J. Org. Chem., 1998, 63(8), , DOI: /jo972289h

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J. Org. Chem., 1998, 63(8), 2774-2777, DO:1.

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1 J. Org. Chem., 1998, 63(8), , DO:1.121/jo972289h Terms & Conditions Electronic Supporting nformation files are available without a subscription to ACS Web Editions. The American Chemical Society holds a copyright ownership interest in any copyrightable Supporting nformation. Files available from the ACS website may be downloaded for personal use only. Users are not otherwise permitted to reproduce, republish, redistribute, or sell any Supporting nformation from the ACS website, either in whole or in part, in either machinereadable form or any other form without permission from the American Chemical Society. For permission to reproduce, republish and redistribute this material, requesters must process their own requests via the RightsLink permission system. nformation about how to use the RightsLink permission system can be found at Copyright 1998 American Chemical Society

2 ... u.-td1 *.Jf a. CL E BPh 4 AP: 31 O(~CU "Vwwvo~o OOW 9 /CUCL.J 1 Q w~ " q~-4 a " (M Current Data NAME EXPNO PRO Parameters Ju Acquisition Parameters Date Time 4.38 PULPROG 29pg3 SQLVENT CO3CN AG sec FDES Hz ON 19.1 usec ps see 1 1. sec P31 1. usec S NHz P1 DE MHz SM Hz TO,32768 NS 4 OS see - S ON 55 SSS B PC Processing parameters Mz EN.8 Hz i i Pi l 2i 1 pm2 15 5' 5' 1 NMR plot Cx FP F1 P PPNCN HZCN parameters 2. ca ppm Hz ppm Hz ppm/cm Hz/cm

3 CL C. 9 BPh 4 AP: 3b WO N MW Mu O VN U M~t CO N V G CO O.' N inj e'2 u n NO r- 6 to CO Wu UC O 4C W WV W W to u t Mf M C NO NL inj NC N N N qoc Nco om o Cq to M ( W N M 3u N N N--.. C K~ K~ K~4fr Current Data Parameters NAM4E Aug1 EXPNO 11 PROCHO - Acquisition Parameters Date 9782 Time.47 PULPROG zgpg3o SOLVENT CO3CN AG sec FDRES Hz. DW 15.7 usec PG sec 1 1. sec P31 1. usec S MHz P1 DE MHz SWH Hz TO NS 124 DS sec - S WDW SS8 GB PC Processing parameters MHz EN 1. Hz 1.4. ~. o 1 NMR plot parameters CX 2. cm FP ppm F Hz P ppm Hz PPNCM ppm/cm HZCM Hz/cm pp l 26 l l ~ i' PPM ,....

4 CL e BPh 4 CU AP- 3d r-. cu N CU N V MO.l.q....u..... nvmm ~MMNm ' CU CU -4 jf to N, 1 P,~.* CM U Cu Cj Cu C 'r4pho'd M AR %1 111 ft VA;k? WAN j N"4w*,- 6-. No 11, 1 -A--..~~ 1 11 pp' 6 i~ 5A Cu M M N, OvN vto (Y _; W* ;Z 2' ) R NM, MM,,-4.1 CU O~ C u C L-- ooooo NM tw'fent NAME EXPNO PROCNO Data Parameters - Acquisition Paaeters Date.9782 Time 2.1 PULPROGS pg3 SOLVENT CD3CN AG sec FDES Hz O usec RG see Di 1. sec P3 1. usec S MHz P OE MHz SH Hz TO NS 124 OS sec - Processing parameters S MHz wow EM Hz MB PC NMR plot parameters CX 2. ce FP ppm F Hz P ppm Hz PPMCM J ppm/cm HZCM Hz/cm PPM

