J O U R N A L O F C H E M I S T R Y Materials A comparison of two convergent routes for the preparation of metalloporphyrin-core dendrimers: direct condensation vs. chemical modification† Keith W. Pollak,a Elizabeth M. Sanfordb and Jean M. J. Fre�chet*a aDepartment of Chemistry, University of California, Berkeley, CA 94720–1460 USA bHope College, Holland,Michigan 49422-9000, USA Porphyrin-core dendrimers consisting of benzyl ether dendrons assembled around a porphyrin core have been prepared by two diVerent convergent syntheses.The first involves the direct condensation of convergent dendrons having 3,5-disubstituted benzaldehyde focal points with an equivalent amount of pyrrole. This route which requires very mild conditions is especially useful for the rapid assembly of small dendrimers but suVers from steric limitations as the size of the dendrons increases above the fourth generation.The second route involves the attachment of pre-formed benzyl bromide dendrons to a functionalized porphyrin through a simple Williamson synthesis. This route is also very practical but it requires careful purification of the final product from the partially functionalized porphyrin dendrimers that are also obtained.MALDI mass spectrometry proved to be a very useful tool both for monitoring the formation of the dendritic porphyrins and for their characterization. Metalloporphyrins with specific architecture have been devel- of dendrons with an aldehyde functionality at their focal point, and their subsequent assembly into a porphyrin by Lindsey12 oped to model various biological systems; two of the common natural archetypes are chlorophyll, and heme proteins.The condensation with pyrrole. Until now, this in situ assembly of porphyrin-core dendrimers had not been reported. light-harvesting and electron-transfer properties of chlorophyll have been modelled by synthetic metalloporphyrins with sub- In view of the potential application of site-isolated porphyrin nuclei for electron transfer or other catalytic processes, this stituents which modify the photochemical behavior of the porphyrin.1 Other metalloporphyrins have been synthesized study explores and compares the synthesis of metalloporphyrin- core dendrimers of generations 1–4 via two routes utilizing with either one or both faces of the porphyrin sterically obstructed to model proteins like hemoglobin and myoglobin the convergent growth approach.Route I, in which dendritic aldehyde and pyrrole are combined in a Lindsey porphyrin which bind and transport molecular oxygen.2 But the most common purpose for synthesizing porphyrins with defined synthesis to generate the porphyrin core in situ (Scheme 1) and route II, in which zinc tetrakis(3,5-dihydroxyphenyl)porphy- architecture is to model natural oxidation catalysts like cytochromes.3,4 rin, a porphyrin core with eight reactive phenolic sites,8 is alkylated with a dendritic bromide in a Williamson ether Some of the latest biological models embed a porphyrin at the core of a dendrimer.The synthesis of such a macromolecule synthesis (Scheme 2).could follow either the divergent5 or convergent6 approach to dendrimers, and indeed both routes have been used by diVerent research groups.7–10 For example Diederich and co-workers7 Results and Discussion have used the divergent approach to grow a polyamide den- Direct formation of the porphyrin core from a dendritic drimer from a porphyrin core. Although this method has been aldehyde and pyrrole successful for the preparation of large porphyrin-core dendrimers, the sensitivity of the porphyrin moiety must be con- Benzyl ether dendrons were prepared through the iterative sidered in the growth of the dendrimers, a process that typically bromination and alkylation steps described by Hawker and involves multiple preparative steps and demanding purification Fre� chet.6a,11 To prepare the desired generation of dendritic procedures.Such potential problems could be avoided by aldehyde, dendritic bromide was used to alkylate 3,5- incorporating the porphyrin core into the macromolecule at dihydroxybenzaldehyde (Scheme 3). Classical Lindsey condenthe last step of the synthesis,8 as is common practice in the sation12 of the dendritic aldehyde and an equivalent amount synthesis of dendrimers through the convergent approach.6 of pyrrole at a concentration of 10-2 M in chloroform was A convenient route for the synthesis of porphyrin-core done at room temperature in the presence of a catalytic amount dendrimers involves the attachment of convergent dendrons of trifluoroacetic acid, under very mild conditions that can be to a pre-formed porphyrin