Supporting Information
Reaction of Henry adducts with aqueous sodium borohydride
AnnadkaShrinidhia
a
Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, Postbus 196
9700 AD, Groningen, The Netherlands
b
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
*Corresponding author. Tel.: +31 50 3635165; Fax: +31 50 3637582
E-mail: ascjnl@gmail.com
Supporting Information
Table of Content:
I. General Information
S2
II.Optimization and mechanistic study
S3
III. Characterization data for products
S6
IV. References
S9
S1
I. General Information:
Instruments employed werePerkin-Elmer 410(FTIR),Bruker AV-400 (NMR),Micromass QTOF AMPSMAX 10/6A (HRMS), Stuart SMP10 (melting point),BüchiRotavapor R-200
(rotary evaporator) and HI 2215 pH/ORP Meter. IR values are for neat samples and are
quoted in cm-1. NMR spectra were recorded in CDCl3 solution with tetramethylsilane as
internal standard at either 400 MHz (δH) or 100 MHz (δC); the coupling constants (J) are in
Hz. Abbreviations: Mp (melting point), s (singlet); d (doublet); t (triplet); q (quartet); br
(broad); dd (doublet of doublet), etc.The nomenclatures of all the compounds were derived
by ChemBioDraw Ultra (CambridgeSoft).
2-nitro alcohols were synthesized from corresponding aldehydes and nitroalkanes according
to the literature procedures.1 Sodium borohydride, sodium borodeuteride and deuterium oxide
were purchased from Sigma-Aldrich and used without any further purification. Wilmad
528PP NMR tubes were used for NMR studies.
S2
II. Optimization and mechanistic study:
i) Reaction in different solvents
Scheme 1.
Table1.
Entry
Solvent
2i, Isolated yield (%)
1
2
3
4
5
H2O
H2O + MeOH
H2O + MeCN
MeOH
MeCN
>99
85
82
73
77
Formation of aldehyde as by-product was observed when only 1 equiv of NaBH4was used in
all cases.
ii) Reaction of NaBH4 in excess water
Scheme 2.Hydrolysis of NaBH4 in water
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iii) pH study: Determined using HI 2215 pH/ORP Meter
Scheme 3.
Condition: NaBH4 + solvent (2.5 mL) at 25 °C
Table 2.
Entry
Solvent
1
2
3
4
5
H2O
H2O + MeOH
H2O + MeCN
MeOH
MeCN
Condition
pH at
10 min 30 min
10.74
10.90
10.85
11.31
11.59
11.95
10.67
11.66
11.50
11.89
iv) Reactionof 1i with NaBH4 and NaBD4
Scheme 4.
S4
Condition + 1a
pH at
10 min 30 min
9.35
9.92
10.90
11.07
11.29
11.71
10.64
10.92
11.02
11.72
Condition + 1i
pH at
10 min
30 min
9.06
9.45
10.25
10.33
10.70
11.31
11.54
11.98
10.72
11.65
Figure 1.1H NMR spectra of reaction (ii)
S5
III. Characterization data for products:
Phenylmethanol (2a/2i).Colorless liquid; νmax 3340, 3031, 2929, 2873, 1607, 1496, 1453,
1208, 1019, 735, 698;H7.33-7.20 (m, 5H),4.55 (s, 2H), 2.81 (br s, 1H);C140.7, 128.4, 127.4,
126.9, 64.9;HRESI-MS: 131.0470 (Calcd. forC7H8O + Na131.0473).
(3,4,5-Trimethoxyphenyl)methanol (2b). White solid; Mp 36-37 ºC (lit.236-38ºC);νmax3467,
2940, 2840, 1593, 1506, 1461, 1422, 1361, 1331, 1236, 1183, 1127, 1061, 1006, 961, 829,
779, 743, 688; H6.59 (s, 2H),4.62 (s, 2H),3.85 (s, 6H),3.83 (s, 3H), 2.11 (br s, 1H); C153.2,
137.1, 136.7, 103.7, 65.3, 60.3, 56.0; HRESI-MS: 221.0787 (Calcd. for C10H14O4 +
Na221.0790).
(4-Chlorophenyl)methanol (2c). White solid; Mp 70-71 ºC (lit.370-71ºC); νmax3310, 3222,
2915, 2866, 1598, 1572, 1469, 1448, 1365, 1195, 1127, 1066, 1043, 1031, 812, 756, 711,
649; H7.33-7.26 (m, 4H),4.64 (s, 2H),2.36 (br s, 1H); C139.2, 133.3, 128.6, 128.2, 64.5;
HRESI-MS: 165.0080 (Calcd. for C7H7ClO + Na165.0083).
