Electrochimica Acta 46 (2001) 1899–1903

Tetraarylporphyrin synthesis by electrochemical oxidation ofporphyrinogens

Arnaud Bondon a,*, Emmanuel Porhiel a, Cecile Pebay b, Laurent Thouin b,Jacques Leroy b, Claude Moinet c

a Laboratoire de Chimie Organometallique et Biologique, UMR CNRS 6509, Uni6ersite de Rennes 1, Campus de Beaulieu,35042 Rennes Cedex, France

b Departement de Chimie, UMR CNRS 8640, Ecole Normale Superieure, 24 rue Lhomond, 75231 Paris Cedex 05, Francec Laboratoire d’Electrochimie et Organometalliques, UMR CNRS 6509, Uni6ersite de Rennes 1, Campus de Beaulieu,

35042 Rennes Cedex, France

Received 20 November 2000; received in revised form 3 January 2001

Abstract

The electrochemical synthesis of tetraarylporphyrins has been reinvestigated. Whereas the direct electrolysis of amixture of benzaldehyde and pyrrole gave only a 1% yield of tetraphenylporphyrin (A. Stanienda, Z. Naturforschg.22b (1967) 1107), the electrochemical oxidation for 2 h of preformed porphyrinogens, obtained under the Lindseyconditions, can be successfully performed using catalytic amount of quinone as mediator. Furthermore, whencondensation involves 3,4-difluoropyrrole, the electrolysis, at 1.2–1.45 V versus ECS, can be realized without anymediator, owing to the good electrochemical stability of the compound. The porphyrins yields (21–41%) depend onthe nature of the aldehyde (benzaldehyde, pentafluorobenzaldehyde) and of the pyrrole (pyrrole, 3-fluoropyrrole,3,4-difluoropyrrole). They are slightly smaller in the case of a redox catalysis and a little larger for the directelectrolysis. An improvement of the purification step was obtained by decreasing the quantity of quinone andperforming the chromatography of the dication porphyrins. © 2001 Elsevier Science Ltd. All rights reserved.

Keywords: Electrolysis; Redox catalysis; Porphyrinogen; Porphyrin; Synthesis

www.elsevier.nl/locate/electacta

1. Introduction

Incredible development of porphyrin research in vari-ous fields such as biomimetic catalysis, materials chem-istry or photodynamic therapy necessitates more andmore complex porphyrins [1]. Since the first synthesis ofa tetraarylporphyrin, in 1935 by Rothemund [2], sub-stantial improvements in the chemical synthesis wereobtained by Adler et al. [3] and more recently by

Lindsey et al. [4,5]. An attempt to prepare meso-te-traphenylporphyrin by electrochemical oxidation of amixture of benzaldehyde and pyrrole in acetonitrile wasmade in 1967, but only 1% yield was obtained [6].While the Adler–Longo method is efficient in term ofyields and quantities in the case of simple tetraarylpor-phyrins, the Lindsey method is widely used for thesynthesis of porphyrins bearing sensitive substituentson the phenyl rings. Several new strategies have beendevelopped and recently reviewed [7]. Condensations ofaldehydes and pyrrole have been performed usingmesoporous promoters [8,9] or micelles [10], followedby oxidation with quinone. A one-step synthesis in thegas phase, from pyrrole and aryl aldehydes was de-

* Corresponding author. Tel.: +33-2-99286373; fax: +33-2-99281646.

E-mail address: arnaud.bondon@univ-rennes1.fr (A. Bon-don).

0013-4686/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.

PII: S 0013 -4686 (01 )00429 -7

A. Bondon et al. / Electrochimica Acta 46 (2001) 1899–19031900

Scheme 1.

scribed, the oxidation being realized by air [11]1. Con-densation was realized also in presence of mangane-se(II) chloride as a template in 2,4,6-trichlorophenolgiving metallated porphyrin in high yield [12]. The useof high-valent transition metal salts was also reported[13].

However, the Lindsey two-step one-flask method dis-plays the mildest reaction conditions and the broadestscope of application (Scheme 1). Nevertheless, twodrawbacks can be noticed: (i) the relatively low concen-tration of the reactives requiring large quantities ofsolvent and (ii) the difficulties of purification (throughtedious column chromatography) due to the largeamount of quinone used as oxidant. These points havebeen reinvestigated by Lindsey and coworkers [14,15].Higher reactant concentrations gave a decrease in yieldthat can be partially offseted using higher acid concen-tration [14] or various salts [15]. While stoichiometricoxidation by quinone required large amount of oxidant,an elegant alternative was proposed by the same groupinvolving the use of phtalocyanine and dioxygen tooxidize the porphyrinogens [14,16].

Herein, we report the results of our reinvestigation ofthe electrochemical synthesis of tetraarylporphyrins ei-ther by direct electrolysis or by redox catalysis usingcatalytic amount of quinone.

