SUPPORTIG IFORMATIO Catalytic Reductive Dehydration of Tertiary Amides to Enamines under Hydrosilylation Conditions Alexey Volkov, a Fredrik Tinnis, a and Hans Adolfsson.* a a Department of Organic Chemistry, Stockholm University, the Arrhenius Laboratory, SE-106 91 Stockholm, Sweden 1
Table of content Instrumentation...2 Material...2 General...3 General procedures for synthesis of amides....3 Optimization studies...4 Substrate scope investigation...4 Additionally evaluated substrates not isolated...11 Spectroscopic data....13 Instrumentation Characterizations were made by 1 H and 13 C MR spectroscopy. MR spectra were recorded at Bruker 400 MHz ( 1 H) and 100 MHz ( 13 C), and were referenced internally with CDCl 3 (δh 7.26, δc 77.16 ppm). Low temperature experiments were performed at Bruker 500 MHz ( 1 H) and 125 MHz ( 13 C). HRMS was performed on Bruker microtof/esi. Material Unless otherwise noted, materials were purchased from commercial suppliers and were used without purification. THF was purchased from Fischer Scientific, and dispersed from a solvent drying system. Certificate of analysis of the 99.99% potassium tert-butoxide: Sodium (a) 1040.3 ppm Rubidium (Rb) 26.8 ppm Scandium (Sc) <0.7 ppm Calcium (Ca) <0.8 ppm Yttrium (Y) 0.5 ppm Hafnium (Hf) 0.7 ppm Manganese (Mn) 0.5 ppm 2
General The 1 mmol scale catalytic amide reductions were performed in oven dried microwave tubes 2-5 ml from Biotage, with a Teflon-coated magnetic stirring bar. The tubes were fitted with a cap containing a septum and the reactions were run under nitrogen atmosphere. General procedures for synthesis of amides. Route 1. Carboxylic acid (10 mmol), molecular sieves 4Å (3 g) and zirconium(iv)chloride (20 mol %) were treated under vacuum for 10 min in a sealed 20 ml microwave tube. Dry THF (15 ml) was added under nitrogen atmosphere and the mixture was heated to 100 ºC while stirring. The amine (11 mmol) was added drop wise. The reaction was stirred at the same temperature for 24 h and then cooled to r.t. The mixture was filtered through a pad of silica with 100 ml of a mixture of EtOAc : Et 3 200:1. The solvent was removed under reduced vacuum. If necessary, the amide was purified with column chromatography on SiO 2 eluted with Pentane/EtOAc. Route 2. Commercially available acid chloride (10 mmol) was slowly added to a solution of corresponding amine (11 mmol) and Et 3 (1.7 ml, 12.5 mmol) in DCM (20 ml) and stirred for 1 h. Reaction mixture was washed with aq. HCl (1 M, 50 ml) and aq. aoh (2 M, 50 ml). Organic layer was dried with a 2 SO 4 and the solvent was removed under reduced pressure resulting in a pure product. If necessary, the amide was purified with column chromatography on SiO 2 eluted with Pentane/EtOAc. 3