5 * JA-A-38 9~V~ a 2 BPh AP: 3h o- NmCmn rtoolr i % tao rucnm6 V w M at, L " Mto M a V U) U(MMc)MC CU -a C> 4- W CD o 4 utomantomom ta niona Cr toc omcdeatotoman Ctomeo m ooooooo 'C -~td M -C1 M - ~ (11'( f L ml Ll] Current NAME EXPNO PRON Data Parameters Ju Acquisition Parameters Date Time 5.58 PULPROG zgpg3 SOLVENT COCH AD sac FDRES Hz D 15.7 usec AG sec 1 1. sec P31 1. usec S NHz P DE MHz SwH Hz TD MS 124 DS see - S WON SS8 GB Processing parameters MHz EN 1. Hz 1.4 A 1111 ill L- 1 NNR plot parameters CX 2. cm FP ppm Fl Hz P ppm Hz PPMCN ppm/cm HZCN Hz/cm ppm

6 JR C. G BPh 4 AP: 3j ~~ C%4f (V r GO Co.Co rcou Lo Ce LoC w M L C 4 M A MMCMU M Cu C; Current Data NAME EXPNO PROCNO Parameters Aug Acquisition Parameters Date 9781 Time PULPROG zgpg3 SOLVENT CO3CN AG sec FDRES Hz OW 15.7 usec AS sec 1 1. sec P31 1. usec S MHz Pt DE MHZ SWH Hz TO NS 124 OS sec - Processing parameters S MHz wow EM SS8 68 PC 1. Hz 1.4 '. ii ii ii iii in n 1' 1 NMA plot parameters CX 2. cm FP ppm F Hz P ppa Hz PPMCM ppm/cm HZCM Hz/Cm ppm 2 15 i alill 1 5 p

7 Ar,1 M~654z6 &651 A\soo 3R-4- GLX. CH3 or CH A CH2 only E) BPh 4 AP: 3c 11 ~ *1 *~4 4 1~- 1 C cuj 18 ACQUSTON Spec. freq * MHz Nucleus - Ci3 Pulse prog.- s2pul A-q. time sec points - 64 k ' " ' " " Spec. width- Pulse width- Trans..- No. scans * Relax. del Hz 1. us see PROCESSNG Line broad.- 1. Hz/a 'ala''. 1 8 SPECAL Temp -25 deg C 9deg pulse- 15. US systemid - CAAO#8 1 probe - sw27 DECOUPLNG ~ a a V T v. 6 Dec mode - YYY Dec power - 42 ds 4 2 File Solvent, Orig. ndex Dato Chemist Me Cr Lab CcA)3 W2 8243ctS d so Ml85/28 May 2 97 t ppnr

8 -i - 44'' E. ebm. AP:3e to in to n cr) o ~ Fu cu Fu c.1~~'..i wno w fn a m~ cmn cu cucr- N v- wn M :1: r *-~.1 Current NAME EXPNO PROMN Data Parameters Aug AcQuisition Parameters Date 9782 Time 4.52 PULPROG zgpg3o SOLVENT CO3CN AG sec FDRES Hz DW 19.1 usec RS sec 1 1, sec P31 1. usec S NHz P DE MHz SWH Hz TO NS 4 DS 2 D.3 sec - S NOW SSB s6 PC Processing parameters MHz EN.8 Hz 1.4 i 1 NMR plot Cx FP F1 P PPMCM HZCM parameters 2. cm ppm Hz ppm Hz ppm/cm Hz/cm.. A p '

9 O * g*@e* JR-4-41 ebp AP: 3g * 4

10 JR-4-MBA Cx CU NCU Cr NN Y2 SBPh 4 AP 3a MOMM tenm 1 -vm O toc'-n CU N to r, M E -' ( N M m C.o w U wo M M v u3' o- o N OC ~' u(c NU CU CV r C C 9 -io... C v M CU N O to 3 C3 O CO N N U- M MO M v- "N to~~~ to to Mo No Nv Nv Nv Nv Nv Nu NU NU Nu U NUc tn * Cu O LD CU- Current Data Parameters NAME Jan21 EXPNO 3 PROGNO - Acquisition Parameters Date Time 2.49 PULPROG zgpg3 SOLVENT CD3CN AG sec FDRES Hz DN 15.7 usec RS sec 1 1. sec P31 1. usec S MHz P DE MHz Hz SWH TO NS 124 DS 2 i.3 sec - Processing parameters S WDW SSB 8B PC MHz EN 1. Hz NMR Cx FP F1 P PPM1CM HZCM plot parameters 2. cm ppm Hz ppm HZ ppm/cm Hz/cm ppm iso PPM 2 15 a

