The reduction of substituted benzylamines by means of electrochemically generated solvated electrons in LiCl + methylamine Citation for published version (APA): Andel-Scheffer, van, P. J. M., Wonders, A. H., & Barendrecht, E. (1994). The reduction of substituted benzylamines by means of electrochemically generated solvated electrons in LiCl + methylamine. Journal of Electroanalytical Chemistry, 366(1-2), 135-141. https://doi.org/10.1016/0022-0728(93)02927-A DOI: 10.1016/0022-0728(93)02927-A Document status and date: Published: 01/01/1994 Document Version: Publisher’s PDF, also known as Version of Record (includes final page, issue and volume numbers) Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. 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If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.tue.nl/taverne Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim. Download date: 26. Sep. 2021 Journal of Electroanalytical Chemistry, 366 (1994) 135-141 135 The reduction of substituted benzylamines by means of electrochemically generated solvated electrons in LiCl + methylamine * P.J.M. van Andel-Scheffer, A.H. Wonders and E. Barendrecht Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven (Netherlands) (Received 6 May 1993) Abstract Methoxy-substituted and N-methylated benzylamines were reduced to their 1,Cdihydro derivatives using the electrochemical Benkeser reduction. N,N-dimethyl-veratrylamine decomposed during the reduction. The differences in current efficiencies can be explained by differences in the stabilization of the radical anions and by differences in protonation rates. Rotating ring-disk electrode (RRDE) experiments showed that in the reduction of benzylamines, the first protonation can be achieved either intramolecularly or intermolecularly. 1. Introduction 2. Experimental Several substituted benzenes can be reduced chemi- 2.1. Reagents cally and/or electrochemically to their 1,4-dihydro Benzylamine (99%, Janssen Chimica), N-methyl- derivatives. The electrochemical reduction of several benzylamine (98%, Alfa), 1-phenyl-3-aminopropane substituted aromatic amines is described here. The (98%, Janssen Chimica), p-methoxy-benzylamine (98%, investigation was initiated by the question as to whether Janssen Chimica), m-methoxy-benzylamine (Janssen galanthamine (Fig. l(A)) could be electrochemically Chimica) and veratrylamine (95%, Janssen Chimica) reduced to its 1,Cdihydro derivative without affecting were used as received for the organic reduction reac- the functional groups present. The reduction of N,N- tions. Methylamine (Ucar) was distilled over lithium dimethyl-veratrylamine (Fig. l(B)) served as a model. before use. N,N-dimethyl-be&amine, N,N-dimeth- The electrochemical aromatic reduction described by yl-p-methoxy-benzylamine and N,N-dimethyl-m- Benkeser and Kaiser [l] (Fig. 2) was used for the methoxy-be&amine were synthesized by standard reduction. The reaction is carried out in LiCl + methods [2] and purified by distillation. For the rotat- methylamine. Either a divided or an undivided cell can ing ring-disk electrode (RRDE) experiments, benzy- be used, with each leading to different products. When lamine was distilled twice before use. Lithium chloride benzene is reduced in a divided cell, the product is (Janssen Chimica) and lithium bromide were dried at cyclohexene. In an undivided cell, the product is 1,4- 150°C for 24 h before use. The purification of hexa- cyclohexadiene. Because little is known about the in- methylphosphoramide (HMPA) is described in detail fluence of the presence and position of the functional in ref. 3. groups on the overall reaction rate and on the product, the influence of the position of the methoxy group relative to various amine groups was studied. An undi- 2.2. Reaction cell and measuring devices for the electro- vided cell was used, which gave the most olefinic chemical studies substituted 1,4-cyclohexadiene derivative as the major The cell and measuring devices are described in product. detail in ref. 3. The electrochemical cell is shown in Fig. 3. The glassy carbon-glassy carbon CC,-C,) RRDE rl = l Dedicated to Professor Jan Sluyters on the occasion of his 65th used had dimensions 0.350 cm, r2 = 0.464 cm and birthday. r3 = 0.599 cm, with Nt = 0.358. 