Synthesis of novel chiral thioether ligands containing imidazole rings based on natural amino acids

Article abstract of DOI:10.1080/10426501003671460

Using commercially available natural amino acids (L-Val, L-Leu, L-Phe) as chiral precursors, a series of N-substituted imidazole derivatives containing chiral groups was synthesized from the condensation reaction of amino acids, formaldehyde, glyoxal, and

Full text of DOI:10.1080/10426501003671460

Phosphorus, Sulfur, and Silicon, 185:2418–2425, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003671460
SYNTHESIS OF NOVEL CHIRAL THIOETHER LIGANDS
CONTAINING IMIDAZOLE RINGS BASED ON NATURAL
AMINO ACIDS
Pu Mao,1,2 Yajing Cai,2 Yongmei Xiao,2 Liangru Yang,2
Yuan Xue,2 and Maoping Song1
1Department of Chemistry, Zhengzhou University, Zhengzhou, P. R. China
2School of Chemistry and Chemical Engineering, Henan University of Technology,
Zhengzhou, P. R. China
Using commercially available natural amino acids (L-Val, L-Leu, L-Phe) as chiral precur-
sors, a series of N-substituted imidazole derivatives containing chiral groups was synthe-
sized from the condensation reaction of amino acids, formaldehyde, glyoxal, and ammonia.
Through esterification, reduction, chlorination, and subsequent substitution by thiols, chiral
thioethers containing imidazole rings were synthesized, and the synthetic conditions were
optimized. All the intermediates and the final products were characterized by NMR, ESI MS,
HR MS, and IR.
Keywords Chiral ligands; imidazole derivatives; natural amino acids; thioethers
INTRODUCTION
Due to the high coordination ability of the sulfur atom to most transition metals, sulfur
donor ligands have been interestingly applied in transition metal–catalyzed homogeneous
processes, and the most successful examples belong to chelates.1–4 An extensive series of
S, X- (X = N, P, O, etc.) heterodonor ligands, which can provide a variety of electronic and
steric properties, have been developed.5–9 Compared to the widely used phosphine ligands,
sulfur ligands are poor σ-donor and π-acceptor ligands, while the trans-effect of sulfur
ligands was found to be higher than those of nitrogen- and oxygen-containing ligands.
Moreover, sulfur-containing ligands feature the advantages of easy availability and high
stability, allowing convenient storage and handling compared to phosphine derivatives.
Furthermore, chelating asymmetrically disubstituted thioether ligands opens new possi-
bilities over other chelates because a new stereogenic center is formed at the sulfur by
coordination to a metal. Although the low inversion barrier (10–15 kcal·mol−1) sometimes
leads to difficult control of the new stereogenic center, a chiral center close to the sulfur
atom may control the new chiral center effectively when the sulfur atom coordinates to
a transition metal. In additional, a sulfur atom in a thioether has only two substitutents,
Received 14 December 2009; accepted 1 February 2010.
Address correspondence to Pu Mao, Department of Chemistry, Zhengzhou University, Zhengzhou 450001,
P. R. China. E-mail: henangongda@yahoo.com
2418

NOVEL CHIRAL THIOETHER LIGANDS
2419
creating a less hindered environment than trivalent phosphorous. A diverse array of chiral
sulfur-containing ligands has been synthesized and applied in coordination chemistry and
asymmetric catalysis.
N-heterocyclic carbenes (NHCs) derived from imidazolium salts have emerged as a
very powerful class of ligands. A series of chelating carbenes generated from imidazole
derivatives carrying N-substituents with different donor atoms (X = N, P, S, etc.) has been
widely used in organometallic chemistry and homogeneous catalysis.10–16 However, chiral
chelating sulfur ligands containing a potential carbene center have been less extensively
explored.17,18 In this article, we report for the first time the preparation and characteriza-
tion of a series of chiral thioether ligands containing an imidazole ring, which may be
further utilized as a precursor of chiral bidentate sulfur, carbine ligands for organometallic
chemistry and homogeneous catalysis, or functionalized chiral ionic liquids.
RESULTS AND DISCUSSION
For the synthesis of imidazole derivatives, Heinrich Debus first reported a “three
component–one pot” reaction, in which condensation of ammonia, formaldehyde, and gly-
oxal afforded C-2 substituted imidazole.19 Yet the yields were usually quite low. Arduengo
III et al.20 made an adaption of Debus’s method and proposed a “four component–one pot”
procedure, in which combination of formaldehyde, glyoxal, ammonia, and an amine could
produce optionally substituted imidazole derivatives, and the yields were improved.
