A Novel Method for the Synthesis of Dipyrromethanes Under

ISSN: 0973-4945; CODEN ECJHAO

E-Journal of Chemistry

http://www.ejchem.net 2012, 9(4), 1796-1800

A Novel Method for the Synthesis of Dipyrromethanes

Under Solvent-Free Condition

KABEER A. SHAIKH*1

, VISHAL A. PATIL1, AND AZEEM AHMED

2

1Organic Synthesis Laboratory, Sir Sayyed College, Dr. Babasaheb Ambedkarb Marathwada

University, Aurangabad 431001, India 2MVS Goverment Degree and P. G. Collegs, Mahbubnagar, India

[email protected]

Received 25 July 2011; Accepted 05 September 2011

Abstract: This study describes a successful approach for the synthesis of

dipyrromethanes using iodine as a catalyst on grinding. This protocol does not

require any solvent and carried out at lowest pyrrole/aldehyde ratio which

makes this method economically and environmentally attractive. This protocol

affords the products immediately with excellent yield.

Keywords: Pyrrole, Ketone, Dipyrromethanes, Iodine, Solvent free.

Introduction

As we know, green chemistry is defined as the design of chemical products and processes

that reduce or eliminate the use and generation of hazardous substances. For the purposes of

this definition, synthetic chemists have great interest in developing highly efficient

transformations for the preparation of organic compounds. One of the main themes of

contemporary synthetic organic chemistry is the use of environmentally feasible reagents

particularly in solvent-free conditions and environmentally benign catalytic systems, which

are also required to be efficient and economic. Solvent-free organic reactions are usually

rapid, eco-friendly, high yielding, and economically viable. In this context, organic reactions

under solvent-free conditions at room temperature have been achieved.

Dipyrromethanes are compounds known for more than a century and are widely being

used as important building blocks for the synthesis of porphyrins 1, Calixpyrrols

2 and

Corroles3. Which have recent applications as chiral catalysts, chiral sensors, synthetic

receptors for small molecular devices, potential sensitizers for photodynamic cancer therapy 4-6

. In the past decades, a variety of conditions have been established for the synthesis of

dipyrromethanes in the presence of various catalysts such as p-toluenesulfonic acid 7,8

, TiCl4 9, CF3COOH

10-12, pyrrolidinium tetrafluoroborate

13. Recently, several methods have been

developed, for the synthesis of dipyrromethanes in various catalysts such as ionic liquid

A Novel Method for the Synthesis of Dipyrromethanes 1797

[Hmim] BF4 14

, HCL/water 15

, cation exchange resin 16

, metal triflate catalysis 17

, HCl 18

,

iodine/CH2Cl2 19

, InCl3 20

and methanesulfonic acid 21

. However, all of the synthetic

protocols reported so far suffer from disadvantages such as, use of metal 17

and expensive

reagent 16

, prolonged reaction time 18

, use of organic solvent 19

, harsh reaction condition 18,21

,

use of excess pyrrole 17

and low yield.14

, because of that the researcher still continuous to

have a better methodology for the synthesis of dipyrromethanes in terms of simplicity, eco-

friendly, economic viability and high yielding at lowest pyrrole/aldehyde ratio. This is

achieved by using iodine under solvent free condition. In recent years I2 in solvent free

conditions was found to be an efficient catalyst in terms of handling, temperature, reaction

time and yield for various organic transformations 22-25

.

Experimental

Purity of the compounds were checked by thin layer chromatography (TLC) on Merck silica

gel 60 F254 pre-coated sheets Melting points of the synthesized compounds were

determined in open-glass capillaries on a stuart-SMP10 melting point apparatus. 1H-NMRs

were recorded on a Bruker spectrometer operating at 200 MHz. The 1H-NMR chemical

shifts are reported as parts per million (ppm) downfield from TMS (Me4Si) used as an

internal standard. Mass spectra were recorded on LCQ ion trap mass spectrometer.

All compounds were known, and all physical and spectroscopic data were compared with

authentic samples.

General Procedure for the synthesis of dipyrromethanes

A mixture of pyrrole (2 mmol), ketone (1 mmol) and I2 (0.1 mmol) was crushed in a mortar

with a pestle at room temperature. Progress of reaction was monitored by TLC. After

completion of reaction (< 1 min) the crude product was washed with water, dried and

purified by column chromatography using silica gel with petroleum ether/chloroform as the

eluent. Pure products were obtained as solids.

Data

meso-Methyl-meso-phenyl- 2,2_-pyrromethane (1): mp: 103-104 °C. 1HNMR: (CDCl3, 200

MHz), δ: 7.34, (2H, s, NH), 7.22 (3H, m, phenyl), 7.15 (2H, m, phenyl), 6.61 (2H, m,

pyrrole), 6.17 (2H, m, pyrrole), 5.95 (2H, m, pyrrole), 2.1 (3H, s, CH3), MS (ES): m/z 236

(MH+).

Diphenyldipyrrolylmethane (4): mp: 258-260 °C.1HNMR: (CDCl3, 200 MHz), δ: 7.90 (2H,

br s, NH), 7.21 (6H, m, phenyl), 7.10 (4H, m, phenyl), 6.75 (2H, m, pyrrole), 6.18 (2H, dd, J

= 2.8, 5.8 Hz, pyrrole), 5.92 (2H, m, pyrrole). MS (ES): m/z 298 (MH+).

Results and Discussion

We began our study by grinding the mixture of pyrrole (2 mmol) ketone (1 mmol) and

iodine (0.1 mmol) under solvent free condition (Scheme 1).

KABEER A. SHAIKH 1798

NH

2 +Grinding

NHNH

Ph CH3I2

Ph CH3

O

Scheme 1. Synthesis of meso-Methyl-meso-phenyl-2,2’-pyrromethane.