11 JR-4-MYRT * acr1 oo G B~h, O AP. 3f V M m no en N to W M Co M to OotomOnaoO N Cm 1UM C a o cokm4om)il mcm tmssom oso m nwo -o -tommer-4 mom -om-coo4 r4om <ve mm-otoo4 an w CUCU tolo C O CMCM MM M U C~ C U3 w WM M U Cj C rj Current Data Parameters NAME Jan21 EXPNO 4 PROCHO - Acquisition Parameters Date Time 22.7 PULPROG zgpg3 SOLVENT CD3CN AG sec FDRES Hz DN 15.7 usec RG sec 1 1. sec P31 1. usec S MHz P DE O MHz SWH Hz TO NS 124 DS sec - S MW SS8 GB PC Processing parameters MHz EN 1. Hz 1.4 ilili liii 1 NMR plot ex FP F P CzMM parameters 2. cm ppm Hz ppm Hz ppm/cm Hz/cm pp 2 15 l l PPtM

EXPERMENTAL DETAL 2-(2-Bromoethyl)-benzaldehyde Bromine (6 g,.37 mol) is added through a reflux condenser over a period of 5 minutes with stirring to an ice cooled solution of isochroman (5 g,.

12 EXPERMENTAL DETAL 2-(2-Bromoethyl)-benzaldehyde Bromine (6 g,.37 mol) is added through a reflux condenser over a period of 5 minutes with stirring to an ice cooled solution of isochroman (5 g,.37 mol) in carbon tetrachloride (2 ml). After the vigorous reaction subsides, (ca 5 minutes), the cooling bath is removed and the dark brown solution heated under reflux until the reaction mixture becomes pale yellow (indicative of complete consumption of bromine; ca 1 hour). The solution is then allowed to reach ambient temperature and the solvent is removed under reduced pressure. To the yellow oil obtained (1- bromo-isochroman), 75 ml of 48% aqueous hydrobromic acid is added and the reaction mixture is brought to reflux (dark green-blue). After approximatelly 1-15 minutes the solution is allowed to cool and extracted with diethyl ether (4x5 ml). (Care: The solution must be at room temperature or below prior to extraction with ether; first ether extract may be the lower layer as it is very concentrated with organic material). The organic extracts are washed with water (2x3 ml), then with dilute sodium bicarbonate solution and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure furnishes 67.5 g (65% yield) of crude 2-(2-bromoethyl) benzaldehyde as an orange oil approximately 85-9% pure. Analytically pure samples may be obtained by vacuum distillation; chromatography is not recommended. The crude material, which does not decompose when stored in a flask in the presence of light and air (do not store under nitrogen), was used for subsequent reactions. vmax (neat) 2742, 1697, 16, 1575, 126, 1193, and 755 cm-1; 8H (4 MHz, CD 3 CN) (4 H, m), 7.33 (1 H, d, Hz), 7.48 (1 H, t, Hz), 7.54 (1 H, t, J 7.94 Hz), 7.8 (1 H, d, J 7.56 Hz), and 1.14 (1 H, s); 8c (25 MHz) (CH 2 ), 36.7 (CH 2 ), (CH arom.), (CH arom.), (CH arom.) (C arom.), (CH arom.), (C arom.), (HC=O). Typical procedure for the synthesis of tetrahydroisoquinolinium salts A flask containing neat bromoaldehyde (1.1 eq, or 1.6 eq if crude) is cooled by means of an ice bath. The appropriate amine (1. eq) is dissolved in ethanol (15 ml/g of amine) and the solution added dropwise with vigorous stirring to the cooled bromoaldehyde. After the addition is complete, stirring is continued for one hour; then the cooling bath is removed and the reaction mixture is stirred for a further hour while attaining ambient temperature (Somewhat increased yields are obtained if the reaction mixture is left to stand overnight, particularly with hindered amines). Sodium tetraphenyl borate (1 eq) is added to the reaction mixture in acetonitrile solution (precipitation of sodium bromide may occur). After 5 minutes, the solvents are removed in a rotary evaporator and the solid or viscous oil obtained is macerated in hot ethanol, causing the organic salt to precipitate. The salt is isolated by suction filtration, washed with ethanol/water (1:1) to remove sodium bromide, with ethanol to remove water, and finally with diethyl ether. The product thus obtained is of high purity and may be recrystallized from ethanol/acetonitrile (9-95/1-5) if required (crystallinity depends upon parent amine). (S)-(-)-ax-Methylbenzylamine derivative 42% yield, m.p 'C. [aj 2 D -9.42, c = 1.57, (CH 3 CN); vmax (nujol) 1647, 165, and 1572 cm- 1 ; 8H (4 MHz, CD 3 CN) 1.82 (3 H, d, J 6.9 Hz), 2.99 (2 H, t, J 7.63 Hz), (2 H, m), 5.24 (1 H, q, J 6.81 Hz), 6.82 (4 H, t, J 7.22 Hz), 6.97 (8 H, t, J 7.43 Hz), (8 H, m), 7.37 (1 H, d, J 7.62 Hz), 7.45 (5 H, m), 7.54 (1 H, t, Hz), 7.75 (1 H, t, J 7.59 Hz), 7.83 (1 H, d, Hz), and 8,97 (1 H, s); 8c (4 MHz, CD 3 CN) (CH), (CH 2 ), (CH), (CH), 117. (4xCB arom. quart.), (8xCH arom.), (C arom. quart.), (4xCH arom.), (2xCH arom.) (CH arom.), (CH arom.), (2xCH arom.), (CH arom.), (C arom. quart.), (CH arom.), (8xCH arom.), (C arom. quart.), (CH arom.), (HC=N).

(R)-(+)-Cyclohexylethylamine derivative 58% yield, m.p. 178-18 oc. [ct2d +22.53, c = 1.26 (CH 3 CN); vmax (nujol) 1641, 163, and 1573 cm- 1 6H (4MHz, CD 3 CN) 1.-1.4 (1 H, m), 1.18-1.27 (3 H, m), 1.

