Solvent-free microwave michael addition of isatin and aniline schiff base of isatin to α,β-unsaturated esters

Article abstract of DOI:10.4067/S0717-97072011000100021

The rapid, simple, microwave-assisted Michael addition of isatin and aniline Schiff base of isatin to a wide variety of alkyl and aryl acrylates in the presence of, tetrabutylammonium bromide (TBAB) and 1,4-diazabicyclo[2.2.2] octane (DABCO), under solvent-free conditions, is presented. Under these conditions the addition of isatin to some of alkyl and aryl acrylates afford both related Baylis-Hillman adducts as minor products and the corresponding Michael adducts as major products. Addition of isatin to ethyl acrylate leads to produce Baylis-Hillman/Michael adduct in good yield. This system dose not work on Michael acceptors of methyl acrylate and methyl methacrylate.

Full text of DOI:10.4067/S0717-97072011000100021

J. Chil. Chem. Soc., 56, Nº 1 (2011)
SOLVENT-FREE MICROWAVE MICHAEL ADDITION OF ISATIN AND ANILINE SCHIFF BASE OF ISATIN TO
α,β-UNSATURATED ESTERS
GHOLAMHASSAN IMANZADEHa*, TOORAN AGHAALIZADEHa, MOHAMMADREZA ZAMANLOOa,
YAGOUB MANSOORIa
aDepartment of Chemistry, College of Science, University of Mohaghegh Ardabili 56199-11367, Ardabil, Iran
(Received: July 19, 2010 - Accepted: March 26, 2011)
ABSTRACT
The rapid, simple, microwave-assisted Michael addition of isatin and aniline Schiff base of isatin to a wide variety of alkyl and aryl acrylates in the presence
of, tetrabutylammonium bromide (TBAB) and 1,4-diazabicyclo[2.2.2]octane (DABCO), under solvent-free conditions, is presented. Under these conditions the
addition of isatin to some of alkyl and aryl acrylates afford both related Baylis-Hillman adducts as minor products and the corresponding Michael adducts as major
products. Addition of isatin to ethyl acrylate leads to produce Baylis-Hillman/Michael adduct in good yield. This system dose not work on Michael acceptors of
methyl acrylate and methyl methacrylate.
Keywords: Aza-Michael addition, Microwave, Isatin, Isatin Schiff base, α,β-Unsaturated Esters.
INTRODUCTION
In1841, isatin
1 (1H-indol-2,3-dione) was obtained by oxidation
of indigo with nitric and chromic acids.1 Isatin and its derivatives have
proved to be versatile starting material for the synthesis of natural products,
heterocyclic, and non-cyclic compounds.2 Isatin and some of its derivatives
are also pharmacologically relevant, for example isatin inhibits natriuretic
peptide-induced hyperthermia in rats,3 and some of its semicarbazones show
anticonvulsive activity.4 In nature, isatin is found in plants of the genus Isatis5
and in human as it is a metabolic derivative of adrenaline.6 This important
compound as also been found to be a component of coal tar.7 Analogs and
derivatives of isatin have found wide applications in the manufacture of dyes,
pigments, flavors, pharmaceuticals. In industries, isatin and its derivatives
have been also used as UV light absorbers, blowing agents, flame-proofing
agents, corrosion inhibitors, dry bleaches, disinfectants, and sanitizing agents.8
Additionally, Schiff bases and Mannich basses of isatin were reported to
possess antibacterial,9 antifungal,10 antiviral,11 anti-HIV,12 antiprotozeal,13 and
antihelminthic14 activities.
Michael addition is an important and useful reaction in organic
synthesis.15 In this field, recently, many attentions have been focused on the
aza-Michael reaction for the construction of valuable compounds such as
β-amino carbonyl compounds16 which are attractive precursors in preparation
of a variety of biologically important natural products, antibiotics, β-amino
alcohols, and chairal auxiliaries.17-22
In contrast to the various aza-Micheal addition methods, there are few
examples of the addition of amides and their analogs, due to their low reactivity,
to α,β-unsaturated systems. Neutral amides have very restricted nucleophilicity
but under strong basic conditions, nitrogen anions derived from them can take
part in Michael-type additions to α,β-unsaturated compounds.23 For instance, in
the NaOH media the addition of δ-valerolactam to ethyl acrylate produces the
desired N-substituted of this lactam in 5% yield.24 In the other media such as
CsF-Si(OR)4 this aza-Michael addition affords the corresponding N-substituted
lactam in 95% yield.25
Scheme 1.
RESULTS AND DISCUSSION
Firstly, we focused on the reaction of isatin and n-butyl acrylate under MW
irradiation condition. We found that reaction was completed in the presence
of DABCO and in TBAB media at 300 W of microwave power. Under these
conditions the aza-Michael adduct as a major product and Baylis-Hillman
adduct as a minor product were obtained. Using these optimized reaction
conditions, the scope and efficiency of this method was explored for a wide
variety of alkyl and aryl acrylates. The results are summarized in Table 1. As
Table 1 indicates, in some cases (Table 1, entries 2-7 and entry 9) the Baylis-
Hillman adduct of isatin is formed along with Michael adduct as a side product.
Surprisingly, treatment of ethyl acrylate with isatin under optimized conditions
produced the Baylis-Hillman/Michael adduct in good yield (Table1, entry 1).
