Nitrosonium (NO+) Initiated O-Alkylation of Oximes with N-Vinylpyrrolidinone

Indian Journal of Chemistry Vol. 54B, May 2015, pp. 656-661

Nitrosonium (NO+) initiated O-alkylation of oximes with N-vinylpyrrolidinone

Guai Li Wua,b*, Jian Liub, Yanli Weib, Yong Jiang Chenb & Long Min Wua aState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China bJiangSu HengRui Medicine Co. Ltd., Jiangsu Lianyungang 222047, China E-mail:[email protected] Received 11 March 2014; accepted (revised) 27 February 2015

An efficient O-alkylation of oximes with N-vinylpyrrolidinone has been achieved using nitrosonium tetrafluoroborate as a catalyst, giving oxime ethers in good to excellent yields. Keywords: Oxime, N-vinylpyrrolidinone, alkylation, nitrosonium

Oxime ethers are valuable nucleophilic reagents with consideration. The electron-withdrawing group at both nitrogen and oxygen atoms as nucleophiles. They oximes is favorable to O-alkylation of oximes, but the have been, in general, directly prepared from oximes reaction takes a longer time. Although the electron- with alkyl halides under basic conditions1. Acid donating group, such as methoxyl group, in 1g conditions, but, inevitably lead to byproducts of shortens the reaction time, a byproduct, probably a N-alkylation2. Therefore, it is desirable to develop a nitrone6, is produced. Similar results are also obtained in new synthetic protocol for the preparation of oxime substrate 1h and 1k. It is probably attributed to an ethers under neutral or acidic conditions. enhanced nucleophilicity of nitrogen atom caused by As reported, tris(4-bromophenyl)aminium cation electron-donating groups. +· - radical (TBPA SbCl6 ) or ammonium nitrate (CAN) Application of this procedure mentioned above to can efficiently initiate the O-alkylation of oximes with the reaction of thiophenols with N-vinylpyrrolidinone N-vinylpyrrolidinone, producing the corresponding in the presence of nitrosonium tetrafluoroborate (5 mol%) 3 oxime ethers . It inspires us to examine whether in CH2Cl2 affords the corresponding S-alkylation nitrosonium (NO+), on our interests in the synthetic adducts7 in 99% yields (Scheme II). potential of NO+ (Ref 4), is a good initiator for the A possible mechanism rationalization of the reaction of oxime 1 with N-vinylpyrrolidinone 2 O-alkylation of oximes or the S-alkylation of thiophenols (Scheme I) or not. The results are encouraging. Later, with N-vinylpyrrolidinone initiated by NO+ is presented this strategy was successfully applied to thiophenols in Scheme III. The stoichiometry study shows that a (Scheme II). very small NO+ amount of 5 mol% starts reactions. It is assumed that an electron transfer (ET) reaction Results and Discussion initially occurs between NO+ and the C–C double Initial experiment involved the reaction of 1a with bond of 2, forming cation radical 2+. (Ref 4a). A N-vinylpyrrolidinone 2 in the presence nitrosonium nucleophilic addition of oxime or thiophenol to 2+. tetrafluoroborate in dichloromethane led to the corres- provides cation radical [1+2]+., which then transfers a ponding 3a as our desired product. Various substituted proton to 2, forming [1+2]. and 2+, respectively. The conditions afforded the corresponding O-alkylation 2+ so produced will participate in the reaction. The [1+2]. product. abstracts a hydrogen atom from the solvent to give the All the products were identified by 1H and 13C NMR, corresponding oxime ether or sulfide. A mechanism FAB-MS or EIMS, IR, and HR-ESI-MS. The results suggested for byproducts is given in Scheme III by are listed in Table I. route 2. From the Table II, it can be seen that N-vinyl- Solvent effects were investigated using 1a as a pyrrolidinone exhibits very good to excellent reactivity substrate. Solvents examined were carbon tetrachloride, toward all the aldoximes and ketoximes5 under dichloromethane, methanol, tetrahydrofuran, and WU et al.: O-ALKYLATION OF OXIMES 657

Table I — O-Alkylation of oximes with N-vinylpyrrolidinone + 2 O + - initiated by NO R N N NO BF4 , 5 mol% OH + CH2Cl2, r.t Time 1 Yield of R Compd R1 R2 (hr) 3/4 (%)a 1 2 1a m-NO2-Ph H 1.5 96/0 O 1b p-Cl-Ph H 1.0 97/0 N 1c Ph H 1.3 98/0 O N 1d o-OH-Ph H 1.3 94/0 R2 N R2 N+ 1e p-NO -Ph H 2.6 88/0 O + 2 O- 1f PhCH2 H 1.0 86/0 R1 R1 1g p-MeO-Ph H 0.33 76/21 1h p-Me-Ph H 0.5 84/7 3 4 1i Ph CH3 0.67 98/0 1j p-Br-Ph CH3 1.0 90/0 Scheme I 1k p-MeO-Ph CH3 2.2 90/5 NOH

O NO+BF -, 5 mol% N O 1l 0.83 95/0 R4SH + N 4 CH2Cl2, r.t R S NOH 5 2 6 1m 0.67 94/0 Scheme II acetonitrile. Among them, dichloromethane was found to be highly favorable for the O-alkylation of oximes 1n 1.5 94/0 NOH under consideration (Table III). aIsolated yield based on oxime. bAll the oximes are anti-configurations. Experimental Section

