PPh3-catalyzed knoevenagel condensation: A facile synthesis of 5-(1H-indol-3-yl)meth-ylene)-2, 2-dimethyl-1, 3-dioxane-4, 6-dione, and their N-alkyl derivatives by using peg-600 as the reaction medium

Article abstract of DOI:10.1002/hc.20750

Triphenylphosphine (TPP) has been utilized as a novel and efficient catalyst for the Knoevenagel condensation of indole-3-carboxaldehydes 1(a-e), 1-methyl-1H-indole-3-carboxaldehydes 4(a-e), and 1-ethyl-1H-indole-3- carboxaldehydes 6(a-e) with the active methylene compound, that is, meldrum's acid (2), to afford substituted derivatives 5-((1H-indol-3-yl) methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione 3(a-e), 2,2-dimethyl-5-((1-methyl- 1H-indol-3-yl)methylene)-1,3-dioxane-4,6-dione 5(a-e), and 2,2-dimethyl-5-((1- ethyl-1H-indol-3-yl)methylene)-1,3-dioxane-4,6-dione 7(a-e), respectively, in ethanol medium at RT just within 1 h in excellent yields. The products 3(a-e) were reacted independently with alkylating agents, that is, DMS and DES in the presence of PEG-600 as an efficient and green solvent, to afford the corresponding N-substituted methyl and ethyl derivatives 5(a-e) and 7(a-e), respectively.

Full text of DOI:10.1002/hc.20750

Heteroatom Chemistry
Volume 23, Number 1, 2012
PPh -Catalyzed Knoevenagel Condensation:
3
A Facile Synthesis of 5-(1H-indol-3-yl)Meth-
ylene)-2, 2-Dimethyl-1, 3-Dioxane-4, 6-Dione,
and Their N-Alkyl Derivatives by Using
PEG-600 as the Reaction Medium
Muvvala Venkatanarayana, and Pramod Kumar Dubey
Department of Chemistry, Jawaharlal Nehru Technological University,
Hyderabad College of Engineering, Kukatpally, Hyderabad 500 085, India
Received 17 March 2011; revised 12 June 2011; 18 June 2011
INTRODUCTION
ABSTRACT: Triphenylphosphine (TPP) has been
utilized as a novel and efficient catalyst for the Knoeve-
nagel condensation of indole-3-carboxaldehydes 1(a–
e), 1-methyl-1H-indole-3-carboxaldehydes 4(a–e), and
1-ethyl-1H-indole-3-carboxaldehydes 6(a–e) with the
active methylene compound, that is, meldrum’s acid
(2), to afford substituted derivatives 5-((1H-indol-3-yl)
methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione3(a–e),
2,2-dimethyl-5-((1-methyl-1H-indol-3-yl)methylene)-
1,3-dioxane-4,6-dione 5(a–e), and 2,2-dimethyl-5-((1-
ethyl-1H-indol-3-yl)methylene)-1,3-dioxane-4,6-dione
7(a–e), respectively, in ethanol medium at RT
just within 1 h in excellent yields. The products
3(a–e) were reacted independently with alkylating
agents, that is, DMS and DES in the presence of
PEG-600 as an efficient and green solvent, to afford
the corresponding N-substituted methyl and ethyl
Knoevenagel condensation is an important
carbon–carbon bond-forming reaction in organic
synthesis [1,2]. Ever since its discovery, the Kno-
evenagel reaction has been widely used in organic
synthesis to prepare coumarins and their deriva-
tives, which are known to be important intermedi-
ates in the synthesis of cosmetics, perfumes, and
pharmaceuticals [3–5]. In recent times, there has
been a growing interest in Knoevenagel products
because many of them have significant biological
activity.
The Knoevenagel reaction is generally carried
out in the presence of different catalysts such
as ethylenediamine, piperidine or corresponding
piperidinium salts, potassium fluroiodide [6–11],
acid catalysts [12–15], heterogeneous catalyst such
as xonotlite/tert-butoxide, cation-exchanged zeo-
lites, alkali containing MCM-41, SiO2 [16–25], and
recently, ionic liquids have also been employed to
accomplish this reaction [26].