Methyl acrylate methyl methacrylate did not undergo the Michael addition and
Baylis-Hilman addition reaction (Table 1, entries 11 and entry 12). In contrast
to these results, exposure of isatin to 1-phenylethyl acrylate and to 2-isopropyl-
5-methylcyclohexyl acrylate under the same conditions gave the desired
Michael adducts in 40% and 60% yield respectively as the sole products (Table
1, entries 8, 10).
Although, there are a few reports in literature on the aza-Michael addition
of isatin to α,β-unsaturated systems.26,27 However, no data are available on
the addition of isatin Schiff base to these systems. In view of the emerging
application of microwave (MW) chemistry in solvent-free reaction medium28-30
and in keeping with our ongoing program on the development of cleaner
pathways,31-34 herein we report microwave assisted Michael addition of
isatin and its aniline Schiff base (2) to α,β-unsaturated esters in the presence
of tetrabutylamonium bromide (TBAB) and 1,4-Diazabicyclo[2.2.2]octane
(DABCO) by using the microwave irradiation (Scheme 1).
e-mail: Imanzad2000@yahoo.com
616

J. Chil. Chem. Soc., 56, Nº 1 (2011)
Table 1. Reaction of isatin wth different α,β-unsaturated esters in the
presence of DABCO and TBAB under the solvent-free microwave (300 W)
conditions.
These results encouraged us to investigation the Michael addition of isatin
Schiff base 2 to different alkyl and aryl acrylates under the same reaction
conditions that the obtained results are summarized in Table 2. It is noteworthy
to mention that in these reactions no Baylis-Hillman adducts are observed, and
Michael adducts are produced as the sole products in good to excellent yields
(Table 2). Our attempts to expedite reaction of isatin Schiff base 2 with methyl
acrylate as well as with methyl methacrylate under microwave irradiation were
unsuccessful.
Table 2. Aza-Micheal reaction of isatin Schiff base to α,β-unsaturated
esters catalyzed by DABCO and MW (300 W).
aIsolated yields. Reactions were performed using 2 mmol Schiff base 2, 2
mmol ester, 1 mmol DABCO, and 1 mmol TBAB.
To investigation the effect of the applied base on this Michael reaction, we
performed the reaction of Schiff base 2 with n-butyl acrylate in the presence
of several different catalysts under the similar reaction conditions. The results
are summarized in Table 3. From these results we can see that, in this reaction
system, basic catalyst is necessary to make it proceed practically. Between
these catalysts, DABCO, possibly for its two base functional groups, promoted
the reaction much more efficiently.
aIsolated yields. Reactions were performed using 2 mmol ester, 1 mmol
DABCO, and 1 mmol TBAB. bIn this case 4 mmol ester was used.
617

J. Chil. Chem. Soc., 56, Nº 1 (2011)
Table 3. Michael reaction of Schiff base 2 with n-butyl acrylate in the
presence of different catalysts and TBAB under MW (300 W).
methacrylate as Michael acceptors. In some cases, isatin Michael acceptor
afforded Baylis-Hilman adduct as side product. It was observed that treatment
of isatin with 1-phenylethyl acrylate and with 2-isopropyl-5-methylcyclohexyl
acrylate gave the desired Michael adducts as the sole products. Surprisingly, it
was, also, observed that the reaction of ethyl acrylate with isatin produced the
Baylis-Hillman/Michael adduct in good yield.
Entry
Basea
Time(min)
Yield(%)b
1
2
3
4
5
6
7
8
9
None
30
6
-
DABCO
NEt3
90
50
60
15
-
15
15
16
20
16
15
20
EXPERIMENTAL
Na2CO3
Pyridine
SrCO3
NaHCO3
K2CO3
MgO
TBAB was purchased from Fluka and DABCO, isatin, acryloylchloride and
alcohols were purchased from Merck companies. All alkyl and aryl acrylates
were synthesized in our laboratory according to the literature procedure and
15
50
-
1
their structures were confirmed by IR and H NMR spectra. The progress of
1
the reactions was followed by TLC using silica gel SILIG/UV 254 plates. H
NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on Bruker
400 Spectrospin, or 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were
recorded on Bruker 300 MHz, JEOL EX-90A. IR spectra were recorded on
Buck-Scientific 500 instrument. Mass spectra were recorded on a Shimadzu
GC-MS-QP 1000PX. Elemental analysis for C, H, and N were performed
using a Heraeus CHN-O-Rapid analyzer. The melting points were determined
in open capillaries with a Stuart Melting Point Apparatus and are uncorrected.
MB 245 domestic microwave oven from Butan Industrial Company was used
for microwave irradiation.
aWith 1 mmol base, 2 mmol Schiff base 2, 2 mmol n-butyl acrylate and 1
mmol TBAB. bIsolated yield.
According to the reaction phenomenon and results, we proposed the
reaction of isatin and acrylates in the presence of DABCO may proceed as
Scheme 2 and Scheme 3.
General Procedure for Michael addition reaction of isatin and aniline
Schiff base of isatin to alkyl and aryl acrylates. To a well mixture of isatin (2
mmol) or isatin Schiff base (2 mmol), TBAB ( 1 mmol), DABCO (1 mmol) in
a test tube was added alkyl and aryl acrylates (2 mmol) and mixed thoroughly
with a glass rod. The resulting mixture was irradiated in a microwave oven
at 300 W for the stipulated time (Table 1 and Table 2). Then, the reaction
mixture was cooled to room temperature and dissolved in chloroform (40 ml).