Flash chromatography was carried out using silica Table II — S-alkylation of thiophenols with gel 60 (200-300 mesh, particle size 0.040-0.062 mm) N-vinylpyrrolidinone initiated by NO+ supplied by Qingdao Ocean Chemical Plant. Melting points were measured on a Yanagimoto melting point Compd R4 Time Yield (hr) of 6 (%)a apparatus and are uncorrected. IR spectra (KBr) were recorded on a Nicolet NEXUS 670 FT-IR spectro- 1 13 5o Ph 1.2 99 photometer. H and C NMR spectra were recorded 5p p-Cl-Ph 0.9 90 on a Varian Mercury Plus 300/400 NMR spectrometer. 5q p-OMe-Ph 1.0 86 1 Chemical shifts (δ) are reported relative to TMS ( H) 5r PhCH2 1.2 97 13 or CDCl3 ( C) as an internal standard. MS-EI (70 eV) 5s CH3CH2CH2 6.0 70 determinations were carried out on an HP 5985A aIsolated yield based on N-vinylpyrrolidinone. spectrometer. FAB-MS determinations were carried out on an ZAB-HS spectrometer. HRMS-ESI detections nitrosonium tetrafluoroborate (5 mol%), which was were run on a Bruker Daltonics APEX II 47e pasted onto a piece of glass. The resulting mixture spectrometer with an ESI. Chemicals were of highest was stirred for a required time (Table I). The completion grade commercially available and used as received, of reaction was indicated by TLC. Consequently, it unless otherwise sated. All reagents were weighed was diluted with water and extracted with 4 × 15 mL and handled in air at room temperature. of CH2Cl2, and dried over anhydrous Na2SO4. The solvent was evaporated and the residue purified by Typical procedure for the preparation of 3a column chromatography on silica gel (200-300 mesh, In a typical experiment procedure, to a mixture of ethyl acetate/hexane) to afford product 3a as a colorless 1a (0.5 mmol) and N-vinylpyrrolidinone (0.75 mmol ) liquid in good yield (96%). Other compounds were in 10 mL of dichloromethane (CH2Cl2) at RT was added obtained by the same procedure. 658 INDIAN J. CHEM., SEC B, MAY 2015

Table III — Solvent effects on the O-alkylation of 1a with N-vinylpyrrolidinone

Solvent Time (hr) Yield of 3a (%)a

Dichloromethane 1.5 96 Tetrahydrofuran 12 85 Acetonitrile 24 52 Methanol 24 0 Carbon tetrachloride 48 0 aIsolated yield based on 1a.

