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1,1’,1’’,1’’’-[Porphyrin-5,10,15,20-tetrayltetrakis(3,1-phenylenemethylene)]tetraquinolinium Tetrabromide
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Jürgen Bachl
1 and
David D. Díaz
Institut für Organische Chemie, Universität Regensburg, Universitätsstr 31, 93040 Regensburg, Germany
ICMA, CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain
Author to whom correspondence should be addressed.
Molbank 2010, 2010(4), M705;
Submission received: 8 October 2010 / Accepted: 1 November 2010 / Published: 4 November 2010


N,N'-1,2-Phenylenebis[4-(chloromethyl)benzamide] (3) was obtained in 61% yield by nucleophilic acyl substitution of 4-(chloromethyl)benzoyl chloride (2) with 1,2-phenylenediamine (1) under basic conditions. The title compound was characterized by FT-IR, 1H NMR, 13C NMR, low- and high-resolution EI-MS, and melting point.

Substituted benzamides have been in clinical use for many years as anti-emetics, anti-arrhythmics, neuroleptics, and/or anti-psychotics in the treatment of various disorders [1]. They also constitute versatile intermediates for the synthesis of anti-tumor and anti-inflammatory agents [2], protease inhibitors [3], dyes [4], and have been extensively used as sensitizers for radio- or chemotherapies [5]. On the other hand, benzyl chloride derivatives are widely used as synthetic building blocks. They constitute, for instance, the precursors to benzyl esters, which are commonly employed in industry as plasticizers, flavorants, and perfumes [6]. Hence, organic molecules bearing both functionalities may be of practical interest.
We report here the synthesis of N,N'-1,2-phenylenebis[4-(chloromethyl)benzamide] (3) by nucleophilic acyl substitution of 4-(chloromethyl)benzoyl chloride (2) with 1,2-phenylenediamine (1) in the presence of Et3N (Scheme 1) [7].

Experimental Section


1H and 13C NMR spectra were recorded at 25 °C on a Bruker 400 spectrometer in DMSO-d6 as solvent, and chemical shifts are reported relative to residual solvent peaks [8]. The low-resolution mass spectrum was obtained using a Varian MAT 311A spectrometer. The infrared spectrum was recorded using a Diamond ATR (attenuated total reflection) accessory (Golden Gate) on a Bio-Rad Excalibur FTS 3000 MX spectrophotometer. The melting point (mp) was measured in an Opti Melt MPA 100 instrument and is uncorrected. Thin-layer chromatography was carried out on Merck aluminium sheets coated with silica gel 60 F254. Compounds were visualized by use of 254 nm UV light and/or phosphomolybdic acid 20% (wt.) solution in ethanol with heating. All solvents were of p.a. grade or were purified by standard techniques [9]. Anhydrous sodium sulfate was used for drying solutions. 1,2-Phenylenediamine (1) and 4-(chloromethyl)benzoyl chloride (2) were purchased from commercial suppliers and used as received without further purification.

Synthesis of N,N'-1,2-phenylenebis[4-(chloromethyl)benzamide] (3)

To a stirred solution of 1,2-phenylenediamine (1) (500 mg, 4.55 mmol) and Et3N (1.59 mL, 11.4 mmol) in CH2Cl2 (20 mL) kept at 0 °C was added dropwise (using a pressure-compensated addition funnel) a solution of 4-(chloromethyl)benzoyl chloride (2) (1.75 g, 9.09 mmol) in CH2Cl2 (20 mL). The reaction mixture was allowed to stir for 5 h at room temperature, after which time TLC analysis showed full conversion of the starting materials. The organic phase was washed with H2O (15 mL × 2) and brine (15 mL × 2), dried (Na2SO4), filtered, and concentrated. The solid residue was recrystallized from CH2Cl2/pentane, affording product 3 (1.1 g, 61% yield [10]) as a white crystalline solid: TLC Rf (AcOEt/hexane 1:1) 0.40; mp = 191–193 °C; 1H NMR (400 MHz, DMSO-d6) δ/ppm = 4.83 (s, 4H), 7.31 (dd, J = 6.0, 3.6 Hz, 2H), 7.59 (d, J = 8.4 Hz, 4H), 7.67 (dd, J = 6.0, 3.6 Hz, 2H), 7.96 (d, J = 8.4 Hz, 4H), 10.08 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ/ppm = 45.23 (2C), 125.51 (2C), 125.80 (2C), 127.81 (4C), 128.83 (4C), 131.19 (2C), 133.97 (2C), 141.22 (2C), 164.92 (2C); FT-IR (ATR) νmax (cm−1) 3287 (N-H stretching), 1644 (C=O stretching, amide I band), 1514 (N-H bending, amide II band), 1305, 1267 (C-H stretching, CH2Cl), 672, 476; MS (ESI) m/z 412 [M+]. HRMS calculated for C22H18Cl2N2O2 412.07453; found 412.07426.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3Supplementary File 4