TBAB was recovered by the addition of water (15 mL), then collected and
dried under vacuum. The chloroform layer was washed with water (3*15 ml).
The organic layer was dried over anhydrous Na SO4. The solvent was removed
under reduced pressure and the resulting crude2material was purified on short
silica-gel column with ethyl acetate:n-hexane (1:9) as the eluent.
Physical and Spectroscopic Data of Isolated Products. (3a) Red oil; IR
νmax(neat)/cm-1: 3372, 3059, 2992, 1710, 1700, 1617, 1490, 1462, 1320, 1183.
1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 1.13 (t, 3H, J = 7.2 Hz), 1.23 (t, 3H,
J = 7.2 Hz), 2.74 (t, 2H, J = 7.8 Hz), 3.93-4.10 (m, 7H), 6.42 (s, 1H), 6.56 (s,
1H), 6.93-7.61 (m, 4H). 13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 13.9, 14.7,
32.2, 36.2, 60.9, 61.1, 75.9, 108.8, 110.4, 122.9, 123.8, 124.0, 127.5, 139.3,
143.3, 164.5, 171.3, 176.2. MS m/z: 347 (73.00, M+), 330 (58.70), 302 (39.00),
273 (94.10), 228 (69.50), 201 (35.00), 186 (91.90), 146 (100.00), 132 (84.50),
104 (27.00), 77 (34.00), 55 (49.80). Anal. Calcd for C18H21NO6: C, 62.24; H,
6.09; N, 4.03. Found: C, 62.36; H, 6.15; N, 4.12.
Scheme 2.
(3b) Red oil; IR νmax(neat)/cm-1: 3080, 2955, 2858, 1722, 1718, 1700,
1605, 1457, 1356, 997, 742. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 0.92 (t,
3H, J = 7.5 Hz), 1.17-1.38 (m, 2H), 1.44-1.61 (m, 2H), 2.75 (t, 2H, J = 6.9 Hz),
3.93 (t, 2H, J = 6.9 Hz), 4.03 (t, 2H, J = 7.5 Hz), 6.92-7.62 (m, 4H). 13C NMR
(CDCl3, TMS, 75 MHz) δ ppm: 14.5, 19.6, 30.1, 32.2, 36.2, 65.0, 110.4, 122.9,
124.0, 129.6, 138.4, 150.5, 164.6, 176.1, 183.1 .MS m/z: 275 (11.00, M+), 228
(19.70), 201 (21.80), 186 (15.60), 146 (30.00), 132 (36.80), 90 (17.00), 77
(22.00), 57 (42.10), 55 (44.50), 41 (100.00). Anal. Calcd for C15H17NO4: C,
65.44; H, 6.22; N, 5.09. Found: C, 65.31; H, 6.40; N, 5.17.
(3c) Orange oil; IR νmax(neat)/cm-1: 3090, 2930, 2858, 1725, 1715, 1700,
1612, 1455, 1362, 1184, 973, 730. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm:
0.85 (t, 3H, J = 7.2 Hz), 1.15-1.27 (m, 4H), 1.54 (t, 2H, J = 7.2 Hz), 2.73 (t, 2H,
J = 6.6 Hz), 3.88-4.05 (m, 4H), 6.90-7.61 (m, 4H). 13C NMR (CDCl3, TMS,
75 MHz) δ ppm: 14.6, 22.2, 28.8, 28.8, 31.7, 36.4, 65.3, 124.0, 124.8, 125.3,
127.5, 138.4, 150.5, 164.7, 176.5, 183.1 .MS m/z: 289 (15.00), 201 (67.00),
145 (74.80), 132 (90.00), 119 (26.80), 90 (38.90), 77 (52.00), 55 (56.00), 43
(100.00), 41 (89.50). Anal. Calcd for C16H19NO4: C, 66.42; H, 6.62; N, 4.84.
Found: C, 66.55; H, 6.43; N, 4.91.
Scheme 3.
(3d) Red oil; IR νmax(neat)/cm-1: 3085, 2973, 2954, 1722, 1719, 1702,
1
1624, 1459, 1459, 1347, 1182, 991,736. H NMR (CDCl , TMS, 300 MHz)
CONCLUSIONS
δ ppm: 1.20 (d, 6H, J = 6.6 Hz), 2.72 (t, 2H, J = 7.1 Hz), 34.02 (t, 2H, J = 7.1
Hz), 4.81-5.00 (m, 1H), 6.93-7.63 (m, 4H). 13C NMR (CDCl , TMS, 75 MHz)
δ ppm: 21.6 (two carbons), 32.5, 36.2, 68.7, 110.4, 122.9, 1233.8, 125.5, 138.5,
150.4, 165.5, 176.1, 183.1. MS m/z: 261 (31.00), 219 (29.40), 201 (54.10), 174
(24.00), 146 (100.00), 132 (66.40), 43 (22.70). Anal. Calcd for C14H15NO4: C,
64.36; H, 5.79; N, 5.36. Found: C, 64.24; H, 5.99; N, 5.38.