13 (R)-(+)-Cyclohexylethylamine derivative 58% yield, m.p oc. [ct2d , c = 1.26 (CH 3 CN); vmax (nujol) 1641, 163, and 1573 cm- 1 6H (4MHz, CD 3 CN) (1 H, m), (3 H, m), 1.44 (3 H, d, Hz), (6 H, m), (1 H, m), 3.16 (2 H, t, J 7.88 Hz), (3 H, m), 6.83 (4 H, t, J 7.2 Hz), 6.98 (8 H, t, J 7.42 Hz), (8 H, m), 7.44 (1 H, d, J 7.62 Hz), 7.51 (1 H, t, J 7.64 Hz), (2 H, m), and 8.67 (1 H, s); 8c (4 MHz) (CH 3 ), (CH 2 ), (CH 2 ), (CH 2 ), (CH 2 ), (CH 2 ), (CF), (CH), (CH 2 ), (CH 2 ), 72.6 (CH), 117. (4xCB arom.), (8xCH arom.), (C arom.), (4xCH arom.), 128. (CH arom.) (CH arom.), (CH arom.), (8xCH arom.), (C arom.), (CH arom.), and (HC=N). (+)-iso-bornylamine derivative 17% yield, m.p oc. [ax] 2 D +6.88, c = 1.22 (CH 3 CN); vmax (nujol) 1649, 161, and 1572 cm-1; 5H (CD 3 CN, 4 MHz).84 (3 H, s),.89 (3 H, s), 1.12 (3 H, s), (1 H, m), (1 H, m), (1 H, m), (2 H, m), 1.97 (1 H, t, 4.34 Hz), (1 H, m), (2 H, m), (1 H, m), (2 H, m), 6.82 (4 H, t, J 7.17 Hz), 6.98 (8 H, t, J 7.44 Hz), (8 H, m) 7.41 (1 H, d, J 7.56 Hz), 7.5 (1 H, t, J 7.6 Hz), 7.75 (1 H, t, J 7.62 Hz), 7.81 (1 H, d, J 7.59 Hz), and 8.81 (1 H, s); 5 c (CD 3 CN, 4 MHz) (CH 3 ), 19.9 (CH 3 ), (CL), (CH 2 ), (CH 2 ), (C 2 ), (CH 2 ), (CH), (C), 5.92 (C), 52. (CH 2 ), (CH), (4xCB arom.), (8xCH arom.), (C arom.), (4xCH arom.), (CH arom.), (CH arom.), (CH arom.), (8xCH arom.), (C arom.), (CH arom.), and (HC=N). (-)-Bornylamine derivative 26% yield, m.p oc. [a] 2 D -33.2, c = 1.53 (CH 3 CN); vmx(nujol) 1645, 16, and 1575 cm-1; 6H (CD 3 CN, 4 MHz),96 (3 H, s),.98 (3 H, s), 1. (3 H, s), (1 H, m), (2 H, m), (1 H, m), (2 H, m), (1 H, m), 3.11 (2 H, t, 7.84 Hz), (2 H, m), (1 H, m), 6.82 (4 H, t, J 7.24 Hz), 6.97 (8 H, t, J 7.66 Hz), (8 H, m) 7.44 (1 H, d, J 7.6 Hz), 7.51 (1 H, t, J 7.63 Hz), 7.75 (1 H, t, J 7.59 Hz), 7.85 (1 H, d, J 7.68 Hz), and 8.67 (1 H, s); 5c (CD 3 CN, 4 MHz) 13.3 (CH 3 ), (CH 3 ), (CH 3 ), (CH 2 ), (CH 2 ), (CH 2 ); (CH 2 ), (CH), 5.11 (C), (C), (CH 2 ), (CH), (4xCB arom.), (8xCH arom.), (C arom.), (4xCH arom.), (CH arom.), (CH arom.), (CH arom.), (8xCH arom.), (C arom.), (CH arom.), and (HC=N). (+)-Fenchylamine derivative 61% yield, m.p 'C. [cx] 2 D , c = 1.5 (CH 3 CN); Vmax (nujol) 1649, 165, and 1577 cm- 1 6H (CD 3 CN, 4 MHz) 1.4 (3 H, s), 1.29 (6 H, s), (7 H, m), 3.15 (2 H, t, 8.7 Hz), (2 H, m), 3.65 (1 H, s), 6.83 (4 H, t, J 7.15 Hz), 6.98 (8 H, t, J 7.45 Hz), (8 H, m) 7.43 (1 H, d, J 7.56 Hz), 7.52 (1 H, t, J 7.62 Hz), 7.76 (1 H, t, J 7.62 Hz), 7.91 (1 H, d, J 7.57 Hz), and 8.75 (1 H, s); 8c (CD 3 CN, 25 MHz), (CH 3 ), 26. (CH 3 ), 3.4 (CH 2 ), 3.64 (CH 2 ), (CH 2 ), (CH 3 ), (C.), (CH 2 ), (CH), (C), (CH 2 ), (CH), (4xCB arom.), (8xCH arom.), 13.6 (C arom.), (4xCH arom.), (CH arom.) (CH arom.), (CH arom.), (8xCH arom.), (C arom.), (CH arom.), and (HC=N). (-)-sopinocampheylamine derivative 7% yield, m.p 'C. [a] 2 D -24.7, c = 1.36 (CH 3 CN); vmax (nujol) 1639, 16, and 1574 cm-1; 5H (CD 3 CN, 4 MHz) 1.12 (3 H, s), 1.18 (3 H, d, J 7.2 Hz), 1.33 (3 H, s), (3 H, m), (2 H, m), (2 H, m), 3.24 (2 H, t, J 7.6 Hz), 4.8 (2 H, t, J7.65 Hz), 4.54 (1 H, m), 6.86 (4 H, t, J 7.2 Hz), 7.1 (8 H, t, J 7.43 Hz), (8 H, m) 7.49 (1 H, d, J 7.5 Hz), 7.56 (1 H, t, J 7.58