Hz), 2.04 (m, 2H, J =7.2 Hz, J = 7.5 Hz, J = 8.1Hz, J = 8.4 Hz), 1.51(d, 3H, J = 6.3 Hz); 13C NMR (75 MHz, CDCl3): δ 175.5, 148.3, 147.2, 133.7, 132.3, 129.7, 124.4, 122.1, 80.8, 41.6, 31.5, 17.9, 16.8; FAB-MS: m/z (%) 278 ((M+H)+, 41), 168 (17), 113 (100); HR- ESI-MS: m/z Calcd for C13H15N3O4 + H: 278.1135. Found: 278.1136. 4-Chloro-benzaldehyde O-[1-(2-oxo-pyrrolidin- 1-yl)-ethyl]-oxime, 3b: Yield 97%, 129 mg, Known compound (lit.3a), Colorless prisms, m.p. 72-73°C; IR (KBr): 2986.6, 2947.5, 1698.5, 1491.2, 1418.3, 1281.7, 1268.9, 1087.8, 949.8 cm-1; 1H NMR (300 MHz, CDCl3): δ 8.02 (s, 1H), 7.51 (d, 2H, J = 8.7 Hz), 7.32 (d, 2H, J = 8.4 Hz), 6.14(m, 1H, J = 6.3 Hz, J = 6.6 Hz, J = 12.5 Hz), 3.43 (m, 2H, J = 6.9 Hz, J = 10.5 Hz), 2.43 (m, 2H, J = 7.5 Hz, J = 8.4 Hz, J = 8.0 Hz), 2.01 (m, 2H, J = 7.5 Hz, J = 10.9 Hz, J = 11.3 Hz), 1.47 (d, 13 3H, J = 6.3 Hz); C NMR (75 MHz, CDCl3): δ 175.9, 148.5, 136.1, 130.7, 129.2, 128.6, 80.7, 41.8, 31.9, 18.3, 17.2; FAB-MS: m/z (%) 267 ((M+H)+, 99), 155 (48), 113 (100); HR-ESI-MS: m/z Calcd for C13H15N2O2Cl + H: 267.0983. Found: 267.0985. Benzaldehyde O-[1-(2-oxo-pyrrolidin-1-yl)-ethyl]- oxime 3c: Yield 98%, 114 mg, Known compound (lit.3a), Colorless liquid, IR (KBr): 2986.2, 2946.2, -1 1698.0, 1418.0, 1284.4, 1268.7, 1087.7, 947.7cm ; 1 H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.58 (m, Scheme III 2H, J = 2.4 Hz, J = 2.8 Hz, J = 3.2 Hz), 7.36 (m, 3H), Characterization Data for Products 6.11 (m, 1H, J = 6.0 Hz, J = 6.4 Hz, J = 12.7 Hz), 3-Nitro-benzaldehyde O-[1-(2-oxo-pyrrolidin-1-yl)- 3.40 (m, 2H, J = 6.4 Hz, J = 6.8 Hz, J = 7.2 Hz), 2.40 ethyl]-oxime, 3a: Yield 96%, 133 mg, Known compound (m, 2H, J =7.6 Hz, J = 8.0 Hz, J = 8.4Hz), 1.97 (m, (lit.3c), Colorless liquid, IR (KBr): 2988.1, 2956.0, 2H, J =7.2 Hz, J = 7.6 Hz, J = 8.4 Hz), 1.44 (d, 3H, 13 1697.4, 1532.1, 1418.3, 1351.9, 1281.9, 1269.5, 1087.0, J =5.6 Hz); C NMR (100MHz, CDCl3): δ 175.5, 149.4, -1 1 957.6 cm ; H NMR (300 MHz, CDCl3): δ 8.34 (dd, 131.8, 129.9, 128.6, 127.1, 80.4, 41.5, 31.6, 18.0, 1H, J = 1.2 Hz, J = 2.4 Hz), 8.23 (dd, 1H, J = 1.2 Hz, 16.9; FAB-MS: m/z (%) 233 ((M+H)+, 16), 113 (100), J = 1.8Hz, J = 8.3 Hz), 8.14 (s, 1H), 7.99 (dd, 1H, J = 1.2 56 (79); HR-ESI-MS: m/z Calcd for C13H16N2O2 + H: Hz, J = 8.7 Hz), 7.57 (t, 1H, J = 2.1 Hz, J = 2.4 Hz, 233.1282. Found: 233.1285. J = 8.3 Hz), 6.18 (dd, 1H, J = 5.7 Hz, J = 6.3 Hz, J = 12.6 3-Hydroxy-benzaldehyde O-[1-(2-oxo-pyrrolidin- Hz), 3.47 (m, 2H, J = 3.0 Hz, J = 6.3 Hz, J = 6.6 Hz, 1-yl)-ethyl]-oxime 3d: Yield 94%, 117 mg, Known J = 22.1 Hz), 2.46 (m, 2H, J =7.5 Hz, J = 7.8 Hz, J = 8.1 compound (lit.3c), Colorless prisms, m.p. 87-88°C; IR WU et al.: O-ALKYLATION OF OXIMES 659