Optimization studies entry time, h catalyst silane temperature, C solvent conversion, % 1 30 5 mol % Fe(II)/Ph-HEMIM PMHS 3 equiv 65 THF 3 ml traces 2 40 5 mol % Fe(II)/Ph-HEMIM PMHS 3 equiv 120 THF 3 ml 87 3 7 5 mol % Fe(II)/iPr HCl PMHS 3 equiv 120 THF 3 ml >95 4 20 5 mol % Fe(II)/iPr HCl PMHS 3 equiv 65 THF 3 ml 40 5 20 5 mol % Fe(II)/iPr HCl (EtO) 3 SiH 3 equiv 65 THF 3 ml 50 6 14 20 mol % LiCl (EtO) 3 SiH 3 equiv 120 THF 3 ml 56 7 14 10 mo l % BuLi 37 8 14 5 mol % aome (EtO) 3 SiH 3 equiv 65 THF 3 ml 43 9 14 10 mo l% KOH 57 10 THF 3 ml >95 11 Tol 3 ml 80 14 10 mol % KOtBu (EtO) 3 SiH 3 equiv 65 12 DCM 3 ml 0 13 MeC 3 ml 0 14 PMHS 3 equiv 0 15 TMDS 3 equiv 0 16 Et 3 SiH 3 equiv 0 17 14 5 mol % KOtBu Ph 2 SiH 2 3 equiv 65 THF 3 ml 0 18 (EtO) 2 MeSiH 3 equiv 0 19 (EtO) 3 SiH 3 equiv 43 20 (MeO) 3 SiH 3 equiv 63 21 (EtO) 3 SiH 3 equiv 63 14 5 mo l % KOtBu (99,99 %) 65 THF 3 ml 22 (MeO) 3 SiH 3 equiv 74 23 (MeO) 3 SiH 3 equiv 90 14 5 mo l % KOtBu (99,99 %) 65 THF 2 ml 24 (MeO) 3 SiH 4 equiv >95 25 14 - (MeO) 3 SiH 4 equiv 65 THF 2 ml 0 Substrate scope investigation General procedure for catalytic reduction of tertiary amides to enamines. The tertiary amide (1 mmol) was treated under vacuum in a sealed tube for 15 min. THF (1.75 ml) was added under nitrogen atmosphere followed by the addition of trimethoxysilane (0.51 ml, 4 mmol). The temperature was increased to 65 C and while stirring a solution of KOtBu in THF (0.25 ml, 0.2 M, 5 mol %) was added. The reaction mixture was stirred at 65 C for 14 24 hours, after which the reaction mixture was cooled to r.t. and the excessive pressure was released. Unless otherwise stated aq. aoh (2 M, 10 ml) was added. The resulting mixture was stirred for 6 hours and extracted with Et 2 O (3 x 30 ml). The combined organic layer was dried 4
with a 2 SO 4 and the solvent was removed under reduced pressure. The products were analyzed by 1 H and 13 C-MR and MS, the spectra are presented below. (E)-1-styrylpiperidine Following the general procedure 2-phenyl-1-(piperidin-1- yl)ethanone 1a (0.203 g, 1 mmol) was reacted for 14 h to yield the title compound 2a (0.171 g, 91% yield 1 H-MR (400 MHz, CDCl 3 ): δ = 7.32-7.26 (m, 4H), 7.10-7.07 (m. 1H), 6.75 (d, J = 14.0 Hz, 1H), 5.45 (d, J = 14.0 Hz, 1H), 3.12-3.08 (m, 4H), 1.72-1.62 (m, 6H); 13 C- MR (100 MHz, CDCl 3 ): δ = 140.3, 139.6, 128.5, 123.9, 123.7, 99.5, 49.7, 25.4, 24.4; HRMS (ESI, m/z) calcd. for C 13 H 18 [M + H + ]: 188.1434; found:188.1436. (E)-,-dimethyl-2-phenylethenamine Following the general procedure,-dimethyl-2-phenylacetamide 1b (0.163 g, 1 mmol) was reacted for 14 h to yield the title compound 2b (0.125 g, 85% yield) 1 H-MR (400 MHz, CDCl 3 ): δ = 7.29-7.22 (m, 4H), 7.07-7.02 (m, 1H), 6.80 (d, J = 13.8 Hz, 4H), 5.23 (d, J = 13.8 Hz, 1H), 2.84 (s, 6H); 13 C-MR (100 MHz, CDCl 3 ): δ = 140.2, 139.8, 128.6, 123.7, 123.4, 98.4, 40.7; HRMS (ESI, m/z) calcd. for C 10 H 14 [M + H + ]: 148.1121; found:148.1122. (E)-4-styrylmorpholine Following the general procedure 1-morpholino-2- phenylethanone 1c (0.205 g, 1 mmol) was reacted for 14 h to yield the title compound 2c (0.168 g, 89% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 7.29-7.22 (m, 4H), 7.10-7.06 (m, 1H), 6.64 (d, J = 14.0 Hz, 1H), 5.46 (d, J = 14.0 Hz, 1H), 3.77 (dd, J = 4.9 Hz, 4H), 3.04 (dd, J = 4.9 Hz, 4H); 13 C- MR (100 MHz, CDCl 3 ): δ = 139.7, 138.7, 128.6, 124.5, 124.3, 101.4, 66.4, 49.0; HRMS (ESI, m/z) calcd. for C 12 H 16 O [M + H + ]: 190.1226; found: 190.1230. 5