2. Experimental

All solvents were distilled prior to use. Chemicalreagents were of analytical grade from commercialsources. 3,4-Difluoropyrrole was prepared as reportedpreviously [17,18]. 3-Fluoro-1-(triisopropylsilyl)pyrrolewas prepared accordingly to Barnes and coll [19]. Thefree 3-fluoropyrrole was obtained in solution by treat-ment of the N-silyl derivative with tetrabutylammo-nium fluoride (to be published).

Conventional electrochemical experiment was usedfor cyclic voltammetry and controlled potential electrol-ysis (EG&G Princeton Applied Research model 362-scanning potentiostat with an XY recorder). For cyclicvoltammetry, the working electrode was a stationaryglassy carbon electrode disc (3 mm diameter). All po-tentials refer to the saturated calomel electrode (SCE)and have not been corrected for the ohmic drop. Con-trolled potential electrolysis were performed for aroundtwo hours at ambiant temperature, at a glassy carbonanode (4 cm diameter) in a cell previously described[20]. The imposed potential corresponded either to theoxidation wave of quinones for indirect oxidation or tothe oxidation wave of the porphyrinogens of8FTPFPPH2 and 8FTPPH2 (Scheme 2) in the absenceof a catalytic amount of quinone. The coulometricmeasurements were determinated with a current inte-grator Tacussel model IG5N.

The condensation of pyrroles and aldehydes as wellas the chemical oxidation of the porphyrinogens were

1 Caution: an attempt to use these conditions for the con-densation of benzaldehyde and 3,4-difluoropyrrole was madeand gave a violent burning of the compounds.

Scheme 2.

A. Bondon et al. / Electrochimica Acta 46 (2001) 1899–1903 1901

performed using the Lindsey procedure as describedpreviously [21]. Typically, aldehyde (1 mmol) and theappropriate pyrrole (1 mmol) were diluted in 100 cm3

of dichloromethane under argon. BF3–etherate (12mm3) was added and the mixture was stirred at roomtemperature for 1 h. 2,3-Dichloro-5,6-dicyano-1,4-ben-zoquinone (85 mg, 0,38 mmol) was added to 50 cm3 ofthe solution. The remaining 50 cm3 were used for theelectrolysis experiment. A catalytic amount of 2 mg ofTCQ (for TPP) or DDQ (for the other porphyrins,except 8FTPPH2 and 8FTPFPPH2) were added andthen 12.5 cm3 of a methanolic 1 N H2SO4 solution.

Improvement of the purification was obtained usingan acidic medium for the chromatographic procedureon silica gel. The porphyrin solutions obtained bychemical or electrochemical oxidation were evaporatedto dryness. Dichloromethane was made acidic by addi-tion of perchloric acid and used as the solubilizing andthe elution media. The green dication porphyrins weremore easily separated because of a better retention ofthe by-products at the top of the column. This proce-dure proved to be particularly efficient for the purifica-tion of porphyrins obtained in low yield. Concentratedsulfuric acid can also be used instead of perchloric acidbut elution of the porphyrins required much polarmixture of solvents by addition of acetone.

The b-octafluoro-5,10,15,20-tetraarylporphyrins havealready been characterized [21,22], and the characteri-zation of the isomeric mixture of the new b-tetrafluoro-5,10,15,20-tetraphenylporphyrin will be reportedelsewhere.

3. Results and discussion

Three types of pyrrole have been condensed withbenzaldehyde or pentafluorobenzaldehyde giving thehydrogenated or fluorinated porphyrins displayed inScheme 2. Porphyrinogen solutions were prepared usingthe standard Lindsey conditions, at reactant concentra-tions of 10−2 M in 100 cm3 of CH2Cl2. After 1 h ofreaction time, the reaction mixture was divided in two

equal fractions. The first one was treated with DDQcorresponding to the standard chemical oxidation con-ditions, whereas the second one was used for the elec-trochemical oxidation. The yields of isolated porphyrinsfor both conditions of oxidation are reported in theTable 1.

In order to perform electrolysis, 1 N H2SO4 inmethanol was added up to 20% (v/v). The sulfuricmethanolic medium permits a good conductivity andprevents the tedious separation of an electrolyte. Fur-thermore, the acidic medium is able to protonate theporphyrin formed during the oxidation of the porphyri-nogen. This protonation protects the porphyrin fromfurther oxidation. Indeed, the first potential of oxida-tion of the dication porphyrins are shifted by about 0.4V when compared to the free base of the tetraarylpor-phyrins (unpublished data).

Attempts to determine the exact potential of oxida-tion of the porphyrinogen substrates were unsuccessfulbecause the voltammograms were badly defined. Never-theless, unresolved waves were observed in the range1–1.4 V depending on the nature of the pyrrole and thealdehyde.