Our synthesis procedure is shown in Scheme 1. A slight modification of the “four
component–one pot” method was used to form the imidazole ring. By using a chiral amino
R1
R1
R1
N
(ii)
(i) a)
b)
N
O
H
O
H
N
COOH
NH3
HCHO
N
COOEt
H2N
COOH
H
H
H
2a-c
3a-c
1a-c
R1
N
N
N
N
CH2OTs
5'a
R1
Route A
(iv) A)
R1
R1
H
N
N
(iii)
CH2SR2
N
CH2OH
(v)
N
(iv) B)
H
H
4a-c
Route B
6ad-cf
CH2Cl
5a-c
a), CH2CH(CH3)2 (b), CH2Ph (c)
H
R1=CH(CH3)2
(
R2=(CH2)3CH3 (d), Ph (e), CH2Ph (f)
Scheme 1 Synthesis of thioether ligands. Reagents and conditions: (i) a) NaOH (aq), 50◦C, 8 h; b) HCl (5 mol/L);
(ii) Cat., 4 Å molecular sieve, EtOH, reflux, 12 h; (iii) NaBH4, EtOH, 0◦C-reflux overnight; (iv) A) TsCl, Et3N,
THF, reflux overnight; B) Na2CO3, SOCl2, 45◦C, 5 h, reflux 2 h; (v) NaOH, R2SH, EtOH, reflux overnight.

2420
P. MAO ET AL.
Table I Results of esterification using different catalysts
Entry
Catalyst
Yielda
1b
2
3
4
5
6c
NaHSO4
67%
65.5%
81%
53%
40%
Cation exchange resin
NaHSO4 & cation exchange resin
CuSO4·5H2O
FeCl3·6H2O
SOCl2
71.3%
aIsolated yield over two steps based on 1a used.
bEntries 1–5 were all performed using the follow reaction conditions: (i) 0.06 mol of 1a, 0.06
mol of glyoxal water solution, 0.06 mol of formaldehyde water solution, 0.06 mol of NaOH,
12 mL H2O, 50◦C, 8 h; (ii) 0.06 mol cat., except that cation exchange resin was 2 g, 150 mL
EtOH, reflux, 12 h.
cEntry 6 was performed as follows: (i) Same with entries 1–5; (ii) 20 mL of SOCl2, 0◦C–r.t.
overnight.
acid instead of an amine, an imidazole containing an appended chiral functionality was pro-
duced. Because the chiral center did not directly participate in the condensation, there was
little risk for the racemization/epimerization of the chiral center.21 From compounds 1a–c
(L-Val, L-Leu, L-Phe), imidazole derivatives 2a–c carrying an N-substitutent with a chiral
center were obtained, which were then treated successively by esterification, reduction,
chlorination, and substitution by thiols to afford thioethers 6ad–cf.
Without separation of 2a–c from the reaction mixture, the esterification was carried
out to produce compounds 3a–c. Several catalysts have been tested in the esterification
of 3a in ethanol (Table I). The combination of NaHSO4 and cation exchange resin were
chosen for the esterification due to its advantages of mild reaction condition, simple workup
procedure, and high yields (81%). Additionally, a cation exchange resin could be recycled.
SOCl2 produced a yield of 71%, while the harsh reaction conditions required and the
odoriferous gases (HCl, SO2) released during the reaction limited its application. Although
inorganic salt catalysts, such as CuSO4·5H2O and FeCl3·6H2O, were convenient to use,
these catalyst systems usually produce plenty of floccules, resulting in difficult workup
procedure and low separation yields.
To obtain alcohols 4a–c, esters 3a–c were reduced by NaBH4, which has the advan-
tages of mild reaction conditions, simple workup, and low costs. Although LiAlH4 was
more often used due to its high reactivity, it has the disadvantage of requiring harsh reac-
tion conditions. In addition, it usually forms plenty of floccules during the reaction, which
results in low separation yields. In our case, reduction of 3a–c by NaBH4 in anhydrous
EtOH afforded 4a–c with separation yields between 65–75%.