Hz), 7.8-7.84 (2 H, m), and 9.9 (1 H, s); 5 c (CD 3 CN, 4 MHz)18.71 (CH 3 ), 22.15 (CH 3 ), 25. (CH 2 ), 26.95 (CH 3 ), 31.38 (CRl 2 ), 33.6 (CH), 38.72 (C), 39.66 (CH), 4.76 (CH), 46.73 (CH), 44.

14 Hz), (2 H, m), and 9.9 (1 H, s); 5 c (CD 3 CN, 4 MHz)18.71 (CH 3 ), (CH 3 ), 25. (CH 2 ), (CH 3 ), (CRl 2 ), 33.6 (CH), (C), (CH), 4.76 (CH), (CH), (CH 2 ), (CH), (4xCB arom.), (8xCH arom.), (C arom.), (4xCH arom.), (CH arom.), (CH arom.), (CH arom.), (8xCH arom.), (C arom.), (CH arom.), and (HC=N). (-)-Menthylamine derivative 38% yield, m.p oc. [aj 2 D -28.1, c = 1.71 (CH 3 CN); vmax (nujol) 1643, 165, and 1576 cm-1; 8H (CD 3 CN, 4 MHz).79 (3 H, d, J 6.9 Hz),.94 (3 H, d, J 6.81 Hz),.96 (3 H, d, J 6.51 Hz), (1 H, m), (1 H, m), (2 H, m), (3 H, m), (2 H, m), 3.13 (2 H, t, J 7.94 Hz), (3 H, m), 6.81 (4 H, t, J 7.14 Hz), 6.98 (8 H, t, J 7.41 Hz), (8 H, m) 7.42 (1 H, d, J 7.13 Hz), 7.5 (1 H, t, J 7.27 Hz), (2 H, m), and 8.74 (1 H, s); 8c (CD 3 CN, 4 MHz) 14.3 (CH 3 ), (CH 3 ), 2.81 (CH 3 ), (CR 2 ), (2xCH 2 ), 26.1 (CH), (2xCH), (2xCH 2 ), (CH), 117. (4xCB arom.), (8xCH arom.), (C arom.), (4xCH arom.), (CH arom.), (CH arom.), (CH arom.), (8xCH arom.), (C arom.), (CH arom.), and (HC=N). (-)-Myrtanylamine derivative 75% yield, m.p oc. [a 2 D -1.66', c = 1.8 (CH 3 CN); vmax (nujol) 1651, 164, and 1574 cm-1; 8 H (CD 3 CN, 4 MHz) 1.13 (3 H, s), 1.28 (3 H, s), (1 H, m), (6 H, m), (1 H, m), (1 H, m), 3.13 (2 H, t, J 7.89 Hz), (4 H, m), 6.87 (4 H, t, J 7.16 Hz), 7.2 (8 H, t, J 7.39 Hz), (8 H, m) 7.46 (1 H, d, J 7.27 Hz), 7.54 (1 H, t, J 7.33 Hz), (2 H, m), and 8.68 (1 H, s); 8c (CD 3 CN, 4 MHz) (CH 2 ), 22.5 (CH 3 ), (CH 2 ), (CR 