Access to imidazolidines via 1,3-Dipolar cycloadditions of 1,3,5-triazinanes with aziridines

Article abstract of DOI:10.1021/acs.joc.9b01959

The unprecedented 1,3-dipolar cycloaddition of 1,3,5-triazinanes and aziridines has been described. With readily available starting material, this method offers efficient access to a wide range of functionalized imidazolidine derivatives in moderate to good yields (up to 92percent) under mild conditions. Preliminary mechanistic investigations show that the ring opened zwitterionic pathway product dominated over the second-order nucleophilic substitution-like product. This protocol is very promising because the reaction is scalable, and gives versatile transformation of the products into other functionalized imidazolidines.

Full text of DOI:10.1021/acs.joc.9b01959

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Article
Access to Imidazolidines via 1,3-Dipolar
Cycloadditions of 1,3,5-Triazinanes with Aziridines
Liang Tu, Zheng-Hui Li, Tao Feng, Shuyan Yu, Rong Huang,
Jing Li, Wenxuan Wang, Yong-Sheng Zheng, and Ji-Kai Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01959 • Publication Date (Web): 29 Jul 2019
Downloaded from pubs.acs.org on July 29, 2019
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The Journal of Organic Chemistry
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Access to Imidazolidines via 1,3-Dipolar Cycloadditions of 1,3,5-
Triazinanes with Aziridines
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†
,⊥
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‡
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Liang Tu, Zhenghui Li, Tao Feng, Shuyan Yu, Rong Huang, Jing Li, Wenxuan Wang,
Yongsheng Zheng, and Jikai Liu
*,†
*,†
†
School of Pharmaceutical Sciences, National Demonstration Center for Experimental Ethnopharmacology Education, South-
Central University for Nationalities, Wuhan 430074, China
‡
College of Pharmacy, Inner Mongolia Medical University, Hohhot 010010, China
ABSTRACT: The unprecedented 1,3-dipolar cycloaddition of 1,3,5-triazinanes and aziridines has been described. With readily
available starting material, this method offers efficient access to a wide range of functionalized imidazolidine derivatives in moder-
ate to good yields (up to 92%) under mild conditions. Preliminary mechanistic investigations show that the ring opened zwitterionic
pathway product dominated over the S 2-like product. This protocol is very promising because the reaction is scalable, and the
N
versatile transformation of the products into other functionalized imidazolidines.
■ INTRODUCTION
Scheme 1. Imidazolidines synthesis and our work
Imidazolidine frameworks are ubiquitous in a myriad of natu-
1
ral alkaloids (e. g., (-)-Chaetominine ) and chiral ligands or
2
catalysts in organic catalysis (e. g., MacMillan’s catalyst) .
They also constitute important structural motifs in synthetic
3
biologically active compounds and could find great potential
4
in drug discovery, such as antipyretic agents and cannabinoid
5
CB2 receptor agonist (Figure 1.) . Although the importance of
imidazolidines has stimulated considerable interest from
chemists, limited approaches for the synthesis of imidazoli-
dines have been developed. Among the developed strategies,
the 1,3-dipolar cycloaddition of azomethine ylides with imines
is the most straightforward and convenient method for the
6
synthesis of functionalized imidazolines (Scheme 1a). Re
cently, Punniyamurthy reported the copper catalyzed nucleo-
3
philic ring opening, oxidative sp C−H functionalization, and
C−N bond formation of aziridines with N-alkylanilines for the
7
synthesis of imidazolidines (Scheme 1b). The Sun group de-
scribed the [4+1]/[2+1+2] cycloaddition of 1,3,5-triazines with
diazo esters and tosylhydrazones to form imidazolidines, re-
8
spectively (Scheme 1c). In addition, Wang and Zhang devel-
oped the [3+2] cycloaddition of imines with donor-acceptor
9
aziridines via C-C bond cleavages, respectively. Despite these
significant progresses in this field, most strategies reported so
far were limited to a few special substrates, mainly due to the
Figure 1. Representive biologically active compounds and
catalyst
6a-6c
dimerization of the azomethine ylides
philicity of imines . Therefore, the development of novel
and the low electro-
6d-6f
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method to access imidazolidines is challenge and highly desir- 11-12). For the solvent, dioxane, DCM and MeCN all led to
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able.
dramatically decreased yields, compared to that with toluene
(Table 1, entries 13-15 vs entry 8).
Aziridines are versatile synthons in 1,3-dipolar or zwitterion
cycloaddition for the synthesis of heterocyclic ring system.
1
0
Having established the optimal reaction conditions, we
thereby examined the substrate scope of this protocol by em-
ploying a variety of 1,3,5-triazinanes 1, and the results are
summarized in Scheme 2. First, 1,3,5-triazinanes with elec-
tron-donating groups were well tolerated, providing the corre-
sponding imidazolidines with decent yields (Scheme 2, 3ba-
3fa). However, the substrates with electron-donating substitu-
ents gave lower yields than the electron-neutral one did
(Scheme 2, 3ba-3fa vs 3aa). Next, several substrates with
electron-withdrawing groups were investigated under the reac-
tion conditions. Satisfyingly, the imidazolidines 3ga-3oa were
obtained in good to excellent yields, probably because of the
relative high electrophilicity of the corresponding formal-
dimines generated in situ. Polysubstituted 1,3,5-triazinanes
could also be compatible (Scheme 2, 3na-3pa). Moreover,
On the other hand, 1,3,5-triazinanes are bench stable precur-
sors of formaldimines which bear a nucleophilic nitrogen and
an electrophilic carbon atom, has been widely utilized in vari-
ous nitrogen-containing heterocycles construction and ami-
nomethylation reaction. Our group has recently reported the
first inverse-electron-demand [4+2]-cycloaddition of 1,3,5-
triazinanes for the efficient synthesis of tetrahydro-
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12
quinazolines. As our ongoing research program in the 1,3,5-
triazinanes chemistry, we envisioned that the 1,3-dipolar cy-
cloadditions of 1,3,5-triazinanes with aziridines would afford a
novel approach to the synthesis of biologically active imidaz-
olidines. This protocol represents the first example of 1,3-
dipolar cycloaddition of 1,3,5-triazinanes and aziridines.
