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DOI: 10.1055/s-2008-1078505
Efficient Silver-Mediated Acetalation of β,β′-Functionalized Chlorins
Publication History
Publication Date:
19 June 2008 (online)
Abstract
We present a novel synthetic strategy to 2,2-dialkoxy-3-oxochlorins [M = 2H, Ni(II), Cu(II)] (i.e., acetaloxochlorins). Reaction of the corresponding 2,3-dioxochlorin with stoichiometric amounts of silver triflate (AgOTf) in the presence of excess alcohol yields the desired acetaloxochlorins within several hours of reflux in up to 90% yield for n-alcohols, and in 25-89% yields for functionalized alcohol substrates. Similar reaction conditions applied to 2-diazo-3-oxochlorins generates the 2,2-dialkoxy-3-oxochlorins (12-60% yields) accompanied by alkoxyporphyrins (10-27% yields). Electronic spectroscopy reveals for the acetaloxochlorins characteristic π-π* absorption features throughout the visible region and their X-ray crystal structures exhibit marked distortion from planarity of the π-conjugated macrocycle due in part to the steric bulk at the periphery.
Key words
chlorin - silver triflate - acetal - pyrroloquinoline quinine - PQQ
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References and Notes
General Procedure for Isolation of M3 Derivatives from M1: To a solution of dioxochlorin M1 (0.015 mmol) in CH2Cl2-alcohol (1:1.5, 5 mL, a-f respectively), silver triflate (1 equiv) was added and the resulting mixture was stirred under reflux for several hours (Table [¹] ). After completion of the reaction the mixture was cooled to r.t. and poured into H2O (35 mL). The obtained porphyrinoids were extracted using EtOAc (3 × 10 mL) and the combined organic layers were concentrated under reduced pressure. The crude compounds were purified by silica gel column chromatography using solvent gradients of hexanes, CH2Cl2, and EtOAc.
34
Product Characterization
Data: Cu3a: MALDI (TOF):
m/z (isotope
pattern) = 807.2 [M]. HRMS (ESI): m/z [M + Na+] calcd
for C50H40N4O3CuNa:
830.2294; found: 830.2267. UV-Vis (CH2Cl2):λmax = 346,
383, 432, 592, 630 nm. IR: 2961, 2924, 1734, 1599, 1539, 1489, 1441,
1384, 1344, 1319, 1225, 1153, 1086, 1073, 1029, 1009, 995, 791, 752,
700, 502 cm-¹.
Cu3b:
MALDI (TOF): m/z (isotope
pattern) = 835.4 [M]. HRMS (CI): m/z [M+] calcd
for C52H44N4O3Cu: 835.2704; found:
835.2710. UV-Vis (CH2Cl2): λmax = 346,
383, 432, 592, 630 nm. IR: 2960, 2922, 1734, 1599, 1540, 1508, 1489, 1441,
1318, 1233, 1225, 1152, 1091, 1074, 1040, 1009, 995, 890, 833, 791,
752, 710, 700, 502 cm-¹.
Cu3c: MALDI (TOF): m/z (isotope pattern) = 863.4 [M]. HRMS
(ESI): m/z [M + Na+] calcd
for C54H48N4O3CuNa: 886.2920;
found: 886.2905. UV-Vis (CH2Cl2): λmax = 346, 383,
432, 592, 630 nm. IR: 2960, 2928, 2856, 1734, 1599, 1557, 1539,
1508, 1489, 1459, 1441, 1430, 1344, 1319, 1269, 1232, 1150, 1093,
1074, 1026, 1009, 995, 880, 833, 793, 756, 718, 700, 502 cm-¹.
Cu3d: MALDI (TOF): m/z (isotope pattern) = 839.5 [M]. HRMS
(CI): m/z [M+] calcd
for C50H40N4O5Cu: 839.2289; found:
839.2286. UV-Vis (CH2Cl2): λmax = 347,
388, 435, 595, 635 nm. IR: 2924, 1733, 1598, 1539, 1501, 1489, 1440, 1343,
1318, 1231, 1197, 1151, 1127, 1094, 1072, 1029, 1009, 994, 883,
833, 790, 758, 710, 717, 700, 670, 553, 504 cm-¹.
Cu3e: MALDI (TOF): m/z (isotope pattern) = 849.3 [M + H+].