To synthesize the target compounds 6, two commonly used procedures for the syn-
thesis of thioethers were investigated (Scheme 1, routes A and B).22–24 As the tosylation of
alcohols was a common transformation usually used to facilitate subsequent substitution
reaction, we first used route A for the synthesis of compounds 6. 5ꢁa was obtained with a
yield of 28%, which was much lower than reported in the literature (78–97%).25 This was
tentatively attributed to the high reactivity of the sulfonate and the strong basicity of N-3
(pKb = 6.95) in compound 5ꢁ, which led to the inter-substitution reaction and resulted in
the quarternization of compound 5ꢁa.

NOVEL CHIRAL THIOETHER LIGANDS
2421
To avoid the inter-substitution reaction, we chose relatively low reactive intermediates
chlorides instead of sulfonates (route B). In addition, route B had the merit of simple workup
of the reaction mixture, and intermediates 5 could react with thiols to produce thioethers
without separation. Maybe due to the low conversion of chlorides to thioethers, the yields
of 6 were only acceptable, not high.
CONCLUSION
We developed a highly versatile method for the synthesis of chiral thioether ligands
containing an imidazole ring using natural amino acids as chiral precursors. Investigation
of different routes showed that by tuning the reactivity of the intermediates, thioethers
were obtained with reasonable yields. Tuning the reaction conditions to obtain thioethers
containing different numbers of imidazole rings for transition metal catalysis is now under
investigation, and the results will be published in due course.
EXPERIMENTAL
All reagents and solvents were pure analytical grade materials purchased from com-
mercial sources and were used without further purification unless stated otherwise. All
reactions were carried out under atmosphere. The products were purified by column chro-
matography using silica gel (100–200 mesh), and visualization was accomplished by I2
staining. NMR spectra were recorded in CDCl3 on a Bruker 400 MHz spectrometer. The
chemical shifts were reported as ppm downfield using TMS as internal standard. Mass
spectra (MS) were measured on Bruker Esquire 3000 ESI MS. High resolution mass spec-
tra (HR MS) were obtained on a Waters Micromass Q-Tof Micro instrument using the
ESI technique. IR spectra were recorded on a Nicolet Spectrum 2000 infrared spectropho-
tometer using KBr pellets. Molar optical rotations were measured on a WZZ-2B digital
polarimeter.
General Procedure to Prepare Compounds 3a–c
A formaldehyde/water solution (36% w/v, 4.6 mL, 0.06 mol) and aqueous glyoxal
(40% w/v, 7.6 mL, 0.06 mol) were mixed before an ammonia (25% w/v, 6.8 mL, 0.09 mol)
and sodium hydroxide solution (10% w/v, 24 mL, 0.06 mol) containing L-Val 1a (7.03 g,
0.06 mol) was added dropwise. The mixture was stirred at 50◦C for 8 h before hydrochloric
acid (5 mol/L) was added to adjust the pH to 1–2. Water was then evaporated, and the
residue was dried under vacuum at 60◦C to afford the crude product 2a.
Compound 2a and sodium hydrosulfate (7.20 g, 0.06 mol) were dissolved in anhy-
drous ethanol (150 mL), then cation ion exchange resin (2 g) was added, and the mixture
was heated to reflux for 12 h before being filtered. The filtrate was evaporated, and the
residue was dissolved in water. The pH value was adjusted to 8–9 by saturated aqueous
sodium bicarbonate solution before being extracted with ethyl acetate (3 × 20 mL). The
combined organic phase was concentrated and purified by silica column chromatography
(petroleum ether:ethyl acetate, 3:1 v/v) to afford 3a. Compounds 3b–c were prepared by
similar procedures, and characterization data of 3a,b are consistent with the literature.26
Compound 3c: Purified by silica column chromatography (petroleum ether:ethyl
acetate, 3:1 v/v). Yield: 83%; yellow oil; [α]2D5 (c = 2.0, EtOH): –39.2; IR (ν cm−1): 3381
(N H), 3112 ( C H), 2962 (C H); 1H NMR (400 MHz, CDCl3) δ: 7.41(s, 1H, Himi-2),

2422
P. MAO ET AL.
7.21–7.19 (m, 3H, Himi & HAr), 6.98–6.04 (m, 4H, HAr), 4.92–4.89 (m, 1H, NCH), 4.17 (q,
J = 7.2 Hz, 2H, OCH2CH3), 3.42–3.17 (m, 2H, PhCH2), 1.22 (t, J = 7.2 Hz, 3H,
OCH2CH3); 13C NMR (100 MHz, CDCl3) δ: 169.1 (C O), 136.9 (Cimi-2), 135.4,
129.3, 128.7, 127.3, 126.6, 118.1, 62.0 (NCHCO), 61.4 (OCH2CH3), 39.6 (CH2Ph), 13.9
(OCH2CH3); ESI MS m/z : 244.6 [M + H]+.
