Supporting information for J. Org. Chem., 1977, 42(7), , DOI: /jo00427a012

Transcription

1 Supporting information for J Org Chem (7) DOI: /jo00427a012 Terms & Conditions Electronic Supporting Information files are available without a subscription to ACS Web Editions The American Chemical Society holds a copyright ownership interest in any copyrightable Supporting Information 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 Information from the ACS website either in whole or in part in either machine-readable 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 Information about how to use the RightsLink permission system can be found at Copyright 1977 American Chemical Society

2 G-//Sf-! SUPPLEMENTARY MATERIAL FOR MICROFILM with BASE-INDUCED CYCLOADDITION OF SULFONYLMETHYL ISOCYANIDES TO CN DOUBLE BONDS SYNTHESIS OF 15-DISUBSTITUTED AND 145-TRISUBSTITUTED IMIDAZOLES FROM ALDIMINES AND IMIDOYL CHLORIDES Albert M van Leusen* Jurjen Wildeman and Otto H Oldenziel Department of Organic Chemistry The University Zernikelaan Groningen The Netherlands 15-Di-p nitrophenylimidazole (3c) was prepared analogously to 3a from WWX/X *- 'WWWWVWWW\MM W 34 TosMIC (975 mg 50 mmol) N-jD-nitrobenzylidene- -nitroaniline (807 mg 30 mmol) and ^CO^ (828 mg 60 mmol) Washing with ether-petroleum ether bp provided 3c as a light yellow solid (840 mg 87%) ca r\y\t 210 (under decoosition) By treatment with charcoal in absolute EtOH and one crystallization from absolute EtOH an analytically pure sale was obtained 215 (under decoosition) ; ir (nujol) 3120 (2C-H) 1510 and 1350 (N02) ; NMR (DC13) 794 (broad s 1 2-CH) 736 (s 1 4-CH) and (AB q 4 5-p-NO^H^) and (AB q 4 I-jd-NO^H^ Anal Calcd for c15h10n4o4: c' 5805; H 325; N 1805 Found: C 579; H 32; Di-p chlorophenylimidazole (3d) was prepared analogously to 3a from TosMIC wwvx VWWlA^/VWWV/X/WW*/ / 'Wi 34 C190 g 10 mmol) N-]>-chlorobenzylidene-]3-chloroaniline (225 g 90 mmol) and K2C 3 ( mmol) After washing with Et20 and one crystallization from MeOH d was obtained as a white solid (110 g 43%) Two further rez\zv ; crystallizations from MeOH gave an analytically pure sale ir (nujol) 3120 (2C-H); NMR (CDC13) 772 (d J = 1 Hz 1 2-CH) (m 9 p-clc^ and 4-CH) Anal Calcd for C15H10C12N2: C' 62 30; H' 349; N 968; CI 2452 Found: C 624; H 35; N 97; CI Diphenylimidazole (3e) was obtained by the two step method (B+C) only WWXAAZXZVVVWWXAA/X/VV /V According to the procedure for 3b imidazoline 4e (see below 370 mg 10 mmol) and rv/\j r\/\j (272 mg 20 mmol) were re fluxed in MeOH Addition of saturated NaCl solution