ꢀ
C
derivatives 5(a–e) and 7(a–e), respectively.
2011
Wiley Periodicals, Inc. Heteroatom Chem 23:41–48, 2012;
View this article online at wileyonlinelibrary.com. DOI
10.1002/hc.20750
Earlier in 1986, Jones et al. reported [27] the re-
action of meldrum’s acid with indole-3-carboxalde-
hyde under flash-vacuum pyrolysis to yield the
Knoevenagel derivative of 5-((1H-indol-3-yl)methy-
lene)-2,2-dimethyl-1,3-dioxane-4,6-dione with 61%
yield. This method is more time-consuming and not
so good for the preparation of large amounts of these
Correspondence to: M. Venkatanarayana; e-mail: venkatphdm@
gmail.com.
Contract grant sponsor: University Grants Commission, Govt.
of India, New Delhi.
c
ꢀ
2011 Wiley Periodicals, Inc.
41

42 Venkatanarayana and Dubey
SCHEME 1 PPh3 Catalyzed Knoevenagel reaction.
products, moreover, it is a very good intermediate for
the preparation of anticancer drug [28].
adducts with high yields in less time. TPP acted as
a mild Lewis base to induce the reaction. In the ab-
sence of TPP, the reaction did not proceed even after
refluxing the reactants in ethanol for ≈24 h. The use
of TPP as a catalyst helps to avoid the use of environ-
mentally unfavorable organic solvents (DMF, C6H6,
DMSO, CHCl3, CH3CN, etc.) as the reaction medium.
The TPP was readily soluble in EtOH compared to
other solvents such as DMF, C6H6, etc.; that is why
the yield was also very high when the reaction was
carried out in the presence of the EtOH medium.
To compare the rate of the reaction in the pres-
ence of PPh3 in EtOH, we carried out the reaction
in different solvent media for conversion of 2a → 3a
(Table 2).
In this report, we have introduced the novel and
efficient catalyst, that is, triphenylphosphine (TPP)
for condensation of active methylene compound,
that is, meldrum’s acid (2), with different indole-3-
carboxaldehydes.
RESULTS AND DISCUSSION
Treatment of indole-3-carboxaldehydes 1(a–e), 4(a–
e), and 6(a–e) with active meldrum’s acid (2) in
ethanol at RT within 1 h furnished corresponding
Knoevenagel products 3(a–e), 5(a–e), and 7(a–e) in
excellent yields (90%–98%) (Scheme 1) (Table 1).
In all cases, the reaction proceeded smoothly with
30 mol% of TPP.
In some cases, yields were very high when the
nucleophile was very active, such as 5-nitroindole-3-
carboxaldehyde, N-methyl-5-nitroindole-3-carboxa-
ldehyde, and N-ethyl-5-nitroindole-3-carboxaldehyde.
This method was very facile and convenient for
the preparation of large amounts of Knoevenagel
Heteroatom Chemistry DOI 10.1002/hc

Facile Synthesis of 5-(1H-indol-3-yl)Methylene)-2, 2-Dimethyl-1, 3-Dioxane-4, and 6-Dione 43
TABLE 1 TPP Catalyzed Synthesis of 2, 2-Dimethyl-5-((1-methyl-1H-indol-3-yl)methylene)-1, 3-dioxane-4, 6-dionesa,b