(E)-8-styryl-1,4-dioxa-8-azaspiro[4.5]decane Following the general procedure 2-phenyl-1-(1,4-dioxa-8- azaspiro[4.5]decan-8-yl)ethanone 1d (0.261 g, 1 mmol) was reacted for 14 h to yield the title compound 2d (0.236 g, 96% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 7.29-7.21 (m, 4H), 7.08-7.03 (m, 1H), 6.69 (d, J = 14,0 Hz, 1H), 5.43 (d, J = 14,0 Hz, 1H), 4.00 (s, 4H), 3.24-3.19 (m, 4H), 1.83-1.78 (m, 4H); 13 C-MR (100 MHz, CDCl 3 ): δ = 139.3, 139.1, 128.6, 124.0, 123.9, 107.2, 100.7, 64.4, 46.9, 34.2; HRMS (ESI, m/z) calcd. for C 15 H 20 O 2 [M + H + ]: 246.1489; found: 246.1494. (E)-1-(4-fluorostyryl)piperidine Following the general procedure 2-(4-fluorophenyl)-1- (piperidin-1-yl)ethanone 1e (0.221 g, 1 mmol) was reacted for 14 h to yield the title compound 2e (0.189 g, 92% yield). 1 H- MR (400 MHz, CDCl 3 ): δ = 7.15-7.10 (m. 2H), 6.94-6.90 (m, 2H), 6.57 (d, J = 14.1 Hz, 1H), 5.34 (d, J = 14.1 Hz, 1H), 3.03-3.00 (m, 4H), 1.67-1.53 (m, 6H); 13 C-MR (100 MHz, CDCl 3 ): δ = 160.2 (d, J = 242.2 Hz), 140.2 (d, J = 1.4 Hz), 135.7 (d, J = 2.9 Hz), 125.0 (d, J = 7.4 Hz), 115.3 (d, J = 21.2 Hz), 98.6, 49.8, 25.4, 24.4; HRMS (ESI, m/z) calcd. for C 13 H 17 F [M + H + ]: 206.1340; found: 206,1344. (E)-1-(4-chlorostyryl)piperidine Following the general procedure 2-(4-chlorophenyl)-1- (piperidin-1-yl)ethanone 1f (0.238 g, 1 mmol) was reacted for 14 h. All volatile components were removed under reduced pressure from the reaction mixture. The mixture was diluted with pentane and filtered through a plug of Et 3 deactivated silica (4 x 3.5 cm) with 80 100 ml of pentane. The solvent was removed under reduced pressure to yield the title compound 2f (0.136 g, 61% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 7.18 7.15 (m, 2H), 7.12 7.09 (m, 2H), 6.65 (d, J = 14.0 Hz), 5.30 (d, J = 14.0 Hz), 3.07 3.03 (m, 4H), 1.65 1.61 (m, 6H); 13 C-MR (100 MHz, CDCl 3 ): δ = 140.8, 138.4, 128.6, 125.0, 98.0, 49.8, 25.5, 24.4; HRMS (ESI, m/z) calcd. for C 13 H 17 Cl [M + H + ]: 222,1044; found: 222.1034. 6
(E)-1-(4-methoxystyryl)piperidine Following the general procedure 2-(4-methoxyphenyl)-1- (piperidin-1-yl)ethanone 1g (0.233 g, 1 mmol) was reacted for 16 h to yield the title compound 2g (0.188 g, 87% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 7.16 7.13 (m, 2H), 6.83 6.79 (m, 2H), 6.34 (d, J = 14.1 Hz, 1H), 5.38 (d, J = 14.1 Hz, 1H), 3.78 (s, 3H), 3.01-2.98 (m, 4), 1.67-1.55 (m, 6H); 13 C-MR (100 MHz, CDCl 3 ): δ = 156.7, 139.3, 132.3, 125.0, 114.1, 99.7, 55.3, 49.8, 25.4, 24.4; HRMS (ESI, m/z) calcd. for C 14 H 22 O [M + H + ]: 218.1539; found:218.1543. (E)-1-(2-(thiophen-2-yl)vinyl)piperidine Following the general procedure 1-(piperidin-1-yl)-2-(thiophen- 