General Procedure to Prepare Compounds 4a–c
Compound 3a (11.80 g, 0.06 mol) was dissolved in anhydrous ethanol (60 mL). The
solution was cooled to 0◦C, and sodium borohydride (9.08 g, 0.24 mol) was added. The
mixture was then heated to reflux overnight. Water (20 mL) was added, and the pH was
regulated by sodium hydroxide to 14 before being extracted by ethyl acetate (3 × 20 mL).
The crude product was purified by silica column chromatography (ethyl acetate:alcohol,
18:1 v/v), and 4a was obtained. Compounds 4b–c were prepared by similar procedures.
The characterization data of 4a,b are consistent with literature.26
Compound 4c: Purified by silica column chromatography (ethyl acetate:alcohol,
11:1 v/v), yield: 65%; light yellow solid; mp 75–77◦C; [α]D25 (c = 2.0, EtOH): –109.5;
IR (ν cm−1): 3401 (N H), 3156 ( C H), 2938 (C H); 1H NMR (CDCl3, 400 MHz) δ:
7.26–6.87 (m, 8H, Himi & HAr), 5.62 (bs, 1H, OH), 4.25–4.19 (m, 1H, NCH), 3.85–3.79 (m,
2H, CH2OH), 3.17–3.12 (m, 1H, PhCH2), 3.00–2.84 (m, 1H, PhCH2); 13C NMR (CDCl3,
100 MHz) δ: 137.1 (Cimi-2), 136.4, 128.8, 128.8, 128.3, 127.3, 117.6, 63.9 (CH2OH), 62.1
(NCHCH2OH), 38.4 (CH2Ph); ESI MS m/z : 202.6 [M + H]+.
Procedure to Prepare Compound 5ꢀa
In a 100 mL flask, 4a (0.39 g, 2.50 mmol), triethylamine (0.7 mL, 5 mmol), and tosyl
chloride (0.72 g, 3.75 mmol) were dissolved in tetrahydrofuran (15 mL). The mixture was
heated to reflux, and the reaction was followed by TLC detection until the starting material
disappeared. The mixture was then filtered. The filtrate was concentrated and purified by
silica column chromatography (chloroform:acetone, 5:1 v/v). 5ꢁa was obtained with a yield
1
of 28%; H NMR (CDCl3, 400 MHz) δ: 7.64 (d, J = 8.3 Hz, 2H, HAr), 7.48 (s, 1H,
Himi-2), 7.32 (d, J = 8.0 Hz, 2H, HAr), 7.02 (s, 1H, Himi), 6.84 (s, 1H, Himi), 4.29–4.27
(m, 2H, NCHCH2O), 3.91–3.88 (m, 1H, NCH), 2.45 (s, 3H, PhCH3), 2.15–2.09 (m, 1H,
CH(CH3)2), 1.01 (d, J = 6.6 Hz, 3H, CH(CH3)2), 0.75 (d, J = 6.7, 3H, CH(CH3)2); 13C
ꢁ
NMR (100 MHz, CDCl3) δ: 145.4 (CPh-4 ), 139.9 (Cimi-2), 132.0, 130.1, 128.8, 127.9, 125.9,
69.6 (CH2OSO2), 55.0 (NCHCH2O), 30.0 (CH2Ph), 21.5 (CH(CH3)2), 19.5 (CH(CH3)2);
ESI MS m/z: 308.8 [M + H]+.
General Procedure to Prepare Compounds 6ad–cf
To a 100 mL flask containing 4a (1.54 g, 0.01 mol) and sodium carbonate (1.06 g, 0.01
mol), thionyl chloride (20 mL) was added dropwise at 45◦C. The mixture was kept at 45◦C
for 5 h before being heated to reflux for 2 h. The excessive thionyl chloride was removed
under reduced pressure. The residue was dissolved in water (10 mL), and the pH was
regulated to 7 by sodium bicarbonate before being extracted with ethyl acetate (3 × 10 mL).