In summary, we presented a rapid, simple, microwave-promoted method
for Michael addition reaction of isatin and aniline Schiff base of isatin to
alkyl and aryl acrylates in the presence of DABCO and TBAB. The reactions
were performed at 300 W of microwave power under solvent-free conditions.
The reaction was not successful on methyl acrylate as well as on methyl
618

J. Chil. Chem. Soc., 56, Nº 1 (2011)
(3e) Brown oil; IR νmax(neat)/cm-1: 3085, 2979, 2925, 1715, 1605, 1463,
ppm: 21.4 (two carbons), 68.4, 76.1, 108.8, 117.6, 122.9, 124.1, 127.3, 129.6,
139.5, 143.4, 170.8, 170.8. MS m/z: 261 (35.00), 219 (30.00), 201 (28.00), 174
(20.00), 146 (100.00), 132 (65.00), 43 (22.00). Anal. Calcd for C14H15NO4: C,
64.36; H, 5.79; N, 5.36. Found: C, 64.18; H, 5.91; N, 5.53.
1
1356, 1301, 1174, 979, 742. H NMR (CDCl , TMS, 300 MHz) δ ppm: 1.41
(s, 9H), 2.65 (t, 2H, J = 7.2 Hz), 3.99 (t, 2H, 3J = 7.2 Hz), 6.92-7.62 (m, 4H).
13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 28.0 (three carbons), 33.3, 36.3,
66.3, 110.5, 122.9, 123.8, 125.5, 138.4, 150.6, 164.8, 176.0, 184.4. MS m/z:
275 (4.00, M+), 219 (18.00), 201 (14.00), 146 (20.90), 132 (24.00), 90 (34.50),
77 (24.00), 57 (100.00), 43 (68.30), 41 (84.00). Anal. Calcd for C15H17NO4: C,
65.44; H, 6.22; N, 5.09. Found: C, 65.52; H, 6.17; N, 5.04.
(4e) Brown oil; IR νmax(neat)/cm-1: 3405, 3075, 2979, 2925, 1710, 1604,
1
1480, 1356. H NMR (CDCl3, TMS, 300 MHz) δ ppm: 1.281 (s, 9H), 2.66
(s, OH), 6.23 (1H, s, CH vinyl), 6.63 (1H, s, CH vinyl), 6.92-7.623 (m, 4H),
7.66 (s, NH). 13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 27.7 (three carbons),
76.1, 108.8, 117.6, 121.5, 124.1 (two carbons), 126.8, 129.4, 140.2, 143.1,
170.5, 170.1. MS m/z: 275 (5.00, M+), 219 (10.00), 201 (15.00), 174 (10.00),
146 (20.00), 132 (25.00), 119 (12.00), 104 (10.00), 90 (35.00), 77 (25.00), 57
(100.00), 43 (58.00), 41 (84.00). Anal. Calcd for C15H17NO4: C, 65.44; H, 6.22;
N, 5.09. Found: C, 65.68; H, 6.15; N, 4.87.
(3f) Orange oil; IR νmax(neat) / cm-1: 3065, 2931, 1730, 1727, 1698, 1612,
1
1496, 1472, 1362, 1313. H NMR (CDCl3, TMS, 300 MHz) δ ppm: 2.92 (t,
2H, J = 7.2 Hz), 4.11 (t, 2H, J = 7.2 Hz), 6.91-7.67 (m, 9H). 13C NMR (CDCl3,
TMS, 75 MHz) δ ppm: 31.9, 36.0, 110.4, 121.4 (two carbons), 123.2, 124.1,
125.6, 129.4 (two carbons), 129.5, 130.5, 138.9, 150.4, 166.5, 176.1, 183.8.
MS m/z: 295 (6.00, M+), 202 (100.00), 174 (85.20), 146 (25.50), 132 (96.00),
90 (36.00), 77 (77.10), 65 (22.00), 55 (44.00). Anal. Calcd for C17H13NO4: C,
69.15; H, 4.44; N, 4.74. Found: C, 69.12; H, 4.51; N, 4.66.
(4f) Red oil; IR νmax(neat)/cm-1: 3400, 3065, 2931, 1705, 1612, 1496,
1
1472, 1313. H NMR (CDCl3, TMS, 300 MHz) δ ppm: 3.47 (s, OH), 6.71
(1H, s, CH vinyl), 6.87 (1H, s, CH vinyl), 6.91-7.75 (m, 9H), 7.97 (s, NH). 13
C
(3g) Red oil; IR νmax(neat)/cm-1: 3049, 2949, 1728, 1617, 1462, 1345,
1253, 1187, 766. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 2.82 (t, 2H, J = 6.9
Hz), 4.04 (t, 2H, J = 6.9 Hz), 5.11 (s, 2H), 6.99-7.61 (m, 9H). 13C NMR (CDCl ,
TMS, 75 MHz) δ ppm: 32.2, 36.2, 65.0, 110.5, 123.0, 123.8, 125.5, 128.4 (tw3o
carbons), 128.6, 130.3 (two carbons), 135.3, 139.4, 150.4, 164.8, 176.2, 183.2.
MS m/z: 309 (7.00, M+), 203 (30.00), 190 (14.50), 146 (20.00), 132 (27.10),
91 (100.00), 77 (23.50). Anal. Calcd for C18H15NO4: C, 69.89; H, 4.89; N, 4.53.