■
RESULTS AND DISCUSSION
1
,3,5-triazinanes with groups at ortho position reacted well to
a
Table 1. Optimization of Reaction Conditions
yield the desired products without any losses of yield com-
pared to the meta- or para-substituted ones (Scheme 2, 3da vs
3
ba-3ca, 3ma-3pa vs 3ga-3la). Notably, the 1,3,5-triisobutyl-
1
,3,5-triazinane could also be subjected to the cyclization reac-
tion to give the desired product 3sa, albeit in slightly low
yields. However, no product was isolated and most of the sub-
strate decomposed when 1,3,5-tris(1-phenylethyl)-1,3,5-
triazinane was employed, and only trace of product was de-
tected by HRMS. Last, 1,3,5-triazinanes with ester group was
also suitable substrate to afford desired product 3ta in 78%
yield.
entry
Lewis acid
FeCl3
Sc(OTf)3
AlCl3
solvent
toluene
toluene
toluene
toluene
t (h)
24
48
22
10
48
48
24
36
20
36
63
63
36
48
48
yield
30
NR
34
1
2
3
4
5
6
7
8
9
Cu(OTf)2
52
a
Scheme 2. Scope of 1,3,5-triazianes
Cu(OAc)2 toluene
BF3
Zn(OTf)2
ZnBr2
ZnCl2
NR
NR
46
78
67
NR
71
78
56
36
toluene
toluene
toluene
toluene
10
Zn(OAc)2 toluene
b
ZnBr2
ZnBr2
ZnBr2
ZnBr2
ZnBr2
toluene
toluene
dioxane
DCE
1
1
c
1
1
2
3
1
1
4
5
MeCN
42
d
1
6
ZnBr2
toluene
36
69
a
The reactions were performed with 1a (0.2 mmol), 2a (0.24
mmol), and Lewis acid (0.04 mmol) in solvent (2.0 mL) at 80 ℃.
b
c
d
The reaction was ran at 60 ℃. The reaction was ran at 70 ℃. 1a
0.067 mmol) and 2a (0.20 mmol) were used.
(
Initially, 1,3,5-triphenyl-1,3,5-triazinane 1a and 2-phenyl-1-
tosylaziridine 2a were chosen as the substrates for the reaction
optimization. As shown in Table 1, the desired product imid-
azoline 3aa could be obtained in 30% yield in the presence of
2
0% FeCl in toluene at 80 ℃ (Table 1, entry 1). Because
3
Lewis acids can facilitate the nucleophilic ring opening of the
N-tosylaziridines and the formation of formaldimines from
1,3,5-triazinanes, a variety of Lewis acids were screened to
improve the reaction efficiency (Table 1, entries 2-10). ZnBr2
was found to be the most efficient catalyst and afforded the
desired product in 78 % yield (Table 1, entry 8), whereas oth-
ers resulted in a drop of the yield (Table 1, entries 3, 4, 7 and 9)
or no reaction (Table 1, entries 2, 5, 6 and 10). The reaction
efficiency was significantly decreased when the reaction was
conducted under lower temperature (Table 1, entry 8 vs entries
a
Reaction condition: 1 (0.2 mmol), 2a (0.24 mmol), and ZnBr2
(0.04 mmol) in toluene (2.0 mL) at 80 ℃ for 36 h.
a
Scheme 3. Scope of aziridines
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aromatic ring of 1,3,5-triazinanes on the reaction efficiency
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has been observed. Sterically more bulky group on the phenyl
ring of aziridines did not conspicuously influence the reaction
efficiency (Scheme 3, 3ad, 3aj and 3al). Reaction with sub-
strate bearing ester group also proceeded smoothly to afford
the desired product 3am. Vinyl substituted aziridines also
could be well tolerated under the conditions and gave the
product in 79% yield. Then aziridines bearing other functional
groups such as acetyl, Boc, Ms and Bn were examined. N-Ms
and N-Bn aziridines gave the corresponding product in 83%
and 76% yield (3aq and 3ar), respectively. However, the N-
acetyl aziridine is totally inactive under the reaction conditions
(3ao). The N-Boc aziridine gave the Boc-deprotected imidaz-
olidine in 36% yield under the acidic condition (3ap).
1
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To further explore the synthetic application of this trans-
formation, we performed the reaction of 1k with 2a on a 4.2
mmol scale and isolated the 3ka in 81% yield, which could be
converted to 4 via Suzuki coupling (Scheme 4). The N-Ts
group of cycloadduct 3ka could be easily removed with mag-
nesium in methanol to give the imidazolidine 5 in 71% yield,
which could be further converted to a pharmaceutically im-
portant imidazolidine 6 in 70% yield.
