A New Approach to Allylamines and Pyrrolidines (original) (raw)

Abstract

The 1,4-adducts 3a-c and 4, readily available from the reaction between diethyl N,Ndichlorophosphoramidate (1) and 1,3-dienes, were found to be convenient precursors for the efiicient synthesis of the 6-chloroallylamine hydrochlorides 5a-d and N-phosphorylated allylamines 6a-c and 7. The three-step transformation of 3a-c affords the cis-3,4-dibromopyrrolidine hydrochlorides 10a-c. The preparation of the 2,5-dihydro-IH-pyrrole hydrochlorides 11 ac and trans-3,4-dibromopyrrolidine hydrochlorides 13ac is also described. The stereochemistry of the reaction is studied. Eine neue Synthese von Allylaminen und Pyrrolidinen Die 1,4-Addukte 3 a-c und 4, leicht zuganglich aus Diethyl-N,N-dichlorphosphoramidat (1) und 1,3-Dienen, bewahren sich als Ausgangsprodukte fur eine effektive Synthese von 6-Chlorallylamin-hydrochloriden 5a-d und N-Phosphorylallylaminen 6a-c und 7. Die dreistufige Umwandlung von 3a-c fuhrt zu cis-3,4-Dibrompyrrolidin-hydrochloriden 10a-c. Weiterhin wird uber die Darstellung von 2,5-Dihydro-lH-pyrroI-hydrochloriden 11 a-c und trans-3,4-Dibrompyrrolidin-hydrochloriden 13a-c berichtet. Die Stereochemie der Reaktionen wird untersucht.

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References (29)