S. NO.
Substrate
Product
Yield (%)
Time (min)
M.P. (◦C)
1
2
3
4
5
6
7
8
1a (R = H, R1= H)
3a (R = H, R1= H)
96
91
93
94
97
92
94
90
93
96
91
94
92
92
98
60
50
60
55
60
60
60
55
60
54
60
60
60
60
50
242–244
256
261
250–252[17]
240
219–220[17]
199–200
231–233
>260
1b (R = OMe, R1= H)
1c (R = H, R1= OMe)
1d (R = Br, R1= H)
1e (R = NO2, R1= H)
4a (R = H, R1= H)
3b (R = OMe, R1= H)
3c (R = H, R1= OMe)
3d (R = Br, R1= H)
3e (R = NO2, R1= H)
5a (R = H, R1= H)
4b (R = OMe, R1= H)
4c (R = H, R1= OMe)
4d (R = Br, R1= H)
4e (R = NO2, R1= H)
6a(R = H, R1= H)
5b (R = OMe, R1= H)
5c (R = H, R1= OMe)
5d (R = Br, R1= H)
5e (R = NO2, R1= H)
7a (R = H, R1= H)
9
10
11
12
13
14
15
212
201–202
141–143
169-170
198–199
150–152
6b (R = OMe, R1= H)
6c (R = H, R1= OMe)
6d (R = Br, R1= H)
6e (R = NO2, R1= H)
7b (R = OMe, R1= H)
7c (R = H, R1= OMe)
7d (R = Br, R1= H)
7e (R = NO2, R1= H)
aReaction Conditions: PPh3, indole-3-carboxaldehyde, meldrum’s acid, ethanol, RT.
bReaction Conditions: PEG-600 (Polyethylene glycol), DMS, DES, ꢀ (50–60◦C).
TABLE 2 The Rate of the Reactions Carried Out in Different Solvent Media for Conversion of 1a (R = H, R1= H) to 3a (R =
H, R1= H)
S. No.
Substrate Used
Reaction Conditions
Time (h)
Product Obtained
Yield (%)
1
2
3
4
5
1a
1a
1a
1a
1a
PPh3/EtOH/RT
PPh3/DMF/RT
Without catalyst/
PPh3/C6H6/RT
PPh3/CHCl3/RT
1
7
24
12
24
3a
3a
3a
3a
3a
96
44
NIL
32
NIL
However, 5-methoxyindole-3-carboxaldehyde, 6-me-
thoxyindole-3-carboxaldehyde, 5-bromoindole-3-
K2CO3 and TEBAC as phase transfer catalyst in
CH3CN at RT for 4–5 h gave the correspond-
ing N-methyl-indole-3-carboxyldehydes 4(a–e) and
N-ethyl-indole-3-carboxyldehydes 6(a–e). The com-
pounds 4(a–e) and 6(a–e) were obtained from 1(a–
e) by alkylation with DMS and DES using our earlier
described method [29].
It is obvious from the above results that PEG-
600 was a very effective solvent for methylation
and ethylation of 3a, resulting in 5a and 7a.
These results can be mechanistically explained by
PEG-600 dissolving the substrates [3a] and the
reagent (i.e., alkylating agents DMS and DES),
bringing them together and thereby providing
an effective mean for chemical reaction to oc-
cur. Furthermore, PEG-600 is able to extract the
hydrogen from the NH of olefin 3a and is able
to retain it by chelation through several lone pairs
of electrons in its oxygen-containing chain. This
role of PEG-600 is very similar to that of the
crown ethers or that of the proton sponge (i.e., 1,
8-dimethylaminonaphthalene). The proton sponge
carboxaldehyde, underwent condensation very
easily with meldrum’s acid in the presence of TPP.
A plausible mechanism for the formation of 3
from 1 and 2 in the presence of TPP as catalyst is
shown in Scheme 2. First the PPh3 abstracts the pro-
ton from meldrum’s acid (2) to form the carbanion
of meldrum’s acid, that is, 2II, which then attacks
the protonated indole-3-carboxaldehyde (1II) form-
ing the corresponding intermediate 1IV that loses wa-
ter to form the end product 3.
Treatment of 3(a–e) independently with DMS
and DES, each, in the presence of PEG-600 as a
facile and versatile reaction medium at 60◦C for
1 h, without using any base, gave corresponding
N-alkylated derivatives 5(a–e) and 7(a–e), respec-
tively, in excellent yields 95%–98% (Scheme 1).
