SUPPLEMENTARY MATERIALS Differentiation of Diastereoisomers of Protected 1,2-Diaminoalkylphosphonic Acids by EI Mass Spectrometry and Density Functional Theory Ewelina Drabik, 1 Grzegorz Krasiński, 2 Marek Cypryk, 2 Roman Błaszczyk, 3 Tadeusz Gajda, 3 Marek Sochacki 1 1 Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Laboratory for Analysis of Organic Compounds and Polymers, Sienkiewicza 112, 90-363 Łódź, Poland 2 Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Computer Modeling, Sienkiewicza 112, 90-363 Łódź, Poland 3 Lodz University of Technology, Institute of Organic Chemistry, Żeromskiego 116, 90-924 Łódź, Poland Table of contents The procedure for synthesis of compounds 7_a and 8_a...2 Diethyl dideuteriohydroxymethylphosphonate [1] (1)...2 Diethyl azidodideuteriomethylphosphonate [2] (2)...3 Diethyl dideuterioisothiocyanatomethylphosphonate [3] (3)...4 Diethyl trans- and cis-(4-deuterio-5-phenyl-2-thioxoimidazolidin-4-yl)phosphonates [4] (cis- 7_a and trans-8_a)...4 References...5 Mass spectra...6 Theoretical calculations...8 1
The procedure for synthesis of compounds 7_a and 8_a Diethyl dideuteriohydroxymethylphosphonate [1] (1), diethyl azidodideuteriomethylphosphonate [2] (2), diethyl dideuterioisothiocyanatomethylphosphonate [3] (3), diethyl trans- and cis-(4-deuterio-5- phenyl-2-thioxoimidazolidin-4-yl)phosphonates [4] (4) were prepared according to the procedures described in the literature. N-tert-Butyl-benzylidenecarbamate [5] (N-Boc-imine) was prepared as described previously. Diastereoisomeric mixture of compound 7_a and 8_a was resolved into individual cis- and trans-diastereoisomers using preparative TLC (Analtech UV254 plates were used). The homogeneity of the samples was confirmed by TLC analysis and 31 P and 1 H NMR spectroscopy. Scheme S1. Synthesis of diethyl trans- and cis-(4-deuterio-5-phenyl-2-thioxoimidazolidin-4- yl)phosphonates (7_a and 8_a). Diethyl dideuteriohydroxymethylphosphonate [1] (1) A mixture of paraformaldehyde-d 2 (1.0 g, 31.2 mmol), diethyl phosphonate (3.9 g, 28.3 mmol) and triethylamine (1.44 g, 14.2 mmol) was slowly heated to 60 o C for 30 minutes. Next, the suspension was heated for 1.5 h at 75-85 o C until all paraformaldehyde was dissolved. Excess of triethylamine was evaporated under reduced pressure, and the oily residue was subjected to bulb 2