2 ), 26.6 (CH 3 ), (CH 2 ), 37.7 (CH), (C quart.), 4.59 (CH), (CH), (CH 2 ), (CH 2 ), (4xCB arom. quart.), (8xCH arom.), (C arom. quart.), (4xCH arom.), (CH arom.), (CH arom.), (CH arom.), (8xCH arom.), (C arom. quart.), (CH arom.), (HC=N). (+)-(2S,3S)-3-Amino-2-phenylpiperidine derivative 39% yield, m.p oc (dec.). [ajl 2 D , c = 1.11 (CH 3 CN); Vmax, (nujol) 332, 1634, 163, and 1576 cm-1; 6H (CD 3 CN, 4 MHz) (1 H, s), (4 H, s), 2.47 (1 H, br), (1 H, m), (2 H, m), 3.24 (1 H, m), 3.39 (1 H, m), 4.1 (1 H, m), 4.22 (1 H, m), 4.37 (1 H, m), 6.88 (4 H, t, J 7.1 Hz), 7.2 (8 H, t, J 7.2 Hz), (12 H, m) (2 H, m), 7.49 (1 H, t, J 7.24 Hz), (2 H, m), and 9.86 (1 H, s); 8c (CD 3 CN, 4 MHz) 2.28 (CH 2 ), 26.6 (CH 2 ), (CH 2 ), (CH 2 ), (CH 2 ), (CH), (CH), (4xCB arom.), (8xCH arom.), (C arom.), (4xCH arom.), (2xCH arom.), (CH arom.), (CH arom.), (CH arom.), (2xCH arom.), (CH arom.), (8xCH arom.), (C arom.), (CH arom.), (C arom.), and (HC=N). Steroidal amine derivative 11% yield, m.p oc. [a] 2 D -1.2 c = 1.33 (CH 3 CN); Vmax (nujol) 342, 1644, 165, and 1578 cm-1; 8 H (CD 3 CN, 4 MHz).74 (3 H, s),.79 (3 H, s), (22 H, m), 2.44 (1 H, m), 3.13 (2 H, m), (4 H, m), 6.82 (4 H, t, J 7.17 Hz), 6.98 (8 H, t, J 7.42 Hz), (8 H, m) 7.47 (1 H, d, J 7.32 Hz), 7.51 (1 H, t, J 7.35 Hz), (2 H, m), and 8.78 (1 H, s); 8c (CD 3 CN, 4 MHz) 1.92 (CH 3 ), (CH 3 ), 2.7 (CH 2 ), (CH 2 ), (CH 2 ), (CH 2 ), 28.1 (CH), (CH 2 ), 32.2 (CH 2 ), (CH 2 ), (CH), (C), (CH 2 ), (CH 2 ), (CH), (C), (CH 2 ), (CH), (CH), (CH), (CH), (4xCB arom.), (8xCH arom.), (C arom.), (4xCH arom.), (CH arom.), (CH arom.), (CH arom.), (8xCH arom.), (C arom.), (CH arom.), and (HC=N).