3 "2 &a;-/is9-mi after removal of the solvent provided a white solid which was crystallized once ; from Et-0 to give 180 mg (82%) of 3e NMR (CDC1-) 772 (broad s 2 /» j 1 2-CH) (m and 5-C^ and 4-CH) Anal Calcd for C15H12N2I C 8178; H 549; N 1272 Found: C 817; H 55; Diphenyl-4-tosyl-2-imidazoline (4e) A solution of TosMIC (147 g 75 mmol) 'WWX/X/WWVWVWWVWX/WWVWX/WVV / 30 and N-benzylideneaniline (09 g 05 mmol) in 15 ml of DME was added in 15 hr to a suspension of NaH (55% in mineral oil 480 mg 10 mmol) in 10 ml of DME under N^ at -20 After stirring for another 15 hr at ml of a saturated NaCl solution was added and the aqueous layer was extracted with CH2CI2 The organic layer was dried (MgSO^) and filtered After removal of the solvent the residue was washed with ether-petroleum ether bp solid (127 g 68%) (1:2) providing 4e as a light brown < W( An analytically pure sale was obtained after three crystallizations from CH2Cl2-MeOH ; ir (nujol) 1560 (C=N) 1320 and 1155 (SC> 2) ; NMR (CDC13) (m and 5-C^ jj-ch^gh^ and 2-CH) 574 (d J = 5 Hz 1 5-CH) 506 (d of d 1 J = 5 and 1 Hz 4-CH) 242 (s 3 p-chch) Anal Calcd for Co_H^N0oS: C 7017; H 536; N 744; * * S 852 Found: C 699; H 54; N 73; S 85 l-phenyl-5-p-tolylimidazole (3f Method B+C) was prepared analogously to 3b /WWW/ 'VWVWVWWWX/ 'W w from crude imidazoline 4f (see below 082 g 21 mmol) and K_CO_ (058 g 42 mmol) w 2 J The residue from the C^C^ solution was chromatographed over neutral alumina (act I CHCI) providing 3f as a white solid (021 g 44%) 2 2 1Ai An analytically pure sale was obtained after crystallization (twice) from C^C^petroleum ether bp (1:1) ; *H NMR (CDCl^) 772 (d «J = 1 Hz 1 2-CH) (m 10 C^ 2-CH^H^ and 4-CH) 23 (s 3 -CH3C6H4) Anal Calcd for C_HNn: C 8201; 602; N 1195 Found: C 820; 61; l-phenyl-5-p-tolyl-4-tosyl-2-imidazoline (4 ) was prepared analogously to 4e 'VWWWWV ^/WWWV/WVWVXA/X/wvwvwvA' w 35 from TosMIC (147 g 75 mmol) and N-jD-xylylideneaniline (098 g 50 mmol) and was obtained as a brown rather unstable solid (082 g 42%); which was not obtained in an analytically pure state; ir (nujol) 1575 (C=N) 1320 and

4 //sr- * (S02); NMR (CDC13) (m 14 C6 H5 P E-CH-^Cgi^SOg and 2-CH) 575 (d J = 5 Hz 1 5-CH) 509 (d of d 1 J = 5 and 12 Hz 4-CH) 238 (s 3 -CH3C6H4S02) 229 (s 3 -CH3C6H4) <&am p;) Using t-bunh2 A solution of TosMIC (098 g mmol) N-ethylidene-ethylamine (083 g 120 mmol) and t-butylamine (088 g 120 mmol) in 5 ml of DME was stirred first for 4 hr at 0 and next 16 hr at 20 The reaction mixture was filtered and the solvent remove^ Imidazole cf was obtained as an oil which could not be purified coletely partly due to its hygroscopic character Therefore ^ was converted to a picrate by refluxing for 05 hr in a saturated ethanolic picric acid solution providing 122 g (70% based on TosMIC) of picrate Crystallization from absolute EtOH gave an analytically pure sale Ir of ^cj (nujol) 3110 cm* (2C-H); *H NMR of ^ (CDC13) 724 (broad s 1 2-CH) 658 (broad s 1 4-CH) 389 (q J = 7 Hz 2 CHCHg) 217 (s 3 5-CH3> 136 (t J = 7 Hz 3 CH3CH2) Anal Calcd for C12H10N5 7 (Picrate> : C' 42 48'* H 387; N 2064 Found: C 424; H 38; 205 Using K^CC^ Imidazole 3cj was prepared also analogously to 3m (see below) from TosMIC (195 g 100 mmol) N-ethylidene-ethylamine (142 g 200 mmol) and K2C03 (417 g 30 mmol) providing an oil (074 g) which conteiined 068 g (62%) of as determined by NMR using Me2S02 as an internal standard 5-t-Butyl-l-methylimidazole (3h) A solution of TosMIC (049 g 25 mmol) ///\(/\/// 'W 37 N-neopentylidenemethylamine (120 g 120 mmol) and t-bunh2 (088 g 120 mmol) in 5 ml of MeOH was stirred for 72 hr at room teerature After removal of the solvent 10 ml of Et20 was added The Jt-BuNH^Tos precipitate was removed by filtration The solvent was removed and the residual oil was distilled providing 95 * 3h as a colorless liquid (033 g 96%) bp (005 mm); ir (neat) 3120 cm r\y\j (2C H) ; NMR (CC14) (broad s 1 2-CH) 667 (d J = 10 Hz 1 4-CH) 374 (s 3 1-CH3) 135 (s 9 t-bu) Due to its hygroscopic character ^ was cinalysed as a picrate Anal Calcd for C^H^N^O^: C 4578; H 467; N 1906 Found: C 458; H 47; 191