5(a–e) and 7(a–e) could also be synthesized in an
alternative manner. Earlier it was reported from our
lab that the reaction of indole-3-carboxyldehydes
1(a–e) with DMS and DES in the presence
Heteroatom Chemistry DOI 10.1002/hc

44 Venkatanarayana and Dubey
SCHEME 2 Plausible mechanism for the formation of 3a in the presence of PPh3.
acts as a very strong base due to its ability to extract
hydrogen from an acidic substrate and then retain it
by chelation through a lone pair of electrons on the
two nitrogen atoms of the proton sponge (Scheme 3).
General Procedure for the Preparation of
3 from 1
A mixture of 1 (10 mmol), 2 (10 mmol, 1.44 g),
and TPP (30 mol%, 0.783 g) in ethanol (20 mL) was
stirred at RT for a specified period of time (Table 1).
After completion of reaction (as shown by TLC ex-
amination of the reaction mixture), the mixture was
poured into ice-cold water. The separated solid was
filtered, washed with water, and dried to obtain
crude 3. The latter were then recrystallized from
ethyl acetate to afford pure 3.
5-((1H-indol-3-yl)methylene)-2, 2-dimethyl-1, 3-
dioxane-4, 6-dione (3a) Yellow solid; Yield = 2.69g
(96%); m.p. 242–244◦C. IR (KBr): 3191 cm−1 (very
broad, NH), 1733 cm−1 (very strong, CO) and 1684
cm−1 (very strong, CO); 1H NMR (DMSO-d6/TMS):
δ 1.7 (s, 6H, 2CH3), 7.3–7.9 (m, 4H, aryl protons
of the indole ring), 8.8 (s, 1H, α-proton of the in-
dole ring), 9.3–9.4 (s, 1H, vinylic proton of the in-
dole ring), 12.8–12.9 (br, s, 1H, NH proton); 13C
spectrum (DMSO-d6/TMS): δ 27.2, 103.44, 103.86,
111.74, 113.78, 118, 123.46, 124.44, 129.30, 134, 140,
146.58, 159.4; MS (70 eV) m/z = 270 (M H); Calcd
for C15H13NO4 (271.27): C, 66.41; H, 4.83; N, 5.16.
Found: C, 66.43; H, 4.82; N, 5.20.
CONCLUSION
In summary, TPP has been employed for the first
time as a novel and efficient catalyst for the prepa-
ration of olefinic compounds by a Knoevenagel
reaction in ethanol. This method is applicable to
a wide range of indole-3-carboxyldehydes, includ-
ing N-substituted-indole-3-carboxyldehydes. The
attractive features of this procedure are the mild
reaction conditions, high conversions, operational
simplicity, and inexpensive and readily available
catalyst, all of which make it a useful and attrac-
tive strategy for the preparation of Knoevenagel
adducts. PEG-600 is also a very effective and green
solvent for making large amounts of N-substituted
Knoevenagel products.
EXPERIMENTAL
General
Melting points were determined using a Buchi melt-
ing point B-545 apparatus and are uncorrected. TLC
checking was done on glass plates coated with Sil-
ica Gel G and spotting was done using iodine or UV
lamp. IR spectra were recorded using Perkin Elmer
model-446 FTIR in KBr. 1H NMR and 13C NMR spec-
tra were recorded on a Gemini AV-400 instruments
operating at 400 MHz, respectively.
5-((5-methoxy-1H-indol-3-yl)methylene)-2, 2-di-
methyl-1, 3-dioxane-4, 6-dione (3b) Yellow solid;
Yield = 2.73 g (91%); m.p. 256◦C; IR(KBr): 3171
cm−1 (very broad, NH), 1727 cm−1 (very strong,
1
CO-) and 1676 cm−1(very strong, CO ); H NMR
(DMSO-d6/TMS): δ 1.72 (s, 6H, 2CH3), 3.83 (s,
3H, OCH3), 6.9–7.49 (m, 3H, aryl protons of the
indole ring), 8.7 (s, 1H, α-proton of the indole ring),
Heteroatom Chemistry DOI 10.1002/hc

Facile Synthesis of 5-(1H-indol-3-yl)Methylene)-2, 2-Dimethyl-1, 3-Dioxane-4, and 6-Dione 45
SCHEME 3 A plausible mechanism for the reaction of alkylation of olefins in the presence of PEG-600.
