Complementary Syntheses Giving Access to a Full Suite of Differentially Substituted Phthalocyanine‐Porphyrin Hybrids

Abstract Phthalocyanines and porphyrins are often the scaffolds of choice for use in widespread applications. Synthetic advances allow bespoke derivatives to be made, tailoring their properties. The selective synthesis of unsymmetrical systems, particularly phthalocyanines, has remained a significant unmet challenge. Porphyrin‐phthalocyanine hybrids offer the potential to combine the favorable features of both parent structures, but again synthetic strategies are poorly developed. Here we demonstrate strategies that give straightforward, controlled access to differentially substituted meso‐aryl‐tetrabenzotriazaporphyrins by reaction between an aryl‐aminoisoindolene (A) initiator and a complementary phthalonitrile (B). The choice of precursors and reaction conditions allows selective preparation of 1:3 Ar‐ABBB and, uniquely, 2:2 Ar‐ABBA functionalized hybrids.


Synthesis and characterisation details General Methods
Reagents and solvents were obtained from commercial sources and used without further purification unless otherwise stated. Phthalonitrile was recrystallised from hot xylene. THF was freshly distilled from sodium and benzophenone.
Reactions and distillation were carried out under an inert atmosphere (argon or nitrogen gas), in most air-sensitive reactions argon was preferred. Brine is a saturated aqueous solution of sodium chloride. Organic layers were dried using anhydrous magnesium sulphate. Evaporating of solvent was performed using a Buchi rotary evaporator at reduced pressure. 1 H NMR spectra were recorded either at 400 MHz on Ultrashield Plus TM 400 spectrometer or 500 MHz on a Bruker Ascend TM 500 spectrometer in 5 mm diameter tubes. Signals are quoted in ppm as δ downfield from tetramethylsilane (δ=0.00) and coupling constants J given in Hertz. 13 C[ 1 H] NMR spectra were recorded at 100.6 MHz or 125.7 MHz on the same spectrometers. NMR spectra were performed in solution using deuterated chloroform, methanol, dichloromethane or tetrahydrofuran at room temperature unless otherwise stated. Ultraviolet-Visible absorption spectra were recorded on Hitachi U-3310 Spectrophotometer in solvent as stated. MALDI-TOF mass spectra were carried out using a Shimadzu Biotech Axima instrument. Characterization of hybrids by MALDItof mass spectrometry was achieved by comparison of isotopic distribution to theory. IR spectra were recorded using a Perkin-Elmer Spectrum BX FT-IR spectrometer. Thin layer chromatography (TLC) was performed using aluminium sheets coated with Alugram ® Sil G/UV254 (Macherey-Nagel), and the compounds were visualised under short-wavelength UV-light at 245 nm or 366 nm. Column chromatography was carried out using silica gel 60Å mesh 70-230 (63-200 µm) under gravity or moderate pressure at ambient temperature. Solvent ratios are given as v:v.
Melting points were taken on a Reichart Thermovar microscope with a thermopar based temperature control.
Reactions using microwave irradiation were carried out in Biotage Initiator+ Microwave system.

General synthesis of 2-bromobenzamidine hydrochlorides
Following the method reported by Dalai et al., [12]  and washed with diethyl ether to give the title compound which was then recrystallized from methanol.

ABBA-TBTAP 10
Synthesised following the general synthesis of TBTAPs using 2,3-Naphthalonitrile 9 and aminoisoindolene 6 by the slow addition method. Recrystallisation from acetone and ethanol gave the title compound as purple crystals (

ABBA-TBTAP 14d
Synthesised following the general synthesis of TBTAPs using 1,2-Dicyano-4,5-bis(phenoxy)benzene 12d and aminoisoindolene 6 and the one-pot procedure. Recrystallization from acetone and ethanol gave the title compound as a green powder (105 mg, 52%).        General. Single bluish green plate-shaped crystals (7 and 8) were supplied. A suitable crystal 0.04×0.04×0.01 mm 3 (7) or 0.05×0.03×0.01 mm 3 (8) was selected and mounted on a MITIGEN holder in oil on a Rigaku FRE+ equipped with VHF Varimax confocal mirrors and an AFC12 goniometer and HG Saturn 724+ detector. The crystal was kept at a steady T = 100(2) K during data collection. The structure was solved with the ShelXT [15] structure solution program using the dual methods solution method and by using Olex2 [16] as the graphical interface. The model was refined with version 2018/3 of ShelXL [17] using full matrix least squares minimisation on F 2 minimisation. All nonhydrogen atoms were refined anisotropically. Hydrogen atom positions were calculated geometrically and refined using the riding model.

7.
Solvent masking as implemented in Olex2 was used to eliminate the electron contribution equivalent to 10 EtOH molecules per unit cell. Geometric equal distance and thermal restraints were applied to equivalent atom pairs in both disorder components of the Mg coordinated EtOH.

8.
Geometric equal distance and thermal restraints were applied to equivalent atom pairs of all disorder components. with I > 2σI.
Data were processed using the CrysAlisPro-CCD and -RED programs. [18] The structure was determined by the intrinsic phasing routines in the SHELXT [15] program and refined by full-matrix least-squares methods, on F 2 's, in SHELXL. [17] The non-hydrogen atoms were refined with anisotropic thermal parameters. The phenyl ring hydrogen atoms were included in idealised positions and their Uiso values were set to ride on the Ueq values of the parent carbon atoms. The remaining hydrogen atoms were located in a difference map and were refined freely and isotropically. At the conclusion of the refinement, wR2 = 0.054 and R1 = 0.021 for all 2424 reflections weighted w = [σ 2 (Fo 2 ) + (0.0277 P) 2 + 0.5283 P] -1 with P = (Fo 2 + 2Fc 2 )/3.
In the final difference map, the highest peak (ca 0.3 eÅ -3 ) was near Br(1).

