Method for the synthesis and evaluation of porphyrins, calix (4) pyrroles and allied macrocycles

#The present invention relates to a method for the in-situ synthesis and screening of tetra-arylporphyrins, meso-octamethyl calix(4)pyrroles and allied macrocycles by reacting pyrrole and corresponding aldehydes and ketones using a specific zeolite based molecular sieve catalyst as sorbent in thin layer chromatography under microwave irradiation. In particular, the present invention provides new opportunities for parallel synthesis and screening on a single plate for producing tetraphenyl porphyrins by reacting pyrrole with benzaldehyde and calix(4)pyrroles from pyrrole and acetone in presence of zeolites and MCM-41 molecular sieves as sorbents in TLC under microwave irradiation with an online spectroscopic evidence.

#The process of the invention leads to efficient and quantitative method for the screening of the selective catalytic activity of a zeolite catalyst as sorbents in TLC for in-situ synthesis of tetraaryl porphyrins, calix(4)pyrroles and allied macrocycles. The zeolite based TLC plays the role of a microreactor cum separator exemplified by rapid processing for possible applications to combinatorial chemistry.

#In recent years, significant effort has been directed towards the design and synthesis of macrocycles such as porphyrins and calix(4)pyrroles over mesoporous molecular sieves. Among the various macrocycles, extensive research in the area of synthesis, characterization and utilization of porphyrins and calixpyrroles is in progress. Synthesis of Porphyrin and Calix(4)pyrrole compounds as well as methods for synthesising the same are well recognised in the art. Porphyrins are conjugated macrocyclic species composed of four pyrrole rings linked to the position via sp2 hybridized carbon atoms. However porphyrin and pyrrole compounds are expensive. For example, porphyrin is offered at costs as high as $15,000/g. Even though a great variety of catalysts like organic and inorganic acid catalysed syntheses are reported they suffer from the reusability of the catalyst and poor yields. Further, the impure corroles formation makes the separation of the pure compound difficult. The first such report of synthesis of porphyrin molecules under microwave irradiation by A. Petit et al (Synthetic Communication 22(8) (1992) 1139) by employing silica alumina, clay and montmorillonite as a catalyst is popular but it suffers from poor yields (not more than 10%).

#The present invention provides an improved process that comprises a combinatorial approach with environmentally clean technology, low wastage, less cumbersome, very fast, easily separable method with an online spectroscopic screening facility.

#The catalyst used in this process is easily coated on the glass backed TLC plate with a help of a binder. The zeolite support used acts as a micro reactor type stationary phase and also as an acid catalyst. The method provides a reaction, which is accelerated by microwave irradiation, development and evaluation by online spectroscopic data in a combinatorial approach. The present invention relates to novel method for in-situ synthesis of tetraphenyl porphyrins by reacting pyrrole with aromatic aldehyde over zeolite backed TLC plates under microwave irradiation, where in the catalyst could be obtained by commercial outlet or by synthesis. The aromatic aldehydes used in the present invention include, benzaldehyde, o, m and p-substituted benzaldehydes and a plethora of aliphatic aldehydes. Representative examples of ketones include, acetone, methyl ethyl ketone, diethyl ketone, cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, cyclododecanone, substituted cyclohexanones, acetophenone and alkyl and aryl derivatives thereof. The molecular sieves used in the present invention include commercially available HZSM-5, HY, Hβ, HX, and synthetically prepared SAPO-5 and mesoporous MCM-41. For example, zeolites of HZSM-5 series are available from Conteka, Sweden, HY and Hβ from PQ corporation USA. The methods for producing them are described in detail in U.S. Pat. No. 3,702,886 (ZSM-5). Furthermore, MCM-41 (C. T. Kresge, M. E. Leonowicz, W. J. Roth, J. C. Vartuli and J. S. Beck, Nature 359 (1992) is synthesized by an aqueous solution of aluminum isopropoxide (0.76 g) to which an aqueous solution of sodium hydroxide (0.3 g) was added in 50 ml beaker and stirred in hot conditions, till a clear solution was formed. Now, to the above mixture 9.4 ml of tetraethyl ammonium hydroxide (TEAOH) is added under cooling conditions. Tetraethyl orthosilicate (23.4 ml) (TEOSi) was dissolved in 50 ml of water in another 250 ml beaker separately and allowed to stirring at room temperature for 30 minutes. Solution of TEAOH, NaOH mixture was then added dropwise to TEOSi with constant stirring. Subsequently, hexadecyl trimethyl ammonium bromide (10.55 g) was added slowly to the above solution. Maintaining the pH of the mixture at 11.0-11.5. Finally, the gel mixture was transferred into an autoclave and heated at 100° C. for 24 h. Solid product was recovered by filtration, washed with deionized water and dried in air. All as-synthesized samples were calcined at 773K in air. The obtained Al-MCM-41 catalyst was modified with 1% ammonium nitrate.