-1 1 (KBr): 3202.0, 2988.8, 2953.1, 1699.9, 1613.6, 1489.3, 945.1 cm ; H NMR (400 MHz, CDCl3): δ 7.93 (d, 1418.6, 1266.6, 1086.6, 968.1, 759.9 cm-1; 1H NMR 1H, J = 4.0 Hz), 7.43 (m, 2H, J = 2.0 Hz, J = 2.8 Hz, (400 MHz, CDCl3): δ 9.68 (s, 1H), 8.13 (s, 1H), 7.26 J = 7.2 Hz), 6.80 (m, 2H, J = 2.0 Hz, J = 2.8 Hz), 6.03 (t, 1H, J = 7.2 Hz, J = 7.8 Hz, J = 8.4 Hz), 7.14 (dd, (m, 1H, J = 6.0 Hz, J = 6.4 Hz, J = 12.6 Hz), 3.74 (s, 1H, J = 1.6 Hz, J = 6.8 Hz), 6.97 (d, 1H, J = 8.0 Hz), 3H), 3.34 (m, 2H, J = 3.2 Hz, J = 4.0 Hz, J = 7.2 Hz), 6.88 (dd, 1H, J =7.2 Hz, J = 7.4 Hz, J = 7.6 Hz), 6.18 2.34 (m, 2H, J =7.6 Hz, J = 8.0 Hz, J = 8.4 Hz), 1.92 (m, 1H, J =6.4 Hz, J = 12.4 Hz), 3.40 (m, 2H, J =2.0 (m, 2H, J =7.2 Hz, J = 7.4 Hz, J = 7.6Hz), 1.38 (d, 13 Hz, J = 5.2 Hz, J = 7.2Hz), 2.45 (m, 2H, J =8.0 Hz, 3H, J =6.0 Hz); C NMR (100 MHz, CDCl3): δ 175.5, J = 8.2Hz, J = 8.4Hz), 2.01 (m, 2H, J =7.2 Hz, J = 15.2 160.9, 149.0, 128.6, 124.5, 113.9, 109.7, 80.2, 55.2, Hz), 1.47(d, 3H, J =6.0 Hz); 13C NMR (100 MHz, 48.2, 31.6, 17.9, 16.9; FAB-MS: m/z (%) 263 ((M+H)+, CDCl3): δ 176.1, 157.5, 151.8, 131.2, 130.6, 119.2, 14), 153 (35), 113 (100); HR-ESI-MS: m/z Calcd for 116.9, 115.9, 80.3, 41.0, 31.2, 17.9, 16.3; FAB-MS: C14H18N2O3 + H: 263.1390. Found: 263.1400. + m/z (%) 249 ((M+H) , 65), 139 (89), 113 (100); HR- 4-Methyl-benzaldehydeO-[1-(2-oxo-pyrrolidin- ESI-MS: m/z Calcd for C13H16N2O3 + H: 249.1233. 1-yl)-ethyl]-oxime 3h: Yield 84%, 103 mg, Known Found: 249.1233. compound (lit.3a), Colorless liquid; IR (KBr): 2985.7, 4-Nitro-benzaldehyde O-[1-(2-oxo-pyrrolidin-1- 2943.8, 2889.1, 1699.8, 1417.6, 1281.9, 1268.3, 1088.0, -1 1 yl)-ethyl]-oxime 3e: Yield 88%, 122 mg, Known 945.5, 817.4 cm ; H NMR (300 MHz, CDCl3): δ 8.03 compound (lit.3a), Colorless prisms, m.p. 98-99°C;IR (s, 1H), 7.47 (d, 2H, J = 7.5 Hz), 7.15 (d, 1H, J = 7.8 Hz), (KBr): 2988.3, 2949.4, 2890.5, 1697.9, 1519.8, 1417.9, 6.13 (m, 1H, J = 6.0 Hz, J = 6.6 Hz, J = 12.6 Hz), -1 1 1344.9, 954.5, 856.5 cm ; H NMR (400 MHz, CDCl3): 3.43 (t, 2H, J = 6.9 Hz, J = 7.1 Hz, J = 7.2 Hz), 2.42 δ 8.21 (d, 2H, J = 8.0 Hz), 8.13 (s, 1H), 7.75 (d, 2H, (t, 2H, J = 7.5 Hz, J = 8.0 Hz, J = 8.4 Hz), 2.35 (s, J = 7.6 Hz), 6.20 (m, 1H, J = 5.6 Hz, J = 6.4 Hz, J = 12.0 3H), 1.99 (m, 2H, J = 7.8 Hz, J = 8.4Hz), 1.46 (d, 3H, 13 Hz), 3.46 (m, 2H, J = 7.6 Hz, J = 8.0 Hz, J = 10.0 J = 6.3 Hz); C NMR (75 MHz, CDCl3): δ 175.5, 149.4, Hz), 2.46 (m, 2H, J = 8.0 Hz), 2.04 (m, 2H, J = 7.6 Hz, 140.2, 129.3, 129.1, 127.1, 80.2, 41.5, 31.6, 21.4, 18.0, J = 14.4 Hz), 1.51(d, 3H, J =6.0 Hz); 