To gather information for a mechanistic study, we conduct-
ed this 1,3-dipolar cycloaddition reaction using enantioen-
riched aziridines 2a to explore the stereochemistry of this
transformation (Scheme 5). The corresponding 3aa was ob-
tained in 83% yield with 22% ee, a significant loss in the ste-
reochemical purity from the enantioriched aziridine.
Scheme 5. Stereochemistry and mechanistic investigation.
a
Reaction condition: 1 (0.2 mmol), 2a (0.24 mmol), and ZnBr2
0.04 mmol) in toluene (2.0 mL) at 80 ℃ for 36 h.
(
Scheme 4. Gram scale experiment and product derivation
13
Based on these obtained results and literature information,
we proposed a mechanism. As depicted in Scheme 6, the for-
maldimine was first generated in the presence of Lewis acid.
Next, formaldimine attacked the activated aziridine through an
SN2-like pathway, leading to the inversion of configuration
and the ring open of the aziridine. Meanwhile, the racemic
product was generated through the ring opened zwitterion,
which served as both a nucleophile and an electrophile to react
with N-phenyl formaldimine. The ee value of 3aa suggested
that the ring opened zwitterionic pathway product dominated
over the S 2-like product.
N
Scheme 6. A Plausible Reaction Mechanism
Subsequently, a variety of substituted aziridines was tested
for the imidazolidines formation. As shown in Scheme 3. The
substrates bearing electron-donating or electron-withdrawing
groups could take part in this transformation smoothly, afford-
ing the corresponding products (3ab−3an) in moderate to high
yields. It was noteworthy that aziridines with electron-
donating groups were more efficient than substrates bearing
electron-withdrawing groups (Scheme 3, 3ab-3ad vs 3ae-3al).
Furthermore, strong electron-withdrawing substituent, such as
trifluoromethyl group, has significant adverse effect to the
reaction efficiency (Scheme 3, 3ae), presumably due to the
electronic effects. Negligible steric effect of substitutent on the
In summary, we have established an unprecedented 1,3-
dipolar cycloadditions of 1,3,5-triazinanes with aziridines un-
der mild conditions, providing an efficient access to function-
alized imidazolidines. Preliminary mechanistic studies were
also conducted to elucidate the mechanism. This protocol is
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very promising because the reaction is scalable, and the prod-
ucts can be readily converted to other functionalized imidazol-
idines.
4-Phenyl-3-(m-tolyl)-1-tosylimidazolidine (3ca). White sol-
id (54.9 mg, yield: 70 %); mp 126-127︒C. H NMR (600
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
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4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
MHz, CDCl ): δ 7.67 (d, J = 8.1 Hz, 2H), 7.26-7.19 (m, 5H),
3
7.10 (d, J = 6.4 Hz, 2H), 6.97 (t, J = 7.8 Hz, 1H), 6.54 (d, J =
7.4 Hz, 1H), 6.21 (s, 1H), 6.15 (d, J = 8.1 Hz, 1H), 5.02 (d, J =
.8 Hz, 1H), 4.72 (d, J = 5.8 Hz, 1H), 4.60-4.35 (m, 1H), 3.88
■
EXPERIMENTAL SECITON
5
(
2
1
1
General Information. Unless otherwise specified, all reac-
tions were carried out under a nitrogen atmosphere in anhy-
drous conditions. All chemicals and solvents which are com-
mercially available were used without further purification.
Analytical thin-layer chromatography (TLC) was performed
on silica gel plates (GF-254) using UV-light (254 and 365 nm).
Flash chromatography was conducted on silica gel (200-300
dd, J = 10.2, 7.5 Hz, 1H), 3.44 (dd, J = 10.3, 5.0 Hz, 1H),
1
3
1
.38 (s, 3H), 2.21 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ
3
44.9, 144.3, 140.6, 138.9, 132.7, 129.9, 129.9, 128.9, 127.9,
27.6, 125.9, 119.2, 113.7, 110.3, 66.1, 61.4, 55.6, 21.8, 21.6;
IR 3032, 2918, 1603, 1489, 1344, 1159, 1030, 853, 665, 550;
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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3
4
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6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
+
HRMS (ESI) m/z calcd for C H N SO [M+H] 393.1631,
23
25
2
2
found 393.1629.
mesh). NMR spectra were recorded at ambient temperature in
1
4-Phenyl-3-(o-tolyl)-1-tosylimidazolidine (3da). A white
CDCl on a Bruker AMX600 ( H NMR at 600 MHz and
1
3
1
3
1
solid (54.9 mg, yield: 70 %); mp 118-119︒C. H NMR (600
C{ H} NMR at 150MHz) spectrometer. Chemical shifts
MHz, CDCl ): δ 7.75 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 8.0 Hz,
3
were reported in parts per million (ppm) downfield from an
internal standard, tetramethylsilane (0 ppm). All high resolu-
tion mass spectra were obtained on a Agilent 6200 Q-TOF MS.
Melting points were determined on a WRX-4 melting point
2
H), 7.16-7.14 (m, 3H), 7.12-7.05 (m, 3H), 6.96 (t, J = 7.3 Hz,
1H), 6.90 (t, J = 7.1 Hz, 1H), 6.79 (d, J = 7.9 Hz, 1H), 4.85 (d,
J = 6.8 Hz, 1H), 4.58 (t, J = 7.4 Hz, 1H), 4.22 (d, J = 6.8 Hz,
1H), 3.96 (dd, J = 9.9, 6.6 Hz, 1H), 3.34-3.26 (m, 1H), 2.46 (s,
12,14
15
apparatus. 1,3,5-Triazinanes , N-Ts aziridines , N-Benzyl
1
3
1
1
6
17
18
3H), 2.16 (s, 3H); C{ H} NMR (150 MHz, CDCl ); δ 144.1,
3
aziridine , N-Boc aziridine and N-Ms aziridine were pre-
1
1
2
43.9, 137.8, 133.6, 133.2, 131.2, 129.9, 128.6, 127.9, 127.8,
26.9, 126.6, 124.2, 119.9, 68.9, 63.9, 54.8, 21.7, 18.6; IR
976, 2830, 1597, 1495, 1341, 1167, 1094, 665, 592, 546;
pared according to the literature procedures.