core.Aida and co-workers8 have tolerated by various functionalities which might be present in used the convergent approach to prepare polyether dendrons the dendrons. Monitoring by TLC proved to be eVective and then attached the dendrons to a functionalized tetraaryl because the starting materials, desired product, and polypyrrylporphyrin, tetrakis(3,5-dihydroxyphenyl)porphyrin, through a methane by-products exhibit very diVerent Rf values.However, Williamson ether synthesis. Similarly, Moore et al. attached analysis by UV–VIS spectroscopy allowed for a more accurate polyester dendrons, prepared through the convergent evaluation of the progress of the condensation because the approach, to a metalloporphyrin core using dicyclohexycar- desired product absorbs at sharp, characteristic wavelengths: bodiimide (DCC) coupling.10 A less obvious convergent route a strong Soret band at 424 nm and four weak additional bands to porphyrin-core dendrimers might involve the preparation at 510, 550, 590 and 650 nm while the polypyrrylmethane byproducts have a broader absorption (Fig. 1). When the relative intensities of these bands stabilize, the condensation is at † Presented at the Third Internation Conference on Materials equilibrium.As the generation number is increased the reaction Chemistry, MC3, University of Exeter, Exeter, July 21–25 1997. * E-mail: Frechet@cchem.berkeley.edu became more sluggish and reaction times increased from 1.5 h J. Mater. Chem., 1998, 8(3), 519–527 519for generations 1 and 2, to 10 and 36 h for generation 3 and NMR was facilitated by the high degree of symmetry in the macromolecule.Evidence for the free-base porphyrin core of 4, respectively, though the latter required diVerent reaction conditions. For the first three generations, the porphyrinogen 3a–d is provided by the eight b-pyrrole and two free-base protons seen as singlets at 8.9 and -2.9 ppm, respectively.The condensation product was oxidized directly after condensation and in the same reaction flask to the free-base porphyrin-core spectral features of the dendrons, which surround the porphyrin core with generational tiers of benzyl ethers, are also readily dendrimers 3a–c in 25–30% yield by heating it to reflux in the presence of chloranil.Preparation of the fourth generation attributed. The phenyl protons located on the outermost phenyl rings are seen at 7.2–7.5 ppm, and those on the aromatic free-base porphyrin-core dendrimer 3d was attempted using these reagents and conditions, but it failed. In the condensation ring at the meso position of the porphyrin appear as a oneproton triplet at 7.10 ppm and a two-proton doublet at step, formation of porphyrin was observed in the reaction samples both by TLC and UV–VIS spectroscopy, yet after the 7.50 ppm.The benzyl protons appear as a series of singlets around 4.6–5.0 ppm, depending on the generation number. oxidation step, no porphyrin was produced. This was probably due to in situ decomposition of the product as a result of the Not all of the 13C NMR resonances for the dendrons can be assigned because of the many overlapping signals,11 and at elevated reaction temperature required for the oxidation reaction using chloranil.Using a stronger oxidizing agent, 2,3- high generation, the intensities of some of the resonances of the core carbons are too weak to be seen. However when the dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the oxidation could be performed at room temperature,reby preserving core carbons are detectable, the porphyrin gives rise to three distinct resonances:13 Ca at 145.8 ppm, Cb at 130.6 ppm, and the porphyrinogen and producing 3d in 14% yield.Purification of all of the free-base porphyrin-core dendrimers by column Cmeso at 119.6 ppm. Analysis of the free-base porphyrin-core dendrimers 3a–d by matrix-assisted laser-desorption ionization chromatography proved to be very simple because the desired product elutes much faster than the polypyrrylmethane by- (MALDI) mass spectrometry (Fig. 2) shows that well defined macromolecules exhibiting the expected peaks corresponding products. Analysis of the free-base porphyrin core dendrimers by 1H toM+H+, M+Na+ and/or M+K+ are obtained. 520 J. Mater. Chem., 1998, 8(3), 519–527Scheme 1 Reagents and conditions: i, CF3CO3H; ii, DDQ; iii, Zn(OAc)2 J. Mater. Chem., 1998, 8(3), 519–527 521Scheme 2 Reagents and conditions: i, K2CO3, 18-crown-6 522 J. Mater. Chem., 1998, 8(3), 519–527Fig. 1 (a) UV–VIS spectrum of the crude reaction mixture obtained in the preparation of a generation 3 porphyrin-core dendrimer 3c via Route I.