to bulb distillation (130 140 o C/0.3 Torr) to give pure diethyl dideuteriohydroxymethylphosphonate (1) (2.88 g, 59.8%) as a pale yellow oil. 31 P NMR (101 MHz, CDCl 3, δ): 24.8 1 H NMR (250 MHz, CDCl 3, δ): 1.33 (brt, 3 J HH 7.1 Hz, 6H, 2CH 3 CH 2 O), 4.09-4.21 (m, 4H, 2CH 3 CH 2 O), 4.35 (brs, 1H, OH) 13 C NMR (63 MHz, CDCl 3, δ): 14.5 (d, 3 J CP 5.6 Hz, 2CH 3 CH 2 O), X (dqu, 1 J CP Hz, 1 J CD Hz, CD 2 ), 60.6 (d, 2 J CP 6.8 Hz, 2CH 3 CH 2 O) IR (ATR, ν): 3311, 2908, 1229, 1017, 967 HRMS (EI, 70 ev): m/z calcd for C 5 H 11 D 1 P 1 O 4 : 170.0677; found: 170.0680. Diethyl azidodideuteriomethylphosphonate [2] (2) A solution of DEAD (1.89 g, 10.8 mmol) in anhydrous CH 2 Cl 2 (3 ml) was added dropwise with stirring and external cooling (dry ice/acetone bath) to a solution of Ph 3 P (2.84 g, 10.8 mmol) in CH 2 Cl 2 (25 ml) at 5 o C. The mixture was cooled to 10 o C and 1.0 M solution of HN 3 in toluene (11.25 ml, 11.25 mmol) was added dropwise at this temperature. The solution of diethyl dideuteriohydroxymethylphosphonate (1) (8.0 mmol) was then added and stirring was continued for 24 hours at room temperature. The mixture was cooled to 0 o C, partialy precipitated ethyl 3- (ethoxycarbonyl)carbazate was filtered off, the filtrate was evaporated under reduced pressure, and the semi-solid residue was extracted with hexane (4 50 ml). The combined extracts were evaporated under reduced pressure to give crude azide 2. The oily residue was next subjected to bulb to bulb distillation (75 90 o C/0.2 Torr) to give pure diethyl azidodideuteriomethylphosphonate (2) (1.4 g, 89.7%) as a pale yellow oil. Warning: Since hydrazoic acid (HN 3 ) is highly toxic azidation reaction should be carried out under the well ventilated hood and behind the protective screen. 31 P NMR (101 MHz, CDCl 3, δ): 20.5 1 H NMR (250 MHz, CDCl 3, δ): 1.33 (brt, 3 J HH 7.1 Hz, 6H, 2CH 3 CH 2 O), 4.20 (dq, 3 J HH 7.1 Hz, 3 J HP 8.2 Hz, 4H, 2CH 3 CH 2 O) 13 C NMR (63 MHz, CDCl 3, δ): 14.6 (d, 3 J CP 5.7 Hz, 2CH 3 CH 2 O), X (dqu, 1 J CP Hz, 1 J CD Hz, CD 2 ), 61.1 (d, 2 J CP 6.6 Hz, 2CH 3 CH 2 O), IR (ATR, ν): 2921, 2124, 2095, 1241, 1018, 968 HRMS (EI, 70 ev): m/z calcd for C 5 H 10 D 2 P 1 N 3 O 3 : 195.0742; found: 195.0743. 3
Diethyl dideuterioisothiocyanatomethylphosphonate [3] (3) Ph 3 P (1.76 g, 6.71 mmol, 1.05 equiv) was added in one portion with stirring and external cooling (ice bath) to a solution of diethyl azidodideuteriomethylphosphonate (2) (1.25 g, 6.41 mmol) in anhydrous toluene (20 ml). Stirring was continued for 3 h at room temperature, and CS 2 (3.91 g, 3.1 ml, 51.0 mmol) was then added in one portion. Next, the mixture was kept at room temperature for 2 days. Toluene and excess of CS 2 was evaporated under reduced pressure, and the semi-crystalline residue was extracted with hexane (4 40 ml) to remove most of Ph 3 PS. The combined extracts were evaporated under reduced pressure, and the oily residue was subjected to bulb to bulb distillation (100 120 o C /0.2-0.4 Torr) to give pure diethyl dideuterioisothiocyanatomethylphosphonate (3) (0.95 g, 70.2%) as a colorless oil [R f (AcOEt/Hexanes 3:1 v/v) 0.45]. 