  1. -3.4-Dibromopyrrolidine hydrochlorides 13a -c. -General procedure: A solution of 30% aqueous sodium hydroxide (20 ml) was added dropwise at 0-5°C with vigorous stirring and external cooling (ice-salt bath) to a mixture of diethyl phosphite (1.72 g, 0.0125 mol), 2,5-dihydro-lH-pyrrole hydrochlorides 11 a -c (0.01 rnol), carbon tetrachloride (20 ml), dichloromethane (20 ml), and triethylbenzylammonium chloride (0.1 9). The result- Liebigs Ann. Chem. 1986
  2. 3000,2940, 2710; 1560 (@ NHJ, 1450, 1395, 1285, 845 2920, 2890, 2700; 1580 (@NH2), 1450, 1410, 1375, 875 2900, 2860, 2500, 2430; 1575 (QNHz), 1445, 1420, 1385, 1085,990, 855 2960, 2860,2590, 2400; 2555 (@ NHZ), 1435, 1410, 1380, 1025, 855 2960, 2700, 2410, 2360; 1560 (@ NH2), 1440, 1410, 1385, 1080, 2030, 865 2970, 2710, 2630, 2400; 1575 (@NHz), 1435, 1375, 1085, 855 4.0-4.2 (m, 4H, NCH2), 5.05-5.15 (m, 2H, CHBr), 5.07 (s, @NH2) 2.21 (s, 3H, CH3), ABX system (12 li- nes, 3 H), for NCHAHB -CHxBr: 8~ = 4.02, 88 = 4.35, 6x = 4.69, J A B = 11.8, JBX -11.41, JAx = -7.59, AB SY- stem (4 lines. 2H). for NCHAHn-CBr: 2.37 (s, 6H, CH3), AB system (4 lines, 4H) for NCHAHB-CBr: 8~ = 4.18, AMX system (8 lines, 6H) for 88 = 4.44, J A B = 13.4, 5.07 (s, @NHz) NCHAHM-CHxBr: S A = 4.4,8M = 4.81, 6.x = 5.47, J A m = 14.8, J M x = 4.2, JAX =: 0, 5.2 (bs, @NH2) 2.65 (s, 3H, CH3), 4.28-4.75 (m, 2H, NCH2-CHBr), 5.1 -5.25 (rn, 1 H, NCH2 -CHBr), AB system (4 lines, 2 H) for NCHAHB-CBr: 8~ = 5.01, 8~ = 5.69, J A B = 4.4, 5.3 (s, @NHJ 2.6 (s, 6H, CH& 4.63 (s, 4H, NCH2), 5.22 (s, @NH2)
  3. ing two-phase system was stirred for 2 h at room temp., then diluted with dichloromethane (30 ml), and separated. The organic layer was washed with 5% aqueous HCl (I0 ml), water (2 x 15 ml), dried, and evaporated. -A solution of bromine (1.76 g, 0.011 mol) in chlo- roform (10 ml) was slowly added at 0°C to the oily residue dissolved in chloroform (20 ml). After the addition was complete the mixture was kept at 0°C for 0.5 h. The resultant orange solution was washed successively with 1 YO aqueous Na2S03 (30 ml) and water (30 ml), dried, and evaporated. The crude adduct was dissolved in THF (50 ml) and degraded with gaseous HC1 according to the method described for 5a -d. The crude trans-3,4-dibromopyrrolidine hydrochlorides 13a -c were recrystallized from absolute ethanol. Their yields, melting points, elemental analyses, and spectroscopic data are listed in Tables 3 and 4. 2,5-Dihydro-IH-pyrrole hydrochlorides 11 a-c. -General procedure: Freshly activated zinc dust (3.3 g, 0.05 g at) was added in four portions to the solution of cis-3,4-dibromo- pyrrolidine hydrochloride 10a-c (0.01 mol) in absolute ethanol (70 ml) at 50°C. A strongly exothermic effect was observed. The mixture was refluxed for 1.5 h and then cooled to room temp. The precipitate was filtered off and washed successively with ethanol (10 ml) and water (10 ml). An excess of solid sodium hydroxide was added to the filtrate, which was then steam-distilled. The distillate (ca. 400 ml) was acidified with 5% aqueous HCl, decolourized with charcoal, and evaporated to dryness. The crude products l l a -c were recrystallized from absolute ethanol.
  4. 5-Dihydro-lH-pyrrole hydrochloride (11 a): Yield 99%, needles, m. p. 169.5 -171.5"C (ethanol). -(lit.") m. p. 173-174"C), picrate m. p. 155.5-156.5"C (lit.") m. p. 176°C).
  5. -Methyl-2,5-dihydro-lH-pyrrole hydrochloride (11 b): Yield 93%, prisms, m. p. 57 -60°C (ethanol). -IR (KBr): 2940, 2720, 2440; 1590 (@NH2), 1675 (C=C), 1440, 1410, 1030, 775 cm-'. -'H NMR: 6 = 2.17 (s, 3H, CHJ, 4.3-4.55 (m, 4H, NCH2), 5.06 (s, @NH2), 5.84-6.0 (m, 1 H, CH=C). CSHloCIN (1 19.6) Calc. C 50.21 H 8.43 N 11.71 Found C 50.24 H 8.44 N 11.89
  6. 3,4-Dimethyl-2,5-dihydro-~H-pyrrole hydrochloride (11 c): Yield %YO, colourless needles m. p. 151-152°C (ethanol). -IR (KBr): 2940, 2700, 2560, 2470; 1600 (@NH2), 1455, 1435 cm-'. -'H N M R 6 = 1.93 (s, 6H, CH3), 4.26 (bs, 4H, NCH2), 5.06 (s, @NH2). C6Hj2ClN (133.6) Calc. C 53.92 H 9.05 N 10.48 Found C 53.76 H 9.20 N 10.52 CAS Registry Numbers 3a: 100351-05-1 / 3 b 100351-06-2 / 3c: 100351-07-3 / 4 100351-08-4 / 5a: 100350-86-5 / 5 b 100350-87-6 / 5c: 100350-88-7 / 5 d 100350-89-8 / 6a: 100350-90-1 / 6 b 100350-91-2 / 6c: 100350-92-3 / 7: 100350-93-4 / 8a: 77498-36-3 / 8b: 100350-99-0 / 8c: 100351-00-6 / 9a: 77484-75-4 / 9b: 100351-01-7 / 9c: 100351-02-8 / 10a: 77484-76-5 J 10b 100350-94-5 / 1Oc: 100350-95-6 / l l a : 63468-63-3 / l l b 100351-03-9 / l l c : 100351-04-0 / 13a: 100350-96-7 / 13b: 100350-97-8 / 13c: 100350-98-9 / (EtO),P(O)H: 762-04-9 / 2,5-Dihydro-lH-pyrroI (Pikrat): 1 003 5 1-09-5
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