(b) UV–VIS absorption spectrum of pure 3c. phyrin 6 is obtained. Metallation of this porphyrin with zinc acetate produced zinc 5,10,15,20-tetrakis(3,5-dihydroxyphenyl )porphyrin 4, the octafunctional core for the porphyrincore dendrimers. The dendrons used for the subsequent alkylation are readily obtained through the iterative bromination and alkylation steps described by Hawker and Fre� chet.11 Formation of the porphyrin-core dendrimers requires that all eight phenolic pendant groups of the core be alkylated.This Scheme 3 Reagents and conditions: i, K2CO3, 18-crown-6 is best done using a 20% excess of the benzylic bromide dendron while monitoring the progress of the reaction. Thin layer chromatography (TLC) is not suYcient for this purpose The free-base porphyrin-core dendrimers 3a–d were quantibecause some of the partially alkylated cores such as those tatively metallated by dissolving the macromolecule and zinc with six or seven dendrons added to the core exhibit an Rf acetate in methanol–chloroform (151) and heating at reflux value similar to that of the fully alkylated product.In the final overnight.Spectroscopic confirmation of the metallation reacstages of the reaction, monitoring by MALDI mass spection is provided by the UV–VIS absorption spectra since the troscopy is more eVective as the partially alkylated cores are metallated dendrimers 1a–d exhibit a strong Soret band at readily identified as shown in Fig. 3. 430 nm and two additional bands at 560 and 600 nm.14 In Careful control of the reaction temperature is required addition, the 1H NMR spectra of the products no longer during the alkylation as temperature aVects both the rate and exhibit the characteristic signal for the two protons located the site of alkylation.If the temperature is significantly higher inside the porphyrin ring of the free-base starting materials. than 60 °C, the reaction rate increases but significant Calkylation involving the 2 position of the phenyl ring of the Preparation by dendron alkylation of a pre-formed porphyrin porphyrin core is observed as evidenced by the presence of core two singlets of equal intensity at 7.82 and 8.59 ppm characteristic of the two remaining phenyl protons in the 1H NMR As will be seen below, a comparison of this approach first reported by Aida and co-workers8 with the direct Lindsey- spectrum of the product mixture.Below 60 °C, the extent of C-alkylation is insignificant but the reaction times increase type synthesis shows that each route has its own advantages and shortcomings. considerably. A reaction temperature of 60 °C produced a good compromise aVording primarily O-alkylated product in a Specifically, this route requires that a porphyrin core with multiple reactive functionalities be prepared first then coupled reasonable reaction time.As expected in view of increased steric requirements around the core, the reaction time required to the appropriate number of benzyl ether dendrons. For example, Scheme 4 shows the preparation of a core with eight for complete alkylation varies as a function of generation: 1, 3 and 5 d for generation 2, 3 and 4, respectively. Regardless of protected phenolic functionalities by condensation of pyrrole and 3,5-dimethoxybenzaldehyde.The resulting porphyrinogen conditions used the final product must be purified by column chromatography to remove by-products or partially alkylated is then oxidized to the free base 5,10,15,20-tetrakis(3,5-dimethoxyphenyl) porphyrin 5 in 52% yield.Following removal of products. Purification is best achieved by chromatography through silica, eluting with a continuous linear gradient from the methoxy protecting groups by reaction with boron tribromide, the free base 5,10,15,20-tetrakis(3,5-dihydroxyphenyl)por- hexane to CH2Cl2. Isolation of the desired product by column J.Mater. Chem., 1998, 8(3), 519–527 523Fig. 2 MALDI mass spectra of the generation 1–4 free-base porphyrin-core dendrimers prepared via Route I. Sodium and potassium adducts are clearly seen at the right of the main peaks. (a) Generation 1, (b) 2, (c) 3 and (d) 4. Fig. 3 MALDI mass spectrum of the crude product obtained in the preparation of fourth generation porphyrin-core dendrimer 1d via Scheme 4 Reagents and conditions: i, BF3 OEt2; ii, DDQ; iii, BB3; Route II. Partly alkylated dendrons are clearly seen at m/z 10 200 iv, Zn(OAc)2 and 11 800. chromatography is diYcult since the excess dendritic bromide, be recovered. Since high generation dendrons require considersome partially alkylated core, and any by-products (i.e.C- able synthetic eVort, recovering the unreacted starting material alkylated core) behave very similarly to the desired product