31 P NMR (101 MHz, CDCl 3, δ): 16.3 1 H NMR (250 MHz, CDCl 3, δ): 1.38 (brt, 3 J HH 7.1 Hz, 6H, 2CH 3 CH 2 O), 4.17-4.29 (m, 4H, 2CH 3 CH 2 O) 13 C NMR (63 MHz, CDCl 3, δ): 16.3 (d, 3 J CP 5.7 Hz, 2CH 3 CH 2 O), 39.8 (dqu, 1 J CP 152.8 Hz, 1 J CD 21.8 Hz, CD 2 ), 61.1 (d, 2 J CP 6.6 Hz, 2CH 3 CH 2 O), 135.3 (brs, NCS). IR (ATR, ν): 2982, 2074, 1253, 1052,1012, 971 HRMS (EI, 70 ev): m/z calcd for C 6 H 10 D 2 P 1 N 1 O 3 S 1 : 211.0401; found: 211.0402. Diethyl trans- and cis-(4-deuterio-5-phenyl-2-thioxoimidazolidin-4-yl)phosphonates [4] (cis- 7_a and trans-8_a) A solution of NaHMDS (0.5 M, 0.6 ml, 1.2 mmol) in THF (15 ml) was cooled to 75 o C. Next a solution of diethyl dideuterioisothiocyanatomethylphosphonate (3) (0.211 g, 1.0 mmol) and N- tert-butyl-benzylidenecarbamate (N-Boc-imine) (0.205 g, 1.0 mmol) in THF (3 ml) was added dropwise to the reaction mixture. The mixture was stirred for 3 h at 75 o C and then quenched with D 2 O (1.5 ml). The mixture was stirred for 30 min at 0 o C. A saturated aq solution of NH 4 Cl (3 ml) was added and the mixture was diluted with methylene chloride (60 ml). Organic layer was separated and was washed successively with saturated aq NH 4 Cl (2 ml), water (2 ml), then dried (MgSO 4 ) and concentrated under reduced pressure to give 0.369 g (88.8%) of crude imidazolidine-2-thiones 4. Analytically pure trans- and cis-isomers of 4 were isolated after preparative TLC (AcOEt/hexanes 5:1 v/v). 4
cis-7_a. Yield: 63 mg (15%), colorless solid, mp 154-156 o C; R f (AcOEt/hexanes 5:1 v/v) 0.23 31 P NMR (101 MHz, CDCl 3, δ): 15.4 1 H NMR (250 MHz, CDCl 3, δ): 1.03 (t, 3 J HH 7.1 Hz, 3H, CH 3 CH 2 O), 1.18 1.28 (m, 12H, C(CH 3 ) 3 + CH 3 CH 2 O), 3.18 3.29 (m, 1H, CH 3 CH 2 O), 3.55 3.63 (m, 1H, CH 3 CH 2 O), 3.88 4.00 (m, 2H, CH 3 CH 2 O), 6.83 (brs, 1H, NH), 7.20 7.40 (m, 5H ar ); 13 C NMR (63 MHz, CDCl 3, δ): 16.2, 16.3 (2d, 3 J CP 5.8 Hz, 2CH 3 CH 2 O), 27.6 (s, C(CH 3 ) 3 ), 55.0 (dt, 3 J CP 169.5 Hz, 3 J CD 21.0 Hz, CDP), 62.8(d, 2 J CP 6.4 Hz, 2CH 3 CH 2 O), 64.2 (s, CHP), 83.7 (s, C(CH 3 ) 3 ), 128.3, 128.8 (CH ar ), 136.4 (d, 3 J CP 6.0 Hz, CHC ar ), 149.0 (s, C=O), 181.5 (d, 3 J CP 9.8 Hz,, C=S). IR (ATR, ν): 3164, 2977, 1744, 11496, 1250, 1139, 1012, 960. HRMS (EI, 70 ev): m/z calcd for C 18 H 26 D 1 P 1 N 2 O 6 S 1 : 415.1441; found: 415.1446. trans-8_a. Yield: 108 mg (26%), colorless viscous oil; R f (AcOEt/hexanes 5:1 v/v) 0.33 31 P NMR (101 MHz, CDCl 3, δ): 17.7 1 H NMR (250 MHz, CDCl 3, δ): 1.28 (s, 9H, C(CH 3 ) 3 ), 1.35, 1.36 (2t, 3 J HH 7.1 Hz, 6H, 2CH 3 CH 2 O), 4.15 4.34 (m, 4H, 2CH 3 CH 2 O), 5.54 (d, 3 J HP 19.6 Hz, 1H, CHCHP), 7.24 7.38 (m, 5H ar ), 7.75 (brs, 1H, NH). 