2-yl)ethanone 1h (0.209 g, 1 mmol) was reacted for 16 h. All volatile components from the reaction mixture were removed under reduced pressure. The mixture was diluted with pentane and filtered through a plug of Et 3 deactivated silica (4 x 3.5 cm) with 80 100 ml of pentane. The solvent was removed under reduced pressure to yield the title compound 2h (0.126 g, 65% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 6.89 6.87 (m, 2H), 6.67 6.65 (m, 1H), 6.59 (d, J = 13.9 Hz, 1H), 5.56 (d, J = 13.9 Hz), 3.01 3.00 (m, 4H), 1.63 1.60 (m, 6H); 13 C-MR (100 MHz, CDCl 3 ): δ = 144.8, 140.7, 127.4, 119.7, 119.0, 93.7, 49.7, 25.4, 24.4; HRMS (ESI, m/z) calcd. for C 11 H 16 S [M + H + ]: 194.0998; found: 194.1001. (E)-1-(2-(phenylthio)vinyl)piperidine Following the general procedure 2-(phenylthio)-1-(piperidin- 1-yl)ethanone 1i (0.235 g, 1 mmol) was reacted for 14 h to yield the title compound 2i (0.208 g, 95% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 7.37-7.27 (m, 4H), 7.15-7.10 (m, 1H), 6.60 (d, J = 12.9 Hz, 1H), 4.85 (d, J = 12.9 Hz, 1H), 3.13-3.06 (m, 4H), 1.69-1.62 (m, 6H); 13 C-MR (100 MHz, CDCl 3 ): δ = 151.7, 142.0, 128.6, 125.3, 124.4, 81.1, 49.5, 25.3, 24.3; HRMS (ESI, m/z) calcd. for C 13 H 18 S [M + H + ]: 220.1154; found: 220.1150. 7
1-((1E,3E)-hexa-1,3-dienyl)piperidine Following the general procedure (E)-1-(piperidin-1-yl)hex-3- en-1-one 1j (0.181 g, 1 mmol) was reacted for 24 h. All volatile components from the reaction mixture were removed under reduced pressure. The mixture was diluted with pentane and filtered through a plug of Et 3 deactivated silica (4 x 3.5 cm) with 80 v 100 ml of pentane. The solvent was removed under reduced pressure to yield the title compound 2j (0.142 g, 86% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 6.05 (d, J = 13.5 Hz, 1H), 5.94 (dd, J = 10.3, 15.1 Hz, 1H), 5.34 (dt, J = 6.8, 15.1 Hz, 1H), 5.14 (dd, J = 10.2, 13.5 Hz, 1H), 2.88 2.85 (m, 4H), 2.04 (qd, 6.8, 7.5 Hz, 2H), 1.59 1.48 (m, 6H), 0.98 (t, 7.4 Hz, 3H); 13 C-MR (100 MHz, CDCl 3 ): δ = 142.0, 128.8, 126.2, 101.2, 49.8, 25.9, 25.4, 24.4, 14.4; HRMS (ESI, m/z) calcd. for C 11 H 20 [M + H + ]: 166.1590; found: 166.1584. (E)--butyl--styrylbutan-1-amine Following the general procedure,-dibutyl-2- phenylacetamide 1k (0.247 g, 1 mmol) was reacted for 24 h. All volatile components from the reaction mixture were removed under reduced pressure. The mixture was diluted with pentane and filtered through a plug of Et 3 deactivated silica (4 x 3.5 cm) with 80 100 ml of pentane. The solvent was removed under reduced pressure to yield the title compound 2k (0.185 g, 80% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 7.22 7.14 (m, 4H), 6.97 6.92 (m, 1H), 6.78 (d, J = 13.8 Hz, 1H), 5.12 (d, J = 13.9 Hz, 1H), 3.12 3.07 (m, 4H), 1.61 1.52 (m, 4H), 1.41 1.30 (m, 4H), 0.99 0.94 (m, 3H); 13 C-MR (100 MHz, CDCl 3 ): δ = 140.5, 138.7, 128.6, 123.2, 122.7, 95.5, 51.6, 30.2, 20.4, 14.1; HRMS (ESI, m/z) calcd. for C 16 H 26 [M + H + ]: 232.2060; found: 232.2068. 