9.24 (s, 1H, vinylic proton of the indole ring), 12.77
(br, s, 1H, NH proton); 13C spectrum (DMSO-
d6/TMS): δ 27.81, 54.21, 102.98, 104.23, 112.40,
117.28, 119.1, 120.71, 124.12, 128.48, 132.10, 147,
151, 159.8; MS (70 eV) m/z = 300 (M H); Calcd for
C16H15NO5(301.1): C, 63.78; H, 5.02; N, 4.65. Found:
C, 64.12; H, 4.99; N, 4.68.
dole ring), 12.68 (br, s, 1H, D2O-exchangeble NH
proton); 13C spectrum (DMSO-d6/TMS): δ 27.61,
55.11, 103.14, 103.99, 111.92, 118 120.23, 122.2,
124.32, 128.12, 133.10, 149, 153, 159.76; MS 970 eV)
m/z = 300 (M H); Calcd for C16H15NO5 (301.1): C,
63.78; H, 5.02; N, 4.65. Found: C, 64.12; H, 4.99;
N, 4.68.
5-((6-methoxy-1H-indol-3-yl)methylene)-2, 2-di-
methyl-1, 3-dioxane-4, 6-dione (3c) Red color solid;
Yield = 2.79 g (93%); m.p. 261◦C. IR (KBr): 3163
cm−1 (very broad, NH) 1728 cm−1 (very strong,
CO) and 1680 cm−1(very strong CO); 1H NMR
(DMSO-d6/TMS): δ 1.68 (s, 6H, 2CH3), 3.78 (s,
3H, OCH3), 6.93–7.77 (m, 3H, aryl protons of
the indole ring), 8.64 (s, 1H, α-proton of the in-
dole ring), 9.21 (s, 1H, vinylic proton of the in-
5-((5-Bromo-1H-indol-3-yl)methylene)-2, 2-di-
methyl-1, 3-dioxane-4, 6-dione (3d) Orange color
solid; Yield = 3.28 g (94%); m.p. 250–252◦C.
IR(KBr): 3142 cm−1 (very broad, NH), 1731 cm−1
(very strong, CO) and 1679 cm−1(very strong, CO);
1H NMR (DMSO-d6/TMS): δ 1.69 (s, 6H, 2CH3) 7.44–
7.57 (m, 3H, aryl proton of the indole ring), 8.66
(s, 1H, α-proton of the indole ring), 9.27 (s, 1H
vinylic proton of the indole ring); 12.93 (br, s, 1H,
Heteroatom Chemistry DOI 10.1002/hc

46 Venkatanarayana and Dubey
NH proton); 13C spectrum
123.9, 127.48, 132.4, 146.4, 150, 159.7; MS (70 eV)
m/z = 286 (M+H); Calcd for C17H17NO5(315.32): C,
64.75; H, 5.43; N, 4.44. Found: C, 64.81; H, 5.39; N,
4.40.
5-((6-methoxy-1-methyl-1H-indol-3-yl)methyle-
ne)-2, 2-dimethyl-1, 3-dioxane-4, 6-dione (5c) Orange
solid; Yield = 2.83 g (90%); m.p. 231–233◦C; IR
(KBr): 1741 cm−1 (very strong, CO) and 1684
cm−1 (very strong, CO); 1H NMR (DMSO-d6/TMS):
δ1.70 (s, 6H, 2CH3), 3.49 (s, 3H, -OCH3), 4.03 (s,
D2O-exchangeble
(DMSO-d6/TMS): δ 27.12, 103.12, 103.93, 112.12,
116.12, 117.14, 123.12, 124.91, 130.8, 138.12, 146.12,
153.12, 159.12; MS (70 eV) m/z = 348 (M H); Calcd
for C15H12BrNO4(348.99): C, 51.45; H, 3.45; N, 4.00.
Found: C, 51.59; H, 3.34; N, 3.98.
