4
Tetrahedron
desired compounds (Scheme 6). The aldehyde substituent (R2)
3.
Santo, R. Di; Tafi, A.; Costi, R.; Botta, M.; Artico, M.; Corelli, F.;
Forte, M.; Caporuscio, F.; Angiolella, L.; Palamara, A. T. J. Med.
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Bialer, M.; Yagen, B.; Mechoulam, R.; Becker, Y. J. Med. Chem.
1980, 23, 1144.
(a) Dannhardt, G.; Kiefer, W.; Krämer, G.; Maehrlein, S.; Nowe,
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(a) Wakabayashi, K.; Imai, K.; Miyachi, H.; Hashimoto, Y.;
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(a) Takase, M.; Yoshida, N.; Narita, T.; Fujio, T.; Nishinaga, T.;
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(a) Knorr, L. Ber. 1884, 17, 1635; (b) Knorr, L. Ann. 1886, 236,
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Cheng, L.; Lightner, D. A. Synthesis 1999, 46; (e) Rapoport, H.;
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was found to significantly affect the course and yield of the
reaction (Table 4).
4.
5.
Scheme 6. A convenient synthesis of 4-alkyl-3-benzoylpyrrole derivatives
Table 4. Synthesis of 4-alkyl-3-benzoylpyrrolesa
Entry
1
6.
R1
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
OCH3
OCH3
OCH3
OCH3
OCH3
CH3
CH3
CH3
CH3
CH3
R2
-CH3
-CH2CH3
-CH2CH2CH3
-CH(CH3)2
-CH2CH(CH3)2
-CH3
Product
16aa
16ab
16ac
16ad
16ae
16ba
16bb
16bc
16bd
16be
16ca
16cb
16cc
16cd
16ce
16da
16db
16dc
16dd
16de
16ea
16eb
16ec
16ed
16ee
Yieldb (%)
75
7.
8.
2
3
4
5
6
7
8
9
76
80
85
81
73
75
79
86
81
74
77
78
82
79
68
70
73
83
78
69
72
76
85
84
-CH2CH3
-CH2CH2CH3
-CH(CH3)2
-CH2CH(CH3)2
-CH3
9.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
10. (a) Hantzsch, A. Ber. 1890, 23, 1474; (b) Feist, F. Ber. 1902, 35,
1538; (c) Trautwein, A. W.; Submuth, R. D.; Jung, G. Bioorg.
Med. Chem. Lett. 1998, 8, 2381; (d) Roomi, M. W.; MacDonald,
S. F. Can. J. Chem. 1970, 48, 1689.
11. (a) Paal, C. Ber. 1885, 18, 367; (b) Knorr, L. Ber. 1885, 18, 299;
(c) Minetto, G.; Raveglia, L. F.; Sega, A.; Taddei, M. Eur. J. Org.
Chem. 2005, 70, 5277; (d) Rao, H. S. P.; Jothilingam, S.;
Scheeren, H. W. Tetrahedron 2004, 60, 1625; (e) Amarnath, V.;
Anthony, D. C.; Amarnath, K.; Valentine, W. M.; Wetterau, L. A.;
Graham, D. G. J. Org. Chem. 1991, 56, 6924.
-CH2CH3
-CH2CH2CH3
-CH(CH3)2
-CH2CH(CH3)2
-CH3
-CH2CH3
-CH2CH2CH3
-CH(CH3)2
-CH2CH(CH3)2
-CH3
12. Trofimov, B. A.; Nedolya, N. A. Comprehensive Heterocyclic
Chemistry III; Elsevier, 2008; p. 45.
-CH2CH3
13. (a) Maiti, S.; Biswas, S.; Jana, U. J. Org. Chem. 2010, 75, 1674;
(b) Sarkar, S.; Bera, K.; Maiti, S.; Biswas, S.; Jana, U. Synth.
Commun. 2013, 43, 1563; (c) Li, L.; Zhao, MN.; Ren, ZH.; Li J.;
Guan, ZH. Synthesis 2012, 532; (d) Khan, A. T.; Lal, M.; Bagdi,
P. R; Basha, R. S.; Saravanan, P.; Patra, S. Tetrahedron Lett.
2012, 53, 4145.
