November 1987 of Ketones and Aldehydes at the Communisations 1005 the electrochemical reduction of cyclohexanone in presence of Iethyhimine ata mercury cathode to yield N-methyl cyclohexylamine has been reported.” This single evample Prompted us to investigate the conversion of a variety of aklchydes and Ketones to secondary amines (Table 1) All reductions were carried out with a 10-5 fold exeess of the primary amine, half neutralized with hydrochloric avid to givea, batlered solution of pH 10-11, Ethanol was added in some eases tofnprove the solubility of the aldehyde or ketone. After simple work-up, pure products were obtained in good! yiekls, Only in the reaction of hexanal with ethylamine to form -N-ethyl- Thexyiamine (1), was st bysprodue:, $4.\-eths laminomethyl)- C wl, formed in 10% yield, probably by autoconden- sation of the aldehyde and amination of the resultant aldol Double bonds and aromatic rings are not attacked under the applied potential-controlled conditions Reductive amination of monosubstituted eyclohexanones and bieyelo[2.2,1Theptan-2-one results in a mixture of cis/erams- oF endo, exonisomers; their ratios are given in Table 2. [Lis obvious that there isan increase in diastereoselectvity when the bulkier isopropylamine isused instead of methylamine. Thermodyaim cally favored rans-amines are obtained from exclohexanones.. Mercury-Cathode 2 R ° ins gy Thomas Pienemann, Hans. Se whet a OrginsehConiscss tt der Universitit, Orin Ring 2 140 Detion Munster, Wes Germany pen way ity Amines are preparcd in goo yickls by potential cmteolled , ._ a eds or fetes amateur cathode in ays ning 2 primary snine. For che Ketone. igh de ‘ : ' . tereoselcetivities are chtained in some eases. NaF Mw ay te j ioe one Secondary amines can be prepared by reductive amination of moos carbonyl compounds, In aqueous medium, an alichyde or & : oe rs Ketone and & primary amine equilibrate to the conreponding Schi ase, Because ofits lover reduction potential eompared with the aldshye or Ketone, the Schiff hase may be reduced | C J selectively to yield a secondary amine after clection- and X protonansfrs, In genera, (hee reductions are ured Gut » » es & using the expensive sodium cyanoborohydride! or hydrogen in reste of pln, palladium o kl eats Te ef A I ‘method has the disadvantage of being able to hydrogenate 7) La ay Lh ye ‘other groups such as double bonds oF stromatic rings: fre wh a aT thermore, most catalysts cannot be used in the presence of T sulphucecontaiing substrates. * * e wes Tabet Preparation of Sssondary Amin by Cabadic Retase Amintion Aldea or Ketone ‘inet Rolistion Pro vient Prac a Hvar Tayi ary 1 ° (2r2 Amo-t-hutarol anv 2 2 Seistmin as 3 ” islamine tas i a {4 Acaomometiy pest tstplamin uy 3 2 Phvonanone dMetinkpeleheanone Mailamine ‘ ” Erunlgelohewammn Mainkinns ; x Satskpelonecnon * a Wise 22 hepa > “0 bye. ap: ” % 5 uno in sate, halla ith hyde * Yiek! of holated product, purity checked by GLC tol used instead of water. Punta by Kugelohe distifation (7S Coven tomporature, 20 mba) " Mistateelvtrans 11006 Communications while bieyelo[2.2.tJheplan-2-one leads to an excess of emdo= product. A sintlar selectivity was found for the reduction of ‘ketones with dissolving metals in protic media.