TRIO 1000 under 70 eV.
Infrared (IR) spectra were recorded from KBr disks with a Bruker
Vector 22 FT-IR spectrometer.
Typical Procedure for 1,4-Dihydropyridines (2) Synthesis using
TMSCl
A mixture of aldehyde (1 mmol), methyl 3-aminocrotonate
(4 mmol) and chlorotrimethylsilane (1 mmol) was stirred at 80 ◦ C
for appropriate time (Table 1). After completion of the reaction
as indicated by TLC, the mixture was poured into ice-cold water
and extracted with ethyl acetate. The organic layer was dried and
concentrated in vacuum. The crude products were purified by
recrystallization in ethyl acetate–petroleum ether, 9 : 1.
Typical Procedure for 1,4-Dihydropyridines (2) Synthesis using
CH3 I–Et3 SiH–PdCl2
Appl. Organometal. Chem. 2009, 23, 267–271
2a:[16] m.p. 196–198 ◦ C. 1 H NMR (CDCl3 , 500 MHz): δ = 2.38 (s,
6H, 2CH3 ), 3.69 (s, 6H, 2OCH3 ), 5.05 (s, 1H, CH), 5.72 (s,
1H, NH), 7.16–7.31 (m, 5H, 5CH arom). MS (70 eV): m/z (%)
301 (6) (M+ ), 286 (4) (M − Me)+ , 270 (7) (M − OMe)+ , 242
(8) (M − COOMe)+ , 224 (100) (M − Ph)+ , 192 (10) (M −
Ph − OMe)+ . IR (KBr): ν = 3342, 3242, 3080, 3026, 2949,
1699, 1645, 1489 cm−1 .
2b:[17] m.p. 198–200 ◦ C. 1 H NMR (CDCl3 , 500 MHz): δ = 2.40 (s,
6H, 2CH3 ), 3.68 (s, 6H, 2OCH3 ), 5.14 (s, 1H, CH), 5.77 (s,
1H, NH), 7.47 (d, 2H, 2CH arom, J = 8.5 Hz), 8.12 (d, 2H,
2CH arom, J = 8.5 Hz). MS (70 eV): m/z (%) 346 (10) (M+ ),
331 (12) (M − Me)+ , 315 (12) (M − OMe)+ , 287 (27) (M −
COOMe)+ , 224 (100) (M − NO2 C6 H4 )+ . IR (KBr): ν = 3340,
3244, 3074, 3001, 2953, 1703, 1647, 1595 cm−1 .
2c:[18] m.p. 210–212 ◦ C. 1 H NMR (CDCl3 , 500 MHz): δ = 2.41 (s,
6H, 2CH3 ), 3.69 (s, 6H, 2OCH3 ), 5.15 (s, 1H, CH), 5.77 (s, 1H,
NH), 7.42 (t, 1H, J = 7.9 Hz, 1CH arom), 7.67 (d, 1H, J = 7.6,
1CH arom), 8.05 (d, 1H, J = 7.3 Hz, 1CH arom), 8.14 (s, 1H,
1CH arom). MS (70 eV): m/z (%) 346 (40) (M+ ), 331 (30) (M
− Me)+ , 315 (42) (M − OMe)+ , 287 (48) (M − COOMe)+ ,
224 (100) (M − NO2 C6 H4 )+ , 192 (70) (M − NO2 C6 H4 −
OMe)+ . IR (KBr): ν = 3348, 3246, 3095, 2953, 1705, 1645,
1527 cm−1 .
2d:[19] m.p. 186–188 ◦ C. 1 H NMR (CDCl3 , 500 MHz): δ = 2.37 (s,
6H, 2CH3 ), 3.69 (s, 6H, 2OCH3 ), 3.79 (s, 3H, OCH3 ), 4.99 (s,
1H, CH), 5.69 (s, 1H, NH), 6.78 (d, 2H, J = 8.6 Hz, 2CH arom),
7.22 (d, 2H, J = 8.6 Hz, 2CH arom). MS (70 eV): m/z (%) 331
(62) (M+ ), 316 (47) (M − Me)+ , 300 (51) (M − OMe)+ , 272
(86) (M − COOMe)+ , 224 (100) (M − C6 H4 OMe)+ , 192(49)
(M − OMeC6 H4 − OMe)+ . IR (KBr): ν = 3348, 3244, 3074,
2995, 1697, 1649, 1625 cm−1 .