The combined organic phase was dried over anhydrous sodium sulfate. After filtration and
concentration, 5a was produced.

NOVEL CHIRAL THIOETHER LIGANDS
2423
In a 100 mL flask, sodium hydroxide (1.20 g, 0.03 mol) and thiophenol (3.0 mL,
0.03 mol) were dissolved in ethanol (30 mL), and the solution was heated to 50◦C. An
ethanol solution (20 mL) of 5a was added dropwise, and the mixture was heated to reflux
overnight. The solvent was removed under reduced pressure, and the residue was extracted
by ether (3 × 10 mL). The crude product was purified by silica column chromatography
(petroleum ether:ethyl acetate, 2:3 v/v), and 6ad was obtained. Compounds 6ae–cf were
prepared by similar procedures.
Compound 6ad: Yellow oil; yield: 23.2%; [α]2D5 (c = 2.0, EtOH): +17.6; IR (ν
cm−1): 3105 ( C H), 2990 (C H), 2735 (CH2 S); 1H NMR (CDCl3, 400 MHz) δ: 7.51
(s, 1H, Himi-2), 7.23 (s, 1H, Himi), 6.94 (s, 1H, Himi), 3.81–3.76 (m, 1H, NCH), 2.98 (d
d, J = 13.8 Hz, J = 4.2 Hz, 1H, NCHCH2S), 2.85 (d d, J = 13.8 Hz, J = 9.2 Hz, 1H,
NCHCH2S), 2.28 (t, J = 7.2 Hz, 2H, SCH2CH2CH2CH3), 2.15–2.06 (m, 1H, CH(CH3)2),
1.50–1.43 (m, 2H, SCH2CH2CH2CH3), 1.38–1.26 (m, 2H, SCH2CH2CH2 CH3), 1.02 (d,
J = 6.7 Hz, 3H, CH(CH3)2), 0.87 (t, J = 7.3 Hz, 3H, SCH2CH2CH2CH3), 0.79 (d, J =
6.7 Hz, 3H, CH(CH3)2); 13C NMR (CDCl3, 100 MHz) δ: 137.1 (Cimi-2), 129.2, 117.2, 65.3
(NCHCH(CH3)2), 35.7, 32.7, 32.3, 31.6, 21.8, 20.0, 18.7, 13.6; HR MS m/z: 227.1501 [M
+ H]+ (calculated for C12H22N2O 226.1504).
Compound 6ae: Yellow oil; yield: 31.5%; [α]2D5 (c = 2.0, EtOH): +62.0; IR
(ν cm−1): 3341 (N H), 3098 ( C H), 2980 (C H), 2730 (CH2 S); 1H NMR (CDCl3,
400 MHz) δ: 7.42 (s, 1H, Himi-2), 7.28–7.20 (m, 5H, HAr), 7.06 (s, 1H, Himi), 6.86 (s, 1H,
Himi), 3.79–3.74 (m, 1H, NCH), 3.46 (d d, J = 13.9 Hz, J = 4.2 Hz, 1H, CH2S), 3.16 (d d,
J = 9.8 Hz, J = 4.2 Hz, 1H, CH2S), 2.16–2.04 (m, 1H, CH(CH3)2), 0.99 (d, J = 6.7 Hz, 3H,
CH(CH3)2), 0.77 (d, J = 6.7 Hz, 3H, CH(CH3)2); 13C NMR (CDCl3, 100 MHz) δ: 137.3
(Cimi-2), 134.8, 130.5, 129.4, 129.1, 127.0, 117.1, 63.6 (NCHCH2S), 38.1 (NCHCH2S),
32.9 (CH(CH3)2), 20.0, 18.7; HR MS m/z: 247.1189 [M + H]+ (calculated for C14H18N2O
246.1191).