13C NMR (100 16.9; FAB-MS: m/z (%) 247 ((M+H)+, 16), 137 (24), MHz, CDCl3): δ 175.9, 148.6, 147.5, 138.3, 128.0, 113 (100); HR-ESI-MS: m/z Calcd for C14H18N2O2 + H: 124.2, 81.3, 41.8, 31.8, 18.3, 17.2; FAB-MS: m/z (%) 247.1441. Found: 247.1435. + 278 ((M+H) , 12), 137 (17), 113 (100); HR-ESI-MS: 1-[1-(1-Phenyl-ethylideneaminooxy)-ethyl] - pyrro- m/z Calcd for C13H15N3O4 + H: 278.1135. Found: lidin-2-one, 3i: Yield 98%, 121 mg, Known 278.1139. compound (lit.3c), Colorless liquid; IR (KBr): 2985.3, Phenyl-acetaldehyde O-[1-(2-oxo-pyrrolidin-1- 2943.6, 2887.3, 1700.7, 1417.6, 1282.0, 1287.9, yl)-ethyl]-oxime, 3f: Yield 86%, 123 mg, New com- 985.9, 765.6, 696.0 cm-1; 1H NMR (300 MHz, pound, Colorless prisms, m.p. 89-90°C; IR (KBr): 2985.8, CDCl3): δ 7.65 (m, 2H), 7.33 (m, 3H), 6.16 (m, 1H, 2945.7, 2889.0, 1698.6, 1419.3, 1281.9, 1097.3, 982.6, J = 6.3 Hz), 3.40 (m, 2H, J = 1.8 Hz, J = 2.1 Hz, J = -1 1 941.6, 701 cm ; H NMR (300 MHz, CDCl3): δ 7.47 3.6 Hz, J = 6.9 Hz), 2.42 (t, 2H, J = 8.1 Hz), 2.23 (s, (t, 1H, J = 2.4 Hz, J = 6.3 Hz, J = 6.5 Hz), 7.26 (m, 3H), 1.99 (m, 2H, J = 7.5 Hz, J = 6.9 Hz, J = 15 Hz), 13 5H), 6.06 (m, 1H, J = 6.3 Hz, J = 12.6 Hz), 3.51(d, 1.49 (d, 3H, J = 6.6 Hz); C NMR (75 MHz, CDCl3): 2H, J = 6.6 Hz), 3.37 (m, 2H, J = 1.8 Hz, J = 2.4 Hz, δ 175.4, 154.9, 135.9, 129.1, 128.2, 125.8, 80.1, 41.4, J = 3.0Hz), 2.44 (t, 2H, J = 7.8 Hz, J = 8.1 Hz, J = 31.6, 17.9, 16.9, 12.1; FAB-MS: m/z (%) 247 8.4 Hz), 1.99 (m, 2H, J = 3.0 Hz, J =6.9 Hz, J = ((M+H)+, 9), 137 (20), 113 (33) 56 (100); HR-ESI- 7.2 Hz, J = 14.6 Hz), 1.39 (d, 3H, J =7.2 Hz); MS: m/z Calcd for C14H18N2O2 + H: 247.1441. Found: 13 C NMR (75 MHz, CDCl3): δ 175.3, 150.6, 136.2, 247.1440. 128.7, 128.6, 126.7, 79.8, 41.3, 35.8, 31.6, 18.0, 16.9; 1-{1-[1-(4-Bromo-phenyl-ethylideneaminooxy)- + FAB-MS: m/z (%) 247 ((M+H) , 9), 137 (22), 113 (88), ethyl]-pyrrolidin-2-one 3j: Yield 90%, 146 mg, New 56 (100); HR-ESI-MS: m/z Calcd for C14H18N2O2+ H: compound, Colorless liquid; IR (KBr): 2985.1, 2950.4, 247.1452. Found: 247.1441. 2885.8, 1702.6, 1417.6, 1281.5, 1267.7, 1093.7, 1002.3, -1 1 4-Methoxy-benzaldehydeO-[1-(2-oxo-pyrrolidin-1- 984.5, 930.1 cm ; H NMR (300 MHz, CDCl3): δ 7.44 yl)-ethyl]-oxime 3g: Yield, 76%, 99 mg, Known com- (m, 4H), 6.10 (m, 1H, J = 6.0 Hz, J = 6.6 Hz, J = pound (lit.3a), Colorless liquid; IR (KBr): 2985.6, 2957.4, 12.6 Hz), 3.36 (m, 1H), 2.38 (m, 2H, J = 8.4 Hz, J = 2839.1, 1696.6, 1607.4, 1513.3, 1419.0, 1252.8, 1089.0, 8.5 Hz, J = 8.7 Hz), 2.16 (s, 3H), 1.95 (m, 2H, J = 660 INDIAN J. CHEM., SEC B, MAY 2015