is often desirable. After evaporating the solvent, the product on a silica gel column. However, with careful chromatography, was isolated as a violet glass. Subsequent trituration with methanol allowed the porphyrin-core dendrimer to be handled pure product is isolated, and the excess dendritic bromide can 524 J.Mater. Chem., 1998, 8(3), 519–527as a powder. Dendrimers 1b, 1c, and 1d were prepared by this inside the porphyrin ring, and specific sites of the porphyrin ring are designated by a, b and meso. route in 71, 68 and 20% yields respectively. General procedure for the preparation of dendritic benzyl bromides11 Conclusions To a mixture of the appropriate dendritic benzylic alcohol This study demonstrates the versatility of the convergent (1.00 equiv.) and carbon tetrabromide (1.25 equiv.) in the synthesis for the preparation of dendritic porphyrins.A clear minimum amount of dry THF was added triphenylphosphine advantage of the two convergent approaches described herein (1.25 equiv.), and the reaction mixture was stirred under is that few steps involving dendrimers are involved; this helps nitrogen for 20 min.The reaction mixture was then poured ensure that impurities or unreacted functionalities do not onto water and extracted with CH2Cl2. The combined organic accumulate as might be the case in a divergent synthesis extracts were dried (MgSO4) and evaporated to dryness. The involving multiple steps for the growth of the dendrimer onto crude product was purified by column chromatography.the porphyrin core. This may be particularly useful in instances Analyses agreed with those published.11 where very accurate structural control is required or where the end-functionalities of the porphyrin ring itself might not General procedure for preparation of porphyrin-core dendrimers survive the reactions used during multistep syntheses. via Williamson ether synthesis While both convergent routes benefit from the architectural control aVorded by the convergent synthesis, each route oVers The second, third and fourth generation porphyrin-core dendriunique synthetic advantages. The direct Lindsey-type conden- mers were synthesized by coupling zinc tetrakis(3,5-dihydroxysation is done in the presence of a catalytic amount of acid, phenyl)porphyrin 4 to the appropriate dendric bromide in a Williamson ether synthesis.Under nitrogen, zinc tetrakis(3,5- while the alkylation route is done under prolonged basic dihydroxyphenyl)porphyrin (1.00 equiv.) and the dendritic conditions. As a result, the choice of a specific route may be bromide (9.60 equiv) were dissolved in acetone.To this solution, determined by any sensitive functionality that may be present K2CO3 (16.0 equiv.) and 18-crown-6 (1.60 equiv) were added, on the dendrons. A clear advantage of the Lindsey-type route and the mixture was stirred and warmed to 60 °C. The solvent is the ease of both monitoring of product formation and was evaporated, and the residual solids were partitioned purification of the desired free-base dendritic porphyrins by between water and CH2Cl2.The layers were separated, and simple column chromatography. Reaction times for the direct the aqueous layer was extracted with CH2Cl2 (3×). The solvent condensation are also consistently shorter than those for route was evaporated, and the residual solids were adsorbed onto II.However, despite the larger number of steps required for silica (20 ml ), and the crude product was purified by chroma- the chemical modification route it aVords higher yields than tography through a 40 ml silica column eluting with a linear the direct Lindsey-type synthesis, especially in the preparation gradient of solvent from pure hexane to pure CH2Cl2.The of low generation porphyrin-core dendrimers. The chemical product fractions were collected, and the solvent was evapor- modification route appears to be more suitable than the ated. The product was dissolved in a minimum amount of Lindsey route for very large dendrimers since it does not CHCl3 then precipitated into methanol. The precipitate was appear to be as sensitive to steric constraints.It is anticipated then dissolved in a minimum amount of diethyl acetate and that similar trends would be observed for syntheses using other precipitated into diethyl ether. The product was obtained as a types of dendrons. dark purple powder. Finally, since the convergent synthesis of the dendritic porphyrin aVords precise control of the dendrimer architecture Zn[G-2]4P 1b.This was prepared as above from zinc it provides the means for incorporating potential prosthetic tetrakis(3,5-dihydroxyphenyl)porphyrin 4 and [G-1]Br; yield: functionalities at precise locations within the assembly. 