General procedure for the synthesis of 3. To a dried test
tube with a magnetic stirring bar under N at room temperature
+
+
2
HRMS (ESI) m/z calcd for C H N SO [M+H] 393.1631,
23
25
2
2
were added 1,3,5-triazinane 1a (0.24 mmol, 75.6 mg) and
aziridine 2a (0.20 mmol, 54.6 mg), followed by the addition of
found 393.1629.
3
-(4-Isopropylphenyl)-4-phenyl-1-tosylimidazolidine (3ea).
ZnBr (0.04 mmol, 9.0 mg). Then toluene (2.00 mL) was in-
2
1
White solid (49.2 mg, yield: 59 %); mp 100-101︒C. H NMR
600 MHz, CDCl ): δ 7.67 (d, J = 8.2 Hz, 2H), 7.25-7.21 (m,
troduced by syringe, and the mixture was stirred at 80 ℃ in an
oil bath for 36 h. The reaction was then quenched with an
aqueous Na CO solution (10 mL) and extracted with ethyl
(
5
3
H), 7.11 (d, J = 7.8 Hz, 2H), 6.98 (d, J = 8.6 Hz, 2H), 6.33 (d,
J = 8.6 Hz, 2H), 5.04 (d, J = 5.8 Hz, 1H), 4.68 (d, J = 5.8 Hz,
H), 4.50 (dd, J = 7.2, 5.5 Hz, 1H), 3.88 (dd, J = 10.3, 7.5 Hz,
H), 3.43 (dd, J = 10.3, 5.3 Hz, 1H), 2.83-2.65 (m, 1H), 2.39
2
3
acetate (15 mL) for three times. The combined organic layer
was washed with brine (15 mL × 3), dried over Na SO and
1
1
2
4
the solvent was removed by rotary evaporation. The residue
was purified by column chromatography on silica gel (petrole-
um: ethyl acetate = 10:1 to 5:1) to afford the desired product
(s, 3H), 1.15 (d, J = 3.6 Hz, 3H), 1.14 (d, J = 3.6 Hz, 3H);
1
3
1
C{ H} NMR (150 MHz, CDCl ): δ 144.3, 143.1, 140.7,
3
1
6
1
38.8, 132.7, 129.9, 128.9, 127.9, 127.6, 127.0, 125.9, 113.1,
6.4, 61.9, 55.6, 33.1, 24.2, 24.2, 21.6; IR 1616, 1522, 1387,
350, 1163, 814, 698, 667, 590, 548; HRMS (ESI) m/z calcd
3
aa.
3
,4-Diphenyl-1-tosylimidazolidine (3aa). White solid (60.7
1
+
+
mg, yield: 80 %); mp 110-111︒C. H NMR (600 MHz,
for C H N SO [M+H] 421.1944, found 421.1943.
2
5
29
2
2
CDCl ): δ 7.67 (d, J = 8.2 Hz, 2H), 7.24-7.21 (m, 5H), 7.12-
3
3
-(4-Methoxyphenyl)-4-phenyl-1-tosylimidazolidine (3fa).
7
5
.09 (m, 4H), 6.72 (t, J = 7.3 Hz, 1H), 6.36 (d, J = 8.1 Hz, 2H),
.02 (d, J = 5.9 Hz, 1H), 4.74 (d, J = 5.9 Hz, 1H), 4.58-4.43
1
White solid (56.9 mg, yield: 70 %); mp 135-136︒C. H NMR
600 MHz, CDCl ): δ 7.69 (d, J = 8.1 Hz, 2H), 7.25-7.22 (m,
(
3
(m, 1H), 3.91 (dd, J = 10.4, 7.4 Hz, 1H), 3.44 (dd, J = 10.4,
1
3
1
5H), 7.09 (d, J = 7.5 Hz, 2H), 6.69 (d, J = 8.9 Hz, 2H), 6.35 (d,
J = 9.0 Hz, 2H), 5.03 (d, J = 5.8 Hz, 1H), 4.65 (d, J = 5.8 Hz,
H), 4.44 (t, J = 6.6 Hz, 1H), 3.93 (dd, J = 10.3, 7.5 Hz, 1H),
5.2 Hz, 1H), 2.38 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ
3
144.8 , 144.4, 140.4, 132.7, 129.9 , 129.1, 128.9, 127.9, 127.7,
1
3
1
1
25.9, 118.3, 113.0, 66.1, 61.5, 55.5, 21.6; IR 3028.2, 2918.3,
599, 1508, 1346, 1159, 1030, 747, 667, 550; HRMS (ESI)
.68 (s, 3H), 3.38 (dd, J = 10.4, 6.0 Hz, 1H), 2.40 (s, 3H);
1
3
1
+
+
C{ H} NMR (150 MHz, CDCl ): δ 152.7, 144.3, 140.3,
3
m/z calcd for C H N SO
[M+H] 379.1475, found
2
2
23
2
2
1
39.4, 132.9, 129.9, 128.9, 127.9, 127.7, 126.0, 114.8, 114.6,
3
79.1473.