D.D.D. thanks the Alexander von Humboldt Foundation for a research fellowship for experienced researchers.

References and Notes

  1. Norman, M.H.; Rigdon, G.C.; Hall, W.R.; Navas, F. Structure-activity relationships of a series of substituted benzamides: Potent D2/5-HT2 antagonists and 5-HT1a agonists as neuroleptic agents. J. Med. Chem. 1996, 39, 1172–1188. [Google Scholar] [CrossRef] [PubMed]
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  3. Reich, S.H.; Johnson, T.; Wallace, M.B.; Kephart, S.E.; Fuhrman, S.A.; Worland, S.T.; Matthews, D.A.; Hendrickson, T.F.; Chan, F.; Meador, J., III; Ferre, R.A.; Brown, E.L.; DeLisle, D.M.; Patick, A.K.; Binford, S.L.; Ford, C.E. Substituted Benzamide Inhibitors of Human Rhinovirus 3C Protease: Structure-Based Design, Synthesis, and Biological Evaluation. J. Med. Chem. 2000, 43, 1670–1683. [Google Scholar] [CrossRef] [PubMed]
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  6. Rossberg, M.; Lendle, W.; Pfleiderer, G.; Tögel, A.; Dreher, E.-L.; Langer, E.; Rassaerts, H.; Kleinschmidt, P.; Strack, H.; Cook, R.; Beck, U.; Lipper, K.-A.; Torkelson, T.R.; Löser, E.; Beutel, K.K.; Mann, T. Chlorinated Hydrocarbons. In Ullmann’s Encyclopedia of Industrial Chemistry; Wiley-VCH: Weinheim, Germany, 2006. [Google Scholar]
  7. For the synthesis of the linear analogues using p-phenylenediamine, see: Misawa, Y.; Koumura, N.; Matsumoto, H.; Tamaoki, N.; Yoshida, M. Hydrogels Based on Surfactant-Free Ionene Polymers with N,Nʹ′-(p-Phenylene)dibenzamide Linkages. Macromolecules 2008, 41, 8841–8846. [Google Scholar]
  8. See Supplementary Files.
  9. Armarego, W.L.F.; Perrin, D.D. Purification of Laboratory Chemicals, 4th ed.; Butterworth-Heinemann: Oxford, UK, 1996. [Google Scholar]
  10. The qualitative TLC analysis of the reaction crude showed the presence of additional minor products. Unfortunately, we were unable to isolate and identify such products by column chromatography. Nevertheless, the major loss in the yield comes most likely from the recrystal¬lization, filtration and washing procedures used to purify the title compound.
Scheme 1.
Scheme 1.
Molbank 2010 m705 sch001

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Bachl, J.; Díaz, D.D. N,N'-1,2-Phenylenebis[4-(chloromethyl)benzamide]. Molbank 2010, 2010, M705.

AMA Style

Bachl J, Díaz DD. N,N'-1,2-Phenylenebis[4-(chloromethyl)benzamide]. Molbank. 2010; 2010(4):M705.

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Bachl, Jürgen, and David D. Díaz. 2010. "N,N'-1,2-Phenylenebis[4-(chloromethyl)benzamide]" Molbank 2010, no. 4: M705.

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