2e:[19] m.p. 173–175 ◦ C. 1 H NMR (CDCl3 , 80 MHz): δ = 2.25 (s,
6H, 2CH3 ), 3.58 (s, 6H, 2OCH3 ), 3.69 (s, 3H, CH3 ), 4.93 (s,
1H, CH), 5.64 (s, 1H, NH), 6.73–7.19 (m, 4H, 4CH arom).
MS (70 eV): m/z (%) 331 (13) (M+ ), 316 (6) (M − Me)+ , 300
(8) (M − OMe)+ , 272 (14) (M − COOMe)+ , 224 (100) (M −
C6 H4 OMe)+ , 192 (20) (M − OMeC6 H4 − OMe)+ . IR (KBr):
ν = 3342, 3240, 3089, 3001, 2951, 1703, 1645, 1606 cm−1 .
2f: m.p. 225–227 ◦ C. 1 H NMR (CDCl3 , 500 MHz): δ = 2.37 (s,
6H, 2CH3 ), 3.69 (s, 6H, 2OCH3 ), 4.65 (s, 1H, OH), 4.97 (s, 1H,
CH), 5.6 (s, 1H, NH), 6.71 (d, 2H, J = 8.4 Hz, 2CH arom), 7.16
(d, 2H, J = 8.4 Hz, 2CH arom). 13 C NMR (CDCl3 /DMSOd6 , 125 MHz): δ = 18.77 (2Me), 38.09 (C4), 50.66 (2OMe),
102.94 (C3, C5), 114.83 (2C arom), 128.46 (2C arom), 139.20
(C arom), 145.29 (C2, C6), 155.40 (C arom), 168.34 (CO). MS
(70 eV): m/z (%) 317 (37) (M+ ), 302 (48) (M − Me)+ , 286
(40) (M − OMe)+ , 258 (56) (M − COOMe)+ , 224 (100) (M
− C6 H4 OH)+ , 192 (68) (M − OHC6 H4 − OMe)+ . IR (KBr):
ν = 3336, 3319, 3020, 2949, 1639, 1614, 1506 cm−1 .
2g: m.p. 230–232 ◦ C. 1 H NMR (CDCl3 /DMSO-d6 , 500 MHz):
δ = 2.18 (s, 6H, 2CH3 ), 3.50 (s, 6H, 2OCH3 ), 4.81 (s, 1H, CH),
6.47 (d, 1H, J = 4.8 Hz, 1CH arom), 6.60 (m, 2H, 2CH arom),
6.86 (t, 1H, J = 8.1 Hz, 1CH arom), 7.56 (s, 1H, NH), 8.30 (s,
1H, OH). 13 C NMR (CDCl3 /DMSO-d6 , 125 MHz): δ = 18.65
(2Me), 38.72 (C4), 50.72 (2OMe), 102.12 (C3, C5), 113.17 (C
c 2009 John Wiley & Sons, Ltd.
Copyright www.interscience.wiley.com/journal/aoc
269
A mixture of aldehyde (1 mmol), methyl 3-aminocrotonate
(2 mmol) in 3 ml of acetonitrile was added to a mixture of
methyliodide (1 mmol), triethylsilane (1.2 mmol) and 10 mol% of
palladium dichloride. The mixture was stirred at room temperature
for 2 h. After completion of the reaction, the mixture was poured
into ice-cold water. The precipitate was dissolved in ethyl acetate
and filtered. The solvent was dried and concentrated in vacuum.
The crude products were purified by recrystallization in ethanol.