15 Typical epoxidation procedure: Sodium carbonate (4 eq) in water (8 ml/g) is added in one portion to an ice cooled flask containing OxoneTm (2 eq), and the effervescence manifested is allowed to subside (3 minutes). The tetrahydroisoquinolinium salt (5 or 1 mol%) is dissolved in the same volume of acetonitrile as that of water used and added to the reaction mixture. The alkene is dissolved in the same volume of acetonitrile and added to the reation mixture in one portion. For alkenes that exist in the solid state and are insoluble in acetonitrile, addition should be carried out using the solid, but the appropriate volume of acetonitrile should also be added. The reaction mixture (a suspension) is stirred for one hour (two hours for more substituted alkenes) and then transferred to a separating funnel where the acetonitrile layer is collected. The aqueous phase is diluted with water and extracted thoroughly with diethyl ether (or dichloromethane). The combined organic extracts are washed with brine and dried over sodium sulphate. Evaporation of the solvents gives a brown oil from which the epoxide is obtained by chromatography on silica gel, using 5 or 1% ethyl acetate in light petroleum ether as eluent. 1-Phenyl-1-cyclohexene oxide 1,2 68% yield; vmax (neat) 384, 162, 1495, 1446, 1359, 1249, 1173, 1132, 179, 13, 993, and 974 cm- 1 ; 8H (CDCl 3, 25 MHz) (1 H, m), (3 H m), (2 H, m) (1 H, m), (1 H, m), 3.1 (1 H, t, J2.4 Hz), and (5 H, m); 8c (CDCl 3, 25 MHz) (CH 2 ), 2.9 (CH 2 ), (CH 2 ), (CBU), 6.13 (C), (CH) (2xCH arom.), (CH arom.), (2xCH arom.), and (C arom.). 1-Phenyl-3,4-dihydronaphthalene oxide' 72% yield, m.p oc. vmax (nujol) 162, 1486, 137, 1155, 174, 142, and 953 cm- 1 ; 8H (CDC13, 25 MHz) 2.1 (1 H, td, J 13.69, 5.76 Hz), (1 H m), 2.77 (1 H, dd, J 15.53, 5.63 Hz) (1 H, m), 3.71 (1 H, d, J 3.8 Hz), (4 H, m), and (5 H, m); 8c (CDCl 3, 25 MHz) (CH 2 ), (CH 2 ), 6.89 (C), (CH) (CH arom.), (CH arom.), (2xCH arom.), (CH arom.), (2xCH arom.), (CH arom.), (CH arom.), (C arom.), (C arom.), and (C arom.). trans -Stilbene oxide 2,3 76% yield, m.p oc. vmax (nujol) 161, 1492, 1284, 1176, 1157, 194, 172, and 125 cm- 1 ; 8H (CDCl 3, 4 MHz) 3.84 (2 H, s), and (1 H m); 8c (CDC1 3, 4 MHz) (2xCH), (4xCH arom.), (2xCH arom.), (4xCH arom.), and (2xC arom.). trans -(oc-methyl)-stilbene oxide 2 75% yield; vmax (neat) 361, 162, 1495, 1449, 1381, 1279, 1157, 1118, 165, 127, and 98 cm- 1 ; 5H (CDCl 3, 4 MHz) 1.46 (3 H, s), 3.96 (1 H, s), and (1 H m); Sc (CDCl 3, 4 MHz) (CH 3 ), (C), (CH), (2xCH arom.), (2xCH arom.), (CH arom.), (CH arom.), (2xCH arom.), (2xCH arom.), (C arom.), and (C arom.). References for known compounds 1. Brandes, B. D.; Jacobsen, E. N. J. Org. Chem., 1994, 59, Tu, Y.; Wang, Z. X.; Shi, Y. J. Am. Chem. Soc., 1996, 118, Wang, Z. X.; Shi, Y. J. Org. Chem., 1997, 62, 8622.

SUPPLEMENTARY INFORMATION. SYNTHESIS OF NEW PYRAZOLO[1,5-a]QUINAZOLINE DERIVATES

SUPPLEMENTARY INFORMATION. SYNTHESIS OF NEW PYRAZOLO[1,5-a]QUINAZOLINE DERIVATES SUPPLEMENTARY INFORMATION SYNTHESIS OF NEW PYRAZOLO[1,5-a]QUINAZOLINE DERIVATES Dániel Kovács, Judit Molnár-Tóth, Gábor Blaskó G, Imre Fejes, Miklós Nyerges* a Servier Research Institute of Medicinal Chemisrty,