5-((5-nitro-1H-indol-3-yl)methylene)-2, 2-dimeth-
yl-1, 3-dioxane-4, 6-dione (3e)Parrot green color
solid; Yield .= 3.06 g (97%); m.p. 240.◦C; IR(KBr):
3144 cm−1 (very broad, NH) 1732 cm−1 (sharp,
strong, CO), 1678 cm−1 (very strong, CO); 1H
NMR (DMSO-d6/TMS): δ 1.61 (s, 6H, 2CH3), 7.7–8.1
(m, 3H aryl protons of the indole ring), 8.84 (s, 1H,
α-proton of the indole ring), 9.38 (s, 1H, vinylic pro-
ton of the indole ring), 12.8 (br, s, 1H, NH pro-
ton); 13C spectrum (DMSO-d6/TMS): δ 27.38, 103.12,
104.1, 111.12, 113.6, 119, 122.3, 124.1, 128.12,
134.14, 142, 148.12, 160.4; MS (70 eV) m/z = 315
(M H); Calcd for C15H12N2O6(316.07): C, 56.96; H,
3.82; N, 8.86. Found: C, 57.05; H, 3.86; N, 8.80.
3H,
N
CH3), 7.3–7.68 (m, 3H aryl protons of the
indole ring), 8.68 (s, 1H, α-proton of the indole
ring), 9.28 (s, 1H, vinylic proton of the indole ring);
13C spectrum (DMSO-d6/TMS): δ 27.41, 45.4, 55.1,
103.22, 103.30, 111, 117.32, 122.6, 124.2, 128.18,
134.4, 141.4, 149.2, 160.8; MS (70 eV) m/z = 316
(M+H); Calcd for C17H17NO5(315.32): C, 64.75; H,
5.43; N, 4.44. Found: C, 64.81; H, 5.39; N, 4.40.
5-((5-bromo-1-methyl-1H-indol-3-yl)methylene)-2,
2-dimethyl-1, 3-dioxane-4, 6-dione (5d) Yellow solid;
Yield = 3.37 g (93%); m.p. > 260.◦C; IR (KBr): 1708
cm−1 (very strong CO) and 1622 cm−1 (very strong,
CO); 1H NMR (DMSO-d6./TMS): δ1.67 (s, 6H,
General Procedure for the Preparation of
5 from 3
2CH3), 4.21 (s, 3H,
N
CH3), 6.9–7.5 (m, 3H aryl
A mixture of 3 (10 mM), (DMS) (15 mM, 1.6 mL) and
PEG-600 (20 ml) was heated at 50–60◦C for 1 h. At
the end of this period, the mixture was poured into
ice-cold water and neutralized with 5% aq. NaOH.
The separated solid was filtered, washed with water,
and dried to obtain crude 5. The latter were then
recrystallized from ethyl acetate to afford pure 5.
2, 2-dimethyl-5-((1-methyl-1H-indol-3-yl)methyl-
ene)-1, 3-dioxane-4, 6-dione (5a) Yellow solid; Yield
= 2.62 g (92%); m.p. 219–220◦. IR (KBr): 1700 cm−1
(very strong, CO) and 1679 cm−1 (very strong,
CO); 1H NMR (DMSO-d6/TMS): δ 1.69 (s, 6H,
2CH3), 4.01 (s, 3H, N CH3), 7.36–7.91 (m, 4H aryl
protons of the indole ring), 8.68 (s, 1H, α-proton of
the indole ring), 9.30 (s, 1H, vinylic proton of the
indole ring); 13C spectrum (DMSO-d6/TMS): δ 27.41,
44.3, 103.51, 104.61, 111.12, 119.12, 122.9, 123.14,
126.39, 134.12, 136.12, 142.1, 150.21, 160.2; MS (70
eV) m/z = 286 (M+H); Calcd for C16H15NO4(285.29):
C, 67.36; H, 5.30. Found: C, 67.35, H, 5.29.
protons of the indole ring), 8.47 (s, 1H, α-proton of
the indole ring), 8.54 (s, 1H, vinylic proton of the
indole ring); 13C spectrum (DMSO-d6/TMS): δ 27.4,
45.4, 103.55, 104.13, 111.12, 117.1, 119.4, 122.34,
124.32, 130.8, 136.12, 144.1, 151.12,160; MS (70 eV)
m/z = 363 (M H); Calcd for C16H14BrNO4(364.19):
C, 52.77; H, 3.87; N, 3.85. Found: C, 52.80; H, 3.78;
N, 3.91.