2,2-diphenyl-1,3-di(piperidin-1-yl)propan-1-one and diphenylmethane 2,2-diphenyl-1-(piperidin-1-yl)ethanone (0.279 g, 1 mmol) was treated under vacuum in a sealed tube for 15 min. THF (1.75 ml) was added under nitrogen atmosphere followed by the addition of triethoxysilane (0.74 ml, 4 mmol). The temperature was increased to 65 C and while stirring a solution of KOtBu in THF (0.25 ml, 0.2 M, 5 mol %) was added. The reaction mixture was stirred at 65 C for 24 hours, after which the reaction mixture was cooled to rt. and the excessive pressure was released. 8
Aq. aoh (2 M, 10 ml) was added. The resulting mixture was stirred for 6 hours and extracted with DCM (3 x 30 ml). The combined organic layer was dried with aso 4 and the solvent was removed under reduced pressure. The crude mixture was purified with column chromatography on SiO 2 eluted using gradient from pure pentane to pure ethyl acetate to yield title compounds. The products were analyzed by 1 H and 13 C MR and MS, the spectra are presented below. 2,2-diphenyl-1,3-di(piperidin-1-yl)propan-1-one: 0.155 g, 82% yield. 1 H-MR (500MHz, 268K, CDCl 3 ): δ = 7.72 7.66 (m, 4H), 7.39 7.33 (m, 4H), 7.30 7.25 (m, 2H), 3.63 (bs, 2H), 3.19 (s, 2H), 2.79 (bs, 2H), 1.95 (bs, 4H), 1.40 (bs, 2H), 1.33 (bs, 2H), 1.21 (bs, 6H), 0.41 (bs, 2H); 13 C-MR (125MHz, 268K CDCl 3 ): δ = 173.0, 139.8, 129.1, 127.7, 126.4, 71.2, 60.2, 56.4, 48.1, 43.6, 26,4. 25.4, 24.3, 24.1, 23.9; HRMS (ESI, m/z) calcd. for C 25 H 33 2 O [M + H + ]: 377.2587; found: 377.2589. diphenylmethane: 0.131 g, 78% yield. 1 H-MR (400 MHz, CDCl 3 ): δ = 7.35 7.31 (m, 4H), 7.26 7.22 (m, 6H), 4.03 (s, 2H); 13 C-MR (100 MHz, CDCl 3 ): δ = 141.3, 129.0, 128.6, 126.2. 42.1. 2,3-diphenylpropanal Following the general procedure 2-phenyl-1-(piperidin-1- yl)ethanone was reduced to corresponding enamine 2a. The reaction mixture was diluted with 5 ml of aoh (2 M), stirred for 12 h and extracted with DCM (3x15 ml). Organic phase was dried over a 2 SO 4 and the solvent was removed under reduced pressure resulting in yellow oil. The oil without purification was dissolved in MeC (10 ml), benzyl bromide (0.142 ml, 1.2 mmol) was added to the solution and heated to 85 C for 12 h. The reaction mixture was cooled down to room temperature and solution of HCl (1 M, 10 ml) was added and stirred for 1 h. The reaction mixture was extracted with DCM (3 x 15 ml), dried over a 2 SO 4 and the solvent was removed under reduced pressure resulting in an oil. The crude mixture was purified with column chromatography on SiO 2 eluted with toluene to yield title compound 4 as colorless oil (0.162 g, 77% yield). 1 H-MR (400 MHz, CDCl 3 ): δ = 9.76 (d, J = 1,6 Hz, 1H), 7.8 7.3 (m, 3H), 7.25 7.14 (m, 5H), 7.09 7.07 (m, 2H), 3.86 (ddd, J = 1,6, 6.8, 8.0 Hz, 1H), 3.50 (dd, J = 6.8, 14.0 Hz, 1H), 9