* Reduction of 2 hhesamone in the presence of (A)-2-amino-I-butanol gave only poor diasteeoseectvity (1:1): no further assignment of the ‘somers was made. ‘Table 2 Diastoeosletsity of Cathode Reductive Amination| Inomer transiendo ebiexo oa o 2 ™ » 13 Ba * 2m oa ey as Wa 10 mv * Detected by GLC (4 m glass column, 2 2mm, No b could be deteted by GLC und NMR. The scope of the reported reaction is limited by the solubil the aldehyde or ketone in the aqueous electrolyte, even though in, some eases electrolysis of an emulsion was successful. Fur- thermore. sterically hindered substratessuch as camphor or ter! butylamine could not be converted, probubly because the ‘concentrations of Schill base in the equilibrium are too tna In summary. cathodic reduetive amination may be considered as aa good alternasive to existing methods for the preparation of secondary amines, becatie of its high chemoselectivity. good ields, simple work-uo and low reagent cost, Ethy--methy2-C-tfuoromethyphenyDethylamine (Sk “Typical Procedure: ‘A solution of 143 trduoromethylpheny!}2-propanone (2.02. WWaimol) in an eectroly:e consisting of 7O% aqucows ethylamtine GomnL, 180mm), 2N HCI G7 SmL) and ELOH (SO mL} is purged wvith, Ny and clctolycal at 10°C with a ontrolied potenti) of 1.28 (ys. SCE) in a divided cell with a mercury pool as working ecirade and & platinum anode. The curtent drops fron an inti S)mA to 2-31mA when the nsssary 196th As ave been consume ‘Then the ckctrlytes aiid by adding 2N HCI (Qo pL. After the HOH is removed under reduced pressure, the aqueous solution cvircted with ethsr (> MimL) and NaOH is added (to pH 1). The “kali solution i extracted with ether (3> Sm. and de combined ‘orga phase dre (MgSOq1, Removal 0” the solvent unl reduce rash gives §: yel: 0g (87% X-Fahylhesrlamine (2 nit = 14208 (Lit 1.4200), MS eV: mis 96) = -29UM,S} HCD: $9 (4, $8 10. ALD KY (62 416). SHENMR (CDC. /TMS, «MLZ 3 = 071-7, HD: 18S (1 Nie 24-39 (x. 411, SCH) 2 (LeMethyipent lamin t-butanal 2) a = 1.8895, CyHzyNO Gk, COM HAIR N SON Oa) found as BRT (MS (7H eVy: om 424) = $8 (8): 142 NDA 126 (10); 116 (M0, SCD (10, 70 15) 6 (14, $8 (100) 1 my: ¥ = 3000-3669, 2970, 298, 2870, 1460, 1380, 1080em AHENMR (CD,OD-TMS, HOMIES 5 = 09 (m. 6H, CH, 5) Clot 101d, 3S = 6212, 01 CH Lm, SH, Clg 224), 200 VAL OH i 227 ms 2H CH ei 32 m, 1H, CH, 36 Gn, TH CHE2Y N-Methyl.2-yclohesersincty anne (QX §° = 1ATI7. MS (EV) 2 ed SEM, Ae (9K: A 1 SENMR(CDCh/TMS. EDM i "29 ~ Let 2.8 (01.8 1h gy NUD 24 (in. SH. NCH, NCH 1 £7 ts, 2H. CCH, Netty eye Mersdamine (nh = A869. CyallasN eile, C799 W127 N772 Ghia fourd WAS 767 MS 7 Ve my 410). IR em); ¥ = 3230, 2800-2950, 1460, 1440, 1110-1140, 970, 958, 700-7309 MINMR (CDCL TMS, 300 MEL} 5 = 08-20 (mn, 17H, HAL HL 4-610, NILA GST, = 7.2 He, CH gh 2.47 (08 FH (a. 2H,J= 72He, NCH, | 2ifworamestiphensethshanine (8) (75) — EBL M8, LE (22: 84 LO, TL 1; 56 (14; iso, 1300, 160, ue = 230¢ 72 10D: S6 he 4, UgeNMR (CDCI) TMS, 0 ME): 3 = 1.1 (6H, CH 25-20, TA (0, SH, Ha Hydrochloride of §:m.p. 168°C (Lit m.p. 166°C) rane cand_cis-N-Merhyl(2methvlevelaexy amine (oa and 6 13505, MS (70 eV): m= (1) 2,2), HL-NMR (CDCIyTMS, 300 MLZ" 68 5 = 094-1.77 (mL 2 HG 095 |. 