5-((5-nitro-1-methyl-1H-indol-3-yl)methylene)-2,
2-dimethyl-1, 3-dioxane-4, 6-dione (5e) Yellow solid;
Yield = 3.17 g (96%); m.p. 212◦C; IR (KBr): 1722
cm−1 (very strong, CO) and 1672 cm−1 (very strong,
CO); 1H NMR (DMSO-d6/TMS): δ 1.71 (s, 6H,
2CH3), 4.20 (s, 3H, N CH3), 7.6–8.0 (m, 3H aryl
protons of the indole ring), 8.74 (s, 1H, α-proton
of the indole ring), 9.28 (s, 1H, vinylic proton of
the indole ring); 13C spectrum (DMSO-d6/TMS): δ
27.38, 47.2, 103.12, 104.1, 111.12, 113.6, 119, 122.3,
124.1, 128.12, 134.14, 142, 148.12, 159.9; MS (70 eV)
m/z = 331 (M+H); Calcd for C16H14N2O(330.09): C,
58.18; H, 4.27; N, 8.48. Found: C, 558.99; H, 4.29; N,
8.51.
3.4. General Procedure for the preparation of 7
from 3 A mixture of 3 (10 mM), (DES) (15 mM, 1.96
mL) and PEG-600 (20 mL) was heated at 50–60◦C
for 1 h. At the end of this period, the mixture was
poured into ice-cold water and neutralized with 5%
aq. NaOH. The separated solid was filtered, washed
with water and dried to obtain crude product 7. The
latter were then recrystallized from ethyl acetate to
afford pure 7.
5-((5-methoxy-1-methyl-1H-indol-3-yl)methyle-
ne)-2, 2-dimethyl-1, 3-dioxane-4, 6-dione (5b) Light
orange color solid; Yield = 2.96 g (94%); m.p.
199–200◦C; IR (KBr): 1743 cm−1 (very strong,
1
CO) and 1664 cm−1 (very strong, CO). H NMR
(DMSO-d6/TMS): δ 1.68 (s, 6H, 2CH3), 3.45 (s, 3H,
-OCH3), 3.96 (s, 3H,
N CH3), 6.9–7.58 (m, 3H aryl
protons of the indole ring), 8.65 (s, 1H, α-proton of
the indole ring), 9.23 (s, 1H, vinylic proton of the
indole ring); 13C spectrum (DMSO-d6/TMS): δ 27.36,
45.2, 53.11, 103.18, 104.23, 111.60, 118.18, 121.8,
Heteroatom Chemistry DOI 10.1002/hc

Facile Synthesis of 5-(1H-indol-3-yl)Methylene)-2, 2-Dimethyl-1, 3-Dioxane-4, and 6-Dione 47
2, 2-dimethyl-5-((1-ethyl-1H-indol-3-yl)methyl-
ene)-1, 3-dioxane-4, 6-dione (7a) Yellow solid;
for C17H16BrNO4(377.03): C, 53.99; H, 4.26; N, 3.70.
Found: C, 53.98; H, 4.25; N, 3.76.
Yield = 2.72 g (91%); m.p. 201–202◦C; IR (KBr):
1711 cm−1 (very strong, CO) and 1689 cm−1 (very
strong, CO); 1H NMR (DMSO-d6/TMS): δ 1.53
(t, 3H, CH3), 1.66 (s, 6H, 2CH3), 4.03 (q, 2H,
N CH2), 7.33–7.82 (m, 4H aryl protons of the in-
dole ring), 8.61 (s, 1H, α-proton of the indole ring),
9.34 (s, 1H, vinylic proton of the indole ring); 13C
spectrum (DMSO-d6/TMS): δ 14.7, 27.2, 44.5, 103,
110, 111, 113, 120.1, 121, 122, 127, 136.6, 138.2,
148.2, 161. MS (70 eV) m/z = 300 (M+H); Calcd for
C17H17NO4(299.32): C, 68.21; H, 5.72; N, 4.68. Found:
C, 68.19; H, 5.73; N, 4.70.