67.1, 62.2, 55.6, 21.6; IR 2916, 2849, 1514, 1348, 1242, 1161,
4
-Phenyl-3-(p-tolyl)-1-tosylimidazolidine (3ba). White solid
+
1034, 812, 667, 548; HRMS (ESI) m/z calcd for C H N SO
[M+H] 409.1580, found 409.1578.
2
3
25
2
3
1
+
(
60.4 mg, yield: 77 %); mp 130-131︒C. H NMR (600 MHz,
CDCl ): δ 7.67 (d, J = 8.0 Hz, 2H), 7.27-7.15 (m, 5H), 7.09 (d,
3
3-(4-Fluorophenyl)-4-phenyl-1-tosylimidazolidine
White solid (67.4 mg, yield: 85 %); mp 138-139︒C. H NMR
(3ga).
J = 7.2 Hz, 2H), 6.91 (d, J = 8.2 Hz, 2H), 6.29 (d, J = 8.3 Hz,
1
2
H), 5.02 (d, J = 5.7 Hz, 1H), 4.69 (d, J = 5.7 Hz, 1H), 4.49 (t,
(600 MHz, CDCl ): δ 7.68 (d, J = 8.2 Hz, 2H), 7.28-7.21 (m,
3
J = 6.3 Hz, 1H), 3.90 (dd, J = 10.2, 7.5 Hz, 1H), 3.41 (dd, J =
13
1
5H), 7.13-7.04 (m, 2H), 6.81 (t, J = 8.7 Hz, 2H), 6.29 (dd, J =
1
0.3, 5.4 Hz, 1H), 2.38 (s, 3H), 2.18 (s, 3H); C{ H} NMR
9
1
3
.1, 4.2 Hz, 2H), 5.00 (d, J = 5.9 Hz, 1H), 4.71 (d, J = 5.9 Hz,
H), 4.44 (t, J = 6.6 Hz, 1H), 3.95 (dd, J = 10.5, 7.4 Hz, 1H),
(
150 MHz, CDCl ): δ 144.3, 142.7, 140.5, 132.8, 129.9, 129.7,
3
128.9, 127.9, 127.6, 127.6 125.9, 113.4, 66.5, 61.7, 55.6, 21.6,
20.4; IR 3030, 2920, 1618, 1524, 1348, 1163, 1028, 799, 669,
1
3
1
.40 (dd, J = 10.5, 5.9 Hz, 1H), 2.40 (s, 3H); C{ H} NMR
): δ 156.20 (d, J = 237.1 Hz), 144.4, 141.4
d, J = 1.7 Hz), 140.0, 132.8, 129.9, 128.9, 127.9, 125.9, 115.6
d, J = 22.3 Hz), 114.1 (d, J = 7.5 Hz), 66.7, 62.0, 55.7, 21.6;
+
+
(150 MHz, CDCl
3
588; HRMS (ESI) m/z calcd for C H N SO [M+H]
2
3
25
2
2
(
(
3
93.1631, found 393.1630.
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The Journal of Organic Chemistry
(m, 1H), 3.95 (dd, J = 10.6, 7.4 Hz, 1H), 3.44 (dd, J = 10.7,
IR 2920, 1518, 1344, 1227, 1161, 1030, 814, 669, 588, 548;
HRMS (ESI) m/z calcd for C H FN SO [M+H] 397.1381,
+
+
13
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
5.4 Hz, 1H), 2.40 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ
2
2
22
2
2
3
found 397.1381.
-(3-Fluorophenyl)-4-phenyl-1-tosylimidazolidine
White solid (65.4 mg, yield: 83 %); mp: 148-151︒C.
145.9, 144.5, 139.6, 132.6, 130.3, 129.9, 129.0, 127.9, 127.7,
125.8, 123.1, 121.0, 115.5, 111.5, 65.9, 61.2, 55.6, 21.6; IR
1593, 1487, 1346, 1159, 1092, 1028, 849, 762, 669, 550;
3
(3ha).
1
H
+
+
HRMS (ESI) m/z calcd for C H BrN SO [M+H] 457.0580,
2
2
22
2
2
NMR (600 MHz, CDCl ): δ 7.67 (d, J = 8.2 Hz, 2H), 7.26-
3
found 457.0580.
3-(2-Bromophenyl)-4-phenyl-1-tosylimidazolidine
White solid (74.2 mg, yield: 81 %); mp: 130-132︒C. H
7.22 (m, 5H), 7.10 (d, J = 7.7 Hz, 2H), 7.04 (dd, J = 15.1, 8.1
Hz, 1H), 6.40 (m, 1H), 6.13 (d, J = 8.3 Hz, 1H), 6.01 (d, J =
(3ma).