3.00 (dd, J = 8.0, 14.0 Hz, 1H); 13 C-MR (100 MHz, CDCl 3 ): δ = 200.0, 138.9, 135.9, 129.2, 129.1, 128.5, 127.8, 126.4, 61.1, 36.3. 2-(dibenzylamino)ethanol,-dibenzylacetamide (0.239 g, 1 mmol) was treated under vacuum in a sealed tube for 15 min. THF (1.75 ml) was added under nitrogen atmosphere followed by the addition of trimethoxysilane (0.51 ml, 4 mmol). The temperature was increased to 65 C and while stirring a solution of KOtBu in THF (0.25 ml, 0.2 M, 5 mol %) was added. The reaction mixture was stirred at 65 C for 16 hours, after which the reaction mixture was cooled to r.t. and the excessive pressure was released. All volatile components were removed under reduced pressure resulting in oil. THF (3 ml) was added and the reaction mixture was cooled down to 0 C. BH 3 THF complex (1 ml of a 1 M solution in THF, 1 mmol) was added drop wise and the reaction was stirred for 12 h. Ethanol (0.5 ml) was added followed by aoh (1 ml, 3 M) and hydrogen peroxide (1 ml, 30% in water). The mixture was stirred at r.t. for 12 h. Saturated solution of a 2 SO 3 was added untill all remaining hydrogen peroxide was quenched. The reaction mixture was extracted with ethyl acetate (3 x 15 ml), dried over a 2 SO 4 and the solvent was removed under reduced pressure resulting in an oil. The crude mixture was purified with column chromatography on SiO 2 eluted with pentane ethyl acetate 10:1 to yield title compound 5 as colorless oil (0.181 g, 75% yield) 1 H-MR (400 MHz, CDCl 3 ): δ = 7.40 7.38 (m, 8H), 7.34 7.30 (m, 2H), 3.68 (s, 4H), 3.65 3.62 (m, 2H), 2.80 2.65 (m, 3H); 13 C-MR (100 MHz, CDCl 3 ): δ = 138.8, 129.0, 128.4, 127.2, 58.7, 58.2, 54.8; HRMS (ESI, m/z) calcd. for C 16 H 20 O [M + H + ]: 242.1539; found: 242.1534 10
Additionally evaluated substrates not isolated These amides were successfully converted to enamines, however proved difficult to isolate. Yields were determined with MR using internal standard. Procedure for determining MR yield Following the general procedure for the reduction of the amides to enamines 1,3,5- trimethoxybenzene (0.0168 g, 0.1 mmol) was added to the reaction as internal standard. After the reaction an aliquot was taken (0.1 ml), (0.4 ml) was added, and the yield was determined by 1 H-MR. MR yield was determine according to integration of characteristic signal of internal standart (1,3,5- trimethoxybenzene, δ = 5.8 ppm, s, 3H) and characteristic signals of enamines protons at the double bond, which are situated in the same region. 1-(2-phenoxyvinyl)piperidine Following the procedure for determining MR yield 2- phenoxy-1-(piperidin-1-yl)ethanone (0.219 g, 1 mmol) was reacted for 14 h. According to the 1 H-MR the yield of the title compound is 76% (a 9:1 mixture of E and Z products). (E)-3-(2-(piperidin-1-yl)vinyl)pyridine Following the procedure for determining MR yield 1- (piperidin-1-yl)-2-(pyridin-3-yl)ethanone (0.204 g, 1 mmol) was reacted for 18 h. According to the 1 H-MR the yield of the title compound is 90%. (E)-1-(2-cyclohexylvinyl)piperidine Following the procedure for determining MR yield 2- cyclohexyl-1-(piperidin-1-yl)ethanone (0.209 g, 1 mmol) was reacted for 14 h. According to the 1 H-MR the yield of the title compound is 80%. 11