(4-Nitrophenyl)methanol (2d). Light yellow solid; Mp 92-93 ºC (lit.492-93ºC); νmax3325,
3082, 2921, 2887, 1603, 1508, 1459, 1352, 1197, 1058, 831, 736, 682; H8.209-8.187 (d,J
8.6, 2H), 7.54-7.52 (d,J 8.4, 2H), 4.84-4.82 (d,J 5.4, 2H), 2.28-2.25 (t,J 5.6, 1H); C148.2,
147.2, 127.0, 123.7, 63.9; HRESI-MS: 176.0322 (Calcd. for C7H7NO3+ Na176.0324).
Furan-2-ylmethanol (2e). Light brown liquid; νmax 3416, 3121, 2924, 2873, 1597, 1563, 1505,
1357, 1219, 1013, 794, 743, 630; H7.39 (m, 1H),6.34-6.28 (m, 2H), 4.59 (s, 2H),2.17 (br s,
1H); C153.9, 142.5, 110.3, 107.7, 57.3; HRESI-MS: 121.0263 (Calcd. for C5H6O2 +
Na121.0265).
Heptan-1-ol (2f). Colorless liquid; νmax3451, 2962, 2931, 2878, 2731, 1488, 1462, 1425,
1384, 1338, 1279, 1169, 1142, 1016, 976, 774, 690, 665; H3.64-3.61 (t,J 6.4, 2H), 2.02(br s,
1H),1.58-1.53 (m, 2H), 1.33-1.29 (m, 8H),0.90-0.87 (t,J 6.4, 3H); C62.9, 32.7, 31.8, 29.1,
25.7, 22.5, 14.0; HRESI-MS: 139.1097 (Calcd. for C7H16O + Na 139.1099).
S6
(E)-But-2-en-1-ol (2g). Colorless liquid; νmax 3435, 3031, 2985, 2837, 1312, 1596, 1513,
1465, 1422, 1321, 1245, 1175, 1030, 920, 728; H5.68-5.61 (m, 2H), 5.11 (br s, 1H), 4.194.16 (d, J 8.8, 2H), 1.63-1.60 (d, J 8.8,3H); C130.8, 126.5, 64.1, 18.6; HRESI-MS: 95.0474
(Calcd. for C4H8O + Na 95.0473).
(E)-3-Phenylprop-2-en-1-ol (2h). White solid; Mp 31-33 ºC (lit.532 ºC); νmax3340, 3082,
3027, 2919, 2865, 1656, 1599, 1494, 1449, 1335, 1093, 1008, 920, 735, 693; H7.42-7.25
(m,5H), 6.65-6.61(d,J15.6, 1H), 6.41-6.34 (m, 1H), 4.34-4.32 (d,J 5.6, 2H), 2.41 (br s, 1H);
C136.6, 130.9, 128.5, 128.4, 127.6, 126.4, 63.5; HRESI-MS: 157.0628 (Calcd. for C9H10O +
Na157.0629).
Naphthalen-1-ylmethanol (2j). White solid; Mp 60-62 ºC (lit.362-63ºC); νmax3429, 3047,
3010, 2881, 1625, 1598, 1511, 1468, 1454, 1394, 1221, 1165, 1080, 1068, 994, 909, 856,
793, 773, 711, 653; H8.08-8.06(d,J 8.0, 1H), 7.86-7.77(dd,J 8.0, 27.6, 2H), 7.54-7.39(m,
4H), 5.08(s, 2H),2.14 (br s, 1H); C136.2, 133.7, 131.1, 128.6, 128.4, 126.2, 125.8, 125.3,
125.2, 123.6, 63.4; HRESI-MS: 181.0626 (Calcd. for C11H10O + Na 181.0629).
p-Tolylmethanol (2k). White solid; Mp 60-61 ºC (lit.660ºC); νmax 3345, 3035, 2936, 2871,
1602, 1498, 1450, 1200, 1009, 729, 678; H7.79-7.77(d,J 8.0, 2H), 7.35-7.33 (d,J 8.0, 2H),
4.61 (s, 2H), 2.45 (s, 3H); C139.3, 138.9, 129.6, 128.2, 64.7, 21.3; HRESI-MS: 145.0627
(Calcd. for C8H10O + Na145.0629).
(4-Methoxyphenyl)methanol (2l). Colorless liquid; νmax 3421, 3001, 2909, 2935, 2837, 2861,
1312, 1586, 1513, 1464, 1442, 1301, 1247, 1174, 1034, 820, 752, 708; H7.26-7.24 (d,J 8.4,
2H),6.89-6.86 (d,J 8.8, 2H),4.56 (s, 2H),3.78 (s, 3H), 2.41 (br s, 1H); C159.0, 133.0, 128.6,
113.8, 64.8, 55.2; HRESI-MS: 161.0574 (Calcd. for C8H10O2 + Na 161.0578).
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Nitromethyl benzene (3k). TLC Rf 0.65 (20% ethyl acetate-hexane); Purified on silica gel
(ethyl acetate-hexane 3:97-6:94); υmax 3064, 3033, 1603, 1554, 1455, 1375, 1114, 787; δH
7.76-7.35 (5H, m), 5.42 (s, 2H); δC 130.3, 130.2, 130.0, 129.4, 80.3; HRESIMS: 160.0375
(Calcd. for C7H7NO2 + Na 160.0374).