Found: C, 69.77; H, 4.91; N, 4.74.
NMR (CDCl3, TMS, 75 MHz) δ ppm: 75.9, 109.2, 121.4 (two carbons), 121.5,
123.2, 124.1, 126.1, 126.2, 129.3, 129.4 (two carbons), 138.5, 143.4, 150.1,
169.8, 169.9. MS m/z: 295 (5.00, M+), 247 (3.00), 202 (100.00), 186 (5.00),
174 (85.00), 160 (22.00), 146 (28.00), 132 (95.00), 105 (12.00), 90 (34.00).
Anal. Calcd for C17H13NO4: C, 69.15; H, 4.44; N, 4.74. Found: C, 69.28; H,
4.91; N, 4.39.
(4g) Brown oil; IR νmax(neat)/cm-1: 3436, 3080, 3028, 2936, 1709, 1612,
1465, 1310. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 2.69 (s, OH), 5.10 (s,
2H), 6.46 (1H, s, CH vinyl), 6.64 (1H, s, CH vinyl), 6.99-7.58 (m, 9H), 7.60 (s,
NH). 13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 66.7, 76.6, 109.0, 117.6, 123.0,
123.4, 124.1, 128.2 (two carbons), 128.6, 129.7, 130.3 (two carbons), 138.4,
141.1, 143.5, 168.2, 170.7. MS m/z: 309 (8.00, M+), 203 (35.00), 190 (17.00),
175 (10.00), 161 (11.00), 146 (20.00), 132 (28.00), 119 (7.00), 105 (6.00), 91
(100.00), 77 (25.00), 65 (12.00). Anal. Calcd for C18H15NO4: C, 69.89; H, 4.89;
N, 4.53. Found: C, 69.67; H, 4.57; N, 4.23.
(3h) Brown oil; IR νmax(neat)/cm-1: 3046, 2944, 1726, 1605, 1472, 1352,
1273, 1185, 1008, 736. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 1.51 (d, 3H,
J = 6.6 Hz), 2.79 (t, 2H, J = 6.9 Hz), 4.02 (t, 2H, J = 6.9 Hz), 5.87 (q, 1H, J = 6.6
Hz), 6.95-7.55 (m, 9H). 13C NMR (CDCl , TMS, 75 MHz) δ ppm: 22.1, 32.5,
36.2, 73.4, 110.4, 117.6, 123.8, 125.5, 1236.1 (two carbons), 128.1, 128.6 (two
carbons), 138.4, 141.1, 150.4, 160.0, 170.2, 183.1. MS m/z: 323 (8.70, M+),
203 (17.00), 190 (21.00), 146 (20.10), 132 (35.00), 105 (100.00), 90 (29.80),
77 (60.50), 43 (39.50), 41 (21.80). Anal. Calcd for C19H17NO4: C, 70.58; H,
5.30; N, 4.33. Found: C, 70.62; H, 5.18; N, 4.30.
(4i) Brown oil; IR νmax(neat)/cm-1: 3470, 3075, 2936, 1710, 1611, 1472,
1358. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 1.24-2.19 (m, 10H), 2.16 (s,
OH), 4.69 (m, 1H), 6.37 (1H, s, CH vinyl), 6.55 (1H, s, CH vinyl), 6.92-7.33
(m, 4H), 8.00 (s, NH). 13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 22.1(two
carbons), 25.3 (two carbons), 32.2, 73.5, 76.0, 108.8, 117.6, 122.9, 123.8,
127.2, 131.5, 138.4, 143.6, 170.1, 170.4. MS m/z: 301 (35.00, M+), 219 (42.00),
201 (100.00), 191 (20.00), 175 (58.00), 163 (14.00), 145 (90.00), 132 (98.00),
119 (34.00), 104 (42.00), 90 (50.00), 83 (62.00), 77 (74.00), 67 (20.00), 55
(98.00), 41 (62.00). Anal. Calcd for C17H19NO4: C, 67.76; H, 6.36; N, 4.65.
Found: C, 67.39; H, 6.16; N, 4.45.
(3i) Brown oil; IR νmax(neat)/cm-1: 3040, 2926, 2859, 1722, 1698, 1611,
1472, 1358, 1189, 978, 742. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 1.24-
1.79 (m, 10H), 2.73 (t, 2H, J = 6.9 Hz), 4.01 (t, 2H, J = 6.9 Hz), 4.69 (m,
1H), 6.92-7.62 (m, 4H). 13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 22.1(two
carbons), 25.2, 31.5, 32.2 (two carbons), 36.3, 73.5, 110.5, 123.1, 125.5, 130.1,
138.4, 150.6, 164.0, 176.1, 183.1. MS m/z: 301 (33.00, M+), 219 (40.00), 201
(100.00), 175 (57.10), 145 (91.00), 132 (98.20), 104 (44.10), 90 (50.60), 77
(75.00), 55 (98.40). Anal. Calcd for C17H19NO4: C, 67.76; H, 6.36; N, 4.65.
Found: C, 67.56; H, 6.51; N, 4.82.