5 -4- /»</ <&a;> usln&lt ;? t-bunh2 The reaction was carried out analogously to with TosMIC (098 g 50 mmol) N-ethylidene-t-butylamine 32 (060 g 60 mmol) and t-bunh^ (044 g 60 mmol) by stirring for 20 hr at room teerature in 10 ml of MeOH yielding ^ as a colorless liquid (065 g 94%) bp 105 (005 mm) Crystallization from Et20 at -70 provided ^ as a white hygroscopic solid ; ir (neat) 3120 cm1 (2C-H) ; *H NMR (CCl^) (broad s 1 2-CH) 656 (broad s 1 4-CH) 233 (broad s 3 5-CIi^) 160 (s 9 t-butyl) Anal Calcd for CN0: C 6952; H 1021; N 2027 Found: 15 ^ C 692; 102; 203 Essentially the same results were obtained when DME was used as a solvent (yield 90%) Using K^CO^ A similar reaction using TosMIC (215 g 110 mmol) N-ethylidenet-butylamine (099 g 100 mmol) and K^CO^ (276 g 200 mmol) yielded 075 g (54%) of 3^ as a colorless liquid bp 105 (005 mm) was prepared analogously to $1 from TosMIC 38 (098 g 50 mmol) Nh-ethylidenecyclohexylamine (15 g 120 mmol) and cyclohexylamine (12 g 120 mmol) by stirring for 17 hr The residual oil was distilled providing ^ as a colorless liquid (078 g 96%) bp 110 (01 mm); *H NMR (CCl^) (d J_ = 1 Hz 1 2-CH) 647 (broad s 1 4-CH) 212 (broad s 3 5-CH^) (m 11 cyclohexyl) Anal Calcd for CiqH15N2: c' 7312; 981; 1705 Found: C 731; H 98; Diisopropylimidazole (3k) was prepared analogously to 3h from TosMIC %A/vx/vxzvny\/vx/xAA/vx/vx/\yxAAAAv #x/ v o/v (098 g 50 mmol) N-isobutylideneisopropylamine ' (057 g 50 mmol) and isopropylamine (071 g 120 mmol) Distillation provided ^k as a colorless liquid (058 g 75%) bp 70 (005 mm) which partly solidified on standing; ir (neat) 3100 (2C-H); XH NMR (CDCl^ 724 (broad s 1 2-CH) 651 (d J = 1 Hz 1 4-CH) 419 (septet J = 7 Hz 1 l-ch(ch)3)2) 279 (septet J = 7 Hz 1 5-CH(CH3)2) 144 (d J = 7 Hz 6 1-CH(CH3)2) 122 (d J = 7 Hz 6 5-CH(CH^) Because of its hygroscopic character ^k was analysed as a picrate Anal Calcd for C15H19N5 7: C' 47 25; H' 5 2; N 1837 Found: C 472; 50; N 1804