(E)-1-(pent-1-enyl)piperidine Following the procedure for determining MR yield 1- (piperidin-1-yl)pentan-1-one (0.169 g, 1 mmol) was reacted for 14 h. According to the 1 H-MR the yield of the title compound is 45%. 1-vinylpiperidine Following the procedure for determining MR yield 1-(piperidin-1- yl)ethanone (0.127 g, 1 mmol) was reacted for 14 h. According to the 1 H-MR the yield of the title compound is 86%. 12
Spectroscopic data. 13
7.318 7.303 7.297 7.287 7.281 7.265 7.109 7.103 7.093 7.087 7.082 7.080 7.072 6.761 6.726 5.471 5.436 3.112 3.099 3.085 1.714 1.701 1.694 1.687 1.673 400 MHz 2a 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 4.20 0.99 1.00 1.00 4.08 6.35
140.34 139.60 128.50 123.89 123.70 99.48 49.72 25.37 24.37 100 MHz 2a 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
7.281 7.276 7.265 7.260 7.258 7.244 7.239 7.224 7.059 7.054 7.043 7.038 7.021 6.828 6.793 5.250 5.215 2.835 400 MHz 2b 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 4.22 0.97 1.00 0.99 6.16
140.23 139.77 128.59 123.70 123.43 98.41 40.74 100 MHz 2b 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 3.024 3.037 3.040 3.049 3.762 3.775 3.787 5.445 5.480 6.618 6.653 7.054 7.059 7.065 7.076 7.081 7.087 7.092 7.097 7.221 7.237 7.243 7.260 7.265 7.280 4.02 4.07 1.00 1.00 0.96 4.27 400 MHz O 2c
O 139.71 138.73 128.61 124.45 124.28 101.44 66.43 49.00 100 MHz 2c 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
7.285 7.276 7.271 7.260 7.255 7.238 7.233 7.217 7.077 7.072 7.066 7.060 7.055 7.051 7.044 7.039 7.034 6.715 6.679 5.449 5.413 4.005 3.234 3.220 3.205 1.823 1.808 1.793 400 MHz O O 2d 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 4.40 1.03 1.00 1.00 3.92 4.03 4.06
O O 139.27 139.10 128.55 124.01 123.99 107.21 100.71 64.39 46.89 34.18 100 MHz 2d 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
7.145 7.133 7.132 7.124 7.123 7.110 7.109 7.103 7.101 6.935 6.929 6.918 6.913 6.907 6.896 6.890 6.581 6.546 5.355 5.320 3.023 3.010 2.995 1.655 1.641 1.628 1.614 1.600 1.584 1.580 1.563 1.551 1.545 1.538 400 MHz F 2e 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 2.03 2.00 1.00 1.00 4.04 6.61
161.42 159.02 140.25 140.24 135.72 135.69 125.06 124.99 115.38 115.17 98.58 49.79 25.42 24.39 100 MHz F 2e 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
7.180 7.158 7.115 7.094 6.671 6.636 5.322 5.287 3.065 3.052 3.038 1.642 1.639 1.632 1.629 1.627 1.623 1.615 400 MHz Cl 2f 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 2.03 2.00 1.03 1.02 4.18 6.52
140.77 138.35 128.63 124.96 98.04 49.79 25.47 24.43 100 MHz Cl 2f 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 1.552 1.571 1.581 1.584 1.592 1.595 1.625 1.639 1.652 1.666 2.980 2.994 3.007 3.783 5.362 5.398 6.521 6.556 6.792 6.799 6.805 6.816 6.821 6.829 7.135 7.136 7.140 7.141 7.152 7.152 7.157 6.64 4.00 2.92 1.00 1.00 2.00 2.25 400 Mhz O 2g