(5a) Orange oil; IR νmax(neat)/cm-1: 3059, 2973, 1719, 1660, 1599, 1462,
1348, 1163, 998, 713. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 1.15 (t, 3H,
J = 7.8 Hz), 2.78 (t, 2H, J = 6.9 Hz), 4.55-4.07 (m, 4H), 6.61-7.45 (m, 9H).
13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 14.1, 32.3, 36.1, 61.0, 109.6, 110.0,
116.5, 117.7, 121.1, 122.7 (two carbons), 125.3, 126.3, 129.4 (two carbons),
134.1, 153.0, 162.1, 171.0. MS m/z: 322 (48.00, M+), 221 (13.00), 207 (100.00),
77 (33.00), 43 (15.00). Anal. Calcd for C19H18N2O3: C, 70.79; H, 5.63; N, 8.69.
Found: C, 70.31; H, 5.61; N, 8.28.
(3j) Brown oil; IR νmax(neat)/cm-1: 3050, 2927, 1724, 1612, 1454, 13046,
1202, 981, 719. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 0.655 (d, 3H, J = 7.2
Hz), 0.81-0.88 (m, 6H), 0.92-1.91 (m, 9H), 2.75 (t, 2H, J = 6.9 Hz), 4.15 (t, 2H,
J = 6.9 Hz), 4.62-4.72 (m, 1H), 6.89-7.63 (m, 4H). 13C-NMR (CDCl , TMS, 75
MHz) δ ppm: 16.5, 22.0 (two carbons), 22.9, 25.6, 26.3, 31.3, 32.4, 336.3, 40.3,
46.8, 75.1, 110.6, 123.8, 125.5, 130.6, 138.5, 150.6, 158.3, 170.5, 183.3. MS
m/z: 357 (29.50, M+), 221 (100.00), 201 (89.50), 175 (42.00), 145 (23.00), 132
(42.80), 95 (65.80), 83 (64.00), 69 (28.00), 55 (56.50), 43 (43.90). Anal. Calcd
for C H27NO4: C, 70.56; H, 7.61; N, 3.92. Found: C, 70.88; H, 7.45; N, 3.56.
(241b) Orange oil; IR νmax(neat)/cm-1: 3410, 3085, 2954, 2858, 1702, 1680,
(5b) Red oil; IR νmax(neat)/cm-1: 3046, 2968, 2932, 1717, 1658, 1611,
1484, 1361, 1153, 994. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 1.23 (d, 6H,
J = 7.1 Hz), 2.76 (t, 2H, J = 7.2 Hz), 4.10 (t, 2H, J = 7.2 Hz), 4.80-5.10 (m,
1H), 6.62-7.49 (m, 9H). 13C NMR (CDCl , TMS, 75 MHz) δ ppm: 21.7 (two
carbons), 32.6, 38.0, 76.4, 109.7, 117.7, 3121.1, 122.7 (two carbons), 124.2,
125.3, 126.3, 129.4 (two carbons), 133.3, 147.2, 153.1, 163.2, 173.2. MS m/z:
336 (25.00, M+), 207 (42.00), 122 (17.00), 107 (42.00), 93 (12.00), 77 (45.00),
59 (48.00), 43 (100.00). Anal. Calcd for C20H20N2O3: C, 71.41; H, 5.99; N,
8.33. Found: C, 71.18; H, 5.94; N, 8.13.
1
1605, 1450, 1350. H NMR (CDCl , TMS, 300 MHz) δ ppm : 0.80 (t, 3H, J
= 6.6 Hz), 1.17-127 (M, 2H), 1.38-31.46 (m, 2H), 3.75 (s, OH), 4.o6 (t, 2H, J
= 6.6 Hz), 6.41 (1H, s, CH vinyl), 6.55 (1H, s, CH vinyl), 6.92-7.62 (m, 4H),
7.80 (s, NH). 13C NMR (CDCl , TMS, 75 MHz) δ ppm: 13.8, 18.5, 31.7, 64.8,
76.0, 108.8, 117.6, 123.3, 124.30, 127.5, 129.6, 139.3, 143.3, 171.0, 171.3. MS
m/z: 275 (10.00, M+), 228 (15.00), 201 (25.00), 186 (18.00), 146 (35.00), 117
(10.00), 90 (20.00), 57 (45.00), 41 (100.00). Anal. Calcd for C15H17NO4: C,
65.44; H, 6.22; N, 5.09. Found: C, 65.70; H, 6.15; N, 4.98.
(5c) Brown oil; IR νmax(neat)/cm-1: 3052, 2949, 1712, 1660, 1593, 1161,
1064, 991, 797. 1H NMR (CDCl , TMS, 400 MHz) δ ppm: 1.41 (s, 9H), 2.67
(t, 2H, J = 7.23 Hz), 4.10 (t, 2H3, J = 7.23 Hz), 6.58-7.70 (m, 9H). 13C NMR
(CDCl , TMS, 100 MHz) δ ppm: 26.9 (three carbons), 32.3, 35.1, 80.3, 108.6,
116.6, 3121.6, 122.7 (two carbons), 124.2, 128.3, 133.0 (two carbons), 137.3,
145.8, 149.1, 153.1, 162.1, 169.1. MS m/z: 350 (39.00, M+), 294 (18.10), 221
(18.10), 207 (100.00), 104 (18.00), 77 (70.90), 57 (47.50), 43 (28.50), 41
(24.00). Anal. Calcd for C21H22N2O3: C, 71.98; H, 6.33; N, 7.99. Found: C,
71.59; H, 6.64; N, 8.17.
