Robinson's annelation: Synthesis of sydnone-containing 3′ -arylcyclohexenone derivatives under solvent free conditions

Article abstract of DOI:10.1081/SCC-120024746

3-Aryl-4-(6′-carbethoxy-5′-arylcyclohex-2′-enone- 3′-yl)sydnones 2a-i were prepared following Robinson's annelation by grinding chalcones 1a-i and ethylacetoacetate in the presence of potassium carbonate under solvent-free conditions.

Full text of DOI:10.1081/SCC-120024746

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Robinson's Annelation: Synthesis of Sydnone-Containing
3′-Arylcyclohexenone Derivatives Under Solvent Free
Conditions
Balakrishna Kalluraya a & Ganesha Rai a
a Department of Studies in Chemistry , Mangalore University , Mangalagangothri, Karnataka,
India
Published online: 15 Aug 2006.
To cite this article: Balakrishna Kalluraya & Ganesha Rai (2003) Robinson's Annelation: Synthesis of Sydnone-Containing 3′-
Arylcyclohexenone Derivatives Under Solvent Free Conditions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:20, 3589-3595, DOI: 10.1081/SCC-120024746
To link to this article: http://dx.doi.org/10.1081/SCC-120024746
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 20, pp. 3589–3595, 2003
Robinson’s Annelation: Synthesis of
Sydnone-Containing 30-Arylcyclohexenone
Derivatives Under Solvent Free Conditions
*
Balakrishna Kalluraya and Ganesha Rai
Department of Studies in Chemistry,
Mangalore University, Mangalagangothri,
Karnataka, India
ABSTRACT
3-Aryl-4-(60-carbethoxy-50-arylcyclohex-20-enone-30-yl)sydnones 2a–i
were prepared following Robinson’s annelation by grinding
chalcones 1a–i and ethylacetoacetate in the presence of potassium
carbonate under solvent-free conditions.
The subject of organic solid-state reactivity is a fascinating and a
frontier area of research in the context of green chemistry.[1] Besides
being of great academic interest, the exciting classes of chemical
*Correspondence: Balakrishna Kalluraya, Department of Studies in Chemistry,
Mangalore University, Mangalagangothri 574 199, Karnataka, India; E-mail:
bkalluraya_2001@yahoo.com.
3589
DOI: 10.1081/SCC-120024746
Copyright & 2003 by Marcel Dekker, Inc.
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3590
Kalluraya and Rai
reactions belonging to this field are expected to be of great synthetic
value.[2] Recent reports show that synthetically useful reactions like
Baeyer-Villiger oxidation,[3] FeCl3-assisted coupling of phenols,[4] pinacol
rearrangement[5] aldol condensation[6] formation of coumarins,[7] oxida-
tion of urazoles[8] Dieckmann condensation[9] etc., proceed efficiently in
the absence of solvent. Sydnone derivatives are interesting compounds
due to their electronic structure and also varied types of biological
activity. Among the various classes of sydnone derivatives, sydnone-4-
heterocycles show important pharmacological applications.[10–13]
These observations and our interest on developing eco-friendly
synthetic methods, we planned to synthesize 3-aryl-4-(60-carbethoxy-50-
arylcyclohex-20-enone-30-yl)sydnones under solvent free conditions.
The results of such studies are reported in this article.
RESULTS
The propenones 1a–i were prepared as per the literature method[12]
and well characterized. The title compounds were obtained by grinding
10-(3-arylsydnone-4-yl)-30-aryl-20-propenones 1a–i, ethylacetoacetate and
potassium carbonate in a mortar with a pestle without using any solvent
(Sch. 1). In the case of simple aryl substituted chalcones only aldol
condensation has been reported under the similar conditions.[14]
Surprisingly when one of the aryl groups is replaced with arylsydnone
ring the reaction rate largely enhanced and Robinson’s annelation
occurred in a very short period of 10–20 min. This surprising result may
be due to the electron withdrawing nature of the sydnone ring, which
increases the electrophilicity at the carbonyl carbon and facilitates
R
R
O
COOEt
O
N
CH3COCH2COOEt, grinding
no solvent, rt (10-20min)
N
N
N
Ar
Ar
O
O
O
O
1a-i
2a-i
Scheme 1.

