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Preparation of 4-(1-Pyrenyl)butyl amine hydrochloride; 4-Aryl-butylamine Fluorescent Probe

SyntheticPage 206
DOI: 10.1039/SP206
Submitted Oct 29, 2002, published Oct 29, 2002
Carlos Afonso (cma@dq.fct.unl.pt)
A contribution from Carlos A. M. Afonso, C. D. Maycock Group, New University of Lisbon, Portugal


			Reaction Scheme: Preparation of 4-(1-Pyrenyl)butyl amine hydrochloride

Chemicals Used

1-pyrenebutyric acid (Lancaster), oxalyl chloride (Aldrich), ammonia (gaseous), anhydrous dimethylformamide (distilled from barium oxide powder under a nitrogen atmosphere), dichloromethane (distilled from calcium hydride powder under a nitrogen atmosphere), anhydrous tetrahydrofuran and diethyl ether (pre-dried over sodium wire and distilled from sodium/benzophenone under a nitrogen atmosphere), borane-methyl sulfide complex (Aldrich), hydrogen chloride (prepared from sulfuric acid / hydrochloric acid, following the method described in Vogel’s Textbook of Practical Organic Chemistry).

Procedure

Preparation of 4-(1-Pyrenyl)butyric amide (2): To a stirred solution of 1-pyrenebutyric acid (1) (4.279 g, 14.84 mmol) and anhydrous dimethylformamide (cat. amount) in anhydrous dichloromethane (100 ml) under argon at r.t. was added dropwise oxalyl chloride (1.36 ml, 1.05 equiv). After 30 min (gas liberation after 2 min) the suspension was refluxed for 1.5 h. The yellow solution was cooled to room temperature and excess NH3 bubbled into the reaction mixture (instantaneous formation of precipitate). The reaction mixture was then partioned between water (300 ml) and ethyl acetate (500 ml). The aqueous phase was extracted with ethyl acetate (2 x 400 ml), the combined organic phase was dried with MgSO4 and the solvent removed under reduced pressure. The resulting solid was crystallised from ethyl acetate (400 ml) : n-hexane (100 ml) to give (2) (2.875 g, 67 %) as slightly yellow small needles; m.p. 180-181 °C, m.p. 181.5-182 °C (after three crystallisations); Rf = 0.72 (ethyl acetate : ethanol 9.5 : 0.5). Further quantities of (2) were obtained by crystallisation from the mother fraction using ethyl acetate: n-hexane to give (2) (0.553 g, 13.0 %); m.p. 180-182 °C. Preparation of 4-(1-pyrenyl)butyl amine hydrochloride (4): To stirred reflux solution of (2) (3.154 g, 11.0 mmol) in anhydrous tetrahydrofuran (17 ml) under argon was added dropwise (30 min) BH3.Me2S (2.7 ml, 2.5 mol equiv, gas liberation). The reaction mixture was then distilled over 1.5 h to remove the Me2S / tetrahydrofuran (8 ml). The reaction mixture was cooled to r.t., and methanol (4.5 ml, 3 mol equiv) was added dropwise (vigorous gas liberation). The reaction mixture was poured into an aqueous HCl solution (3M, 100 ml, pH < 4, formation of precipitate). The mixture was cooled (ice/water bath), basified with aqueous NaOH solution (pH > 9), extracted with diethyl ether (3 x 100 ml), the combined organic phase was dried with MgSO4 and the solvent removed under reduced pressure to give 4-(1-pyrenyl)butyl amine (3) (2.916 g, 97 %) as a yellow viscous liquid. HCl gas was bubbled into a solution of the amine (3) dissolved in anhydrous diethyl ether (50 ml). The resulting precipitate was filtered to give 4-(1-pyrenyl)butyl amine hydrochloride (4) (2.942 g, 89 %) as brown cubes; m.p. 232(dec)-259 °C.