Notes on the structure
The principal moiety in this crystal is a 1-Br,2-C(NH2)2,4,5-(OMe)2-benzene cation, with the positive charge distributed through the H2N-C-NH2 group; all the hydrogen atoms in this group were located in a difference map and were refined freely and isotropically. The C(2)-C(21) bond appears to be a normal single bond and the two C-N bonds are both rather short and equivalent at 1.312(2)Å.
The crystal contains, in addition to the cation, a chloride anion and a water molecule.
The bromine substituent, the two methoxy groups and the carbon atom of the diamino-methyl group, all lie on or very close to the plane of the phenyl ring. The C(NH2)2 group forms a separate plane, rotated 62.8(1)° from the phenyl group plane.
All the amino and water hydrogen atoms are involved in hydrogen bonds that link the moieties; the stronger bonds link the cations, through the chloride and water units, in paired chains (ladder-like) parallel to the b-axis, while weaker bonds, through the methoxy groups, connect the ladders to form hydrogen-bonded sheets.
Data were processed using the CrysAlisPro-CCD and -RED programs. [18] The structure was determined by the intrinsic phasing routines in the SHELXT [15] program and refined by full-matrix least-squares methods, on F 2 's, in SHELXL. [17] The non-hydrogen atoms were refined with anisotropic thermal parameters. The hydrogen atoms on N(7) were located in a difference map and refined freely. The remaining hydrogen atoms were included in idealised positions and their Uiso values were set to ride on the Ueq values of the parent carbon atoms. At the conclusion of the refinement, wR2 = 0.075 and R1 = 0.028 (2B) for all 3033 reflections weighted w = [σ 2 (Fo 2 ) + (0.0491 P) 2 + 0.2402 P] -1 with P = (Fo 2 + 2Fc 2 )/3. The absolute structure (Flack) parameter refined to 0.02 (5), and the diagrams show the correct configuration.
In the final difference map, the highest peak (ca 0.2 eÅ -3 ) was near H(14b).

Notes on the structure
The molecule comprises two planar units, viz the isoindole nine-membered group and the phenyl ring of C(41-46). These rings are linked at C(10) and the torsion angle of C(9)-C(10)-C(11)-C(12) is 20.9(3)°. The three methoxy groups lie close to the plane of the adjoining aromatic rings.
Molecules are linked in chains parallel to the a axis through N(7)-H(7b)…N(8') hydrogen bonds. The second hydrogen of the N(7) amino group is not involved in any hydrogen bond formation but has a close contact, H(7a)…C(12) at 2.69 Å, on to the face of the phenyl ring. We note a 'weak hydrogen bond' between C(13)-H(13) and a neighbouring O(5) atom, where the H…O distance is 2.39 Å. of reflections recorded, to θmax = 65, was 207908 of which 6821 were unique (Rint = 0.097 ); 5675 were 'observed' with I > 2σI.
Data were processed using the CrysAlisPro-CCD and -RED programs. [18] The structure was determined by the intrinsic phasing routines in the SHELXT [15] program and refined by full-matrix least-squares methods, on F 2 's, in SHELXL. [17] The structure comprises the magnesium complex and approximately two solvent (water) molecules.
The non-hydrogen atoms were refined with anisotropic thermal parameters. Hydrogen atoms in the solvent region and located in difference maps were refined freely. The remaining hydrogen atoms were included in idealised positions and their Uiso values were set to ride on the Ueq values of the parent carbon atoms. At the conclusion of the refinement, wR2 = 0.220 and R1 = 0.094 (2B) for all 6821 reflections weighted w = [σ 2 (Fo 2 ) + (0.0923 P) 2 + 19.82 P] -1 with P = (Fo 2 + 2Fc 2 )/3; for the 'observed' data only, R1 = 0.083.
In the final difference map, the highest peak (ca 1.1 eÅ -3 ) was near H(10b) of the ethanol ligand.

Notes on the structure
The magnesium is coordinated at the centre of the porphyrin ligand, and removed 0.495(2) Å from the mean-plane of the four coordinating N atoms; it is also bound to an ethanol molecule, forming a square pyramidal pattern. This is all well-resolved and reliable. Then the hydroxyl group of the EtOH ligand is hydrogen bonded to an oxygen atom (probably) of a solvent/water molecule and that has further hydrogen bonds to a second water molecule which is linked by more hydrogen bonds to two further Mg-porphyrin molecules. There is some uncertainty and/or disorder about all the hydrogen atoms and the hydrogen bonds in this water/solvent region -I am assuming the solvent molecules are mostly water molecules, although there is one site of electron density here that refines best as 'half-acarbon' atom, C(201), as part of a methanol molecule.
On the opposite side of the Mg-Porph system, a centrosymmetrically related molecule lies with the C(2-7) and C(26-31) rings of one molecule overlapping the C(26'-31') and C(2'-7') rings of the opposing molecule.
The methoxyphenyl group is linked to the porphyrin ring through the carbon atom C(33

For compounds 16a, 17a, 18a
Scattering factors for neutral atoms were taken from reference. [19] Computer programs used in this analysis have been noted above, and were run through WinGX [20] on a Dell Optiplex 780 PC at the University of East Anglia.