3.6 Hz, J = 9.3 Hz), 1.23 (d, 3H, J = 7.5 Hz); 13C NMR 1-[1-(1, 7, 7-Trimethyl-bicyclo[2.2.1]hept-2-ylidene- (75 MHz, CDCl3): δ 175.4, 153.9, 134.9, 131.3, 127.4, aminooxy)-ethyl]-pyrrolidin-2-one, 3n: Yield 94%, 123.3, 80.2, 41.4, 31.6, 17.9, 16.9, 11.9; FAB-MS: 130 mg, New compound, Colorless liquid; IR (KBr): m/z (%) 325 ((M+H)+, 10), 196 (14), 113 (100); 3490.3, 2957.0, 2876.7, 1703.2, 1417.6, 1280.5, 1268.4, -1 1 HR-ESI-MS: m/z Calcd for C14H17N2O2Br + H: 1087.3, 929.0cm ; H NMR (400 MHz, CDCl3): δ 5.93 325.0546. Found: 325.0560. (m, 1H, J = 6.0 Hz, J = 6.4 Hz, J = 9.4 Hz, J = 11.7 Hz, 1-{1-[1-(4-Methoxy-phenyl - ethylideneaminooxy)- J = 14.0 Hz), 3.29 (m, 2H, J = 4.8 Hz, J = 7.6 Hz, J = 8.0 ethyl]-pyrrolidin-2-one, 3k: Yield 90%, 124 mg, New Hz, J = 9.6 Hz), 2.37 (m, 3H), 1.89 (m, 3H), 1.76 (m, compound, Colorless liquid; IR (KBr): 2984.7, 2939.2, 2H), 1.64 (m, 1H, J = 8.0 Hz, J = 12.0 Hz, J = 21.6 1698.8, 1606.4, 1513.2, 1417.6, 1314.4, 1282.9, Hz), 1.34 (d, 3H, J =5.6 Hz), 1.29 (m, 2H), 0.91 (d, 3H, 1252.7, 926.5 cm-1; 1H NMR (300 MHz, CDCl ): δ J =8.0 Hz), 0.86 (s, 3H), 0.71 (d, 3H, J = 16.4 Hz); 3 13 δ 7.58 (d, 2H, J = 8.7 Hz), 6.84(d, 2H, J = 9.0Hz), C NMR (100 MHz, CDCl3): 174.9, 169.8, 79.2, 6.12(m, 1H, J = 6.3 Hz, J = 12.9Hz), 3.79 (s, 3H), 51.3, 47.5, 43.2, 41.4, 40.9, 33.0, 31.8, 31.3, 26.9, 18.9, + 3.38 (m, 2H), 2.40 (t, 2H, J =8.1 Hz), 2.18 (s, 3H), 17.9, 16.7, 10.5; FAB-MS: m/z (%) 279 ((M+H) , 34), 1.97 (m, 2H, J =3.0 Hz, J = 7.8 Hz, J = 15.3Hz), 1.45 169 (62), 113 (100); HR-ESI-MS: m/z Calcd for 13 (d, 3H, J =6.6 Hz); C NMR (75 MHz, CDCl3): δ 175.5, C16H26N2O2 + H: 279.2067. Found: 279.2078. 160.3, 154.5, 128.6, 127.3, 113.5, 80.1, 55.2, 41.4, 4-Methoxy-benzaldehydeN-[1-(2-oxo-pyrrolidin- 31.7, 18.0, 17.0, 12.1; FAB-MS: m/z (%) 277 ((M+H)+, 1-yl)-ethyl]-nitrone, 4g: Yield 21%, 28 mg, New 26), 149 (56), 113 (100), 78 (35); HR-ESI-MS: m/z compound, Colorless liquid; IR (KBr): 2984.5, 2840.7, Calcd for C15H20N2O3 + H: 277.1547. Found: 277.1560. 1695.9, 1603.5, 1508.2, 1419.9, 1258.3, 1176.9, 909.6 -1 1 δ 1-[1-(3, 4-Dihydro-2H-naphthalen-1-ylideneamino- cm ; H NMR (400 MHz, CDCl3): 7.85 (d, 2H, xy)-ethyl]-pyrrolidin-2-one, 3l: Yield 95%, 129 mg, J = 11.6 Hz), 7.27 (s, 1H), 6.93 (d, 2H, J = 11.6 Hz), 6.16 New compound, Colorless liquid; IR (KBr): 3063.6, (m, 1H, J = 8.0 Hz, J = 8.8 Hz, J = 12.6 Hz), 3.85 (s, 2984.4, 2939.9, 2884.8, 2838.3, 1697.9, 1417.4, 1281.4, 3H), 3.42 (m, 2H, J = 3.2 Hz, J = 11.2 Hz, J = 10.8 Hz), -1 1 1267.1, 1090.9, 948.9 cm ; H NMR (400 MHz, CDCl3): 2.46 (m, 2H, J = 2.4 Hz, J = 2.8 Hz, J = 10.6 Hz, J = 11.2 δ 7.86 (d, 1H, J = 8.0 Hz), 7.07 (m, 3H), 6.05 (m, 1H, Hz), 2.01 (m, 2H, J = 10.4 Hz, J = 15.2 Hz, J = 19.6 Hz), 13 J = 6.0 Hz, J = 6.4 Hz, J = 7.2Hz), 3.03 (m, 2H), 2.66 1.52 (d, 3H, J = 8.8 Hz); C NMR (100 MHz, CDCl3): (m, 4H), 2.31 (m, 2H, J =2.4 Hz, J = 8.0 Hz), 1.90 (m, δ 175.6, 160.7, 146.5, 132.9, 123.5, 113.7, 80.8, 55.3, 2H), 1.75 (m, 2H, J = 4.8 Hz), 1.38 (m, 2H, J =2.4 41.3, 31.6, 17.9, 17.0; MS (EI): m/z 262 (M+), 262, Hz, J = 3.6 Hz), 1.39 (d, 3H, J = 5.2 Hz); 13C NMR 151, 134, 112; HR-ESI-MS: m/z Calcd for (100MHz, CDCl3): δ 175.3, 154.3, 139.2, 130.2, 128.8, C14H18N2O3 + Na: 285.1210. Found: 285.1209. 128.2, 126.1, 124.3, 80.1, 41.3, 31.5, 29.4, 23.9, 21.2, 4-Methyl-benzaldehydeN-[1-(2-oxo-pyrrolidin-1- 17.8, 16.9; FAB-MS: m/z (%) 273 ((M+H)+, 15), 163 yl)-ethyl]-nitrone, 4h: Yield 7%, 9 mg, New (75), 113 (100); HR-ESI-MS: m/z Calcd for compound, Colorless liquid; IR (KBr): 3525.9, C16H20N2O2 + H: 273.1598. Found: 273.1596. 3391.3, 2922.3, 2853.6, 1704.4, 1657.3, 1420.7, -1 1 δ 1-(1-Benzhydrylideneaminooxy-ethyl) - pyrrolidin- 1089.3, 911.2 cm ; H NMR (400 MHz, CDCl3): 2-one, 3m: Yield 94%, 150 mg, Known compound 7.56 (d, 2H, J = 8.0 Hz), 7.29 (s, 1H), 7.21 (d, 2H, J = (lit.3c), Colorless liquid; IR (KBr): 3057.8, 2986.0, 8.0 Hz), 6.16 (m, 1H, J = 6.4 Hz, J = 12.8 Hz), 3.38 (m, 2948.8, 1701.0, 1417.4, 1281.2, 1267.9, 1087.8, 2H, J = 2.4 Hz, J = 2.8 Hz, J = 6.8 Hz), 2.44 (m, 2H, 975.6, 944.2, 776.2, 698.2 cm-1; 1H NMR (400 MHz, J = 3.2 Hz, J = 3.6 Hz), 2.39 (s, 3H), 1.99 (m, 2H, J = 13 CDCl ): δ 7.43 (m, 5H), 7.30 (m, 5H), 6.18 (m, 1H, 7.2 Hz, J = 7.6 Hz), 1.51 (d, 3H, J = 6.4 Hz); C NMR 3 δ J = 6.4 Hz, J = 12.4 Hz ), 3.33 (m, 2H, J = 1.6 Hz, J = 8.0 (100 MHz, CDCl3): 175.4, 146.8, 140.4, 130.8, Hz, J = 9.2 Hz), 2.44 (m, 2H, J = 7.6 Hz, J = 7.8 Hz, 129.0, 127.8, 80.8, 41.3, 31.5, 21.4, 17.9, 16.9; MS J = 8.0 Hz), 1.99 (m, 2H, J = 6.8 Hz, J = 7.2 Hz J = 8.0 (EI): m/z 246 (M+), 149, 135, 118, 112; HR-ESI-MS: 13 Hz, J = 9.2 Hz), 1.37(d, 3H, J = 6.4 Hz); C NMR (100 m/z Calcd for C14H18N2O2+ H: 247.1441. Found: MHz, CDCl3): δ 175.3, 157.4, 135.9, 132.8, 129.3, 247.1446. 128.9, 128.6, 128.0, 127.8(2), 80.5, 41.4, 31.6, 17.9, 4-Methoxy-phenyl-ethylidene N-[1-(2-oxo-pyrro- 16.7; FAB-MS: m/z (%) 309 ((M+H)+, 31), 198 (98), lidin-1-yl)-ethyl]-nitrone, 4k: Yield 5%, 7 mg, New 113 (100); HR-ESI-MS: m/z Calcd for C19H20N2O2 + H: compound, Colorless liquid; IR (KBr): 3389.3, 2983.9, 309.1598. Found: 309.1589. 2922.8, 1695.4, 1510.7, 1418.5, 1249.9, 1028.9, 924.2 WU et al.: O-ALKYLATION OF OXIMES 661