The result demonstrated that this protocol gives excellent yield of the product. Thus,

from this result it was cleared that there is no need of solvent for the synthesis of

dipyrromethanes. In this protocol iodine plays excellent role as a Lewis-acid catalyst,

because its absence did not conduce to the desired product.

The generality of the reaction was authenticated by taking various ketones with pyrrole

under solvent free condition (scheme 2).

NH

2 +Grinding

NHNH

R1 R2I2

R1 R2

O

1 2 3 Scheme 2. Synthesis of various dipyrromethanes.

The results demonstrated that all products give excellent yield (90-97%). When we

compared this result with literature best result (Table 1) then it was cleared that all reported

literatures were suffered from disadvantages such as expensive reagent 14

, prolonged

reaction time 21

, use of hazardous catalyst 15, 21

and use of excess pyrrole/aldehyde ratio 14, 21

.

Thus, in this article our strength is that we overcome all this disadvantages with excellent

yield. The probably mechanism for synthesis of substituted dipyrromethanes has shown in

scheme 3.

NH

+R1 R2

O I2'''''''''''

N

R1

OHR2

N

R1

R2

Pyrrole

NHNH

R2R1

-H2O

Scheme 3. The probably mechanism for the synthesis of dipyrromethanes.

A Novel Method for the Synthesis of Dipyrromethanes 1799

Table 1. Comparison of the yields with best methods found in the literatures.

Entry Ketone Time

(min)

Products Yielda

(%)

Literatures

best yield

(%)

1

Ph Me

O

< 1

NHNH

Ph Me

97

82[15]

2

O

< 1

NHNH

90

44[14]

3

Et Et

O

< 1

NHNH

Et Et

95

90[15]

4

Ph Ph

O

< 1

NHNH

Ph Ph

92

13[21]

5

Et Me

O

< 1

NHNH

Et Me

94

56[14]

a: Isolated yield of the products.

Conclusion

In conclusion, a simple and efficient procedure for the synthesis of dipyrromethanes has

been explored. Mild reaction conditions, absence of solvent, shorter reaction time, easy and

quick isolation of the products and excellent yields are main advantages of this procedure,

which make this method economically and environmentally attractive.

Acknowledgments

We would like to thank DST, New Delhi for financial assistance and Prof. Mohammed

Tilawat Ali for providing necessary facilities for research work.

KABEER A. SHAIKH 1800

References

1. Temelli B, Unaleroglu C. Tetrahedron 2009, 65, 2043-50.

2. Gale P A, Anzenbacher P Jr, Sessler J L. Coord Chem Rev 2001; 222, 57-102.

3. Zhan H-Y, Liu H-Y, Chen H-J, Jiang H-F. Tetrahedron Lett 2009, 50, 2196.

4. Sternberg E D, Dolphin D. Tetrahedron 1998, 54, 4151.

5. Halterman R L, Mei X. Tetrahedron Lett 1996, 37, 6291.

6. Furusho Y, Kimura T, Mizuno Y, Aida T. J Am Chem Soc 1997, 119, 5267.

7. Boyle R W, Xie L Y, Dolphin D. Tetrahedron Lett 1994, 35, 5377.

8. Mizutani T, Ema T, Tomita T, Kuroda Y. Ogoshi H. J Am Chem Soc 1994, 116, 4240.

9. Setsune J-I, Hashimoto M, Shiozawa K, Hayakawa J-Y, Ochi T, Masuda R.

Tetrahedron 1998, 54, 1407.

10. Srinivasan A, Sridevi B, Reddy M V R, Narayanan S J, Chandrashekar T K.

Tetrahedron Lett 1997, 38, 4149.

11. Lee C H, Lindsay J S. Tetrahedron 1994, 50, 11427.

12. Littler B J, Miller M A, Hung C-H, Wagner R W, O’Shea D F, Boyle P D. J Org Chem

1999, 64, 1391.

13. Biaggi C, Benaglia M, Raimondi L, Cozzi F. Tetrahedron 2006, 62, 12375.

14. Gao G H, Lu L, Gao J B, Zhou W J, Yang J G, Yu X Y. Chin Chem Lett 2005, 16, 900.

15. Sobral A J F N, Rebanda N G C L, Silva M D, Lampreia S H, Silva M R, Beja A M.

Tetrahedron Lett 2003, 44, 3971.

16. Naik R, Joshi P, Kaiwar S P, Deshpande R K. Tetrahedron 2003, 59, 2207.

17. Tamelli B, Unaleroglu C A. Tetrhedron 2006, 62, 10130.

18. Rohand T, Dolusic E, Ngo T H, Maes W, Dehaen W. ARKIVOK 2007, (x), 307.

19. Faugeras P-A, Boëns B, Elchinger P-H, Vergnaud J, Teste K. Tetrahedron Lett 2010,

51, 4630.

20. Laha J K, Dhanalekshami S, Taniguchi M, Ambroise A, Lindsey J S. Org Process Res

Dev 2003, 7, 799.

21. Freckmann D M M, Dube T, Be´rube C D, Gambarotta S, Yap, G P A. 2002, 21, 1240.

22. Das B, Laxminarayana K, Ravikanth B, Rao B R. Journal of Molecular Catalysis A:

Chemical 2007, 261, 180.

23. Banik B K, Fernandez M, Alvarez C. Tetrahedron Lett 2005, 46, 2479.

24. Wang H S, Zeng J E. Chin Chem Lett 2007, 18, 1447.

25. Pasha M A, Jayashankara V P. Bioorganic & Medicinal Chemistry Letters 2007, 17,

621.

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A Novel Method for the Synthesis of Dipyrromethanes Under