31 J = Ta He, CCH) 194 fm, LIL NED: 201 nH CHEN 240 6 311, NCH) 6b 3 “O89 (4, IL J = 7.1 He, CCH 9177 (m, 9H? Heo 1.94 4m, 1 NH 2.3848, 3H NCH 2.4 (m, 1H CHIN), C-NMR (CDOD}:6a 5 = 19.5 2-CIy} 264 (C-5K TH (CHK MG (Coy 331 INCH yy 35.7 (C3), IK (CI: 686 (CA). 6S = BIE City. 22.8284; 78.32.65 B81 (NCH 386 (CIE FB (Ce trans and cicN-MethyL(A-ere-butseyetohexs2 amine (Ya and 70) nh 1452, MS (10eVi mis (a) = 169 (MIS SEG): 70-100, $7 2} AT. SLNMR (CDCIVTMS, 30012" Ta 5 092-197, 9HLH-2 16% 1.99.1 HH 911, NCH) BENMR (CD,OD}! Ta 9 = 272 (CB 281 (CCH IBA (ACH ph RNAN CH IER (C29. 49.8 (C4: 89.9 CI). snns-N-sopropyl( er t-butpe selene (Bx) 1 = LAST. [MS (10 eV m/s (4) 197 (MP2; 1N2 10} 1264, 98 10} 75 (341 99 46) 45 18), 4 (Ey, SNM (CDCI,/TM 089-1954, 9H HL? fin, 1H Tey 248, CUWCH I DENMR (CDC) 9 = 284 (ICH 259 (C-3}. 27.2 (CHICH B19 cCICH bg SL (C2, A (CH(CH 9 47S (Code BS (CY end aul ecorN-Methol-2-biepctl2.2 TVeprstonine (Ga and 9by nat — 14739 (Ung = LADD. MS (10) mls (a) ~ 126110 125 (ME 8S}: 124 (56), 96 (901, 9440 6, 70 (0, 57 (100, #4 (Hy. 42 SHENMRCDCI,/TMS, 300 MHP}- ad = 0.66 (dU, 1 HJ = 14.7 He, 48, 32 HASH LOM 10 (mn, 7H, NH HES, 16, eT 189 (edd 11, F147, 121 Hr, SANUS Hr, Slag 246 (TH Heth, 228 Om, 11 He “ity 391 ddd, J 124 He, ARI, 48 He, 12), ENMR (CDCig) 9a 8 200 (C4 28 (CS. MS NCHA 62 (Coa), 37S 1C-7) IHC IB TICLE: OA C2). 9 8 = WAC HE, Se HC, MD UNC MA (CT, 384 (CoRR IS (CNY KC 63412) Hydrochloride of 8 m.p. 199°C (Lit!* mp. 199, 200°C). 16 (3) 159}. 119 2); 109 4) TE: 128 (3) 27 OME 14) SE BE 70.1 STE, (A HD ow O84 (5 IH. CCH 1228, HLNE- 2a MME)! 9 084 (% 9H, C(CHH 6) 1.05(d, 61, J = 6.317, CCH Io 197 TH, NH}, 298 Gopi, 1TH, J = 6.812 endo-Netsopropyl2bicyco| 2.21 Uptsiamine (Oa) ni! = 1.4609 Calle cule. C737 WALD NO (1333) found 78 DSK 98 MS 706V) m= (2) = ESB (M42), 838 (LOM: 124 32}. 12 G29. 10 (46), 98 0}: 95 (38) 85 (36,72 (70: 67 (3 S84 6 (38) 4 {10:33 (4, AT AS), 1 filmy = 2950, 2850, L468, 1445, 1575, 1360, 154 1S, 1055, 670-700 em”! TENMR (CDChyTMS, MOMHZ): 9 = 0.64 (ddd, 1H, 46127 HZ TT gu LOH, GHJ = 6.3 Hz, CIWCH I 120, 1170, 110,November 1987 Communications 1007 fm, TH, NUL HS, HA6, HLT} 1.95 ld, TH d= 12S ti, 108 AB Hy, 29H, Hedy 2.44 fn, Hel) 2.27 om 1 Hedy 277m. TH, CHUCK a) 314 (ddd, TH, J = 108 Hi, Ao He, 43 Ha, L1H, 12) BENMR (CDCI) 0 = 203 (C6; 22.0, 22.6 (CHICH 3), 29 9 C5 BI CA IK (CFE, WA CHI, WL (CoN M2 (CINCH sk 864 1c Suppor of sic work hy the Fons der chemischen Intsivie and the Arbeisgemeinscha industiller Ferschungsveretngumgen is erate veka ledge Received: 15 Ju 1987 (1) Boreh, RE. Bernstein, M.D. Durst, HD. J. tin, Cem, Sov 1971, 93,2997 (2) Frahim. A.W, in: Houbon-Weyh the, Vo. IV) te Ver, Stutiar., 1980, p 4111. 13) Lund, 1, deta Chem. 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