-1 1 cm ; H NMR (400 MHz, CDCl3): δ 7.55 (d, 2H, J = 1-（（（1-Benzylsulfanyl-ethy）））-pyrrolidin-2-one, 6r: 8.4 Hz), 6.89 (d, 2H, J = 8.4 Hz), 6.02 (m, 1H, J = 4.0 Yield 97%, 114 mg, New compound, Colorless liquid; Hz, J = 6.8 Hz), 3.83 (s, 3H), 3.31 (m, 2H, J = 7.2 Hz, J = IR (KBr): 2975.9, 2929.6, 2883.8, 1685.7, 1414.1, 1267.9, -1 1 10.0 Hz, J = 11.2 Hz), 2.45 (m, 2H, J = 8.0 Hz, J = 1200.7, 708.6 cm ; H NMR (300 MHz, CDCl3): 8.4 Hz, J = 12.6 Hz), 2.16 (s, 3H), 1.98 (m, 2H, J = δ 7.21 (m, 5H), 5.56 (m, 1H, J = 6.9 Hz, J = 14.1 Hz), 13 7.2 Hz, J = 7.6 Hz), 1.37 (d, 3H, J = 6.4 Hz); C 3.62 (m, 2H, J = 14.1 Hz, J = 28.8 Hz), 3.31 (m, 1H), NMR (100 MHz, CDCl3): δ 175.5, 159.9, 153.7, 3.11 (m, 1H), 2.22 (m, 1H), 2.03 (m, 1H), 1.76 (m, 130.0, 126.3, 113.2, 80.3, 55.2, 41.6, 31.7, 21.6, 18.1, 1H), 1.43 (m, 1H), 1.34 (d, 3H, J = 7.5 Hz); 13C NMR 17.0; MS (EI): m/z 276 (M+), 276, 165, 148, 133, (75 MHz, CDCl3): δ 174.2, 138.2, 128.1, 127.9, 126.4, 119, 112; HR-ESI-MS: m/z Calcd for C15H20N2O3 + Na: 52.4, 40.5, 35.5, 31.0, 18.8, 16.8; MS (EI): m/z 235 299.1366. Found: 299.1362. (M+), 235, 151, 144, 123, 121, 112, 91; HR-ESI-MS: 1-(1-Phenylsulfanyl-ethyl)-pyrrolidin-2-one, 6o: m/z Calcd for C13H17N1O1S1 + Na: 258.0923. Found: Yield 99%, 109 mg, Known compound (lit.7), Colorless 258.0923. liquid; IR (KBr): 2977.3, 2929.4, 2882.5, 1690.5, 1412.2, 1-1-Propylsulfanyl-ethyl-pyrrolidin-2-one, 6s: Yield, -1 1 1266.9, 1202.7, 746.9, 693.8cm ; H NMR (300 MHz, 70%, 66 mg, New Compound, Colorless liquid; IR CDCl3): δ 7.34 (m, 2H), 7.22 (m, 3H), 5.89 (m, 1H, (KBr): 2963.2, 2931.2, 2874.1, 1689.3, 1413.9, -1 1 J = 3.0 Hz, J = 8.4 Hz), 3.54 (m, 1H), 3.29 (m, 1H), 1267.3, 1200.2cm ; H NMR (300 MHz, CDCl3): 2.25 (m, 1H), 2.10 (m, 1H), 1.84 (m, 2H), 1.47 (d, 3H, δ 5.54 (m, 1H), 3.62 (m, 1H), 3.32 (m, 1H), 2.47 (m, 13 J = 6.9 Hz); C NMR (75 MHz, CDCl3): δ 174.1, 132.7, 3H), 2.31 (m, 1H), 2.04 (m, 2H), 1.60 (m, 2H), 1.37 131.9, 128.5, 127.2, 54.1, 40.9, 30.1, 18.6, 17.4; MS (d, 3H, J =5.1 Hz), 0.94 (m, 3H, J =2.4 Hz, J =5.1 Hz); 13 (EI): m/z 221 (M+), 137, 135, 112, 109, 140; HR-ESI- C NMR (75 MHz, CDCl3): δ 174.6, 51.4, 40.8, 32.7, MS: m/z Calcd for C12H15N1O1S1 + Na: 244.0767. 31.4, 22.7, 19.1, 17.7, 13.3; MS (EI): m/z 187 (M+), 187, Found: 244.0770. 144, 112; HR-ESI-MS: m/z Calcd for C9H17N1O1S1 + Na: 1-[1(4-Chloro-phenylsulfanyl-ethyl)-pyrrolidin-2- 210.0923. Found: 210.0923. one, 6p: Yield 90%, 115 mg, New Compound, Conclusion Colorless liquid; IR (KBr): 2978.1, 2931.7, 2882.7, + 1690.1, 1477.8, 1412.3, 1266.5, 1094.9, 820.4cm-1; 1H In conclusion, NO has been demonstrated to be a good catalyst for the alkylation of oximes or NMR (300 MHz, CDCl3): δ 7.30 (m, 2H, J = 2.4 Hz, J = 3.0 Hz), 7.19 (m, 2H, J = 3.0Hz, J = 5.1 Hz), 5.86 thiophenols with N-vinylpyrrolidinone. It is expected (m, 1H, J = 2.7 Hz, J = 3.0 Hz, J = 6.6 Hz), 3.47 (m, that this approach could be extended to other 1H), 3.28 (m, 1H), 2.24 (m, 1H, J = 3.0 Hz, J = activated olefins.

