A Synthetic Approach of New Trans-Substituted Hydroxylporphyrins

The synthesis of new trans A2B2-substituted porphyrins bearing oxygenic substituent (methoxy, acetoxy, hydroxy) at the periphery of the ring are described. All of the synthesized products were characterized by 1H-N.M.R., 13C-N.M.R., and H.R.M.S. Electrochemical studies revealed two one-electron oxidations and two reductions. In addition, the X-ray structure of one methoxy-derivative was determined.


Introduction
In the last years porphyrin derivatives have been developed or are under development for use as photosensitizers for photoelecronic materials such as sensors [1] and photosensitized solar cells [2]. Because of their interesting optical properties, porphyrin molecules have been investigated as artificial light harvesting antennae. Carbon-based donor-acceptor hybrid materials have been reported where, in many cases, the porphyrin molecule is covalently attached [3,4]. Among the great diversity of porphyrins with a specific pattern of substituents, trans-substituted porphyrins with functional groups at the periphery of the ring act as precursors for supermolecular structures.
During the past decades a great effort has been directed towards the synthesis of porphyrins [5,6]. Porphyrins with nearly all sorts of substituents at the periphery of the 18πelectron system are now accessible. The synthetic procedures followed were mainly based on the Adler-Longo reaction of the condensation of pyrrole with various aldehydes.
In the field of trans-substituted porphyrins an attractive route for the synthesis of these key structural components found in a wide range of model systems [7] was developed by Lindsey's group [8][9][10]. The synthetic approach of Lindsey's group was based on the convenient preparation of 5-substituted dipyrromethanes [8]. Condensation of a dipyrromethane with an aldehyde in a MacDonaldtype synthesis has been used for the preparation of a wide range of trans A 2 B 2 type meso-substituted porphyrins [8,11,12].
Based on this method we tried to explore the possibility of the synthesis of meso-substituted trans hydroxyporphyrins due to the ability of the hydroxy group to link substructures over the porphyrin plane. Hydroxyporphyrins can act as precursors for the synthesis of porphyrin dimers serving as host molecules [13]. Furthermore a series of hydroxyporphyrins has been tested as photosensitizers in photodynamic therapy (PDT) [14,15]. For their synthesis the methoxy-or acetoxyderivatives were prepared first. Absorption spectra were collected on a Perkin-Elmer Lamda 6 grating spectrophotometer. Cyclic voltammetry experiments were performed in an AUTOLAB PGSTAT20. MS spectra were recorded on Bruker MALDI TOF/TOF ultraflextreme.

Experimental
X-ray diffraction measurements were conducted on a STOE IPDS II diffractometer using graphite-monochromated Mo K α radiation. A dark blue crystal with approximate dimensions 0.50 × 0.40 × 0.14 mm was mounted on a capillary. Intensity data were recorded using 2θ scan (2θ max = 46.5, 1 • /min). The structure was solved by direct methods and refined on F 2 o values using SHELX [16]. All nonhydrogen atoms were refined anisotropically; all of the hydrogen atoms were introduced at calculated positions as riding on bonded atoms and were refined isotropically.

Synthesis of Porphyrinic
Compounds. The preparation of 5-mesityl dipyrromethane was based on previously published procedures [8].

5,15
Dimesityl-10,20 Bis(3-Methoxyphenyl)Porphyrin 1. 3.8 mmol (1 gr) of 5-mesityl dipyrromethane and 3.8 mmol of 3-methoxybenzaldehyde were dissolved in 400 mL of CH 2 Cl 2 (A.C.S. grade) under argon atmosphere. 7.12 mmol TFA were added and the reaction mixture was stirred for 30 min at room temperature. 3.8 mmol (0.86 gr) of DDQ were added and the mixture was further stirred for 1 hour. The reaction mixture was filtered through a column of Al 2 O 3 (6 cm × 8 cm) using CH 2 Cl 2 as eluent until the color of the solution was pale brown. The solvent was removed under reduced pressure and the solid was dissolved in 50 mL of toluene, heating at reflux for 1 hour, after the addition of 0.38 mmol of DDQ. After cooling at room temperature the solvent was removed and the solid was purified by a column chromatography. A column of Al 2 O 3 was performed with CH 2 Cl 2 as eluent (yield 22%):  (a) α, β atropisomer, (b) α, α atropisomer.
Method 2. 0.25 mmol (0.2 gr) of porphyrin 3 were added in 10 mL of THF. 7.38 mmol KOH were dissolved in 5 mL of EtOH and the resulting alcoholic solution was added dropwise. The solution was stirred for 30 min at room temperature and then refluxed for a further 2 hours. After cooling at room temperature the solution was acidified by carefully adding glacial acetic acid. 15 mL of CH 2 Cl 2 were

Results and Discussion
Following Lindsey's methodology, trans-methoxyporphyrins 1, 2 and 4 were synthesized as precursors for 5 and 6 while for compound 7 the precursors were 3 and 4 (Scheme 1). The choice of acetoxy-or methoxy-as protecting groups was based on published results for the formation of a dipyrrole product from an attempted synthesis of arylporphyrins with o-acetoxybenzaldehyde [17].
Compound 2 is a mixture of atropisomers that proved to be inseparable despite our repeated efforts for chromatographic separation. Compounds 5 and 6 were obtained by cleavage of the methyl ether by BBr 3 (Scheme 1), while 7 is obtained by alkaline hydrolysis of the ester group or alternative by cleavage of the methoxy group. The two isomers of compound 6 (Scheme 2) in contrast to these of 2 are easily separated by silica gel chromatography. 6αβ is eluted with CH 2 Cl 2 /Hexane (6/4 v/v) while the more polar 6αα is eluted with 0.5% EtOH /CH 2 Cl 2 .
The two isomers (Scheme 2) were characterized by 1 H-N.M.R. spectroscopy. A characteristic feature is that in 6αβ the o-Me of the mesityl group appears as a singlet while in 6αα the o-Me group gives two separate singlets, while no other remarkable spectroscopic difference was observed for the two isomers. In 2 since it is a mixture of the two isomers its N.M.R. spectrum shows these three groups of peaks. For  derivates 3 and 1 the o-H and m-H   For all of the methoxy derivatives electrochemical studies were performed by cyclic voltammetry. The redox potentials measured are the typical ones for meso-substituted porphyrins [18]that exhibited two one-electron reversible oxidations and two one-electron reversible reductions ( Table 1).
The structure of derivative 4 is centrosymmetric (Table 2) and the asymmetric unit contains half of the porphyrin molecule and one water solvate molecule, which was found disordered and refined over three positions with occupation factors summing one (Figure 1).
The rather large values of dihedral angles formed between the porphyrin C 20 N 4 mean plane, the mesityl phenyl ring (84.72 • ), and the methoxyphenyl ring (65.12 • ) indicate that there is no twist distortion of the porphyrin skeleton, together with the small average absolute displacement of the C m atom (0.032Å) from the poprhyrin core. The displacement of the two −OCH 3 groups is 0.643Å alternative from the porphyrin plane.
In conclusion in this work we have reported the preparation of new porphyrinic complexes bearing the appropriate groups in order to functionalize specific sides of the aromatic macrocycle. The formed complexes are fully characterized. The formation and the properties of macromolecule structures with the formed complexes as precursors will be published elsewhere.