(2-Nitroethyl)benzene (3l). TLC Rf 0.65 (20% ethyl acetate-hexane); Purified on silica gel
(ethyl acetate-hexane 3:97-6:94); Mp 56-57 ºC (lit.7 56-58 ºC); υmax 3065, 3032, 1603, 1555,
1455, 1380, 1114, 752; δH 7.35-7.20 (5H, m), 4.63-4.59 (2H, t, J 7.4), 3.34-3.30 (2H, t, J
7.4); δC 135.6, 128.9, 128.5, 127.4, 76.2, 33.4;HRESIMS: 174.0533 (Calcd. for C8H9NO2 +
Na174.0531).
7-Nitroheptan-2-ol (4m). Colorless liquid; νmax 3442, 3000, 2948, 2872, 1531, 1401, 1200,
701; H4.43-4.40 (t, J 6.4, 2H), 4.08-4.03 (m, 1H), 2.04 (br s, 1H), 1.98-1.94 (m, 2H), 1.491.39 (m, 2H), 1.27-1.23 (m, 7H); C76.8, 69.5, 42.1, 28.3, 27.1, 24.2, 23.2; HRESI-MS:
184.0951 (Calcd. for C7H15NO3 + Na 184.0950).
9-Nitrononan-3-ol (4n). Colorless liquid; νmax 3415, 3014, 2964, 2834, 1515, 1422, 1222,
771; H4.42-4.39 (t, J 6.4, 2H), 3.44-3.40 (m, 1H), 2.33 (br s, 1H), 1.98-1.94 (m, 2H), 1.461.25 (m, 10H), 1.02-0.99 (t, 3H); C76.1, 74.6, 38.1, 30.5, 28.8, 27.3, 26.6, 25.8, 14.1;
HRESI-MS: 212.1263 (Calcd. for C9H19NO3 + Na 212.1263).
1-Nitroundecan-6-ol (4o). Colorless liquid; νmax 3445, 3008, 2942, 2868, 1535, 1402, 1217,
752; H4.45-4.42 (t, J 6.4, 2H), 3.44-3.41 (m, 1H), 2.33 (br s, 1H), 1.94-1.90 (m, 2H), 1.421.23 (m, 14H), 0.92-0.89 (t, 3H); C77.9, 71.6, 38.2, 32.3, 27.6, 26.8, 25.3, 24.4, 23.1, 14.2;
HRESI-MS: 240.1575 (Calcd. for C11H23NO3 + Na 240.1576).
6-Nitro-1-phenylhexan-1-ol (4p). Colorless liquid; νmax 3435, 3015, 2935, 2847, 1600, 1514,
1484, 1302, 1257, 1171, 827, 701; H7.46-7.32 (m, 5H), 4.42-4.38 (m, 3H), 2.41 (br s, 1H),
1.90-1.86 (m, 2H), 1.63-1.50 (m, 2H), 1.27-1.25 (m, 4H); C146.6, 129.2, 128.6, 126.4, 76.4,
75.9, 39.5, 31.8, 27.8, 26.4; HRESI-MS: 246.1105 (Calcd. for C12H17NO3 + Na 246.1106).
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IV. References:
(1)
(a) August Jacob, T.; Bachman, G. B.; Hass, H. B. J. Org. Chem.1951, 16, 1572.(b)
Ballini, R.; Bartoli, G.; Gariboldi, P. V.; Marcantoni, E.; Petrini, M. J. Org.
Chem.1993, 58, 3368.(c) Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw, J.
T.; Downey, C. W. J. Am. Chem. Soc.2003, 125, 12692.(d) Gorczynski, M. J.; Huang,
J.; Lee, H.; King, S. B. Bioorg. Med. Chem. Lett.2007, 17, 2013.(e) Majhi, A.;
Kadam, S. T.; Kim, S. S. Bull. Korean Chem. Soc.2009, 30, 1767.
(2)
Lee, T.-H.; Chiou, J.-L.; Lee, C.-K.; Kuo, Y.-H. J. Chin. Chem. Soc. (Taipei,
Taiwan)2005, 52, 833.
(3)
Zeynizadeh, B.; Yahyaei, S. Z. Naturforsch. B Chem. Sci.2004, 59, 704.
(4)
Brown, H. C.; Rao, B. C. S. J. Am. Chem. Soc.1956, 78, 2582.
(5)
Liu, L.; Yu, M.; Wayland, B. B.; Fu, X. Chem. Commun.2010, 46, 6353.
(6)
Cadogan, J. I. G.; Gold, V.; Satchell, D. P. N. J. Chem. Soc.1955, 561.
(7)
Takechi, H.; Machida, M. Synthesis1989, 206.
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