P. Borowiecki et al. / Journal of Molecular Catalysis B: Enzymatic 109 (2014) 9–16
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2.1.1. 1-(1H-Benzimidazol-2-ylsulfanyl)propan-2-one (3a)
at 5 ◦C under nitrogen atmosphere. Next, the heterogeneous white
reaction mixture was additionally stirred at 0–5 ◦C until all start-
ing material was consumed (approx. 2 h, TLC). When the reaction
was over, the methanol was distilled off in vacuo by rotatory evap-
oration, the residual syrup-like mass was suspended in distilled
H2O (30 mL) and then extracted with EtOAc (3× 20 mL). The com-
bined organic layers were washed with saturated NaCl solution,
dried over anhydrous MgSO4, filtrated through short silica pad,
concentrated under reduced pressure and purified on column chro-
matography (SiO2) using mixture of hexane/EtOAc (1:3 or 4:1, v/v
– depending on the substance purified) as an eluent. The title final
products ( )-4a–c were yielded as colored oils in ca. 100% purity
according to GC indications.
Beige solid; yield 90%; mp 112.5–113.5 ◦C (from EtOH) [Lit [67]:
mp 113–114 ◦C (from EtOH/H2O)]; Rf [hexane/EtOAc (1:3, v/v)]
0.54; 1H NMR ((CD3)2SO, 500 MHz) ı: 1.89 (s, 2H, CH3*), 2.28 (s,
3H, CH3), 3.83 (d, J = 11.7 Hz, 1H, CH2*), 4.02 (d, J = 11.7 Hz, 1H,
CH2*), 4.33 (s, 2H, CH2), 6.98–7.24 (m, 4H, Ph), 7.26–7.68 (m, 3H,
Ph), 12.22–12.83 (m, 2H, NH); 13C NMR ((CD3)2SO, 500 MHz) ı:
25.3 (CH3*), 28.8 (CH3), 41.8 (CH2*), 47.1 (CH2), 88.7 (COH*), 109.7
(Ph), 117.9 (Ph), 121.2 (Ph), 121.4 (Ph*), 121.6 (Ph*), 132.1 (Ph*),
149.2 (Ph*), 149.5 (Ph and CS), 155.9 (CS*), 202.3 (C O); 1H NMR
((CD3)2CO, 400 MHz) ı: 2.01 (s, 3H, CH3*), 2.32 (s, 3H, CH3), 3.93
(d, J = 11.7 Hz, 1H, CH2*), 4.06 (d, J = 11.7 Hz, 1H, CH2*), 4.30 (s, 2H,
CH2), 7.08–7.17 (m, 3H, Ph), 7.40–7.48 (m, 3H, Ph), 7.55–7.60 (m,
1H, Ph); 13C NMR ((CD3)2CO, 100 MHz) ı: 25.7 (CH3*), 28.7 (CH3),
42.6 (CH2*), 48.1 (CH2), 89.8 (COH*), 110.3 (Ph*), 114.7 (Ph), 118.9
(Ph*), 121.9 (Ph), 122.3 (Ph*), 122.4 (Ph*), 133.2 (Ph*), 140.7 (Ph*),
150.4 (Ph), 150.6 (CS), 157.0 (CS*), 202.1 (C O) [asterix * refers to 3-
hydroxy-3-methyl-2,3-dihydrothiazolo[3,2-␣]benzimidazole 3aꢀ –
cyclic carbinolamine tautomeric form of 3a]; HRMS (ESI+, m/z):
[M+H]+calcd = 207.0592, [M+H]+found = 207.0275; FTIR ꢀmax(neat):
2986 (O H st.), 2770 (N H st.), 1612 (aryl C C st.), 1473 (C N st.),
1447 (CH3 and CH2 def. asymm.), 1411 (CH2-S sciss.), 1384 (CH2
2.2.1. 1-(1H-Benzimidazol-2-ylsulfanyl)propan-2-ol ( )-4a
Colorless oil; yield 91%; Rf [hexane/EtOAc (1:3, v/v)] 0.45;
1H NMR (CDCl3, 400 MHz) ı: 1.46 (d, J = 6.3 Hz, 3H, CH3), 3.31
(dd, J = 14.7, 7.0 Hz, 1H, CH2), 3.42 (dd, J = 14.7, 2.8 Hz, 1H, CH2),
4.37–4.46 (m, 1H, CH), 7.23–7.31 (m, 2H, Ph), 7.54–7.62 (m, 2H,
Ph); 13C NMR (CDCl3, 100 MHz) ı: 22.7 (CH3), 40.8 (CH2), 68.1 (CH),
114.0 (Ph), 122.2 (2C, Ph), 138.9 (Ph), 151.4 (CS); HRMS (ESI+, m/z):
[M+H]+calcd = 209.0749, [M+H]+found = 209.0563; FTIR ꢀmax(neat):
3053 (O H st.), 2970 (CH3 st. asymm.), 2929 (N H st.), 1618 (aryl
def. symm.), 1345 (in-plane O H def.), 1205 (C N st.), 1152 (C
N
st.), 1084 (C O st. of tertiary alcohol), 743 (out of plane C H bend
[150–260 (10 ◦C/min)]: tR = 11.6 min.
