PDF icon Download PDF
Synlett 2008(1): 45-48  
DOI: 10.1055/s-2007-992410
LETTER
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed N-Arylation of Hydroxypiperidines with meso-Bromophenyl(polyalkyl)porphyrins

Galina A. Artamkinaa, Petr K. Sazonova, Mikhail M. Shterna, Galina V. Grishinaa, Ivan S. Veselova, Alexander S. Semeikinb, Sergey A. Syrbub, Oskar I. Koifmanb, Irina P. Beletskaya*a
a Department of Chemistry, Moscow State University, Leninskie Gory, 119992 Moscow, Russia
e-Mail: beletska@org.chem.msu.ru;
b Ivanovo State University of Chemistry and Technology, F. Engels Avenue 7, 153000 Ivanovo, Russia
Fax: +7(495)9393618;
Further Information

Publication History

Received 16 October 2007
Publication Date:
11 December 2007 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

New amino derivatives of porphyrins containing cyclic amino and hydroxypiperidine groups bound through the meso phen­yl rings are prepared by the Pd-catalyzed amination of meso-bromophenyl(polyalkyl)porphyrins. The reaction allows for the introduction of piperidine, morpholine, 3- and 4-hydroxypiperidine groups with 50-80% product yields, but in the case of trans-3,4-dihydroxypiperidine and trans-3-hydroxy-4-(4-hydroxypiperidin-1-yl)piperidine the reaction leads to extensive hydrodebromination of the porphyrin substrate.

Key words

hydroxypiperidines - porphyrins - palladium catalysis - aminations - arylations

10

5-(4′-Bromophenyl)-2,3,7,8,12,18-hexamethyl-13,17-dibutylporphyrine (3): A solution of 2,3,7,13,17,18-hexamethyl-8,12-dibutylbiladiene-a,c hydrobromide (1.4 g, 2.12 mmol), 4-bromobenzaldehyde (0.8 g, 4.32 mmol) and concd hydrobromic acid (0.5 mL) in n-BuOH (50 mL) was refluxed for 4 h, then iodine (0.3 g, 1.2 mmol) was added and refluxed for an additional 15 min. n-BuOH was removed by steam distillation, the precipitate was collected by filtration, washed with H2O, dried at 70 °C, dissolved in CHCl3 and chromatographed on a column with neutral alumina. The first colored band containing porphyrin was collected, concentrated to a minimum volume and the product 3 (0.52 g, 37%) was precipitated by addition of MeOH, collected by filtration, washed with MeOH and dried at 70 °C. 1H NMR (400 MHz, CDCl3): δ = 10.15 (s, 2 H, 10-H, 20-H), 9.94 (s, 1 H, 15-H), 7.86 (AB quartet, 4 H), 4.02 (t, 4 H, CH2), 3.62 (s, 6 H, Me), 3.53 (s, 6 H, Me), 2.46 (s, 6 H, Me), 2.30 (m, 4 H, CH2), 1.82 (m, 4 H, CH2), 1.14 (t, 6 H, Me), -3.30 (br s, 2 H, NH). MS (MALDI): m/z [M + H] calcd for C40H46BrN4: 661.28; found: 660.95.

11

In the reactions with hydroxypiperidines part of t-BuONa was consumed in the deprotonation of the hydroxyl group in hydroxypiperidine. Therefore we increased the amount of the base (t-BuONa) from 4 equiv to 8 equiv, which improved the product yield (cf. entries 2 and 3, Table [2] ).

12

Representative Experimental Procedure: meso-Bromophenylporphyrin 3 (33 mg, 0.05 mmol), 4-hydroxypiperidine (1c; 15 mg, 0.15 mmol), t-BuONa (40 mg, 0.42 mmol), Pd(OAc)2 (1.35 mg, 0.006 mmol), and ligand L3 (4.8 mg, 0.0122 mmol) were placed in the reactor, which was evacuated and dioxane (5 mL) was vacuum-transferred to the reactor. The reactor was filled with argon and the mixture was stirred at 100 °C for 24 h. Then the solvent was removed under reduced pressure, MeOH (5 mL) was added to the viscous residue, the sediment formed was separated by centrifugation, washed with MeOH, dried and subjected to column chromatography on neutral alumina (5/40) using CHCl3-PE (4:6) as eluent. The debrominated product 8 (5 mg, 17%) was isolated from the first fraction, the amination product 7c (24 mg, 70%) from the second fraction.

14

Aldrich/ACD Library of FT NMR Spectra, Version 1.11, 1999.