With porphyrinogens obtained by condensation ofpyrrole or 3-fluoropyrrole with aldehydes, passivationof the electrode during the oxidation, characterized bya dramatic decrease of current intensity, requires theuse of a quinone as a redox catalyst. The nature of thequinone was chosen depending on the substitution ofthe pyrrole. However, the porphyrinogen obtained bycondensation of 3,4-difluoropyrrole and an aryl alde-hyde can be directly oxidized without any mediator.

The yields of isolated porphyrins (Table 1) obtainedby chemical or electrochemical oxidation of severalporphyrinogens compare well. The redox catalysis giveporphyrins with only a slight decrease in yields whencompared to the chemical oxidation. For example, theyield of the synthesis of TPPH2 is 38% by chemicaloxidation, whereas a 36% yield is obtained by redoxcatalysis. The synthesis of 8FTPPH2 and 8FTPFPPH2

can be performed by direct electrolysis in 41 and 21%yields, respectively. This corresponds to a small increase

Table 1Yields (%) of isolated porphyrins obtained by chemical or electrochemical oxidation of preformed porphyrinogens

Porphyrin Electrolysis conditionsOxidation

MediatorElectrochem.Chemical E (V vs. SCE)

TCQTPPH2 38 0.836DDQ38 354FTPPH2 1.1

1.226 DDQ22TPFPPH2

40 378FTPPH2 DDQ 1.451.2Direct418FTPPH2 40

18 21 Direct 1.458FTPFPPH2

A. Bondon et al. / Electrochimica Acta 46 (2001) 1899–19031902

in yield in comparison with the chemical oxidation. Theimposed potential for the redox catalysis was chosentaking into account two parameters. The first one cor-responds to the observed reversible wave of the quinonein the electrolytic medium. The second one is related tothe first oxidation wave of the porphyrins. The elec-tron-withdrawing character of the fluorine atoms areresponsible for a drastic increase of this potential[22,23]. This increase prevents further oxidation of thedication porphyrin and permits us to use higher poten-tial for the halogenated porphyrins. The potential ofthe direct electrolysis used for the synthesis of theb-octafluoroporphyrins was estimated on the cyclicvoltammogram of the corresponding porphyrinogens.

Porphyrinogen formation by condensation of pyrroleand aldehydes does not follow a completely elucidatedmechanism [7]. Reversible condensation was demon-strated by mixing two different porphyrinogens beforechemical oxidation which gave the parent porphyrinsand the mixed porphyrins as well [5]. However, signifi-cant irreversible reactions occurs during the pyrrole–aldehyde condensation [15]. Exchange reaction betweenlabelled porphyrinogen and unlabelled aldehyde doesnot give any free labelled aldehyde [15]. Furthermore,the extent of the exchange between two different por-phyrinogens is dependent of the duration of the con-densation of the individual porphyrinogen [15]. Thesetwo experiments suggest that the reversibility of theporphyrinogen formation is not associated with thepresence of free pyrrole or free aldehyde, but rather toan irreversible intermediate corresponding probably tothe pyrrole–carbinol [15]. An objective of the electro-chemical oxidation was to displace the equilibriumtoward the porphyrinogen rather than the open-chaintetrapyrroles by synthesis of the porphyrin. Assumingthat the presence of the pyrrole–carbinol is required forthe equilibrium, condensation of aldehyde with pyrroleswhich are sensitive to oxidation (and probably pyrrole–carbinol as well) prevents any displacement of thereaction. This view is consistent with the very low yieldof 1% previously obtained for the electrochemical syn-thesis of TPPH2 [6]. In this context, the high oxidationpotential of the 3,4-difluoropyrrole recently measuredaround 1.6V versus Ag/AgCl [24], could open the wayof a displacement of the equilibrium in favor of theporphyrinogen formation. This will require conditionsallowing both condensation and electrolysis at the sametime.

4. Conclusion

We have reinvestigated the use of the electrochem-istry for the synthesis of porphyrins by oxidation ofpreformed porphyrinogen using the Lindsey conditions.The use of an acidic electrolyte obtained by addition of

methanolic sulfuric acid permits (i) the easy removal ofthe electrolyte, (ii) the protection of the porphyrin byprotonation which induces a large shift of the firstoxidation potential. We show that redox catalysis canbe applied successfully giving yields, in the 21–41%range, depending on the nature of the reactives, close tothose obtained by standard chemical oxidation withquinone. The large decrease of the amount of quinoneused for the redox catalysis allows an easier purifica-tion. The purification procedure was further improvedby performing the chromatography of the dicationicforms of the porphyrins. Finally, the electrosynthesis ofthe electrodeficient b-octafluorotetraarylporphyrins canbe performed directly without any mediator.

Acknowledgements

We gratefully acknowledge the financial support ofthe Brittany Region as a grant to E.P.

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