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Robinson’s Annelation
3591
Michael addition followed by aldol condensation in a faster rate than
expected. Interestingly, in this method the sensitivity of sydnone ring
towards acids, bases, and high temperature, which causes rupture of the
ring, can be avoided. Under our experimental conditions yields are better
and also the reaction time is considerably reduced comparing with the
experiments carried in solvent medium.
The compounds were characterized by comparing their melting point
and mixed melting point with the samples prepared by routine solvent
phase reactions and also by analytical and spectral data. Spectral data for
synthesized compounds are given in experimental section.
EXPERIMENTAL
General
Melting points were determined by open capillary method and are
uncorrected. All compounds were analyzed satisfactorily for C, H, and
N. Infrared spectra (KBr disc) were recorded on a JASCO FT IR 430
1
spectrophotometer. H NMR spectra were recorded on Bruker AC 300F
(300 MHz) NMR spectrometer using CDCl3 as solvent and tetramethyl
silane as internal standard. The chemical shifts are expressed in ꢀ scale
downfield from TMS and proton signals are indicated as s ¼ singlet,
d ¼ doublet, t ¼ triplet, q ¼ quartet, m ¼ multiplet. Mass spectra were
recorded on a Jeol JMS-D 300 mass spectrometer operating at 70 eV.
General Procedure for the Preparation of 3-Aryl-4-(60-
carbethoxy-50-arylcyclohex-20-enone-30-yl)sydnones 2
10-(3-Arylsydnone-4-yl)-30-aryl-20-propenone 1a–i (1 mmol), potas-
sium carbonate (4 mmol) and ethylaetoacetate(1.5 mmol) were ground
together for 10–20 min in a mortar with a pestle at room temperature.
The progress of the reaction was monitored by TLC. After completion
of the reaction the product was poured into cold water, filtered, and
washed with water. Further, the products were purified by recrystalliza-
tion from ethanol–dioxan mixture solvent to get the pure compound
2a–i. The characterization data of the synthesized compounds are given
in Table 1.