Compound 6af: Yellow oil; yield: 29.4%; [α]2D5 (c = 2.0, EtOH): +37.0; IR
(ν cm−1): 3380 (N H), 3112 ( C H), 2985 (C H), 2743 (CH2 S); 1H NMR (CDCl3,
400 MHz) δ: 7.42 (s, 1H, Himi-2), 7.33–7.21 (m, 5H, HAr), 7.07 (s, 1H, Himi), 6.84 (s, 1H,
Himi), 3.59–3.53 (m, 1H, NCH), 3.49–3.40 (m, 2H, SCH2Ph), 2.86 (d d, 1H, J = 14.1 Hz,
J = 4.0 Hz, NCHCH2S), 2.69 (d d, 1H, J = 14.0 Hz, J = 9.6 Hz, NCHCH2S), 2.06–1.93
(m, 1H, CH(CH3)2), 0.88 (d, 3H, J = 6.7 Hz, CH3), 0.69 (d, 3H, J = 6.7 Hz, CH3); 13C
NMR (CDCl3, 100 MHz) δ: 137.9 (Cimi-2), 137.1, 129.2, 128.9, 128.5, 127.2, 117.2, 64.7
(NCHCH2S), 36.6 (PhCH2S), 34.8 (NCHCH2S), 32.7 (CH(CH3)2), 19.9, 18.7; HR MS
m/z: 261.1341 [M + H]+ (calculated for C15H20N2O 260.1347).
Compound 6bd: Yellow oil; yield: 35.6%; [α]2D5 (c = 2.0, EtOH): –10.7; IR
(ν cm−1): 3363 (N H), 3100 ( C H), 2965 (C H), 2710 (CH2 S); 1H NMR (CDCl3,
400 MHz) δ: 7.54 (s, 1H, Himi-2), 7.10 (bs, 2H, Himi), 4.19–4.14 (m, 1H, NCH), 2.85–2.74
(m, 2H, NCHCH2S), 2.25 (t, J = 7.2 Hz, 2H, SCH2CH2CH2CH3), 1.83–1.64 (m, 2H,
CH2CH(CH3)2), 1.50–1.30 (m, 5H, SCH2CH2CH2CH3 & CH(CH3)2), 0.91–0.86 (m, 9H,
3CH3); 13C NMR (CDCl3, 100 MHz) δ: 136.5 (Cimi-2), 129.6, 116.5, 57.2 (NCHCH2S),
43.7, 39.0, 32.5, 31.6, 24.6, 23.0, 21.8, 21.6, 13.6; HR MS m/z: 241.1657 [M + H]+
(calculated for C13H24N2O 240.1660).
Compound 6be: Yellow oil; yield: 38.8%; [α]2D5 (c = 2.0, EtOH): +57.7; IR
(ν cm−1): 3375 (N H), 3107 ( C H), 2956 (C H), 2710 (CH2 S); 1H NMR (CDCl3,
400 MHz) δ: 7.45 (s, 1H, Himi-2), 7.28–7.23 (m, 5H, HAr), 7.05 (s, 1H, Himi), 6.87 (s, 1H,
Himi), 4.16–4.10 (m, 1H, NCH), 3.23 (d d, J = 13.8 Hz, J = 5.7 Hz, 1H, CH2S), 3.14 (d
d, J = 13.8 Hz, J = 7.9 Hz, 1H, CH2S), 1.82–1.68 (m, 2H, CH2CH(CH3)2), 1.36–1.26

2424
P. MAO ET AL.
(m, 1H, CH(CH3)2), 0.84 (d, J = 5.0 Hz, 3H, CH(CH3)2), 0.83 (d, J = 5.0 Hz, 3H,
CH(CH3)2); 13C NMR (CDCl3, 100 MHz) δ: 136.6 (Cimi-2), 134.7, 130.4, 129.7, 129.2,
127.0, 116.3, 55.7 (NCHCH2S), 43.7 (CH2CH(CH3)2), 41.2 (NCHCH2S), 24.6, 23.0, 21.5;
HR MS m/z: 261.1342 [M + H]+ (calculated for C15H20N2O 260.1347).