1
1
1
1.8 Hz, 1H), 4.97 (d, J = 6.1 Hz, 1H), 4.76 (d, J = 6.1 Hz,
H), 4.56-4.38 (m, 1H), 3.94 (dd, J = 10.6, 7.4 Hz, 1H), 3.45
NMR (600 MHz, CDCl ): δ 7.76 (d, J = 8.2 Hz, 2H), 7.46 (d, J
3
1
3
1
(dd, J = 10.7, 5.3 Hz, 1H), 2.39 (s, 3H); C{ H} NMR (150
= 7.9 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.19-7.14 (m, 5H),
7.03 (dd, J = 11.9, 4.8 Hz, 1H), 6.81 (dd, J = 11.9, 4.6 Hz, 1H),
6.77 (d, J = 8.1 Hz, 1H), 5.24 (d, J = 6.9 Hz, 1H), 4.70 (dd, J =
8.1, 6.8 Hz, 1H), 4.34 (d, J = 6.9 Hz, 1H), 4.02 (dd, J = 10.0,
6.5 Hz, 1H), 3.23 (dd, J = 9.9, 8.5 Hz, 1H), 2.43 (s, 3H);
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
MHz, CDCl ): δ 163.59 (d, J = 243.5 Hz), 146.3 (d, J = 10.6
3
Hz), 144.5, 139.8, 132.7, 130.3 (d, J = 10.1 Hz), 129.9, 129.0,
1
=
1
27.9 (d, J = 16.7 Hz), 125.8, 108.6 (d, J = 2.2 Hz), 104.8 (d, J
21.5 Hz), 100.1 (d, J = 26.2 Hz), 65.9, 61.5, 55.6, 21.6; IR
622, 1584, 1506, 1385, 1344, 1196, 1159, 816, 671, 550;
1
3
1
C{ H} NMR (150 MHz, CDCl ): δ 144.2, 144.1, 137.4,
3
+
+
HRMS (ESI) m/z calcd for C H FN SO [M+H] 397.1381,
134.0, 133.5, 129.9, 128.7, 128.1, 128.0, 127.9, 126.9, 125.2,
121.4, 119.1, 68.5, 63.4, 54.8, 21.7; IR 2922, 2851, 1514,
1348, 1244, 1161, 1032, 814, 667, 546; HRMS (ESI) m/z
2
2
22
2
2
found 397.1380.
4
-Phenyl-1-tosyl-3-(4-(trifluoromethyl)phenyl)imidazolidine
+
+
calcd for C H BrN SO [M+H] 457.0580, found 457.0579.
22 22
2
2
(
3ia). White solid (78.1 mg, yield: 88 %); mp: 133-135︒C.
1
H NMR (600 MHz, CDCl ): δ 7.59 (d, J = 8.1 Hz, 2H), 7.24
3-(4-Bromo-2-fluorophenyl)-4-phenyl-1-tosylimidazolidine
3
(d, J = 8.5 Hz, 2H), 7.18-7.16 (m, 3H), 7.12 (d, J = 8.0 Hz,
2H), 7.01 (dd, J = 15.5, 9.4 Hz, 2H), 6.27 (d, J = 8.6 Hz, 2H),
(3na). White solid (81.1 mg, yield: 86 %); mp: 150-152︒C.
1
H NMR (600 MHz, CDCl ): δ 7.72 (d, J = 8.1 Hz, 2H), 7.27
3
4
4
1
.90 (dd, J = 18.2, 6.3 Hz, 1H), 4.77 (d, J = 6.4 Hz, 1H), 4.46-
.41 (m, 1H), 3.91 (dd, J = 10.7, 7.4 Hz, 1H), 3.40 (dd, J =
0.8, 5.3 Hz, 1H), 2.29 (s, 3H); C{ H} NMR (150 MHz,
(d, J = 8.0 Hz, 2H), 7.22-7.16 (m, 3H), 7.11 (d, J = 12.2 Hz,
1H), 7.07-7.02 (m, 2H), 6.85 (dd, J = 8.6, 0.9 Hz, 1H), 6.17 (t,
J = 8.9 Hz, 1H), 5.15 (dd, J = 7.4, 2.5 Hz, 1H), 4.69 (dd, J =
7.4, 2.2 Hz, 1H), 4.47 (t, J = 7.5 Hz, 1H), 4.07 (dd, J = 10.9,
7.1 Hz, 1H), 3.19 (dd, J = 10.9, 8.2 Hz, 1H), 2.41 (s, 3H);
1
3
1
CDCl ): δ 145.8, 143.6, 138.4, 131.6, 128.9, 128.1, 127.0,
3
1
26.7, 125.3, 125.3, 125.3, 124.7, 111.1, 64.5, 60.2, 54.6, 20.5;
13
1
IR 1618, 1533, 1335, 1167, 1105, 1071, 820, 669, 610, 552;
C{ H} NMR (150 MHz, CDCl ): δ 153.11 (d, J = 247.5 Hz),
3
+
+
HRMS (ESI) m/z calcd for C H N F SO [M+H] 447.1349,
144.5, 138.1, 133.2, 132.7 (d, J = 10.2 Hz), 130.0, 129.0,
128.1, 128.0, 127.2 (d, J = 3.1 Hz), 126.2, 119.53 (d, J = 23.9
Hz), 118.5 (d, J = 4.2 Hz), 111.8 (d, J = 9.2 Hz), 67.8 (d, J =
11.4 Hz), 62.0, 55.0, 21.7; IR 1607, 1506, 1341, 1163, 1092,
968, 791, 762, 667, 546; HRMS (ESI) m/z calcd for
2
3
22
2
3
2
found 447.1347.
-(4-Chlorophenyl)-4-phenyl-1-tosylimidazolidine 1 (3ja).
White solid (75.8 mg, yield: 92 %); mp 140-142︒C. H NMR
600 MHz, CDCl ): δ 7.59 (d, J = 8.1 Hz, 2H), 7.17-7.13 (m,
3
(
3
+
+
C H FBrN SO [M+H] 475.0486, found 475.0486.