0022-0728/94/$7.00 0 1994 - Elsevier Sequoia. All rights reserved SSDI 0022-0728(93)02927-A 136 P.J.M. van Andel-Scheffer et al. / Reduction of substituted benzylamines V W&C% H$O “SC Aa reference electrode (A) (B) Pt anode Pt cathode Fig. 1. (A) Galanthamine and (B) N,N-dimethyl-veratrylamine. gas inlet thermocouple Fig. 4. The electrochemical cell used for electrosynthesis. Fig. 2. The electrochemical Benkeser reduction. 2.3. Reaction cell and measuring devices for the electro- filtered. The ether was distilled off in a vacuum. The organic reactions product was purified by distillation or column chro- The reduction cell of volume 125 cm3 is shown in matography (aluminium oxide, chloroform). Fig. 4. Pt electrodes (both of cross-section 3.2 cm’) served as the cathode and the anode. An Ag wire was 2.5. Analysis used as the quasi-reversible reference electrode. The The following techniques we reused in the analysis. reaction temperature was measured using a Pt-Rh ‘H NMR: Varian EM 360A. thermocouple and controlled by means of a Huber 13C NMR: Bruker AM-400. For 13C NMR spectral Variostat. Solvated electrons were generated potentio- data of several methoxy-substituted benzylamines see statically at - 2.7 V using a Wenking POS 73 potentio- ref. 4. stat. This corresponded to a current density of approxi- Gas chromatography-mass spectroscopy (GCMS): mately 300 mA cme2. The charge passed was recorded HP 5790 A series gas chromatograph coupled to an HP using a Wenking EVI 80 voltage integrator. 5970 A series mass selective detector (both from Hewlett Packard). 2.4. Electra-organic reaction procedure Mass spectroscopy (MS): electron impact spectrum, The aromatic substrate (10 mm011 was added to 100 70 eV, mass scale, 30-300. For mass spectra of benzy- ml of a solution of 1 M LiCl chloride in methylamine. lamine and benzylamine derivatives, see refs. 5 and 6. Current was passed through until all the substrate was Gas chromatography (GC): oven temperature, reduced, as shown by lH NMR. During the reaction 100°C; inlet helium pressure, 1.5 bar; column, OV-1, 25 argon gas was bubbled through the solution. The reac- m, with inner diameter 0.2 mm; film thickness, 0.33 pm tion temperature was - 15°C. The methylamine was (Hewlett Packard Ultra Performance); injection split- allowed to evaporate. Water (100 ml) was added and less; injection volume, 1 ~1; dichloromethane solvent. the aqueous layer was extracted with ether (2 X 30 ml). The following reduction products were obtained. The combined organic layers were washed with water (1) 2,5-Dihydro-benzylamine. ‘H NMR G(CDCl,, (2 x 50 ml) and with a concentrated sodium chloride TMS): 1.5(s, 2H); 2.67(m, 4H); 3.2(s(b), 2H); solution (25 ml), dried over magnesium sulfate and 5.53@(b), 1H); 5.67(s(b), 1H). [M- 11= 108.15. gos connectron Pt coun(er A9 wire reference HMPA seal electrode elect rode 90s outle HMPA sealed RRDE working 90s outlet electrode * 90s ond RRDE working’ sohhon inlet Pt counte; A9 wre reference electrode electrode / \ elect rode gloss fril Luggin cochxy (A) @I Fig. 3. The electrochemical ceil: (A) cross-section; (B) tap view. P.J.M. van Andel-Scheffer et al. / Reduction of substituted benzylamines 137 (2) 2,5-Dihydro-N-methyl-benzyl-amine. rH NMR 21 ~(cDcl,, TMS): 1.22(s, 1H); 2.47(s, 3H); 277(m, 4H); 3.13(s(b), 2H); 567(s(b), 1H); 5.77(s(b), 2H). ]M - 1] = 1 122.10 (WI/~ 91.05 = 100%). BP, 37°C (0.2 Torr). (3) 2,5-Dihydro-N,N-dimethyl-benzylamine. ‘H NMR G(CDCl,, TMS): 2.18(s, 6H); 2.62-2.87(m, 6H); 5.58@(b), 1H); 5.73(s(b), 1H). [Ml = 137.10 (m/e 91.05 = 100%). (4) 2,5-Dihydro-4-methoxy-benzylamine. ‘H NMR S(CDCl,, TMS): 1.6(s, 2H); 2.7(m, 4H); 33(s(b), X-0; 0 J 3.5(s, 3H); 4.6(s(b), 1H); 5.48(s(b), 1H). ]M - 1] = 2.50 2.38 2.42 -E," 2.46 138.10 (m/e 122 = 100%). (5) 2,5-Dihydro-4-methoxy-N,N-dimethyl-benzyl- Fig.