71%; UV–VIS l/nm (e): 428 (498 000), 560 (20 000), 600 (7000). Through careful design, functionalizing the dendrons with dH 9.18 (s, 8 H, b-H), 7.48 (d, 8 H, Ar-H), 7.33 (m, 80 H, Ph-H), either specific guest-binding sites or rate-enhancing ligands 7.03 (t, 4 H, Ar-H), 6.73 (d, 16 H, Ar-H), 6.56 (t, 8 H, Ar-H), near the catalytic core could create ‘suprabiotic’4 catalysts. 5.06 (s, 16 H, Bn-H), 4.96 (s, 32 H, Bn-H). dC 160.09, 157.71 (Ar C-O); 149.92 (a C); 144.80 (Ar C-porph); 139.15 (Ar C-CH2); 136.63 (Ph C-CH2); 132.10 (b C); 128.46, 127.88, Experimental 127.43 (Ph C-H); 120.67 (meso C); 115.02, 106.43, 101.65, 96.66 (Ar C-H); 70.00 (Ar/Ph-CH2).Mass spectrum (MALDI-TOF): General directions m/z, calc. 3225.09; found 3228.3 (Calc. for C212H172N4O24Zn; Silica for flash chromatography was Merck Silica Gel 60 C 78.95, H 5.38, N 1.74; found C 79.06, H 5.57, N 1.62%). (230–400 mesh). Matrix-assisted laser-desorption ionization time of flight (MALDI-TOF) mass spectroscopy was per- Zn[G-3]4P 1c.This was prepared as above from zinc formed on a Finnigan Lasermat or Perseptive Voyager DE. tetrakis(3,5-dihydroxyphenyl)porphyrin 4 and [G-2]Br; yield: The energy source was a 337 nm nitrogen laser. Samples were 68%; UV–VIS, l/nm (e): 428 (534 000), 518 (6000), 560 (20 000), prepared as 10-4 M solutions in tetrahydrofuran.The matrix 600 (7000). dH 8.96 (s, 8 H, b-H), 7.48 (s, 8 H, Ar-H), 7.17 (m, was a solution consisting of 0.2 M indoleacrylic acid and 160 H, Ph-H), 7.03 (s, 4 H, Ar-H), 6.67 (d, 16 H, Ar-H), 6.53 7×10-4 M sodium dodecyl sulfate in tetrahydrofuran. Four (d, 32 H, Ar-H), 6.43 (t, 8 H, Ar-H), 6.39 (t, 16 H, Ar-H), 5.06 microlitres of the sample and 40 microlitres of matrix were (s, 16 H, Bn-H), 4.83 (s, 32 H, Bn-H), 4.78 (s, 64 H, Bn-H).dC combined and analyzed. All NMR spectra were recorded as 160.08, 160.00, 157.75 (Ar C-O); 149.79 (a C); 139.25, 139.16 solutions in CDCl3 on a Bruker WM 300 (300 MHz) spec- (Ar C-CH2); 136.62 (Ph C-CH2); 128.40, 127.81, 127.40 (Ph trometer with the solvent proton signal as standard: 7.24 ppm C-H); 120.67, 106.57, 106.25, 101.65, 101.52, 96.67 (Ar C-H); for 1H and 77.0 ppm for 13C.The following abbreviations are 69.89 (Ar/Ph-CH2). Mass spectrum (MALDI-TOF): m/z calc. used: Dendritic aldehydes are referred to as [G-n]CHO, where 6621; found 6630 (Calc. for C436H364N4O56Zn; C 79.09, H 5.54, n designates the dendrimer generation. Dendritic free-base N 0.85; found C 78.98, H 5.96, N 0.50%).porphyrins are referred to as H2[G-n]4P, where n, again, designates the dendrimer generation. Ar refers to the aromatic Zn[G-4]4P 1d. This was prepared as above from zinc repeat units within the dendrimer. Ph refers to the phenyl end- tetrakis(3,5-dihydroxyphenyl)porphyrin 4 and [G-3]Br; yield: groups, the surface, of the dendrimer. Bn refers to the benzylic 20%; UV–VIS, l/nm (e): 430 (463 000), 560 (21 000), 600 (7000).dH 9.00 (s, 8 H, b-H), 7.48 (s, 8 H, Ar-H), 7.19 (m, 320 positions within the dendrimer. Porph refers to the two protons J. Mater. Chem., 1998, 8(3), 519–527 525H, Ph-H), 6.67 (s, 4 H, Ar-H), 6.52–6.38 (overlapping reson- filtrate was flash chromatographed through a silica column, eluting with chloroform.The product fractions were collected ances, 168 H, Ar-H), 4.91 (s, 16 H, Bn-H), 4.75–4.69 (overlapand evaporated to dryness. The residual solid was taken up in ping resonances, 224 H, Bn-H). dC 160.03, 159.90, 159.86, minimal chloroform and precipitated into methanol, so the 157.76 (Ar C-O); 149.68 (a C); 139.16, 139.08 (Ar C-CH2); product could be handled as a powder. 136.62 (Ph C-CH2); 132.10 (b C); 128.40, 127.78, 127.45 (Ph C-H); 106.21, 101.42 (Ar C-H); 69.80 (Ar/Ph-CH2). Mass H2[G-1]4P 3a. This was prepared from [G-1]CHO 2a. The spectrum (MALDI-TOF): m/z calc. 13 413; found 13 437 (Calc. aldehyde and pyrrole were allowed to react for 1.5 h, and the for C884H748N4O120Zn; C 79.16, H 5.62, N 0.42; found C 79.24, oxidation was carried out for 2 h; yield: 30%; UV–VIS, l/nm: H 5.79, N 0.59%). 