22 21
2
2
5
H), 6.99 (d, J = 7.6 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 6.17 (d,
J = 8.9 Hz, 2H), 4.89 (d, J = 6.1 Hz, 1H), 4.66 (d, J = 6.1 Hz,
1H), 4.45-4.30 (m, 1H), 3.87 (dd, J = 10.6, 7.4 Hz, 1H), 3.34
3-(2,4-Dibromophenyl)-4-phenyl-1-tosylimidazolidine (3oa).
1
White solid (85.4 mg, yield: 80 %); mp: 133-136︒C.
H
1
3
1
(dd, J = 10.6, 5.5 Hz, 1H), 2.30 (s, 3H); C{ H} NMR (150
NMR (600 MHz, CDCl ): δ 7.68 (d, J = 8.1 Hz, 2H), 7.53 (d, J
3
MHz, CDCl ): δ 143.4, 142.2, 138.7, 131.6, 128.9, 127.9,
= 2.0 Hz, 1H), 7.23 (d, J = 7.9 Hz, 2H), 7.12-7.10 (m, 3H),
7.07-7.04 (m, 3H), 6.51 (d, J = 8.7 Hz, 1H), 5.14 (d, J = 7.0
Hz, 1H), 4.57 (t, J = 7.5 Hz, 1H), 4.26 (d, J = 7.0 Hz, 1H),
3.96 (dd, J = 10.1, 6.6 Hz, 1H), 3.16-3.13 (m, 1H), 2.37 (s,
3
1
27.9, 126.8, 126.7, 124.8, 122.1, 113.0, 65.0, 60.4, 54.6, 20.5;
IR 1599, 1503, 1348, 1161, 1098, 1028, 810, 669, 611, 554;
+
+
HRMS (ESI) m/z calcd for C H ClN SO [M+H] 413.1085,
2
2
22
2
2
13
1
found 413.1085.
-(4-Bromophenyl)-4-phenyl-1-tosylimidazolidine
White solid (76.2 mg, yield: 84 %); mp: 145-147︒C.
NMR (600 MHz, CDCl ): δ 7.67 (d, J = 8.2 Hz, 2H), 7.27-
3H); C{ H} NMR (150 MHz, CDCl ): δ 143.3, 142.3, 135.9,
3
1
35.1, 132.3, 129.8, 128.8, 127.8, 127.1, 126.9 125.8, 121.2,
118.2, 115.7, 67.2, 62.2, 53.7, 20.6; IR 2916, 2849, 1597,
474, 1341, 1161, 1092, 812, 664, 592; HRMS (ESI) m/z
3
(3ka).
1
H
1
3
+
+
calcd for C H Br N SO [M+H] 534.9685, found =
2
2
21
2
2
2
7
2
.21 (m, 5H), 7.17 (d, J = 9.0 Hz, 2H), 7.08 (d, J = 7.7 Hz,
H), 6.21 (d, J = 9.0 Hz, 2H), 4.96 (d, J = 6.1 Hz, 1H), 4.74 (d,
534.9687.
J = 6.1 Hz, 1H), 4.51-4.38 (m, 1H), 3.96 (dd, J = 10.6, 7.4 Hz,
3-(2,4-Dichlorophenyl)-4-phenyl-1-tosylimidazolidine (3pa).
1
3
1
1
1
H), 3.43 (dd, J = 10.7, 5.6 Hz, 1H), 2.40 (s, 3H); C{ H}
White solid (78.4 mg, yield: 88 %); mp: 155-157︒C. H
NMR (150 MHz, CDCl ): δ 144.5, 143.7, 139.7, 132.7, 131.8,
NMR (600 MHz, CDCl ): δ 7.68 (d, J = 8.1 Hz, 2H), 7.23 (d, J
3
3
129.9, 129.0, 127.9, 127.8, 125.8, 114.6, 110.4, 65.9, 61.5,
55.6, 21.6; IR 1595, 1491, 1387, 1350, 1165, 808, 704, 669,
= 8.0 Hz, 2H), 7.20 (d, J = 2.3 Hz, 1H), 7.12-7.10 (m, 3H),
7.03 (d, J = 7.6 Hz, 2H), 6.84 (dd, J = 8.7, 2.2 Hz, 1H), 6.49 (d,
J = 8.8 Hz, 1H), 5.14 (d, J = 7.2 Hz, 1H), 4.55-4.53 (m, 1H),
4.34 (d, J = 7.2 Hz, 1H), 3.98 (dd, J = 10.4, 6.7 Hz, 1H), 3.12
+
+
610, 552; HRMS (ESI) m/z calcd for C H BrN SO [M+H]
2
2
22
2
2
4
57.0580, found 457.0580.
1
3
1
(
dd, J = 9.9, 9.2 Hz, 1H), 2.37 (s, 3H); C{ H} NMR (150
3-(2-Bromophenyl)-1-tosyl-1,2,3,4-tetrahydroquinazoline
(3la). White solid (73.4 mg, 81 %); mp: 130-133︒C.
1
MHz, CDCl ) δ 143.3, 140.4, 136.1, 132.3, 129.3, 128.9,
3
H
1
5
6
27.9, 127.4, 127.1, 127.0 126.2, 125.6, 119.9, 67.1, 61.8,
3.7, 20.6; IR 2943, 2884, 1597, 1476, 1346, 1165, 1090, 669,
NMR (600 MHz, CDCl ): δ 7.67 (d, J = 8.1 Hz, 2H), 7.29-
3
7
6
4
.20 (m, 5H), 7.09 (d, J = 7.4 Hz, 2H), 6.93 (t, J = 8.1 Hz, 1H),
.83 (d, J = 7.8 Hz, 1H), 6.46 (s, 1H), 6.24 (d, J = 8.2 Hz, 1H),
.96 (d, J = 6.2 Hz, 1H), 4.77 (d, J = 6.2 Hz, 1H), 4.50-4.35
+
10, 550; HRMS (ESI) m/z calcd for C H Cl N SO
2
2
21
2
2
2
+
[
M+H] 447.0695, found 447.0696.