Compound 6bf: yellow oil; yield: 37.6%; [α]2D5 (c = 2.0, EtOH): +31.5; IR
(ν cm−1): 3350 (N H), 3098 ( C H), 2981 (C H), 2723 (CH2 S); 1H NMR (CDCl3,
400 MHz) δ: 7.41 (s, 1H, Himi-2), 7.34–7.23 (m, 5H, HAr), 7.08 (s, 1H, Himi), 6.85 (s,
1H, Himi), 3.93–3.89 (m, 1H, NCH), 3.50–3.39 (m, 2H, SCH2Ph), 2.71 (d d, 1H, J =
14.1 Hz, J = 5.6 Hz, NCHCH2S), 2.64 (d d, 1H, J = 14.1 Hz, J = 7.9 Hz, NCHCH2S),
1.73–1.66 (m, 1H, CH2CH(CH3)2), 1.60–1.53 (m, 1H, CH2CH(CH3)2), 1.27–1.24 (m, 1H,
CH(CH3)2), 0.80 (t, J = 12.4 Hz, 6H, 2CH3); 13C NMR (CDCl3, 100 MHz) δ: 138.0
(Cimi-2), 136.6, 129.6, 128.9, 128.6, 127.3, 116.4, 56.7 (NCHCH2S), 43.5 (CH2CH(CH3)2),
38.1 (PhCH2S), 36.9 (NCHCH2S), 24.5, 23.1, 21.4; HR MS m/z: 275.1498 [M + H]+
(calculated for C16H22N2O 274.1504).
Compound 6cd: Yellow oil; yield: 79.8%; [α]2D5 (c = 2.0, EtOH): –41.8; IR (ν cm−1):
3110 ( C H), 2950 (C H), 2700 (CH2 S); 1H NMR (CDCl3, 400 MHz) δ: (m, 8H, Himi
& HAr), 4.31–4.27 (m, 1H, NCH), 3.23 (d d, J = 13.8 Hz, J = 5.8 Hz, 1H, CH2Ph), 3.04
(d d, J = 13.8 Hz, J = 8.5 Hz, 1H, CH2Ph), 2.94–2.83 (m, 2H, NCHCH2), 2.29 (t, J =
7.4 Hz, 2H, SCH2CH2CH2CH3), 1.48–1.30 (m, 4H, SCH2CH2 CH2CH3), 0.87 (t, J = 7.3
Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz) δ: 136.7 (Cimi-2), 136.5, 129.6, 128.8, 128.7,
127.0, 116.6, 60.5 (NCHCH2S), 55.7 (CH2Ph), 43.8 (NCHCH2S), 41.4, 37.4, 32.4, 31.6,
21.8, 13.6; HR MS m/z: 275.1498 [M + H]+ (calculated for C16H22N2O 274.1504).
Compound 6ce: Yellow oil; yield: 47.5%; [α]2D5 (c = 2.0, EtOH): +104.0; IR (ν
cm−1): 3348 (N H), 3109 ( C H), 2924 (C H), 2810 (CH2 S); 1H NMR (CDCl3, 400
MHz) δ: 7.28–6.86 (m, 13H, Himi & HAr), 4.27–4.20 (m, 1H, NCH), 3.36–3.00 (m, 4H,
NCHCH2S & CH2Ph); 13C NMR (CDCl3, 100 MHz) δ: 136.6 (Cimi-2), 136.4, 134.4, 130.3,
129.6, 129.2, 128.8, 128.7, 127.1, 127.0, 116.5, 59.2 (NCHCH2S), 41.5, 39.4; HR MS m/z:
295.1189 [M + H]+ (calculated for C18H18N2O 294.1191).
Compound 6cf: Yellow oil; yield: 45.6%; [α]2D5 (c = 2.0, EtOH): –67.0; IR (ν cm−1):
3280 (N H), 3098 ( C H), 2900 (C H), 2710 (CH2 S); 1H NMR (CDCl3, 400 MHz) δ:
7.39 (s, 1H, Himi-2), 7.37–6.85 (m, 12H, Himi & HAr), 4.07–4.03 (m, 1H, NCH), 3.51–3.43
(m, 2H, SCH2Ph), 3.13 (d d, 1H, J = 13.8 Hz, J = 6.0 Hz, NCHCH2S), 2.94 (d d, 1H, J =
13.8 Hz, J = 8.4 Hz, NCHCH2S), 2.81 (d d, 1H, J = 14.1 Hz, J = 5.7 Hz, NCHCH2Ph),
2.73 (d d, 1H, J = 14.1 Hz, J = 7.8 Hz, NCHCH2Ph); 13C NMR (CDCl3, 100 MHz)
δ: 137.9 (Cimi-2), 136.6, 136.5, 129.3, 129.0, 128.9, 128.8, 128.67, 128.5, 127.3, 127.0,
116.6, 60.2 (NCHCH2S), 41.4, 36.8, 36.5; HR MS m/z: 309.1345 [M + H]+ (calculated
for C19H20N2O 308.1347).
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