C
C st.), 1498 (C N st.), 1437 (CH3 and CH2 def. asymm.), 1400
(CH2-S sciss.), 1372 (CH2 def. symm.), 1266 (C O st.), 1229 (C
O
st.), 1125 (C O st.), 1042 (C O st.), 737 (out of plane C H bend
in 1,2-disubstitution (ortho) aromatic ring) cm−1; GC [150–260
(10 ◦C/min)]: tR = 8.5 min; UV/vis: ꢁmax = 254 nm (EtOH); HPLC [n-
hexane/i-PrOH (90:10, v/v); f = 0.7 mL/min]: tR = 26.7 min (R)-(+)-4a
(major), 37.0 min (S)-(−)-4a (minor).
2.1.2. 1-(1,3-Benzoxazol-2-ylsulfanyl)propan-2-one (3b)
Beige solid; yield 92%; mp 71.5–72.5 ◦C (from EtOH) [Lit
[68]: mp 78–80 ◦C (from EtOH), Lit [69]: mp 68–69 ◦C (hex-
ane/isopropanol (5:1) or methanol)]; Rf [hexane/EtOAc (1:3, v/v)]
0.76; 1H NMR ((CD3)2CO, 400 MHz) ı: 2.36 (s, 3H, CH3), 4.43
(s, 2H, CH2), 7.27–7.34 (m, 2H, Ph), 7.51–7.58 (m, 2H, Ph); 13C
NMR ((CD3)2CO, 100 MHz) ı: 28.8 (CH3), 43.3 (CH2), 110.7 (Ph),
119.0 (Ph), 124.9 (Ph), 125.2 (Ph), 142.5 (Ph), 152.6 (Ph), 164.8
(CS), 200.8 (C O); 1H NMR (CDCl3, 400 MHz) ı: 2.38 (s, 3H,
CH3), 4.21 (s, 2H, CH2), 7.19–7.30 (m, 2H, Ph), 7.39–7.45 (m, 1H,
Ph), 7.53–7.60 (m, 1H, Ph); 13C NMR (CDCl3, 100 MHz) ı: 28.8
(CH3), 42.7 (CH2), 109.9 (Ph), 118.4 (Ph), 124.0 (Ph), 124.3 (Ph),
141.5 (Ph), 152.0 (Ph), 163.5 (CS), 200.9 (C O); HRMS (ESI+, m/z):
[M+H]+calcd = 208.0432, [M+H]+found = 208.0141; FTIR ꢀmax(neat):
1713 (C O st.), 1603 (aryl C C st.), 1498 (C N st.), 1455 (CH3
and CH2 def. asymm.), 1379 (CH2 def. symm.), 1153 (C N st.),
1128 (ArOC asymm. st.), 1095 (ArOC asymm. st.), 745 (out of plane
2.2.2. 1-(1,3-Benzoxazol-2-ylsulfanyl)propan-2-ol ( )-4b
Yellowish oil; yield 91%; Rf [hexane/EtOAc (1:3, v/v)] 0.65; 1H
NMR (CDCl3, 400 MHz) ı: 1.36 (d, J = 6.3 Hz, 3H, CH3), 3.30 (dd,
J = 14.0, 7.2 Hz, 1H, CH2), 3.46 (dd, J = 14.0, 3.7 Hz, 1H, CH2), 3.87
(br. s., 1H, OH), 4.25 (td, J = 6.5, 3.7 Hz, 1H, J = 14.0, 7.2 Hz, 1H, CH),
7.19–7.29 (m, 2H, Ph), 7.39–7.45 (m, 1H, Ph), 7.53–7.59 (m, 1H,
Ph); 13C NMR (CDCl3, 100 MHz) ı: 22.4 (CH3), 40.6 (CH2), 67.1
(CH), 109.9 (Ph), 118.2 (Ph), 124.0 (Ph), 124.4 (Ph), 141.2 (Ph),
151.8 (Ph), 165.5 (CS); HRMS (ESI+, m/z): [M+H]+calcd = 210.0589,
[M+H]+found = 210.0264; FTIR ꢀmax(neat): 3353 (O H st.), 2971 (CH3
st. asymm.), 1600 (aryl C C st.), 1496 (CH3 and CH2 def. asymm.),
1452 (CH2-S sciss.), 1373 (CH2 def. symm.), 1236 (C O st.), 1214
(C O st.)1126 (C O st.), 1044 (C O st.), 738 (out of plane C H bend
in 1,2-disubstitution (ortho) aromatic ring) cm−1; GC [150–260
(10 ◦C/min)]: tR = 6.9 min; UV/vis: ꢁmax = 254 nm (EtOH); HPLC [n-
hexane/i-PrOH (98:2, v/v); f = 0.7 mL/min]: tR = 42.9 min (R)-(+)-4b
(major), 53.0 min (S)-(−)-4b (minor).