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3592
Kalluraya and Rai

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Robinson’s Annelation
3593

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3594
Kalluraya and Rai
Spectral Data for Compounds 2a–i Are as Follows
2a. 1H NMR: ꢀ 1.01 (t, 3H, CH3), 2.72 (m, 1H, 50-H), 3.1–3.16
(dd, 2H, prochiral 40-H), 3.64 (d, 1H, 60-H), 4.3 (q, 2H, CH2), 5.85
(s, 1H, olefinic 20-H), 7.1–7.58 (m, 10H, Ar-H). MS m/z: 404 (Mþ).
Anal. calcd. for C23H20N2O5: C, 68.32; H, 4.95; N, 6.93. Found: C,
68.30; H, 4.91; N, 6.91.
2b. H NMR: ꢀ 1.21 (t, 3H, CH3), 2.76 (m, 1H, 50-H), 3.2–3.24 (dd,
1
2H, 40-H), 3.58 (d, 1H, 60-H), 3.87 (s, 3H, OCH3), 4.18 (q, 2H, CH2), 6.01
(s, 1H, olefinic 20-H), 6.9–7.4 (m, 9H, Ar-H). MS m/z: 434 (Mþ). Anal.
calcd. for C24H22N2O6: C, 66.36; H, 5.07; N, 6.45. Found: C, 66.37; H,
5.07; N, 6.42.
2c. H NMR: ꢀ 1.03 (t, 3H, CH3), 2.71 (m, 1H, 50-H), 3.0–3.07 (dd,
1
2H, prochiral 40-H), 3.62 (d, 1H, 60-H), 4.1 (q, 2H, CH2), 5.83 (s, 1H,
olefinic 20-H), 5.9 (s, 2H, OCH2O), 7.1–7.48 (m, 8H, Ar-H). MS m/z:
448(Mþ). Anal. calcd. for C24H20N2O7: C, 64.29; H, 4.46; N, 6.25.
Found: C, 64.29; H, 4.41; N, 6.21.
1
2d. H NMR: ꢀ 1.01 (t, 3H, CH3), 2.51 (s, 3H, CH3), 2.76 (m, 1H,
50-H), 3.08–3.17 (dd, 2H, prochiral 40-H), 3.62 (d, 1H, 60-H), 4.02 (q, 2H,
CH2), 5.84 (s, 1H, olefinic 20-H), 7.2–7.43 (m, 9H, Ar-H). MS m/z: 418
(Mþ). Anal. calcd. for C24H22N2O5: C, 68.90; H, 5.26; N, 6.70. Found C,
68.89; H, 5.28; N, 6.71.
1
2e. H NMR: ꢀ 1.18 (t, 3H, CH3), 2.46 (s, 3H, CH3), 2.64 (m, 1H,
50-H), 2.98–3.12 (dd, 2H, prochiral 40-H), 3.57 (d, 1H, 60-H), 3.76 (s, 3H,
OCH3), 4.16 (q, 2H, CH2), 5.91 (s, 1H, olefinic 20-H), 6.87–7.32 (m, 8H,
Ar-H). Anal. calcd. for C25H24N2O6: C, 66.96; H, 5.36; N, 6.25. Found C,
66.91; H, 5.38; N, 6.25.
2f. 1H NMR: ꢀ 1.07 (t, 3H, CH3), 2.49 (s, 3H, CH3), 2.65 (m,
1H, 50-H), 3.0–3.07 (dd, 2H, prochiral 40-H), 4.0 (d, 1H, 60-H), 4.05 (q,
2H, CH2), 5.89 (s, 1H, olefinic 20-H), 5.93 (s, 2H, OCH2O), 6.64 (d, 2H,
o-protons of p-tolyl), 7.39 (d, 2H, m-protons of p-tolyl), 6.61–7.475 (m,
3H, Ar-H). MS m/z: 462 (Mþ). Anal. calcd. for C25H22N2O7: C, 64.94; H,
4.76; N, 6.06. Found: C, 64.91; H, 4.78; N, 6.01.
2g. H NMR: ꢀ 1.05 (t, 3H, CH3), 2.46 (m, 1H, 50-H), 3.2–3.4 (dd,
1
2H, 40-H), 3.63 (d, 1H, 60-H), 3.98 (s, 3H, OCH3), 4.13 (q, 2H, CH2), 6.01
(s, 1H, olefinic 20-H), 6.51 (d, 2H, o-protons of p-anisyl), 7.43 (d, 2H,
m-protons of p-anisyl), 6.7–7.45 (m, 5H, Ar-H). Anal. calcd.
for C24H22N2O6: C, 66.36; H, 5.07; N, 6.45. Found: C, 66.39; H,
5.10; N, 6.46.
2h. H NMR: ꢀ 1.18 (t, 3H, CH3), 2.53 (m, 1H, 50-H), 3.0–3.15 (dd,
1
2H, 40-H), 3.71 (d, 1H, 60-H), 3.89 (s, 3H, OCH3), 4.03 (s, 3H, OCH3),
4.21 (q, 2H, CH2), 5.94 (s, 1H, olefinic 20-H), 6.6–7.62 (m, 8H, Ar-H).

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Robinson’s Annelation
3595
MS m/z: 464 Anal. calcd. for C25H24N2O7: C, 64.66; H, 5.17; N, 6.03.
Found: C, 64.69; H, 5.18; N, 6.06.
2i. 1H NMR: ꢀ 1.14 (t, 3H, CH3), 2.66 (m, 1H, 50-H), 3.0–3.1 (dd, 2H,
40-H), 3.55 (d, 1H, 60-H), 3.92 (s, 3H, OCH3), 4.06 (q, 2H, CH2), 5.87 (s,
1H, olefinic 20-H), 5.95 (s, 2H, OCH2O), 6.65–7.46 (m, 7H, Ar-H). MS
m/z: 478 (Mþ). Anal. calcd. for C25H22N2O8: C, 62.76; H, 4.60; N, 5.86.
Found: C, 62.72; H, 4.61; N, 5.82.
ACKNOWLEDGMENTS
The authors thank Head, RSIC, Chandigarh, and CDRI, Lucknow,
for spectral and analytical data.
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