#The zeolite used in the present invention may be of any alkali ion form such as sodium, potassium or the like, ammonium ion form or proton form The alkali ion, however, is not preferred because it lowers the catalytic activity if it remains in the catalyst till the end. The microwave power varied from low to high power and the time of heating also varied from 3 minutes to 25 minutes. The binder used for the zeolite coating on the glass plate includes CaSO4.2H2O, gypsum, starch and cellulose. The present study attempts to employ microporous zeolites and mesoporous MCM-41 mesoporous sieves as sorbents in thin layer chromatography. The micropores range from 5-15 Å and mesopores range from 20-50 Å. The glass plates are used as solid support and the molecular sieves are coated on the plate as matrix with the help of Calcium sulfate as a binder. The plates are subsequently dried in oven at 110° C. for 45 min and cooled. The reactants are applied on the plates with help of a micro syringe using Linomat IV (CAMAG-HPTLC) with nitrogen gas as application device. The reactants are dissolved in suitable solvents such as chloroform in the case of porphyrin synthesis and dichloromethane in calixpyrrole synthesis prior to application.

#Coating of Zeolites on Glass Plates:

#40 mg of the binder (CaSO4.2H2O, CaSO4.1/2H2O or starch) is taken in 8-10 ml of boiling water and maintained at boiling condition for 10 min. 2 g each of the zeolite (HZSM-5, Hβ, HY) or mesoporous molecular sieve (MCM-41) was added to the boiling solution of the binder and mixed vigorously for one minute. The gel was applied in hot condition uniformly on to the glass plates (2.5×7.5) as thin layers. The plates were further air dried for 30 min, oven dried at 110° C. for 1 h and cooled in a desiccater.

#In-situ synthesis and evaluation of meso-tetra phenyl porphyrin: The equi molar ratio of reactants, pyrrole (0.1 ml) and benzaldehyde (0.15 ml) were dissolved in 5 ml of chloroform and applied on Al-MCM-41 coated TLC plates (2.5×7.5 mm). On each plate, 30 μl of reactant mixture is applied as first track and irradiated in domestic microwave oven (BPL) for 12 min with 2 min interval of time. The irradiation time varied from 3 min to 25 min. After irradiation, 5 μl of authentic (meso-tetraphenyl porphyrin) sample is applied as second track. The plate was subsequently developed in twin trough chamber using chloroform and methanol (9.5:0.5). The plate is now densitometrically scanned using scanner (CAMAG TLC scanner 3) under absorption/reflection mode at 254 nm (deuterium lamp). Parameters, plate width, start position, band, space are input to the software and integrated. Further, the plate is also scanned from 350 to 650 nm under spectrum mode to evaluate the soret band of the porphyrin at 419 nm. Percentage composition is obtained from the densitogram complemented by the characteristic spectra. Yield of the corresponding meso-tetraphenyl porphyrin is about 56.5%(±10% deviation in all the cases studied). In a separate analysis, after scanning the TLC plate, corresponding peak of porphyrin is scrapped and extracted out using chloroform as solvent. Crystals remaining upon evaporation of solvent were subjected to FAB-MS. m/z at 615 which is vividly noticed confirmed the authentic identification of porphyrins. This is in support of the soret band observed at around 419 nm in UV spectrum Matrix effect on UV range is always noticed with a bathochromic shift.