280 (dendrimer units); 424 (porphyrin Soret); 516, 550, 590, 648 (porphyrin Q-region); dH 8.95 (s, 8H, b-H), 7.39–7.51 (m, General procedure for synthesis of dendritic aldehydes 40H, Ph-H), 7.60 (d, 8H, Ar-H), 7.17 (t, 4H, Ar-H), 5.31 (s, A mixture of the appropriate dendritic bromide (2.00 equiv.), 16H, Bn-H), -2.82 (s, 2H, porph-H); dC 143.99 (a C), 127.63 3,5-dihydroxybenzaldehyde (1.00 equiv.), potassium carbonate (b C), 119.68 (meso C), 70.38 (CH2O), 127.68, 128.07, 128.64, (3.00 equiv.), and 18-crown-6 (0.20 equiv.) was refluxed under 136.79 (PhC).Mass spectrum (MALDI): m/z, calc. 1464; nitrogen in dry THF for 48 h. The reaction was allowed to found 1469. cool then evaporated to dryness under reduced pressure. The residue was partitioned between water and methylene chloride, H2[G-2]4P 3b.This was prepared from [G-2]CHO 2b. The and the aqueous layer was extracted with methylene chloride. aldehyde and pyrrole were allowed to react for 1.5 h, and the The combined organic layers were then dried (MgSO4) and oxidation was caried out for 2 h; yield: 26%; UV–VIS l/nm: evaporated to dryness. The product was purified by flash 280 (dendrimer units); 424 (porphyrin Soret); 516, 550, 590, chromatography through a silica column, eluting with methyl- 648 (porphyrin Q-region); dH 8.87 (s, 8H, b-H), 7.21–7.39 (m, ene chloride to give dendritic aldehyde as a colorless glass. 80H, Ph-H), 7.49 (d, 8H, Ar-H), 7.05 (t, 4H, Ar-H), 6.76 (d, 16H, Ar-H), 6.59 (t, 8H, Ar-H), 5.15 (s, 16H, Bn-H), 4.98 (s, [G-1]CHO 2a. 3,5-Dibenzyloxybenzaldehyde was pur- 32H, Bn-H), -2.89 (s, 2H, porph-H); dC 141.45 (a C), 128.51 chased from Aldrich and used directly. (b C), 119.43 (meso C), 70.38, 70.18 (CH2O), 99.02, 161.14, 107.08, 139.14 (ArC), 127.44, 127.90, 128.48, 136.68 (PhC). [G-2]CHO 2b. This was prepared from [G-1]Br; yield: Mass spectrum (MALDI): m/z, calc. 3162; found 3171. 83%; n/cm-1 2873 [Ar(CO)MH st.], 1669 cm-1 [Ar(CNO)H st.]; dH 9.87 (s, 1 H, ArCHO), 7.28–7.41 (m, 20 H, Ph-H), 7.05 H2[G-3]4P 3c.This was prepared from [G-3]CHO 2c. The (d, 2 H, Ar-H), 6.81 (t, 1 H, Ar-H), 6.67 (d, 4 H, Ar-H), 6.59 aldehyde and pyrrole were allowed to react for 10 h, and the (t, 2 H, Ar-H), 5.07 (s, 8 H, Bn-H), 5.03 (s, 4 H, Bn-H); dC oxidation was run for 5 h; yield: 29%; UV–VIS, l/nm: 280 70.4, 70.6 (CH2O); 106.6, 107.7, 137.0, 160.6 (ArC); 102.0, 104.7, (dendrimer units); 424 (porphyrin Soret); 516, 550, 590, 648 136.7, 160.5 (ArC); 128.0, 128.4, 128.9, 139.2 (PhC); 198.6 (porphyrin Q-region); dH 8.91 (s, 8H, b-H), 7.19–7.39 (m, 160H, (ArCHO).Mass spectrum (MALDI): m/z, calc. 743; found 767. Ph-H), 7.51 (d, 8H, Ar-H), 7.08 (t, 4H, Ar-H), 6.72 (d, 16H, Ar-H), 6.60 (d, 32H, Ar-H), 6.56 (t, 8H, Ar-H), 6.49 (t, 16H, [G-3]CHO 2c.This was prepared from [G-2]Br; yield: Ar-H), 5.09 (s, 16H, Bn-H), 4.90 (s, 32H, Bn-H), 4.88 (s, 64H, 49%; n/cm-1 2873 [Ar(CO)MH st.], 1683 cm-1 [Ar(CNO)H Bn-H), -2.91 (s, 2H, porph-H); dC 143.93 (a C), 128.53 (b C), st.]; dH 9.84 (s, 1 H, ArCHO), 7.29–7.42 (m, 40 H, Ph-H), 7.08 119.69 (meso C), 69.89, 69.88, 70.20 (CH2O), 101.51, 101.53, (d, 2 H, Ar-H), 6.84 (t, 1 H, Ar-H), 6.66 (d, 8 H, Ar-H), 6.65 106.59, 106.23, 139.17, 139.14, 157.89, 160.03 (ArC), 127.49, (d, 4 H, Ar-H), 6.55 (t, 4 H, Ar-H), 6.54 (t, 2 H, Ar-H), 5.00 128.06, 128.53, 136.67 (PhC).Mass spectrum (MALDI) m/z, (s, 16 H, Bn-H), 4.99 (s, 4 H, Bn-H), 4.95 (s, 8 H, Bn-H); dC calc. 6557; found 6577. 69.9–70.2 (CH2O); 106.4, 107.5, 136.7, 160.1 (ArC); 101.9, 103.9, 138.8, 160.1 (ArC); 127.7, 128.1, 128.7, 139.0 (PhC); 197.2 H2[G-4]4P 3d.Pyrrole (0.043 ml; 0.626 mmol) and 2d (ArCHO). Mass spectrum (MALDI): m/z, calc. 1592; found (2.059 g; 0.626 mmol) were dissolved in dry CHCl3 and con- 1616. densed in the presence of TFA (0.025 ml; 0.207 mmol). The solution was shielded from ambient light and stirred at room [G-4]CHO 2d.This was prepared from [G-3]Br; yield: temp. for 36 h. Then DDQ (0.177 g; 0.782 mmol) was added, 56%. n/cm-1 2873 [Ar(CO)MH st.], 1694 cm-1 [Ar(CNO)H and the solution was allowed to stir at room temp. for an st.]; dH 9.84 (s, 1H, ArCHO), 7.26–7.41 (m, 80 H, Ph-H), 7.08 additional 2 h. After cooling, the solution was evaporated to (d, 2 H, Ar-H), 6.84 (t, 1 H, Ar-H), 6.64–6.67 (m, 28 H, Ar-H), dryness under reduced pressure and the residue was taken up 6.54–6.56 (m, 14 H, Ar-H), 4.93, 4.96, 5.01 (s, 60 H, Bn-H); dC in a minimum amount of chloroform, then purified by flash 69.8–71.1 (CH2O); 101.6, 106.4, 138.9, 160.1–160.3 (ArC); 127.5, chromatography through a silica column eluting with chloro- 128.0, 128.6, 136.8 (PhC).Mass spectrum (MALDI) m/z, calc.form. The product fractions were collected and evaporated to 3290; found 3313. dryness. The residual solid was taken up in a minimum amount of chloroform and precipitated into methanol, so the product General procedure for the preparation of porphyrin-core could be handled as a powder; yield: 14%; UV–VIS, l/nm: dendrimers via Lindsey synthesis 280 (dendrimer units); 424 (porphyrin Soret); 516, 550, 590, 648 (porphyrin Q-region); dH 8.88 (s, 8 H, b-H), 7.38 (s, br, Ar- A solution of the appropriate dendritic aldehyde 2a–d (1.00 H), 7.19–7.37 (m, Ph-H), 7.02 (s, br, Ar-H), 6.40–6.65 (m, Ar- equiv.), freshly