Author's Comments

The use of fluorescent compounds as probes is of considerable importance and such species have many potential applications. In some cases it is of crucial importance that the fluorescent probe is attached to a particular species by a long alkyl chain. Usually, such probes have to be tailor-made to meet the required specifications. In this protocol we use a readily available commercial compound containing the pyrene unit, and produce the fluorescent probe 4-(1-pyrenyl)butyl amine hydrochloride (4) which contains an amine linker group and a butyl group spacer. The 4-(1-pyrenyl)butyl amine (3) has previously been prepared in the literature from the corresponding alcohol by a three steps procedure in 53% overall yield (D. L. McMinn, M. M. Greenberg, J. Am. Chem. Soc. 1998, 120, 3289). Using the simple protocol described here, were prepared the amine (3) by conversion of 1-pyrenebutyric acid (1) into the corresponding amide (2) followed by reduction with borane-dimethyl sulphide. This simple overall three steps procedure allowed the preparation of the 4-(1-pyrenyl)butyl amine hydrochloride (4) in an improved 69 % overall yield and without chromatographic purification. The reduction of the amide (2) to the amine (3) were first attempted using lithium aluminum hydride (THF, reflux, 24 h) or by using sodium borohydride / iodide method (reported method: A. S. B. Prasad, J. V. B. Kanth, M. Periasamy Tetrahedron 1992, 48, 4623), but no reduced product (3) was observed.

Data

4-(1-Pyrenyl)butyric amide (2): IR (nujol) n = 3400 (NH), 3200 (NH), 1650 (C=O), 1615, 1304, 1179, 837, 721 cm-1; H NMR (400 MHz; CDCl3) 2.20-2.27 (m, 2H, ArCH2CH2), 2.34 (t, 2H, J=6.9 Hz, CH2CONH2), 3.43 (t, 2H, J=7.5 Hz, ArCH2), 5.35 (br, 2H, CONH2), 7.87 (d, 1H, J=7.8 Hz, Ar), 7.80 (t, 1H, J=7.6 Hz, Ar), 8.03 (s, 2H, Ar), 8.11 (d, 2H, J=9.0 Hz, Ar), 8.17 (dd, 2H, J=7.6, 2.4 Hz, Ar), 8.31 (d, 1H, J=9.2 Hz, Ar); 13C NMR (100 MHz; (CD3)2SO) 27.54, 32.46, 34.92, 123.86, 124.53, 124.62, 125.13, 125.27, 126.46, 126.84, 127.56, 127.81, 127.85, 128.54, 129.67, 130.81, 131.27, 137.00, 174.61; Anal. calcd. for C20H17NO: C 83.60%; H 5.96%; N 4.87%. Found: C 83.83%; H 6.00%; N 5.00%. 4-(1-pyrenyl)butyl amine hydrochloride (4): IR (nujol) n = 3381 (NH), 3171, 2725, 1602, 1156, 958, 841, 722 cm-1; H NMR (400 MHz; (CD3)2SO) 1.69-1.76 (m, 2H, ArCH2(CH2)2), 1.79-1.86 (m, 2H, ArCH2(CH2)2), 2.82 (t, 2H, J=7.3 Hz, CH2NH2HCl), 3.33 (t, 2H, J=7.5 Hz, ArCH2), 7.94 (d, 1H, J=7.8 Hz, Ar), 8.04 (t, 1H, J=7.6 Hz, Ar), 8.11 (dd, 2H, J=10.6, 9.0 Hz, Ar), 8.20 (dd, 2H, J=9.2, 7.2 Hz, Ar), 8.25 (dd, 2H, J=7.4, 5.2 Hz, Ar), 8.33 (d, 1H, J=9.3 Hz, Ar); 13C NMR (100 MHz; (CD3)2SO) 27.23, 28.42, 32.23, 38.81, 123.85, 124.51, 124.60, 125.14, 125.27, 126.50, 126.89, 127.60, 127.82, 128.47, 129.68, 130.79, 131.27, 136.81; Anal. calcd. for C20H20NCl: C 77.53%; H 6.51%; N 4.52%. Found: C 77.70%; H 6.55%; N 4.53%.

Lead Reference

Carlos A. M. Afonso, J. P. S. Farinha, J. Chem. Res. (Accepted).

Other References

For an alternative three steps procedure for the preparation of the amine (3) see: D. L. McMinn, M. M. Greenberg, J. Am. Chem. Soc. 1998, 120, 3289. The diborane reduction step was based on the following reported method: H. C. Brown, Y. M. Choi, S. Narasimhan, J. Org. Chem. 1982, 47, 3153.

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Keywords: molecular probes, oxidative addition, oxidation, carboxylic acids, carbonates, alkyl/alkenyl/aryl halides, 206

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