13 C NMR (63 MHz, CDCl 3, δ): 16.5, 16.6 (2d, 3 J CP 5.4 Hz, 2CH 3 CH 2 O), 27.7 (s, C(CH 3 ) 3 ), 57.5 (dt, 3 J CP 159.4 Hz, 1 J CD 21.0 Hz CDP), 63.6 (d, 2 J CP 7.0 Hz, CH 3 CH 2 O), 63.9 (s, CHPh), 64.3 (d, 2 J CP 76.3 Hz, CH 3 CH 2 O), 83.6 (s, C(CH 3 ) 3 ), 125.3, 128.6, 129.1 (CH ar ), 140.5 (d, 3 J CP 12.6 Hz, CHC ar ), 149.4 (brs, C=O), 180.4 (brs, C=S). IR (ATR, ν): 3158, 2979, 1751, 1711, 1492, 1227, 1134, 1012, 972. HRMS (EI, 70 ev): m/z calcd for C 18 H 26 D 1 P 1 N 2 O 5 S 1 : 415.1441; found: 415.1437. References 1. Baraldi, P.G., Guarneri, M., Moroder, F., Pollini, G.P., Simoni, D.: Synthesis of 1- Phthalimidoalkanephosphonates. Synthesis 653-654 (1982) 2. Gajda, T., Matusiak, M.: An Expedient Synthesis of Diethyl 1-Azidoalkylphosphonates via the Mitsunobu Reaction. Synthesis 367-368 (1992). 3. Sikora, D., Gajda, T.: A Facile Synthesis of Diethyl 1-(Isothiocyano)alkylphosphonates. Phosphorus, Sulfur and Silicon 157, 201-201 (2000). 4. Błaszczyk, R., Gajda, T.: Direct synthesis of protected diethyl 1,2- diaminoalkylphosphonates. Tetrahedron Lett. 48, 5859-5863 (2007) 5. Cowen, B.J., Saunders, L.B., Miller, S.J.: Pyridylalanine (Pal)-Peptide Catalyzed Enantioselective Allenoate Additions to N-Acyl Imines. J. Am. Chem. Soc. 131, 6105-6107 (2009) 5
Mass spectra Figure S1. EI mass spectra of a) cis-1, b) trans-2, c) cis-3, d) trans-4, e) cis-5, f) trans-6, g) cis-7 and h) trans-8. 6
Figure S2. Product ion mass spectra of molecular ion of compounds a) cis-1, b) trans-2, c) cis-3 and d) trans-4. 7
Theoretical calculations To confirm the stability of each diastereoisomer the conformer analysis of molecular ion of cis-1 and trans-2 was performed. SUB_cis_1 SUB_cis_1 SUB_cis_1 SUB_cis_1 Figure S3. Different conformations of molecular ion of cis-1 (SUB_cis) isomer. 8
SUB_trans_2 SUB_trans_2 SUB_trans_2 SUB_trans_2 Figure S4. Different conformations of molecular ion of trans-2 (SUB_trans) isomer. 9