6 -5-6- //S9-SXS (W TosMIC <15 0 9' 075 mol>' dissolved in 30 ml of DME and 20 ml of MeOH was added to a stirred mixture of tj-benzylidene- 32 methylamine (60 g 0050 mol) and ^CO^ (147 g 011 mol) in 20 ml of DME over a period of 6 hr at 0 After stirring for 60 hr at 0 the solvent was removed in vacuum 100 ml of water was added and the aqueous layer was extracted with three 75 ml-portions of CH^Cl^ After drying (MgSO^) and removal of the solvent 795 g of oil resulted which contained 16 g (20%) of ^ and 36 g (60%) of starting inline as determined by NMR using Me^SO^ as internal standard The imine was removed by distillation at 45 (1 mm) and the residue (about 4 g) was chromatographed over alumina (neutral activity I chloroform and ethylacetate) Imidazole 3^ was obtained as a white solid (800 mg 10%) which was crystallized twice from methanol (rep^ rap ) ; picrate (rep^ ) : NMR (CC1J (s 6 and 2-CH) 695 (broad s CH) 362 (s 3 l-ch^) Several attets to obtain better yields by varying the reaction conditions were unsuccessful Wwas prepared by stirring a solution of 41 TosMIC (390 g 20 mmol) and N-jD-xylylidenemethylamine (133 g 10 mmol) in 33 ml of MeOH with K2C 3 (4 2 G 30 mmol) for 20 hr after which the methanol was removed Work-up as described for resulted in a pale yellow oil (211 g) containing 076 g (44%) of ^a The oil was distilled providing as an oil (06 g 37%) bp 140 (02 mm) which solidified on standing Crystallization from ether-petroleum ether bp gave an analytically pure sale ; ir (nujol) 3090 cm* (2C-H); *H NMR (CDCl^) (broad s 5 p-ch_c-h and 2-CH) 689 (broad s 1 4-CH) 385 (s 3 5-CH) 237 (s 3 * CH3C6H4) Anal Calcd for cnh12n2: C' 76 72'* 702; N 1627 Found: C 765; 70; 165 l-methyl-5-p-nitrophenylimidazole (3n) was prepared analogously to 3m from VWVWWVV/ *- VWVWWVWWWWWV r\at rw/ 42 TosMIC (146 g 75 mmol) N- -nitrobenzylidenemethylamine (082 g 50 mmol) and K2C03 (1-38 g 100 mmol) in 5 ml of MeOH giving 113 g of crude material

7 -6- -t/sf-mb Chromatography over alumina (neutral activity I ) gave as the first fraction 037 g of starting imine contaminated with some -nitrobenzaldehyde and ^1 as the second fraction This material was washed with Et20 providing 140 mg (14%) of 3n After recrystallization from i-pr^o a pure sale was obtained (rep^ ) Mixed melting point with 40 an authentic sale gave no depression Ir (KBr) 3130 (2C-H) 1520 and 1350 cm"*1 (NO2); NMR (CDC13) (s 1 2-CH) 38 (s 3 1-CH3) These spectra were identical with the ones obtained from the authentic sale No was formed when t-bunh^ was used instead of K2C03 under the conditions indicated in Table I W A mixture of 6 &a;<542 2 mmo1' 32 N-benzylidenemethylamine (238 mg 20 mmol) and K2C03 (414 mg 30 mmol) was stirred overnight in 5ml of MeOH Work-up as described for 3a gave a yellow solid (420 mg 90%) which by crystallization from Et20-CH2C12 (5:1) resulted in nearly white (rep1^ 158 ); 7b r\/\j ir (nujol) 3115 (2C-H) 45-Diphenyl-l-p-nitrophenylimidazole (7d) was prepared analogously to 4e \/\ WWIMAA/WWVWWW/ /\A/ W from 6a (596 mg 22 mmol) 30 N-benzylidene-]D-nitroaniline (452 mg 20 mmol) NaH (55% in mineral oil 150 mg 3 mmol) at -5 Work-up without activated carbon and evaporating the CH2C12 solution to dryness provided a yellow solid which was washed with hexane and CH2Cl2~hexane (2:1): 560 mg (82%) Crystallization from CH_C10 yielded pure 7d Z 'W ; ir (nujol) 3120 (2C-H) and 1510 cm (N02); NMR (CDC13) 837 and 821 (2 lower half AB q -02NCgH^) 793 (s 1 2-CH) (m 12 aryl); mass spectrum M+ m/e_ 341 Anal Calcd for c2ihi5n3 2: 73 88' H' 443; N 1231 Found: C 738; H 45; 122 l-p-nitrophenyl-5-phenyl-4-tosylimidazole (lib) was prepared analogously n -S- %OA/X/\A/\ZVVVVVV\AAA/XA/VV\/X/>/XZVVV\/X/xazvvx/\ZV <\ /V to 11a from TosMIC (390 mg 20 mmol) eind N-p-nitrophenylbenzimidoyl w\* *- chloride11 (522 mg 20 mmol) Recrystallization from 80% MeOH provided ^lb as a light yellow