M. Mirza-Aghayan et al.
2h:
2i:
2j:[21]
2k:
2l:
2m:
270
arom), 114.57 (C arom), 118.29 (C arom), 128.80 (C arom),
145.75 (C2, C6), 149.49 (C arom), 157.23 (C arom), 168.01
(CO). MS (70 eV): m/z (%) 317 (19) (M+ ), 302 (10) (M −
Me)+ , 286 (11) (M − OMe)+ , 258 (20) (M − COOMe)+ , 224
(100) (M − C6 H4 OH)+ , 192 (36) (M − OHC6 H4 − OMe)+ . IR
(KBr): ν = 3325, 3248, 3099, 2985, 1662, 1614, 1587 cm−1 .
m.p. 196–198 ◦ C. 1 H NMR (CDCl3 , 500 MHz): δ = 2.37 (s,
6H, 2CH3 ), 3.68 (s, 6H, 2OCH3 ), 5.01 (s, 1H, CH), 5.75 (s,
1H, NH), 7.20–7.24 (m, 4H, 4CH arom). 13 C NMR (CDCl3 ,
125 MHz): δ = 19.41 (2Me), 38.92 (C4), 51.03 (2OMe),
103.40 (C3, C5), 128.11 (2C arom), 129.04 (2C arom), 131.77
(C arom), 144.63 (C2, C6), 146.04 (C arom), 167.97 (CO).
MS (70 eV): m/z (%) 335 (25) (M+ ), 320 (24) (M − Me)+ ,
304 (31) (M − OMe)+ , 276 (12) (M − COOMe)+ , 224 (100)
(M − ClC6 H4 )+ , 192 (48) (M − ClC6 H4 − OMe)+ . IR (KBr):
ν = 3336, 3244, 3093, 2993, 2949, 1697, 1645, 1487 cm−1 .
m.p. 200–202 ◦ C. 1 H NMR (CDCl3 , 500 MHz): δ = 2.37
(s, 6H, 2CH3 ), 3.68 (s, 6H, 2OCH3 ), 5.00 (s, 1H, CH), 5.71
(s, 1H, NH), 7.18 (d, 2H, J = 8.4 Hz, 2CH arom), 7.37 (d,
2H, J = 8.4 Hz, 2CH arom). 13 C NMR (CDCl3 , 125 MHz):
δ = 19.41 (2Me), 39.01 (C4), 51.01 (2OMe), 103.35 (C3,
C5), 119.94 (C arom), 129.45 (2C arom), 131.05 (2C arom),
144.61 (C2, C6), 146.54 (C arom), 167.91 (CO). MS (70 eV):
m/z (%) 379 (19) (M+ ), 364 (18) (M − Me)+ , 348 (18) (M −
OMe)+ , 320 (27) (M − COOMe)+ , 224 (100) (M − BrC6 H4 )+ ,
192 (52) (M − BrC6 H4 − OMe)+ . IR (KBr): ν = 3317, 3248,
3101, 2981, 2945, 1699, 1649, 1485 cm−1 .
m.p. 174–176 ◦ C. 1 H NMR (CDCl3 , 500 MHz): δ = 2.32 (s,
3H, CH3 ), 2.37 (s, 6H, 2CH3 ), 3.69 (s, 6H, 2OCH3 ), 5.01 (s, 1H,
CH), 5.71 (s, 1H, NH), 7.07 (d, 2H, J = 8.0 Hz, 2CH arom),
7.20 (d, 2H, J = 8.0 Hz, 2CH arom). MS (70 eV): m/z (%) 315
(16) (M+ ), 300 (19) (M − Me)+ , 284 (25) (M − OMe)+ , 256
(38) (M − COOMe)+ , 224 (100) (M − MeC6 H4 )+ , 192 (35)
(M − MeC6 H4 − OMe)+ . IR (KBr): ν = 3315, 3248, 3105,
2983, 1697, 1662, 1647, 1498 cm−1 .