Table S1. Comparison of the B3LYP and M06-2x functionals. cis trans structure B3LYP/ M06-2x/ 6-311+G(2d,p) 6-311+G(2d,p) SUB_cis_1 0.0 0.0 TS1_E_H c _1 45.9 49.6 INT_E_H c _1-4.7-1.4 TS2_E_H c _1-1.4 4.8 IC_E_H c _1-19.6-11.3 SUB_trans_2 0.0 0.0 TS1_E_H c _2 19.4 23.3 INT_E_H c _2 0.3 2.6 TS2_E_H c _2 5.8 10.8 IC_E_H c _2-12.5-3.6 Table S2. Thermodynamic properties of the cis-1 and trans-2 conformers. As a reference for the G relative (B3LYP/6-311+G(2d,p)//B3LYP/6-31G*) the G of most stable conformer was used. E electron 1 G absolut 1 G relative 2 SUB_cis_1-1581.66650-1581.41046 0.00 SUB_cis_1-1581.66739-1581.40503 3.40 SUB_cis_1-1581.66082-1581.39841 7.56 SUB_cis_1-1581.66459-1581.40410 3.99 SUB_trans_2-1581.67464-1581.41983 0.00 SUB_trans_2-1581.67498-1581.41346 4.00 SUB_trans_2-1581.67476-1581.41377 3.81 SUB_trans_2-1581.66608-1581.40509 9.25 1 Ha 2 kcal/mol Table S3. Electron spin density of SUB_cis_1 and SUB_trans_1 structures. SUB_cis_1 SUB_trans_1 Mulliken NPA Mulliken NPA N 1 0.062 0.050 0.060 0.050 C 2-0.074-0.030-0.075-0.034 N 3 0.021 0.011 0.018 0.018 C 4 0.004 0.006-0.006 0.007 C 5-0.018-0.002-0.015-0.002 S 6 0.881 0.839 0.905 0.853 P 7-0.001-0.001 0.005 0.003 O 8 0.000 0.000 0.003 0.003 O 9-0.001 0.000 0.002 0.001 O 10 0.001 0.000 0.002 0.002 10
Table S4. Comparison of the optimized bond lengths [Å] between the ground state and cationic radical form for cis-1 and trans-2. cis-1 trans-2 Bond Neutral Free radical Difference Neutral Free radical Difference C 2 -S 6 1.669 1.719 0.050 1.669 1.723 0.054 N 3 -C 2 1.371 1.339-0.032 1.369 1.332-0.037 N 1 -C 2 1.370 1.339-0.031 1.364 1.335-0.029 C 4 -N 3 1.466 1.477 0.011 1.459 1.471 0.012 C 5 -N 1 1.464 1.483 0.019 1.463 1.495 0.032 C 4 -C 5 1.564 1.569 0.005 1.567 1.567 0.000 C 4 -P 7 1.853 1.858 0.005 1.847 1.861 0.014 Table S5. NPA spin densities for main atoms in function of reaction coordinate for loss of the diethoxyphosphoryl radical, phenyl ring, H c and H d. a) cis isomer substrate transition states SUB_cis-1 TS_L_PO_1 TS_L_Ph_1 TS_L_H c _1 TS_L_H d _1 N 1 0.050-0.002 0.079 0.101-0.006 C 2-0.030-0.019-0.013-0.018-0.022 N 3 0.011 0.107 0.005-0.006 0.126 C 4 0.006 0.096 0.003 0.014-0.028 C 5-0.002-0.001 0.029-0.041 0.010 S 6 0.839 0.052 0.025 0.047 0.055 P 7-0.001 0.414 0.001 0.001 0.001 O 8 0.000 0.158 0.003 0.008 0.003 O 9 0.000 0.085 0.001 0.001 0.021 O 10 0.000 0.071 0.007 0.003 0.007 H a 0.000-0.003 0.000 0.000-0.003 H b -0.002 0.000-0.002-0.003 0.000 H c 0.004 0.005 0.004 0.773-0.002 H d 0.003 0.003 0.004-0.001 0.828 C Ph 0.048 0.006 0.805 0.029 0.004 11
b) trans isomer substrate transition states SUB_trans-2 TS_L_PO_2 TS_L_Ph_2 TS_L_H c _2 TS_L_H d _2 N 1 0.050-0.001 0.084 0.090-0.011 C 2-0.034-0.018-0.023-0.016-0.054 N 3 0.018 0.108 0.015-0.004 0.195 C 4 0.007 0.079 0.001 0.006 0.206 C 5-0.002 0.003 0.026-0.019-0.006 S 6 0.853 0.048 0.020 0.039 0.199 P 7 0.003 0.431-0.003 0.000 0.009 O 8 0.003 0.186 0.009 0.005 0.005 O 9 0.001 0.040 0.005 0.000 0.003 O 10 0.002 