-CH2CH2CH3
-CH(CH3)2
-CH2CH(CH3)2
a1-Phenyl-2-(triphenylphosphoranylidene)ethanone (1.0 mmol), aldehyde
(1.0 mmol), ethanol (5.0 mL), TosMIC (1.1 mmol), LiOH.H2O (0.2 mmol),
room temperature; bIsolated yield.
14. Jadhav, N. C.; Jagadhane, P. B.; Patile, H. V.; Telvekar, V. N.
Tetrahedron Lett. 2013, 54, 3019.
3. CONCLUSION
15. Est´evez, V.; Villacampa, M.; Men´endez, J. C. Chem. Commun.
2013, 49, 591.
16. Meshram, H. M.; Babu, B. M.; Kumar, G. S.; Thakur, P. B.;
Bangade, V. M. Tetrahedron Lett. 2013, 54, 2296.
A
convenient method for the synthesis of 4-alkyl-3-
benzoylpyrroles in good to excellent yields is reported. The
course of the reaction is influenced by the nature of the alkyl
substituents. This methodology also allows a cost effective
synthesis of 4-alkyl-3-benzoylpyrroles with ease in purification.
17. Silveira, C. C.; Mendes, S. R.; Martins, G. M.; Schlösser, S. C.;
Kaufman, T. S. Tetrahedron 2013, 69, 9076.
18. Reddy, G. R.; Reddy, T. R.; Joseph, S. C.; Reddy, K. S.; Meda, C.
L. T.; Kandale, A.; Rambabu, D.; Rama Krishna, G.; Malla
Reddy, C.; Parsa, K. V. L.; Shiva Kumar, K.; Pal, M. RSC Adv.
2012, 2, 9142.
ACKNOWLEDGMENT
19. Smith, G. F. Adv. Heterocycl. Chem. 1963, 2, 287.
20. (a) Kumar, V.; Raghavaiah, P.; Mobin, S. M.; Nair, V. A. Org.
Biomol. Chem. 2010, 8, 4960; (b) Kumar, V.; Nair, V. A.
Tetrahedron Lett. 2010, 51, 966; (c) Khatik, G. L.; Khurana, R.;
Kumar, V. Nair, V. A.; Synthesis 2011, 3123; (d) Kumar, V.;
Khatik, G. L.; Nair, V. A. Synlett 2011, 60, 2997; (e) Chouhan,
M.; Senwar, K. R.; Sharma, R.; Grover, V.; Nair, V. A. Green
Chem. 2011, 13, 2553; (f) Kumar, V.; Pal, A.; Khatik, G. L; Nair,
V. A. Tetrahedron: Asymmetry 2012, 23, 434; (g) Khatik, G. L.;
Kumar, V.; Nair, V. A. Org. Lett. 2012, 14, 2442; (h) Chauhan,
M.; Sharma, R.; Nair, V. A. Org. Lett. 2012, 14, 5672; (i) Kumar,
V.; Kumar, K.; Pal, A.; Khatik, G. L.; Nair, V. A. Tetrahedron
2013, 69, 1747; (k) Khatik, G. L.; Sharma, R.; Kumar, V.;
Chouhan, M; Nair, V. A. Tetrahedron Lett. 2013, 54, 5991. (l)
Kumar, V.; Rachamalla, M.; Nandekar, P.; Khatik, G. L.;
Sangamwar, A. T.; Tikoo, K.; Nair, V. A. RSC Adv. 2014, 4,
37868; (m) Chouhan, M.; Senwar, K. R.; Kumar, K.; Sharma, R.;
Nair, V. A. Synthesis 2014, 46, 0195; (n) Kumar, K.; Mudshinge,
S. R.; Goyal, S.; Gangar, M.; Nair, V. A. Tetrahedron Lett. 2015,
56, 1266.
Research funding from the department of science and technology
(DST), Government of India is gratefully acknowledged.
SUPPLEMENTARY DATA
Supplementary data (experimental procedures, compound data
1
13
and scanned spectra ( H NMR, C NMR and HRMS)) associated
with this article can be found, in the online version.
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