5-((5-nitro-1-ethyl-1H-indol-3-yl)methylene)-2, 2-
dimethyl-1, 3-dioxane-4, 6-dione (7e) Yellow solid;
Yield = 3.51 g (98%); m.p. 150–152◦C; IR(KBr):
1709 cm−1 (very strong, CO) and 1691 cm−1(very
1
strong, CO); H NMR (DMSO-d6/TMS): δ 1.56 (t,
3H, CH3), 1.71 (s, 6H, 2CH3), 4.65 (q, 2H, N CH2),
7.87–8.34 (m, 3H aryl protons of the indole ring),
8.23 (s, 1H, α-proton of the indole ring), 8.54 (s,
1H, vinylic proton of the indole ring); 13C spectrum
(DMSO-d6/TMS): δ 14.5, 27.38, 47.2, 103.12, 104.1,
111.12, 113.6, 119, 122.3, 124.1, 128.12, 134.14, 142,
150.9, 160; MS (70 eV) m/z = 345; (M+1); Calcd
for C17H16N2O6(344.01); C, 59.30; H, 4.68; N, 8.14.
Found: C, 59.32; H, 4.67; N, 8.10.
5-((5-methoxy-1-ethyl-1H-indol-3-yl)methylene)-2,
2-dimethyl-1, 3-dioxane-4, 6-dione (7b) Yellow solid;
Yield = 3.10 g (94%); m.p. 141–143◦C; IR(KBr): 1718
cm−1 (very strong, CO) and 1661 cm−1 (very strong,
CO); 1H NMR (DMSO-d6/TMS): δ 1.54, (t, 3H,
CH3), 1.67 (s, 6H, 2CH3), 3.62 (s, 3H, O CH3),
4.15 (q, 2H, CH2) 7.21–7.98 (m, 3H aryl protons of
the indole ring), 8.61 (s, 1H, α-proton of the indole
ring), 9.28 (s, 1H, vinylic proton of the indole ring);
13C spectrum (DMSO-d6/TMS): δ 14.6, 27.3, 43.4,
56.5, 102, 103.5, 110.1, 111, 113, 120.8, 126.3, 128.4,
152, 153.3, 161.1; MS (70 eV) m/z = 330 (M+H);
Calcd for C18H19NO5(329.35): C, 65.64; H, 5.81; N,
4.25. Found: C, 65.65; H, 5.80; N, 4.28.
5-((6-methoxy-1-ethyl-1H-indol-3-yl)methylene)-2,
2-dimethyl-1, 3-dioxane-4, 6-dione (7c) Yellow solid;
Yield = 3.03 g (92%); m.p. 169–170◦C; IR(KBr): 1721
cm−1 (very strong, CO) and 1686 cm−1 (very strong,
CO); 1H NMR (DMSO-d6/TMS): δ 1.53, (t, 3H,
CH3), 1.66 (s, 6H, 2CH3), 3.72 (s, 3H, O CH3),
4.12 (q, 2H, CH2), 7.43-7.99 (m, 3H aryl protons of
the indole ring), 8.71 (s, 1H, α-proton of the indole
ring), 9.38 (s, 1H, vinyl proton of the indole ring);
13C spectrum (DMSO-d6/TMS): δ 14.5, 27.2, 44, 56.2,
101.8, 104, 110.8, 112, 113.7, 121, 126, 127.9, 150.6,
152.8, 160.9; MS (70 eV) m/z = 330 (M+H); Calcd
for C18H19NO5 (329.35): C, 65.64; H, 5.81; N, 4.25.
Found: C, 65.65; H, 5.80; N, 4.28.
ACKNOWLEDGMENTS
The authors are indebted to the authorities of Jawa-
harlal Nehru Technological University Hyderabad
for providing laboratory facilities.
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1
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Heteroatom Chemistry DOI 10.1002/hc

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