3.6 Hz, J = 9.3 Hz), 2.10 (m, 1H, J =3.0 Hz), 1.85 (m, 13 Acknowledgement 2H), 1.53 (d, 3H, J = 4.5 Hz); C NMR (75 MHz, Project 20572040 was supported by National Natural δ CDCl3): 174.5, 133.5, 133.3, 131.5, 128.9, 54.4, 41.2, Science Foundation of China. 31.1, 18.8, 17.6; MS (EI): m/z 255 (M+), 211, 171, 143, 112, 108; HR-ESI-MS: m/z Calcd for References C12H15N1O1S1Cl1 + Na: 278.0377. Found: 278.0376. 1 (a) Bull S, Davies S & Domingez S, J Chem Soc, Perkin Trans 1-[1(4-Methoxy-phenylsulfanyl-ethyl)-pyrrolidin- 1, 2002, 2141; (b) Davis S, Fox J, Jones S, Price A & Smith A, J 2-one, 6q: Yield 86%, 108 mg, New Compound, Chem Soc, Perkin Trans 1, 2002, 1757; (c) Koenig S, Leonard K, Lowe R & Austin D, Tetrahedron Lett, 41, 2000, 9393. Colorless liquid; IR (KBr): 2974.2, 2887.9, 2836.9, 2 Miyabe H, Yoshida K, Reddy V & Takemoto Y, J Org Chem, 1690.5, 1592.2, 1493.5, 1412.5, 1284.6, 1246.7, 1028.5, 70, 2005, 5630. -1 1 829.9cm ; H NMR (300 MHz, CDCl3): δ 7.31 (m, 3 Jia X, Da Y & Yang L, Tetrahedron Lett, 49, 2008, 1786; (b) Jia 2H, J = 6.9 Hz), 6.81 (m, 2H, J = 2.4 Hz, J = 6.3 Hz), X, Wang X & Yang C, Tetrahedron, 65, 2009, 2334; (c) Wang J, Jia X & Peng L, Chinese Chem Lett, 22, 2011, 655. 5.75 (m, 1H), 3.78 (s, 3H), 3.59 (m, 1H), 3.31(m, 1H), 4 (a) Zhou Y, Jia X & Li R, Tetrahedron Lett, 46, 2005, 8937; (b) 2.26 (m, 1H), 1.96 (m, 3H), 1.46 (d, 3H, J = 6.9 Hz); Wu G & Wu L, Chinese Chem Lett, 19, 2008, 55; (c) Liang R, 13 C NMR (75 MHz, CDCl3): δ 174.3, 159.6,135.3, Wu G & Wu L, Chinese Chem Lett, 20, 2009, 1183. 122.9, 114.2, 55.3, 55.1, 41.0, 31.1, 18.6, 17.6; MS 5 Oximes were prepared by the reaction of the corresponding (EI): m/z 251 (M+), 251, 139, 124, 112, 96; HR-ESI- carbonyl compounds with excess of hydroxylamine in methanol, either at RT or when required under heating (55°C). MS: m/z Calcd for C13H17N1O2S1 + Na: 274.0872. 6 Grigg R, Dorrity M & Heaney F, Tetrahedron, 47, 1991, 8297. Found: 274.0871. 7 Katrizky A, Jurczyk S & Rachwal B, Synthesis, 1992, 1295.