distilled pyrrole (1.00 equiv.), and 1 drop of H), 4.98–4.85 (overlapping resonances, Bn-H), -2.91 (s, 2H, freshly distilled trifluoroacetic acid (TFA) was prepared in dry porph-H); dC 160.03, 159.90, 159.86, 157.76 (ArC-O); 149.68 (a methylene chloride whose volume was calculated so either C); 139.16, 139.08 (ArC-CH2); 136.62 (Ph C-CH2); 132.10 (b starting material had a concentration equal to 10-2 M.The C); 128.40, 127.78, 127.45 (PhC-H); 106.21, 101.42 (ArC-H); reaction was shielded from ambient light and stirred at room 69.80 (Ar/Ph-CH2).Mass spectrum (MALDI-TOF): m/z, calc. temp. for a period of time designated in the following text. 13 350 g mol-1; found 13 376. Then chloranil (8.00 equiv.) was added, and the reaction mixture was warmed to reflux. This was stirred for a period General procedure for the metallation of free-base porphyrinof time designated in the following text.The solution was core dendrimers allowed to cool then evaporated to dryness under reduced pressure. The residue was taken up in minimal chloroform, Introduction of zinc into dendrimers 3a–d was achieved by dissolving the free-base porphyrin-core dendrimer (1.00 equiv.) and insoluble solids (i.e. excess chloranil ) were removed. The 526 J. Mater. Chem., 1998, 8(3), 519–527and Zn(OAc)2 2H2O (1.10 equiv.) in chloroform–methanol saturated NaHCO3, washed once with distilled water, then dried over Na2SO4.The solvent was evaporated, and the (151) (100 ml) and heating the solution at reflux overnight. The solvent was then evaporated, and the residual solids were product was isolated as purple crystals which were dried under vacuum at 40 °C; yield: 100%; UV–VIS l/nm (e): 424 (242 000), partitioned between water and CH2Cl2. The organic layer was separated and dried (Na2SO4).The solvent was evaporated to 516 (14 000), 552 (5000), 592 (4000), 648 (2000); dH ([2H6DMSO, 2.49 ppm) 8.93 (s, 8 H, b-H), 7.05 (s, 8 H, Ar-H), aVord a violet solid. The solid was redissolved in a minimum amount of chloroform then precipitated into methanol, so the 6.64 (s, 4 H, Ar-H), 3.81 (s, br, Ar-OH).dC ([2H6]DMSO, 39.5 ppm) 156.54 (ArC-OH); 144.97 (ArC-porph); 127.50 (b C); compound could be handled as a powder. (Nb the characterization of 1b–d is given earlier in this section.) 117.81 (meso C); 114.15, 102.50 (ArC-H). Mass spectrum (MALDI-TOF): m/z calc. 743; found 753. Zn[G-1]4P 1a. This was prepared from H2[G-1]4P 3a; Financial support of this research by the National Science yield: 100%; UV–VIS l/nm (e) 428 (568 000), 560 (22 000), 600 Foundation (DMR-9641291) and by the MURI program of (7000).dH 8.98 (s, 8 H, b-H), 7.48 (d, 8 H, Ar-H), 7.35 (m, 40 AFOSR is acknowledged with thanks. H, Ph-H), 7.02 (t, 4 H, Ar-H), 5.18 (s, 16 H, Bn-H). dC 157.78 (ArC-O); 149.89 (a C); 144.63 (ArC-porph); 136.75 (PhC-CH2); 131.97 (b C); 128.58, 128.01, 127.63 (Ph C-H); 120.67 (meso References C); 115.06, 96.67 (Ar C-H).Mass spectrum (MALDI-TOF): 1 (a) G. R. Seely, Photochem. Photobiol., 1978, 2, 107; (b) R. Wagner, m/z calc. 1527; found 1538 (Calc. for C100H76N4O8Zn; C 78.65, J. RuYng, B. Breakwell and J. Lindsey, T etrahedron. L ett., 1991, H 5.02, N 3.67; found C 78.60, H 5.05, N 3.54%). 32, (14), 1703; (c) R. Wagner, J. Lindsey, I. Turowska-Tyrk and W. Scheidt, T etrahedron, 1994, 50, 11097. Zinc tetrakis(3,5-dihydroxyphenyl)porphyrin 4. Tetrakis(3,5- 2 J. Collman, J. Brauman, J. Fitzgerald, P. Hampton, Y. Naruta, J. Sparapany and J. Ibers, J. Am. Chem. Soc., 1988, 110, 3477. dihydroxyphenyl)porphyrin 6 (700 mg, 0.942 mmol) and 3 (a) S. Quici, S. Banfi and G. Pozzi, Gazz.Chim. Ital., 1993, 123, 597; Zn(OAc)2 2H2O(228 mg, 1.043 mmol) were dissolved in meth- (b) C. Quintana, R. Assink and J. A. Shelnutt, J. Inorg. Chem., 1989, anol (20 ml ). The solution was heated to reflux for 4 h, then 28, 3421; (c) J. K. M. Sanders, Proc. Ind. Acad. Sci., Chem. Sci., distilled water (60 ml ) was added, and the methanol was 1994, 106 (5), 983; (d) K. M. Faulkner, S.I. Liochev and evaporated under vacuum. The turbid solution was placed in I. Fridovich, J. Biol. Chem., 1994, 269 (38), 23471; (e) T. Katsuki, the refrigerator overnight, and the purple crystalline product Kikan Kagaku Sosetsu, 1993, 19, 67; ( f ) D. R. Benson, R. Valentekovich, S. W. Tam and F. Diederich, Helv. Chim. Acta, was filtered and dried in vacuo at 40 °C; yield: 99%; UV–VIS, 1993, 76 (5), 2034; (g) H.L. Anderson, R. P. Bonar-Law, l/nm (e): 428 (523 000), 560 (20 000), 600 (7000). dH L. G. Mackay, S. Nicholson and J. K. M. Sanders, NATO ASI ([2H6]DMSO, 2.49 ppm) 9.60 (s, 8 H, Ar-OH), 8.86 (s, 8 H, b- Ser., Ser. C, 1992, 371 (Supramol. Chem.), 359; (h) D. Mansuy and H), 7.01 (d, 8 H, Ar-H), 6.62 (t, 4 H, Ar-H). dC ([2H6DMSO, M. Fontecave, Biochem.Biophys. Res. Commun., 1982, 104 (4), 39.5 ppm) 156.21 (ArC-OH); 148.93 (a C); 144.46 (ArC-porph); 1651. 