(4c) Orange oil; IR νmax(neat)/cm-1: 3420, 3950, 2935, 2858, 1715, 1702,
1615, 1455, 1450, 1360. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 0.83 (t, 3H,
J = 7.2 Hz), 1.15-1.26 (m, 4H), 1.45-1.52 (m, 2H), 2.33 (s, OH), 3.88-3.94 (m,
2H), 6.42 (1H, s, CH vinyl), 6.54 (1H, s, CH vinyl), 6.90-7.61 (m, 4H), 7.77
(s, NH). 13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 14.1, 22.2, 28.8, 29.0, 65.2,
75.9, 108.8, 117.6, 122.9, 125.4, 127.2, 129.7, 139.3, 143.3, 171.8, 171.9. MS
m/z: 289 (15.00, M+), 201 (70.00), 191 (10.00), 145 (78.00), 119 (30.00), 77
(53.00), 55 (55.00), 43 (100.00). Anal. Calcd for C16H19NO4: C, 66.42; H, 6.62;
N, 4.84. Found: C, 66.61; H, 6.45; N, 4.79.
(5d) Red oil; IR νmax(neat)/cm-1: 3052, 2931, 2852, 1705, 1599, 1461, 1356,
1181, 979, 742. 1H NMR (CDCl , TMS, 400 MHz) δ ppm: 0.83 (t, 3H, J = 7.3
Hz), 1.21-1.31 (m, 2H), 1.47-1.534 (m, 2H), 2.71 (t, 2H, J = 7.07 Hz), 3.98-4.04
(m, 4H), 6.53-7.65 (m, 9H). 13C NMR (CDCl3, TMS, 100 MHz) δ ppm: 12.3,
17.8, 29.2, 31.0, 34.9, 63.7, 108.4, 116.3, 121.4, 122.5 (two carbons), 124.1,
127.2, 128.1, 132.6 (two carbons), 132.9, 149.0, 153.0, 161.9, 169.8. MS m/z:
(4d) Red oil; IR νmax(neat)/cm-1: 3411, 3085, 2973, 2954, 1702, 1624,
1
1472, 1340. H NMR (CDCl3, TMS, 300 MHz) δ ppm: 1.03 (d, 6H, J = 6.3
Hz), 3.62 (s, OH), 4.81-4.92 (m, 1H), 6.35 (1H, s, CH vinyl), 6.54 (1H, s, CH
vinyl), 6.93-7.59 (m, 4H), 7.60 (s, NH). 13C NMR (CDCl3, TMS, 75 MHz) δ
619

J. Chil. Chem. Soc., 56, Nº 1 (2011)
350 (3.50, M+), 207 (9.00), 93 (1100.00), 77 (7.90), 66 (36.90), 65 (19.80),
51 (7.00), 41 (13.80). Anal. Calcd for C21H22N2O3: C, 71.98; H, 6.33; N, 7.99.
Found: C, 71.41; H, 6.84; N, 8.16.
ACKNOWLEDGEMENTS
The authors thankful to, University of Mohaghegh Ardabili and Tabriz
University Councils for the partial support to the work.
(5e) Red oil; IR νmax(neat)/cm-1: 3052, 2949, 2864, 1727, 1666, 1593, 1350,
1174, 979, 730. 1H NMR (CDCl3, TMS, 300 MHz) δ ppm: 0.897 (t, 3H, J = 6.6
Hz), 1.19-1.31 (m, 4H), 1.50-1.62 (m, 2H), 2.796 (t, 2H, J = 7.2 Hz), 3.95-4.13
(m, 4H), 6.61-7.46 (m, 9H). 13C NMR (CDCl3, TMS, 75 MHz) δ ppm: 13.9,
22.3, 28.0, 28.2, 32.4, 36.2, 65.2, 109.6, 117.7, 119.0, 122.3 (two carbons),
123.2, 125.3, 126.3 (two carbons), 134.1, 146.9, 150.3, 154.1, 163.2, 171.2.
MS m/z: 364 (57.00, M+), 295 (20.00), 250 (10.00), 221 (10.00), 207 (100.00),
77 (31.00), 59 (17.00), 43 (46.00). Anal. Calcd for C22H24N2O3: C, 72.38; H,
6.81; N, 7.98. Found: C, 72.44; H, 6.64; N, 7.69.
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(5f) Brown oil; IR νmax(neat)/cm-1: 3046, 2922, 2840, 1721, 1670, 1587,
1460, 1350, 1201, 973, 739. 1H NMR (CDCl , TMS, 400 MHz) δ ppm: 1.19-
1.80 (m, 10H), 2.75 (t, 2H, J = 7.14 Hz), 4.08 (3t, 2H, J = 7.14 Hz), 4.70-4.77 (m,
1H), 6.59-7.72 (m, 9H). 13C NMR (CDCl3, TMS, 100 MHz) δ ppm: 22.7 (two
carbons), 24.2, 30.5, 31.6 (two carbons), 35.2, 72.5, 108.6, 114.7, 116.7, 121.6
(two carbons), 124.3, 125.2, 128.4 (two carbons), 133.1, 145.9, 149.2, 153.1,
162.2, 169.5. MS m/z: 376 (43.00, M+), 295 (19.00), 221 (18.00), 207 (100.00),
104 (9.00), 77 (29.50), 55 (15.00), 41 (7.50). Anal. Calcd for C23H24N2O3: C,
72.73; H, 6.58; N, 7.62. Found: C, 72.66; H, 6.71; N, 7.98.
