In the Laboratory edited by
Green Chemistry
Mary M. Kirchhoff ACS Green Chemistry Institute Washington, DC 20036
Synthesis of meso-Diethyl-2,2’-dipyrromethane in Water
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An Experiment in Green Organic Chemistry Abilio J. F. N. Sobral Department of Chemistry, University of Coimbra, Coimbra, Portugal;
[email protected] The importance of pyrrolic compounds in the areas of porphyrins (1, 2), materials science (3), optics (4), and medicine (5–7) is well-documented. Dipyrromethanes (or dipyrrilmethanes) are important building blocks for many of the structures of interest in the above-mentioned areas and a variety of conditions have been established for the synthesis of dipyrromethanes of diverse structures, from substituted pyrroles (8–11) to unsubstituted pyrrole and carbonyl compounds (12–15). These reactions are generally based on the acid-catalyzed condensation of pyrrole with aldehydes or ketones. Careful control is needed to stop the reaction when the dipyrromethane concentration is at its maximum, and final workup requires the distillation of the excess pyrrole. Recently we published a green approach to this reaction, obtaining the dipyrromethanes by acid condensation of equimolar amounts of pyrrole and carbonyl compounds in water, under HCl catalysis (16). The use of water as solvent in organic reactions is currently one of the most important issues in green chemistry, a field where new chemical methodologies are being developed to reduce the environmental impact of many chemical processes (17–31). In this laboratory activity we describe its use as a solvent in the synthesis of meso-diethyl-2,2´dipyrromethane from 3-pentanone and pyrrole, constituting an easy and well-defined undergraduate experiment in green organic chemistry. The product, dipyrromethane, is easily isolated by spontaneous phase separation and crystallizes from the melt, allowing its easy characterization (Scheme I).
place. Pyrrole is a flammable liquid and vapor; is harmful if swallowed; may be harmful if inhaled or absorbed through skin; and may cause irritation to skin, eyes, and respiratory tract. 3-Pentanone is highly flammable; readily forms explosive mixtures with air; is incompatible with strong bases, reducing agents, and strong oxidizing agents; and is an eye, skin, and respiratory irritant. HCl 37% (conc) is corrosive; ingestion may cause esophagus and digestive tract burns, circulatory system failure, and possible death; inhalation may cause sore throat, coughing, and delayed lung edema; skin contact causes severe burns and ulceration; and eye contact causes burns and irreversible eye injury. meso-Diethyl-2,2´dipyrromethane has no information available yet, but the compound should be handled as a potential health hazard. Conclusion The synthesis of meso-diethyl-2,2´-dipyrromethane from pyrrole and 3-pentanone in water is an efficient process, adequate for an undergraduate experiment in green organic heterocyclic chemistry. This green synthesis of dipyrromethanes involves negligible subsequent purification procedures since the dipyrromethane product separates from the aqueous phase spontaneously and gives good yields of pure compound in a one-pot reaction in water. Acknowledgment The author is grateful to FCT, FEDER (POCI/AMB/ 55281/2004) for financial support.
Experimental To a solution of 3.8 mL (0.036 mol) of 3-pentanone in 100 mL of hot water (90–100 ⬚C), 0.5 mL of 37% aqueous HCl is added, followed by the dropwise addition of 5 mL (0.072 mol) of pyrrole. After refluxing for 45–50 minutes, the suspension is left to cool to 40–50 ⬚C, the upper layer is then transferred to another flask using a separatory funnel and allowed to cool to room temperature. Over several hours (one day is preferable) the product crystallizes in large pale white crystals, giving 5.8 g of the desired meso-diethyl-2,2´dipyrromethane in near 80% yield. Hazards All experiments should be performed in an efficient fume hood, wearing safety glasses and gloves. Special care should be used in handling the hot water where the reaction takes www.JCE.DivCHED.org
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Scheme I. Synthesis of meso-diethyl-2,2´-dipyrromethane from 3pentanone and pyrrole.
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Supplemental Material
Detailed student procedures; postlab questions and answers; instructor notes with comments on the experiment; CAS numbers; extended hazards section; elemental analysis; MS; 1H NMR; FTIR; and X-ray results are available in this issue of JCE Online. Note This article is dedicated to Hugh D. Burrows from the University of Coimbra, Portugal, on the occasion of his 60th birthday.
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