m.p. 195–197 ◦ C. 1 H NMR (CDCl3 , 80 MHz): δ = 2.30 (s, 6H,
2CH3 ), 3.67 (s, 6H, 2OCH3 ), 5.30 (s, 1H, CH), 5.82 (s, 1H, NH),
6.75–7.00 (m, 3H, 3CH arom). 13 C NMR (CDCl3 , 125 MHz):
δ = 19.30 (2Me), 34.28 (C4), 51.09 (2OMe), 103.14 (C3, C5),
122.90 (C arom), 123.22 (C arom), 126.45 (C arom), 145.12
(C2, C6), 151.40 (C arom), 167.80 (CO). MS (70 eV): m/z (%)
307 (60) (M+ ), 292 (38) (M − Me)+ , 276 (20) (M − OMe)+ ,
248 (98) (M − COOMe)+ , 224 (100) (M − C4 H3 S)+ , 192
(29) (M − C4 H3 S − OMe)+ . IR (KBr): ν = 3321, 3253, 3095,
2945, 1678, 1645, 1571 cm−1 .
m.p. 191–193 ◦ C. 1 H NMR (CDCl3 , 80 MHz): δ = 2.26 (s,
6H, 2CH3 ), 3.63 (s, 6H, 2OCH3 ), 5.15 (s, 1H CH), 5.75 (s, 1H,
NH), 5.95 (m, 1H, 1CH arom), 6.15 (m, 1H, 1CH Arom), 7.02
(m, 1H, 1CH arom). 13 C NMR (CDCl3 , 125 MHz): δ = 19.22
(2Me), 33.23 (C4), 51.10 (2OMe), 100.21 (C3, C5), 104.27 (C
arom), 110.01 (C arom), 140.96 (C arom), 145.81 (C2, C6),
158.50 (C arom), 167.98 (CO). MS (70 eV): m/z (%) 291 (70)
(M+ ), 276 (40) (M − Me)+ , 260 (44) (M − OMe)+ , 232 (100)
(M − COOMe)+ , 224 (62) (M − C4H3 O)+ . IR (KBr): ν = 3338,
3246, 3097, 2951, 1697, 1662, 1637, 1489 cm−1 .
m.p. 124–126 ◦ C. 1 H NMR (CDCl3 , 80 MHz): δ = 0.78 (d, 6H,
J = 5.93 Hz, 2CH3 ), 1.03 (t, 2H, J = 6.72 Hz, CH2 ), 1.35 (m,
1H, CH), 2.21 (s, 6H, 2CH3 ), 3.63 (s, 6H, 2OCH3 ), 3.86 (m, 1H,
CH), 5.65 (s, 1H, NH). 13 C NMR (CDCl3 , 125 MHz): δ = 19.33
(2Me), 22.83 (2Me), 23.71 (CH), 30.81 (C4), 46.79 (CH2 ),
50.83 (2OMe), 103.79 (C3, C5), 144.84 (C2, C6), 168.57 (CO).
MS (70 eV): m/z (%) 281 (7) (M+ ), 266 (2) (M − Me)+ , 250
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(50) (M − OMe)+ , 222 (100) (M − COOMe)+ , 192 (75) [M −
(CH3 )2 CH − OMe]+ . IR (KBr): ν = 3354, 3238, 3012, 2951,
1699, 1662, 1645, 1487 cm−1 .
2n: m.p. 80–82 ◦ C. 1 H NMR (CDCl3 , 80 MHz): δ = 0.78 (t, 3H,
J = 5.12 Hz, CH3 ), 1.01–1.32 (m, 12H, 6CH2 ), 2.20 (s, 6H,
2CH3 ), 3.63 (s, 6H, 2OCH3 ), 3.86 (m, 1H, CH), 5.48 (s, 1H, NH).
13 C NMR (CDCl , 125 MHz): δ = 14.05 (Me), 19.35 (2Me),
3
22.63 (CH2 ), 24.65 (CH2 ), 29.37 (CH2 ), 29.83 (CH2 ), 31.91
(CH2 ), 32.87 (CH2 ), 36.81 (C4), 50.84 (2OMe), 103.02 (C3,
C5), 144.95 (C2, C6), 168.55 (CO). MS (70 eV): m/z (%) 323
(2) (M+ ), 292 (10) (M − OMe)+ , 224 (100) (M − C7 H15 )+ ,
192 (20) (M − C7 H15 − OMe)+ . IR (KBr): ν = 3352, 2953,
2927, 2856, 1732, 1695, 1649 cm−1 .
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