HRMS (ESI): m/z [M+] calcd
for C48H34N4O3Cl2Cu: 848.1377;
found: 848.1395. UV-Vis (CH2Cl2): λmax = 347, 388,
435, 595, 635 nm. IR: 2954, 2920, 2851, 1733, 1635, 1598, 1456,
1440, 1384, 1344, 1269, 1230, 1147, 1096, 1070, 1009, 832, 794,
759, 715, 701, 502 cm-¹.
Cu3f: MALDI (TOF): m/z (isotope pattern) = 835.2 [M]. HRMS
(CI): m/z [M+] calcd
for C52H44N4O3Cu: 835.2704; found:
835.2722. UV-Vis (CH2Cl2): λmax = 346,
383, 432, 592, 630 nm. IR: 2957, 2920, 2870, 1734, 1599, 1541, 1489, 1468,
1365, 1344, 1318, 1232, 1151, 1088, 1073, 1042, 1009, 997, 833,
791, 751, 734, 700, 502 cm-¹.
Ni3b: MALDI (TOF): m/z (isotope pattern) = 830.4 [M]. HRMS
(EI): m/z [M+] calcd
for C52H44N4O3Ni: 830.2761; found:
830.2735. UV-Vis (CH2Cl2): λmax = 344,
386, 435, 596, 632 nm. ¹H NMR (400 MHz, CD2Cl2): δ = 8.24-8.30 (m,
3 H, β-pyrrolic H), 8.16 (s, 2 H, β-pyrrolic H),
7.90-7.91 (d, J = 4.0
Hz, 1 H, β-pyrrolic H), 7.72-7.77 (m, 4 H, meso-ArH),
7.34-7.62 (m, 16 H, meso-ArH), 3.35-3.50 (m, 4
H, OCH2R), 1.20-1.35 (m, 4 H, OCH2CH
2R), 1.04-1.16 (m,
4 H, OCH2CH2CH
2R),
0.68-0.71 (t, J = 7.2,
7.6 Hz, 6 H, OCH2CH2CH2CH
3). IR: 2954, 2925, 2868,
1734, 1599, 1552, 1490, 1441, 1365, 1349, 1325, 1177, 1152, 1089, 1070,
1010, 892, 843, 834, 793, 751, 715, 700, 503 cm-¹.
Ni3d: MALDI (TOF): m/z (isotope pattern) = 834.5 [M]. HRMS
(CI): m/z [M+] calcd
for C50H40N4O5Ni: 834.2347; found:
834.2344. UV-Vis (CH2Cl2): λmax = 345,
388, 436, 597, 634 nm. ¹H NMR (400 MHz, CD2Cl2): δ = 8.34-8.40 (m,
3 H, β-pyrrolic H), 8.26 (s, 2 H, β-pyrrolic H),
8.00-8.02 (d, J = 4.8
Hz, 1 H, β-pyrrolic H), 7.84-7.86 (m, 4 H, meso-ArH),
7.23-7.47 (m, 16 H, meso-ArH), 3.60-3.75 (m, 4
H, OCH
2CH2OCH3),
3.33-3.34 (t, J = 4.8,
4.8 Hz, 4 H, OCH2CH
2OCH3),
3.16 (s, 6 H, OCH2CH2OCH
3).
IR: 2950, 2922, 2868, 1733, 1599, 1553, 1490, 1441, 1349, 1325, 1232,
1199, 1152, 1129, 1071, 1007, 888, 843, 793, 751, 715, 700, 502
cm-¹.
Ni3e:
MALDI (TOF): m/z (isotope
pattern) = 842.5 [M]. HRMS (CI): m/z [M+] calcd
for C48H34N4O3Cl2Ni: 842.1356;
found: 842.1347. UV-Vis (CH2Cl2): λmax = 347, 388,
438, 598, 637 nm. ¹H NMR (400 MHz, CD2Cl2): δ = 8.34-8.39
(m, 3 H, β-pyrrolic H), 8.26-8.27 (m, 2 H, β-pyrrolic
H), 8.06-8.07 (d, J = 4.0
Hz, 1 H, β-pyrrolic H), 7.83-7.88 (m, 4 H, meso-ArH),
7.31-7.32 (m, 2 H, meso-ArH), 7.48-7.66 (m, 14
H, meso-ArH), 3.80-3.85 (m, 4 H, alkoxy-OCH2R),
3.40-3.45 (m, 4 H, alkoxy-OCH2CH
2Cl). IR:
2954, 2922, 2854, 1732, 1599, 1557, 1441, 1384, 1349, 1233, 1210,
1153, 1099, 1071, 1013, 793, 751, 716, 701, 555, 503 cm-¹.