0.078 0.014 0.028 0.020 H a 0.000-0.002 0.000 0.000-0.005 H b -0.002 0.000-0.003-0.002 0.000 H c 0.000 0.001 0.005 0.773 0.009 H d 0.000 0.004 0.009 0.000 0.054 C Ph 0.036 0.007 0.769 0.011 0.149 Table S6. NPA spin densities for main atoms in function of reaction coordinate for elimination of DEPI for exemplary reaction pathways (a) and (c). a) pathway (a) for cis isomer SUB_cis-1 TS1_E_H a _1 INT_E_H a _1 TS2_E_H a _1 IC_E_H a _1 N 1 0.050-0.008-0.022-0.025 0.000 C 2-0.030-0.043-0.068-0.061 0.000 N 3 0.011 0.118 0.217 0.138 0.003 C 4 0.006 0.001-0.007-0.082 0.000 C 5-0.002 0.003 0.004 0.005 0.000 S 6 0.839 0.914 0.852 0.588 0.000 P 7-0.001 0.005 0.007 0.264 0.572 O 8 0.000 0.001 0.000 0.041 0.173 O 9 0.000 0.001 0.001 0.015 0.105 O 10 0.000 0.002 0.002 0.075 0.133 H a 0.000-0.002-0.001-0.001 0.001 H b -0.002 0.000 0.000 0.000 0.000 H c 0.004 0.002 0.001-0.007 0.000 H d 0.003 0.005 0.012 0.004 0.001 C Ph 0.048 0.000-0.001 0.008 0.000 12
b) pathway (a) for trans isomer SUB_trans-2 TS1_E_H a _2 INT_E_H a _2 TS2_E_H a _2 IC_E_H a _2 N 1 0.050-0.005-0.018 0.000 0.000 C 2-0.034-0.038-0.059 0.025 0.111 N 3 0.018-0.001-0.001-0.005 0.021 C 4 0.007 0.002-0.004-0.028-0.008 C 5-0.002 0.002 0.002 0.004 0.005 S 6 0.853 0.928 0.871-0.001-0.001 P 7 0.003 0.002 0.000 0.856 0.395 O 8 0.003 0.001 0.001-0.001-0.002 O 9 0.001 0.002 0.002 0.001 0.001 O 10 0.002 0.000 0.001 0.002 0.001 H a 0.000 0.093 0.185 0.058 0.002 H b -0.002 0.000 0.000-0.037-0.016 H c 0.000 0.000 0.000 0.000 0.000 H d 0.000 0.002 0.009 0.000 0.000 C Ph 0.036 0.002 0.001 0.002 0.002 c) pathway (c) for cis isomer SUB_cis-1 TS1_E_H c _1 INT_E_H c _1 TS2_E_H c _1 IC_E_H c _1 N 1 0.050 0.190 0.101 0.082 0.031 C 2-0.030-0.057-0.012-0.018-0.074 N 3 0.011-0.010 0.003-0.020 0.096 C 4 0.006 0.013-0.029-0.014 0.184 C 5-0.002 0.291 0.490 0.387 0.127 S 6 0.839 0.245 0.104 0.177 0.516 P 7-0.001 0.001 0.045 0.157 0.000 O 8 0.000 0.112 0.006 0.021 0.000 O 9 0.000 0.000 0.003 0.005 0.000 O 10 0.000 0.006 0.010 0.036 0.000 H a 0.000 0.000-0.001 0.000-0.002 H b -0.002-0.005-0.003-0.003-0.001 H c 0.004 0.059 0.003 0.001 0.000 H d 0.003 0.003 0.023 0.007-0.006 C Ph 0.048 0.043-0.096-0.073-0.003 13
d) pathway (c) for trans isomer SUB_trans-2 TS1_E_H c _2 INT_E_H c _2 TS2_E_H c _2 IC_E_H c _2 N 1 0.050 0.219 0.067 0.065 0.033 C 2-0.034-0.067-0.002 0.000 0.000 N 3 0.018-0.020 0.001-0.018 0.096 C 4 0.007 0.000-0.029-0.007 0.189 C 5-0.002 0.228 0.511 0.393 0.123 S 6 0.853 0.263 0.118 0.000 0.000 P 7 0.003 0.012 0.040-0.010-0.079 O 8 0.003 0.106 0.002 0.158 0.519 O 9 0.001 0.001 0.004-0.078-0.003 O 10 0.002 0.003 0.001 0.124 0.057 H a 0.000 0.001 0.000 0.001-0.002 H b -0.002-0.006-0.002-0.001-0.001 H c 0.000 0.067 0.000-0.001 0.000 H d 0.000 0.003 0.029 0.007-0.006 C Ph 0.036-0.004-0.103 0.000 0.000 14