156.71 139.25 132.27 124.99 114.10 99.69 55.31 49.84 25.40 24.38 100 MHz O 2g 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
S 2h 6.882 6.873 6.665 6.663 6.661 6.657 6.655 6.654 6.610 6.575 5.574 5.539 3.013 2.999 1.628 1.615 1.604 1.601 400 MHz 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 2.04 0.98 1.01 1.00 4.04 6.36
144.83 140.69 127.38 119.69 118.92 93.72 49.70 25.41 24.39 100 MHz S 2h 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
S 2i 7.360 7.356 7.344 7.341 7.339 7.336 7.318 7.300 7.296 7.279 7.147 7.129 6.619 6.586 4.863 4.831 3.106 3.100 3.086 1.658 1.647 1.643 1.639 400 MHz 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 4.26 1.01 1.00 1.00 4.06 6.37
S 2i 151.73 142.01 128.58 125.26 124.39 81.12 49.48 25.25 24.27 100 MHz 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
400 MHz 6.063 6.029 5.974 5.948 5.936 5.910 5.372 5.356 5.339 5.335 5.318 5.301 5.172 5.146 5.138 5.112 2.878 2.865 2.850 2.079 2.061 2.042 2.022 2.003 1.585 1.560 1.546 1.531 1.506 1.498 0.989 0.970 0.952 2j 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 1.02 1.00 0.99 1.01 3.99 2.09 6.81 3.07
2j 141.98 128.84 126.24 101.20 49.75 25.94 25.36 24.42 14.42 100 MHz 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 ppm 0.951 0.969 0.987 1.312 1.330 1.349 1.368 1.387 1.405 1.526 1.545 1.547 1.563 1.583 1.601 3.075 3.094 3.112 5.104 5.139 6.760 6.795 6.926 6.943 6.961 7.147 7.163 7.179 7.196 7.217 6.35 4.54 4.18 4.09 0.98 1.00 0.97 4.09 400 MHz 2k
100 MHz 140.52 138.66 128.60 123.17 122.72 95.47 51.58 30.23 20.38 14.08 2k 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
500 MHz 268K 7.695 7.680 7.377 7.362 7.346 7.288 7.276 7.261 O 3.628 3.189 2.787 1.950 1.407 1.330 1.321 1.259 1.212 0.410 3 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 4.03 4.00 2.64 1.99 2.03 2.06 4.15 2.04 2.29 6.01 2.08
172.99 139.76 129.13 127.70 126.39 O 71.18 60.22 56.37 48.13 43.58 26.36 25.36 24.31 24.10 23.87 125 MHz 268K 3 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
7.349 7.347 7.328 7.310 7.309 7.255 7.247 7.245 7.243 7.242 7.224 7.223 4.030 400 MHz 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm 4.00 6.00 2.04
141.25 129.07 128.59 126.20 42.08 100 MHz 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
9.766 9.762 7.379 7.375 7.359 7.358 7.340 7.318 7.301 7.247 7.229 7.211 7.191 7.163 7.146 7.087 7.083 7.067 3.875 3.872 3.855 3.839 3.835 3.520 3.503 3.485 3.468 3.020 3.001 2.985 2.966 O 400 MHz 4 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ppm 0.95 3.07 5.03 2.00 1.01 1.03 1.03
199.98 O 138.93 135.86 129.16 129.15 128.46 127.81 126.43 61.06 36.28 100 MHz 4 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm
7.397 7.396 7.385 7.338 7.329 7.327 7.316 7.309 7.304 3.684 3.649 3.635 3.621 2.727 2.713 2.700 400 MHz HO 5 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 ppm 8.00 2.08 4.07 2.05 3.04
138.82 128.95 128.40 127.19 58.65 58.21 54.80 100 MHz HO 5 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 ppm