Cu4b: MALDI (TOF): m/z (isotope pattern) = 747.3 [M]. HRMS
(CI): m/z calcd
for C48H36N4OCu: 747.2180; found: 747.2168.
UV-Vis (CH2Cl2): λmax = 417,
537, 578 nm. IR: 2955, 2920, 2851, 1586, 1556, 1537, 1516, 1489,
1440, 1384, 1334, 1302, 1240, 1178, 1155, 1070, 1046, 1036, 1005,
994, 796, 783, 759, 715, 703, 502 cm-¹.
Ni4b: MALDI (TOF): m/z (isotope pattern) = 742.3 [M]. HRMS
(CI): m/z [M+] calcd
for C48H36N4ONi: 742.2237; found:
742.2217. UV-Vis (400 MHz, CH2Cl2): λmax = 413, 530,
570 nm. ¹H NMR (400 MHz, CD2Cl2): δ = 8.60-8.70 (m,
6 H, β-pyrrolic H), 7.95-8.00 [m, 5 H,
(1 H, β-pyrrolic H, 4 H, meso-ArH)], 7.57-7.81
(m, 16 H, meso-ArH), 4.11-4.14 (t, J = 6.0,
6.0 Hz, 2 H, OCH2R), 1.42-1.45 (m, 2 H, OCH2CH
2R), 1.16-1.23 (m,
2 H, OCH2CH2CH
2R),
0.85-0.89 (t, J = 7.2,
7.2 Hz, 3 H, OCH2CH2CH2CH
3). IR: 2954, 2922, 2854,
1588, 1525, 1491, 1455, 1440, 1382, 1350, 1322, 1243, 1212, 1180,
1154, 1070, 1007, 970, 837, 790, 752, 715, 700, 555, 503 cm-¹.
H3e: MALDI (TOF): m/z (isotope pattern) = 787.5 [M+]. HRMS
(CI): m/z [M+] calcd
for C48H36N4O3Cl2:
786.2184; found: 786.2159. ¹H NMR (400 MHz,
CD2Cl2): δ = 8.70-8.71
(d, J = 4.0 Hz, 2 H, β-pyrrolic
H), 8.42-8.58 (m, 4 H, β-pyrrolic H), 8.00-8.16
(m, 6 H, β-pyrrolic H), 7.88-7.94 (m, 2 H, meso-ArH),
7.56-7.80 (m, 12 H, meso-ArH), 3.88-3.96 (m, 2
H, alkoxy-OCH2R), 3.68-3.76 (m, 2 H, alkoxy-OCH2R),
3.40-3.50 (m, 4 H, alkoxy-OCH2CH
2Cl), -1.97 (s,
1 H, pyrrolic NH), -2.16 (s, 1 H, pyrrolic NH).
General Procedure for Isolation of M3b and M4b Derivatives from M2: Diazo-oxochlorin M2 (0.015 mmol) was dissolved in p-dioxane (2 mL) and n-butanol (b; 8 mL), followed by the addition of silver triflate (1 equiv). The resulting mixture was stirred under reflux for 20 h which resulted in the formation of two new species. After consumption of all starting material the reaction mixture was cooled to r.t. The solution was poured into H2O (35 mL) and the porphyrinoid products were extracted with EtOAc (3 × 10 mL). The solvent of the combined organic layers was evaporated under reduced pressure and the crude compounds were purified by silica gel column chromatography using the eluent hexanes-CH2Cl2 (3:1).
38Isolation of Cu4b from CuOH: [2-Hydroxy-5,10,15,20-tetraphenylporphyrinato]Cu(II) (CuOH, 0.0145 mmol) was dissolved in p-dioxane (2 mL) and reacted with AgOTf (1 equiv) and n-butanol (b, 8 mL) under reflux for 20 h. The resulting mixture was cooled to r.t. and poured into H2O (35 mL). Extraction with EtOAc (3 × 10 mL), subsequent concentration and silica gel column chromatography purification gave Cu4b in 37% yield.