C
H bend in 1,2-disubstitution (ortho) aromatic ring) cm−1; GC
[150–260 (10 ◦C/min)]: tR = 7.0 min.
2.1.3. 1-(1,3-Benzothiazol-2-ylsulfanyl)propan-2-one (3c)
White solid; yield 80%; mp 64–64.5 ◦C (from EtOH) [Lit [66]: mp
64–64.5 ◦C (from EtOH)]; Rf [hexane/EtOAc (4:1, v/v)] 0.38; 1H NMR
(CDCl3, 400 MHz) ı: 2.40 (s, 3H, CH3), 4.26 (s, 2H, CH2), 7.28–7.45
(m, 2H, Ph), 7.72–7.87 (m, 2H, Ph); 13C NMR (CDCl3, 100 MHz) ı:
28.9 (CH3), 43.1 (CH2), 121.1 (Ph), 121.5 (Ph), 124.5 (Ph), 126.1 (Ph),
135.4 (Ph), 152.5 (Ph), 165.1 (CS), 201.7 (C O); HRMS (ESI+, m/z):
[M+H]+calcd = 224.0198, [M+H]+found = 223.9879; FTIR ꢀmax(neat):
2967 (CH3 st. asymm.), 1717 (C O st.), 1463 (CH3 and CH2 def.
2.2.3. 1-(1,3-Benzothiazol-2-ylsulfanyl)propan-2-ol ( )-4c
Orange oil; yield 91%; Rf [hexane/EtOAc (4:1, v/v)] 0.22; 1H NMR
(CDCl3, 400 MHz) ı: 1.35 (d, J = 6.3 Hz, 3H, CH3), 3.34 (dd, J = 14.3,
7.11 Hz, 1H, CH2), 3.51 (dd, J = 14.2, 3.2 Hz, 1H, CH2), 3.88 (br. s.,
1H, OH), 4.21–4.30 (m, 1H, CH), 7.27–7.45 (m, 2H, Ph), 7.70–7.87
(m, 2H, Ph); 13C NMR (CDCl3, 100 MHz) ı: 22.5 (CH3), 42.1 (CH2),
67.4 (CH), 121.0 (Ph), 121.2 (Ph), 124.6 (Ph), 126.2 (Ph), 135.3 (Ph),
152.3 (Ph), 167.7 (CS); HRMS (ESI+, m/z): [M+H]+calcd = 226.0355,
[M+H]+found = 225.9984; FTIR ꢀmax(neat): 3346 (O H st.), 2966
(CH3 st. asymm.), 1452 (CH2-S sciss.), 1423 (CH3 and CH2 def.
asymm.), 1385 (CH2 def. symm.), 1266 (C O st.), 1246 (C O st.),
1127 (C O st.), 1002 (C O st.), 752 (out of plane C H bend
in 1,2-disubstitution (ortho) aromatic ring) cm−1; GC [175–260
(0.5 ◦C/min)]: tR = 17.5 min; UV/vis: ꢁmax = 254 nm (EtOH); HPLC [n-
hexane/i-PrOH (95:5, v/v); f = 0.7 mL/min]: tR = 38.6 min (R)-(+)-4c
(major), 43.6 min (S)-(−)-4c (minor).
asymm.), 1427 (CH2-S sciss.), 1357 (CH2 def. symm.), 1152 (C
N
st.), 753 (out of plane C H bend in 1,2-disubstitution (ortho) aro-
matic ring) cm−1; GC [150–260 (10 ◦C/min)]: tR = 9.3 min.
2.2. General procedure for the synthesis of
1-(benzoazol-2-ylsulfanyl)propan-2-ols [( )-4a–c]
To the solution of an appropriate ketone 3a–c (800 mg) in MeOH
(45 mL), pulverized NaBH4 (4 equiv.) was added portion-wise with
stirring at a rate sufficient to maintain the internal temperature