131.33 (b C); 120.23 (meso C); 114.16, 101.72 (ArC-H). Mass 4 (a) F. R. Long, ‘Porphyrin Chemistry Advances’ Ann Arbor Science Publishers Inc., Ann Arbor, 1979a; (b) F. Montanari and spectrum (MALDI-TOF): m/z, calc. 806; found 814. L. Casella, ‘Metalloporphyrins Catalyzed Oxidations’, Kluwer Academic Press, Boston, 1994; (c) R.A. Sheldon, Tetrakis(3,5-dimethoxyphenyl)porphyrin 5. 3,5-dimethoxy- ‘Metalloporphyrins in Catalytic Oxidations’, Dekker, New York, benzaldehyde (1.500 g, 9.026 mmol) and freshly distilled pyr- 1994. role (626 ml, 9.026 mmol) were dissolved in dry chloroform 5 (a) D. A. Tomalia, A. M. Naylor and W. A. Goddard III, Angew.(903 ml) under nitrogen atmosphere. After adding BF3 OEt2 Chem., Int. Ed. Engl., 1990, 29, 138; (b) G. R. Newkome, C. N. Moorefield and G. R. Baker, Aldrichim. Acta, 1992, 25, 31; (c) (364 ml, 2.979 mmol) to the mixture, the solution was shielded B. I. Voit, Acta Polym., 1995, 46, 87; (d) E. M. M. de Brabander- from ambient light and stirred at room temperature for 90 min. van den Berg, A.Nijenhuis, M. Mure, J. Keulen, R. Reintjens, After adding DDQ (1.537 g, 6.770 mmol), the mixture was B. Vandenbooren, B. Bosman, R. de Raat, T. Frijns, S. v.d. Wal, stirred for an additional 90 min, then triethylamine (415 ml, M. Castelijns, J. Put and E. W. Meijer, Macromol. Symp., 1994, 77, 2.979 mmol) was added to neutralize the acid. The solvent was 51; (e) D. A.Tomalia, Adv.Mater., 1994, 7/8, 529. evaporated, and the residual solids were adsorbed onto silica 6 (a) J. M. J. Fre� chet, Y. Jiang, C. J. Hawker and A. E. Philippides, Preprints IUPAC Int. Symp. Functional Polym., Seoul, 1989, p. 19; (20 ml ). The crude product was purified by chromatography (b) C. J. Hawker and J. M. J. Fre� chet, J. Chem. Soc., Chem. through a 40 ml silica column eluting with a linear gradient of Commun., 1990, 1010; (c) J.M. J. Fre� chet, Science, 1994, 263, 1710. solvent from pure hexane to pure CH2Cl2. After collecting the 7 (a) P. J. Dandliker, F. Diederich, M. Gross, C. B. Knobler, product fractions and evaporating the solvent, the product A. Louati and E. M. Sanford, Angew. Chem. Int., Ed. Engl., 1994, was obtained as purple crystals; yield: 52%; UV–VIS, l/nm (e) 33, 1739; (b) J.P. Collman, L. Fu, A. Zingg and F. Diederich, Chem. 424 (280 000), 516 (19 000), 548 (9000), 586 (9000), 648 (5000). Commun., 1997, 193. 8 (a) R. Jin, T. Aida and S. Inoue, J. Chem. Soc., Chem. Commun., dH ([2H6DMSO, 2.49 ppm) 8.95 (s, 8 H, b-H), 7.01 (s, 8 H, Ar- 1993, 1260; (b) D. Jiang, R. Jin and T. Aida, Chem. Commun., 1996, H), 6.65 (s, 4 H, Ar-H), 3.33 (s, 24 H, ArO-CH3), -3.07 (s, 2 1523; (c) Y. Tomoyose, D. Jiang, R. Jin, T. Aida, T. Yamashita, H, N-H); dC ([2H6DMSO, 39.5 ppm) 156.60 (ArC-OCH3); K. Horie, E. Yashima and Y. Okamoto, Macromolecules, 1996, 142.89 (ArC-porph); 131.12 (b C); 119.94 (meso C); 114.19, 29, 5236. 102.28 (ArC-H); 48.64 (Ar-OCH3) (Calc. for C52H46N4O8; C 9 K. W. Pollak, J. W. Leon and J. M. J. Fre� chet, Polym. Mater. Sci. 73.05, H 5.42, N 6.55; found C 73.11, H 5.29, N 6.43%). Eng., 1995, 73, 137; K. W. Pollak, J. W. Leon and J. M. J. Fre� chet, Chem. Mater., in the press. 10 P. Bhyrappa, J. K. Young, J. S. Moore and K. S. Suslick, J. Am. Tetrakis(3,5-dihydroxyphenyl)porphyrin 6. Tetrakis(3,5- Chem. Soc., 1996, 118, 5708. dimethoxyphenyl)porphyrin 5 (740 mg, 0.866 mmol) was dis- 11 C. J. Hawker and J. M. J. Fre� chet, J. Am. Chem. Soc., 1990, 112, solved in dry CH2Cl2 (20 ml ) under nitrogen atmosphere. The 7638. solution was cooled to 0 °C, then BBr3 (7.27 ml, 7.271 mmol, 12 J. Lindsey, I. Scheirman, H. Hsu, P. Kearney and A. Marguerettaz, J. Org. Chem., 1987, 52, 827. 1 M in CH2Cl2) was slowly added to the reaction. After 13 R. J. Abraham, G. E. Hawkes, M. F. Hudson and K. M. Smith, addition, the mixture was allowed to warm to room temp. as J. Chem. Soc., Perkin T rans. 2, 1975, 204. it stirred overnight. Enough methanol was then added to 14 (a) D. Dolphin, ‘T he Porphyrins vol. III’, Academic Press, NY 1978, deactivate any unreacted BBr3, distilled water (30 ml ) was pp. 12–16; (b) J. E. Falk, ‘Porphyrins and Metalloporphyrins’, added, and the mixture was stirred for 2 h. After evaporation Elsevier Publishing Company, NY, 1964, vol. 75–76, pp. 243–246. of the organic solvents, a green powder was filtered from the water. It was dissolved in diethyl ether, washed twice with Paper 7/05410F; Received 28th July, 1997 J. Mater. Chem., 1998, 8(3), 519&n