40Hydrolysis of 2,2-Alkoxy-3-oxochlorin Cu3b to Yield Cu1: Heating of a solution of Cu3b (0.006 mmol) in p-dioxane-n-butanol (1:4) for 2 h at 70 ˚C in the presence of aq HCl (10%, 3 mL) resulted in the formation of dioxochlorin Cu1. The reaction mixture was cooled to r.t., poured into H2O (25 mL), and the green compound was extracted with EtOAc (3 × 10 mL). Cu1 was purified by silica gel column chromatography and isolated in 70% yield.
42Crystals suitable for X-ray diffraction
studies were obtained from slow diffusion of methanol into a CH2Cl2 solution. Crystallographic
data (excluding structure factors) for the structures reported in
this paper have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication data CCDC 668819 (Cu1), and CCDC 676199 (Cu3a),
CCDC 676200 (Cu3d), CCDC 676201 (H3e). Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [fax: +44 (1223)336033; e-mail: deposit@ccdc.cam.ac.uk].
Crystal
data for Cu1: red, 0.18 × 0.18 × 0.12
mm, C44H26N4O2Cu, M = 706.23, tetragonal, a = 15.231 (5) Å, b = 15.231 (5) Å, c = 13.452 (7) Å, α = β = γ = 90˚, V = 3121 (2) ų, T = 120 (2) K, space group I42d, Z = 4, ρ
calcd = 1.503 Mgm-³, µ = 0.749 mm-¹,
2θmax = 53˚, Mo-Kα (λ = 0.71073). A total
of 12518 reflections were measured, of which 1609 (R
int = 0.0722)
were unique. Final residuals were R1 = 0.0312
and wR2 = 0.0756 [for
1480 observed reflections with I > 2σ(I), 129 parameters] with GOF
1.088 and largest residual peak 0.224 eÅ-³ and
hole -0.262 eÅ-³.
Crystal data for H3e: black plate, 0.10 × 0.05 × 0.005
mm, C48.50H37N4O3Cl3, M = 656.72, triclinic, a = 12.5326 (11) Å, b = 13.6716 (8) Å, c = 24.8275 (13) Å, α = 88.026 (2)˚, β = 82.395 (3)˚, γ = 70.255 (3)˚, V = 3968.4 (5) ų, T = 100 (2) K, space group P1, Z = 4, ρcalcd = 1.390
Mgm-³, µ = 0.152 mm-¹,
2θmax = 39˚, λ = 0.49595.
A total of 53708 reflections were measured, of which 18775 (R
int = 0.0654) were
unique. Final residuals were R1 = 0.1176
and wR2 = 0.3112 [for 11771
observed reflections with I > 2σ(I), 1061 parameters] with GOF
1.033 and largest residual peak 1.907 eÅ-³ and hole -1.486
eÅ-³.
Crystal data
for Cu3a: black, 0.10 × 0.02 × 0.01
mm, C50H40N4O3Cu, M = 808.40, orthorhombic, a = 24.4909 (14) Å, b = 9.1896 (4) Å, c = 34.6315 (15) Å, α = β = γ = 90˚, V = 7794 (6) ų, T = 120 (2) K, space group Pna21, Z = 8, ρ
calcd = 1.378
Mgm-³, µ = 0.329
mm-¹, 2θmax = 39˚, λ = 0. 49595. A total
of 68079 reflections were measured, of which 19029 (R
int = 0.039) were
unique. Final residuals were R1 = 0.0439
and wR2 = 0.1191 [for
17428 observed reflections with I > 2σ(I), 1058 parameters] with GOF
1.165 and largest residual peak 0.615 eÅ-³ and
hole -0.985 eÅ-³.
Crystal
data for Cu3d: black, 0.10 × 0.01 × 0.005
mm, C50.25H41N4O5.25Cu, M = 848.41, monoclinic, a = 35.9629 (12) Å, b = 9.0840 (4) Å, c = 24.6129 (7) Å, α = 90˚, β = 99.771 (2)˚, γ = 90˚, V = 7924.1 (5) ų, T = 120 (2) K, space group C2/c, Z = 8, ρ
calcd = 1.422
Mgm-³, µ = 0.328
mm-¹, 2θmax = 39˚, λ = 0. 49595. A total
of 35420 reflections were measured, of which 9407 (R
int = 0.0759)
were unique. Final residuals were R1 = 0.0439
and wR2 = 0.1191 [for
7865 observed reflections with I > 2σ(I), 553 parameters] with GOF
1.064 and largest residual peak 0.755 eÅ-³ and
hole
-1.432 eÅ-³.