Table S7. NPA spin densities for intermediates INT. (most significant are in bold) cis-1 trans-2 INT_E_H a INT_E_H b INT_E_H c INT_E_H d INT_E_H e INT_E_H a INT_E_H b INT_E_H c INT_E_H d INT_E_H e N 1-0.0221 0.3375 0.1012 0.0056 0.0061-0.0182 0.0252 0.0669 0.0076-0.0009 C 2-0.0680-0.1153-0.0116-0.0455-0.0023-0.0590-0.0196-0.0021-0.0438 0.0001 N 3 0.2174-0.0222 0.0031 0.2437 0.0008 0.1850 0.0072 0.0012 0.2363 0.0002 C 4 0.0042-0.0148-0.0291 0.5184 0.0132 0.0018 0.0068-0.0294 0.5386 0.0135 C 5-0.0069 0.0035 0.4903-0.0209-0.0012-0.0043 0.0030 0.5114-0.0222-0.0009 S 6 0.8519 0.7761 0.1037 0.1404 0.0059 0.8711 0.9736 0.1179 0.1364 0.0005 P 7 0.0069-0.0003 0.0450 0.0593-0.0002 0.0105 0.0008 0.0400 0.0540-0.0003 O 8 0.0000 0.0000 0.0060 0.0085 0.0286 0.0005 0.0002 0.0019 0.0313 0.0256 O 9 0.0006 0.0003 0.0030 0.0332 0.0020 0.0014 0.0001 0.0039 0.0087 0.0003 O 10 0.0024 0.0000 0.0103 0.0098-0.0001 0.0018 0.0000 0.0015 0.0031 0.0015 C_Ph -0.0010 0.0103-0.0964 0.0195-0.0288 0.0006 0.0004-0.1034 0.0175-0.0268 C_orto 0.0007 0.0013 0.1540 0.0012 0.8916-0.0001 0.0009 0.1699 0.0008 0.8963 C_orto 0.0000 0.0009 0.1698 0.0020 0.0461-0.0005 0.0013 0.1654 0.0007 0.0469 C_meta -0.0002-0.0001-0.0719 0.0009-0.0376 0.0001-0.0003-0.0772-0.0001-0.0199 C_meta 0.0004 0.0004-0.0752-0.0004-0.0232 0.0005-0.0004-0.0775 0.0013-0.0339 C_para 0.0004 0.0011 0.1849 0.0022 0.0536-0.0002 0.0017 0.1900 0.0016 0.0526 Full reference 12: Frisch, M J, Trucks, G. W., Schlegel, H. B., Robb, M. A., Cheeseman, J. R., Montgomery, J. A. Jr., Vreven, T., Kudin, K. N., Burant, J. C., Millam, J. M., Iyengar, S. S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G. A., Petersson, G. A., Nakatsuji, H., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Klene, M., Li, X., Knox, J. E., Hratchian, H. P., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomeli, C., Ochterski, J. W., Ayala, P. Y., Morokuma, K., Voth, G. A., Salvador, P., Dannenberg, J. J., Zakrzewski, V. G., Dapprich, 15
S., Daniels, A. D., Strain, M. C., Farkas, O., Malick, D. K., Rabuck, A. D., Raghavachari, K., Foresman, J. B., Ortiz, J. V., Cui, Q., Baboul, A. G., Clifford, S., Cioslowski, J., Stefanov, B. B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R. L., Fox, D. J., Keith, T., Al-Laham, M. A., Peng, C. Y., Nanayakkara, A., Challacombe, M., Gill, P. M. W., Johnson, B., Chen, W., Wong, M. W., Gonzalez, C., and Pople, J. A. Gaussian 03, Revision C.02. Gaussian, Inc. Wallingford CT 16