(5g) Brown oil; IR νmax(neat)/cm-1: 3044, 2913, 1711, 1605, 1465, , 1472,
1368, 1161, 973, 730. 1H NMR (CDCl3, TMS, 400 MHz) δ ppm: 0.68 (d, 3H,
J = 6.93 Hz), 0.82-0.88 (m, 6H), 1.25-1.91 (m, 9H), 2.75 (t, 2H, J = 7.02 Hz),
4.04 (t, 2H, J = 7.02 Hz), 4.64-4.72 (m, 1H), 6.60-7.61 (m, 9H). 13C NMR
(CDCl3, TMS,100 MHz) δ ppm: 15.2, 20.9, 22.4 (two carbons), 25.3, 28.7,
30.4, 31.4, 31.6, 36.8, 45.8, 74.2, 108.8, 116.7, 121.7, 122.8 (two carbons),
123.7, 124.5, 125.3, 128.4 (two carbons), 133.1, 137.4, 149.6, 157.3, 169.5.
MS m/z: 432 (19.50, M+), 295 28.10), 221 (35.00), 207 (100.00), 194 (19.50),
132 (18.00), 77 (66.50), 55 (66.50), 43 (40.50), 41 (42.50). Anal. Calcd for
C27H32N2O3: C, 74.97; H, 7.46; N, 6.47. Found: C, 74.52; H, 7.19; N, 6.81.
(5h) Orange oil; IR νmax(neat)/cm-1: 3044, 2913, 1730, 1726, 1654, 1599,
1532, 1472, 1356, 1175, 1022, 764. 1H NMR (CDCl3, TMS, 400 MHz) δ ppm:
3.06 (t, 2H, J = 6.98 Hz), 4.21 (t, 2H, J = 6.98 Hz), 6.99-7.60 (m, 14H). 13C
NMR (CDCl3, TMS, 100 MHz) δ ppm: 31.4, 35.04, 108.6, 114.3, 116.7, 119.1,
120.3 (two carbons), 121.8 (two carbons), 124.4, 125.1, 127.7, 128.4 (two
carbons), 128.5 (two carbons), 133.2, 136.8, 145.7, 153.0, 162.4, 168.7. MS
m/z: 370 (27.00, M+), 277 (100.00), 249 (28.00), 223 (55.00), 207 (75.00), 94
(22.70), 77 (65.00), 51 (21.00). Anal. Calcd for C23H18N2O3: C, 74.58; H, 4.90;
N, 7.56. Found: C, 74.26; H, 4.93; N, 7.90.
(5i) Red oil; IR νmax(neat)/cm-1: 3046, 3011, 2949, 1721, 1654, 1605,
1520, 1453, 1368, 1188, 1009, 748. 1H NMR (CDCl3, TMS, 400 MHz) δ ppm:
2.83 (t, 2H, J = 7.02 Hz), 4.10 (t, 2H, J = 7.02 Hz), 5.10 (s, 2H), 6.60-7.72
(m, 14H). 13C NMR (CDCl , TMS, 100 MHz) δ ppm: 31.2, 35.0, 65.7, 107.5,
114.6, 116.5, 121.5, 122.6 3(two carbons), 124.2, 125.1, 127.4 (two carbons),
128.3 (two carbons), 132.7 (two carbons), 132.9, 134.2, 145.7, 149.1, 152.9,
162.1, 169.7. MS m/z: 384 (45.00, M+), 221(19.50), 207 (100.00), 91 (51.00),
77 (51.90), 65 (12.50), 51 (14.00), 43 (5.50). Anal. Calcd for C24H20N2O3: C,
74.98; H, 5.24; N, 7.29. Found: C, 75.21; H, 5.54; N, 7.72.
(5j) Brown oil; IR νmax(neat)/cm-1: 3065, 2967, 2925, 1717, 1698, 1658,
1605, 1490, 1472, 1358, 1155, 991, 675. 1H NMR (CDCl , TMS, 300 MHz) δ
ppm: 1.52 (d, 3H, J = 6.6 Hz), 2.81 (t, 2H, J = 7.2 Hz), 4.038 (t, 2H, J = 7.2 Hz),
5.57 (q, 1H, J = 6.6 Hz), 6.59-7.45 (m, 14H). 13C NMR (CDCl3, TMS, 75 MHz)
δ ppm: 22.1, 32.6, 36.1, 73.2, 109.6, 117.7, 119.0, 122.2 (two carbons), 123.3,
125.3, 126.1, 126.3 (two carbons), 128.0 (two carbons), 129.4 (two carbons),
133.8, 141.2, 146.9, 150.2, 154.1, 163.3, 170.3. MS m/z: 398 (100.00, M+),
221 (21.00), 207 (91.00), 105 (30.00), 77 (28.00), 51 (8.00). Anal. Calcd for
C25H22N2O3: C, 75.36; H, 5.57; N, 7.03. Found: C, 75.86; H, 5.47; N, 6.86.
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