A ‘Click’ Chemistry Route to ‘Capped’ Porphyrins

Abstract

Synthesis of a new ‘capped’ porphyrin 3 with rigid 1,2,3-triazole linkers between the porphyrin and ‘capping’ group has been achieved. A ‘click’ reaction, the copper(I)-catalysed variant of the Huisgen 1,3-dipolar cycloaddition, is used to create four linkages concomitantly under anhydrous conditions in N,N-dimethylformamide.

porphyrin - alkyne - azide - 1,3-dipolar cycloaddition - 1,2,3-triazoles

References and Notes

<A NAME="RD10208ST-1A">1a</A> Almog J. Baldwin JE. Dyer RL. Peters M. J. Am. Chem. Soc.  1975,  97:  226 

<A NAME="RD10208ST-1B">1b</A> Almog J. Baldwin JE. Crossley MJ. Debernadis JF. Dyer RL. Huff JR. Peters MK. Tetrahedron  1981,  37:  3589 

<A NAME="RD10208ST-2A">2a</A> Almog J. Baldwin JE. Huff JR. J. Am. Chem. Soc.  1975,  97:  227 

<A NAME="RD10208ST-2B">2b</A> Hashimoto T. Dyer RL. Crossley MJ. Baldwin JE. Basolo F. J. Am. Chem. Soc.  1982,  104:  2101 

<A NAME="RD10208ST-3">3</A> Baldwin JE. Cameron JH. Crossley MJ. Dagley IJ. Hall SR. Klose T. J. Chem. Soc., Dalton Trans.  1984,  1739 

<A NAME="RD10208ST-4">4</A> Adler AD. Longo FR. Finarelli JD. Golmacher J. Assour J. Korsakoff L. J. Org. Chem.  1967,  32:  476 

<A NAME="RD10208ST-5">5</A> Crossley MJ. Field LD. Forster AJ. Harding MM. Sternhell S. J. Am. Chem. Soc.  1987,  109:  341 

<A NAME="RD10208ST-6">6</A> Jameson GB. Ibers JA. J. Am. Chem. Soc.  1980,  102:  2823 

<A NAME="RD10208ST-7">7</A> Sparapany JW. Crossley MJ. Baldwin JE. Ibers JA. J. Am. Chem. Soc.  1988,  110:  4559 

<A NAME="RD10208ST-8">8</A> Kolb HC. Finn MG. Sharpless KB. Angew. Chem. Int. Ed.  2001,  40:  2004 

<A NAME="RD10208ST-9">9</A>

Selected data for compound 4: mp 119-120 ˚C. ^¹H NMR (200 MHz, CDCl₃): δ = 8.15 (s, 2 H), 4.95 (d, J = 2.45 Hz, 8 H), 2.57 (t, J = 2.45 Hz, 4 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 164.9, 133.9, 130.1, 76.7, 76.0, 53.8.

<A NAME="RD10208ST-10">10</A>

Tetrahydrofuran-H ₂ O Method for the Cycloaddition: To a stirred mixture of porphyrin 5 (65 mg) and Et₃N (40 µL) in THF (100 mL) were added CuSO₄˙5H₂O (4 mg) and ascorbic acid (5 mg) dissolved in H₂O (15 mL). Then a solution of tetraalkyne 4 in THF (35 mL) was added and the mixture was heated at reflux for 24 h. An additional portion of CuSO₄˙5H₂O (4 mg) and l-ascorbic acid (5 mg) in H₂O
(5 mL) was added and refluxed for a further 6 h. The reaction was then filtered, evaporated to approximately 20 mL with CH₂Cl₂ (100 mL) and H₂O (100 mL) added. The organic phase was collected and the aqueous phase was extracted with a mixture of MeOH and H₂O (1:1, 2 × 100 mL). This was then dried over Na₂SO₄, filtered and evaporated. Purification on silica with 4% MeOH in H₂O yielded capped porphyrin 3 in 19% yield.

<A NAME="RD10208ST-11">11</A> Lipshutz BH. Taft BR. Angew. Chem. Int. Ed.  2006,  45:  8235 

<A NAME="RD10208ST-12">12</A>

Selected data for compound 3: mp >300 ˚C. ^¹H NMR (400 MHz, CDCl₃): δ = 8.72 (s, 4 H), 8.68 (s, 4 H), 8.41 (br d, J = 7.6 Hz, 4 H, meso-aryl H6), 7.85 (t, J = 7.6 Hz, 4 H, meso-aryl H3), 7.77 (br d, J = 7.6 Hz, 4 H, meso-aryl H4), 7.64 (br s, 4 H), 7.32 (s, 2 H), 7.08 (br s, 4 H, meso-aryl H2), 5.93 (A of ABq, J = 16.1 Hz, 4 H), 5.79 (B of ABq, J = 16.1 Hz,
4 H), 5.13 (A of ABq, J = 13.0 Hz, 4 H), 5.03 (B of ABq, J = 13.0 Hz, 4 H). MS (ESI): m/z [M + Na] calcd for C₇₀H₄₆N₁₆O₈Zn: 1325.3; found: 1325.4.

<A NAME="RD10208ST-13">13</A>

Dimethylformamide Method for the Cycloaddition: To a stirred solution of 5 (45 mg), (NCCH₃)₄CuPF₆ (4 mg) and Et₃N (28 µL) in DMF (100 mL) was added 4 (20 mg). This was then put under nitrogen and stirred at 70 ˚C for 16 h. This was then added to a mixture of CH₂Cl₂ and EtOAc (1:1, 200 mL), washed with H₂O (2 × 100 mL), and the organic phase was filtered and washed again with H₂O (2 × 100 mL). The organic phase was then dried over Na₂SO₄, filtered and evaporated with the residue subjected to purification on silica, eluting capped porphyrin 3 in 14% yield.

<A NAME="RD10208ST-14">14</A> Cross KJ. Crossley MJ. Aust. J. Chem.  1992,  45:  991