8 -7- solid (680 mg 81%) After one further crystallization an 6 - //<f / 7 analytically pure sale was obtained ; ir (nujol) 3120 and 1610 (2C and C=N respectviely) 1330 and 1155 (SC> 2) 1530 and 1355 cnf1 (NC>2); NMR (CDC13) 241 (s 3 -CH3) 78 (s 1 2-CH) (m 13 AB q of E-N02c6H4 and ^-CH^I^ C H5) ; mass spectrum M+ m/e 419 Calcd for C22H17N3 4S: C/ 6300; H 409; N 1002; S 763 Found: C 632; 41; 104; S 77 was prepared analogously m to from TosMIC (390 mg 20 mmol) and il-phenyl- -nitrobenzimidoyl chloride^ (522 mg 20 mmol) Crystallization from 80% MeOH provided He (710 mg 85%) as a light yellow solid An analytically pure sale was obtained after one further crystallization ; ir (nujol) 3110 (2C-H) 1610 (C=N) 1325 and 1150 (S02> 1520 and 1350 (N02> Anal calcd for C22H17N3 4S: C/ 63 00' H' 409; N 1002; S 762 Found: C 625; H 42; N 99; S 75 l-cvclohexyl-5 phenyl 4 tosylimidazole (lid) A solution of TosMIC (390 mg ///////\///\//> 'WV 20 mmol) and ij-cyclohexylbenzimidoyl chloride (450 mg 20 mmol) in 5ml of THF was added at room teerature to a suspension of NaH (84 mg 35 mmol) in 6 ml of THF and 2 ml of Me^SO under N2«The reaction mixture was stirred for one hour and then slowly poured in water The dark brown precipitate was collected treated with activated coal in absolute ethanol and crystallized from 80% MeOH to give lid as a white solid (600 mg 80%) An W\i analytically pure sale was obtained after one further crystallization from 80% MeOH ; ir (nujol) 3120 (2C-H) 1330 and 1150 cm1 (S02); NMR (CDC13) (m 10 C^ -0^0^ and 2-CH) 24 (s 3 -CH3) 1-2 (m 11 c-hexyl) Anal Calcd for ^*22^24^2^2^: ^*45? H 636; N 736; S 843 Found: C 695; H 64; N 74; S 83 l-cyclohexyl-5-p-nitrcphenyl-4-tosylimidazole (lie) was prepared analogously OAAAA/VXA/X/VA/XAA VVVVXA/VX/VVVX/X/VX/VVVVV/ 'Wv to lid from TosMIC (390 mg 20 mmol) and N-cyclohexyl-p-nitrobenzimidoyl chloride^** (530 mg 20 mmol) providing as a pale yellow solid (637 mg 75%) An analytically pure sale was obtained after crystallization from 96% EtOH ; ir (nujol) 3110 (2C-H) 1610 (C=N) 1325 and 1150 (S02) 1520 and 1355 cm1 (N02) Anal Calcd for C22H23N3 4S: C' ^2 18? H' 5 45; 986; S 753 Found: C 621; H 55; N 98; S 7 6