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3
-(3-Chloro-4-methylphenyl)-4-phenyl-1-tosylimidazolidine 129.6, 129.1, 128.8, 128.6, 127.9, 127.9, 126.5, 125.9, 123.0,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
118.2, 118.2, 113.0, 66.1, 66.1, 61.6, 61.2, 55.7, 55.6, 21.6,
21.5, 21.2; IR 2920, 2860, 1599, 1506, 1350, 1163, 1092, 748,
(
3qa). Yellow solid (70.1 mg, yield: 82 %); mp: 148-150︒C.
H NMR (600 MHz, CDCl ): δ 7.67 (d, J = 8.1 Hz, 2H), 7.25-
7.22 (m, 5H), 7.09-7.06 (m, 2H), 6.91 (d, J = 8.4 Hz, 1H), 6.35
(d, J = 2.3 Hz, 1H), 6.15 (dd, J = 8.4, 2.3 Hz, 1H), 4.96 (d, J =
.1 Hz, 1H), 4.72 (d, J = 6.1 Hz, 1H), 4.43 (t, J = 6.4 Hz, 1H),
.94 (dd, J = 10.6, 7.4 Hz, 1H), 3.41 (dd, J = 10.6, 5.6 Hz, 1H),
.39 (s, 3H), 2.19 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ
44.5, 143.9, 139.9, 134.8, 132.8, 131.2, 129.9, 129.0, 127.9,
27.8, 125.9, 125.3, 113.5, 111.7, 66.2, 61.5, 55.6, 21.6, 18.9;
IR 1613, 1508, 1346, 1161, 816, 791, 762, 700, 669, 550;
HRMS (ESI) m/z calcd for C H ClN SO [M+H] 427.1242,
1
3
+
+
664, 548; HRMS (ESI) m/z calcd for C23
393.1631, found 393.1632.
H N SO [M+H]
25 2 2
6
3
2
1
1
3-Phenyl-4-(o-tolyl)-1-tosylimidazolidine (3ad). White solid
1
(60.1 mg, yield: 77 %); mp: 150-152︒C. H NMR (600 MHz,
1
3
1
3
CDCl ): δ 7.66 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H),
3
7
6
6
.15-7.08 (m, 4H), 7.00-6.89 (m, 2H), 6.71 (t, J = 7.3 Hz, 1H),
.25 (d, J = 8.1 Hz, 2H), 5.04 (d, J = 6.2 Hz, 1H), 4.81 (d, J =
.2 Hz, 1H), 4.68-4.46 (m, 1H), 3.98 (dd, J = 10.5, 7.5 Hz,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
+
2
3
24
2
2
1H), 3.36 (dd, J = 10.5, 5.6 Hz, 1H), 2.38 (s, 3H), 2.32 (s, 3H);
13
1
found 427.1241.
C{ H} NMR (150 MHz, CDCl ): δ 144.8, 144.4, 137.8,
3
3
-Isobutyl-4-phenyl-1-tosylimidazolidine (3sa). Yellow sol-
134.1, 132.8, 130.8, 129.9, 129.1, 127.8, 127.4, 126.7, 125.3,
118.2, 112.8, 66.1, 58.7, 54.1, 21.6, 19.3; IR 1599, 1508, 1385,
1346, 1157, 1094, 1034, 747, 667, 598; HRMS (ESI) m/z
1
id (43.1 mg, yield: 60 %); mp: 70-72︒C. H NMR (600 MHz,
CDCl ): δ 7.76 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H),
.25-7.19 (m, 3H), 7.01 (dd, J = 6.4, 2.9 Hz, 2H), 4.65 (d, J =
6.8 Hz, 1H), 3.72 (dd, J = 9.9, 7.0 Hz, 1H), 3.65 (d, J = 6.8 Hz,
1H), 3.45 (dd, J = 9.0, 7.2 Hz, 1H), 3.07 (t, J = 9.6 Hz, 1H),
2.48 (s, 3H), 2.02-1.84 (m, 2H), 1.61-1.47 (m, 1H), 0.72 (d, J
3
+
+
7
calcd for C23
H N SO [M+H] 393.1631, found 393.1630.
25 2 2
3
-Phenyl-1-tosyl-4-(4-(trifluoromethyl)phenyl)imidazolidine
1
(
3ae). Thick liquid (42.5 mg, yield: 48 %); H NMR (600
MHz, CDCl ): δ 7.65 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.0 Hz,
2H), 7.20 (d, J = 7.3 Hz, 4H), 7.14 (t, J = 7.9 Hz, 2H), 6.76 (t,
J = 7.3 Hz, 1H), 6.34 (d, J = 8.1 Hz, 2H), 5.07 (d, J = 5.9 Hz,
3
1
3
1
=
6.7 Hz, 6H); C{ H} NMR (150 MHz, CDCl ): δ 142.8,
3
1
5
1
37.5, 132.7, 128.6, 127.5, 127.0, 126.9, 126.6, 69.2, 67.5,
8.5, 54.0, 26.2, 20.6, 20.0, 18.9; IR 2963, 2805, 1599, 1337,
165, 1107, 1011, 667, 588, 548; HRMS (ESI) m/z calcd for
1
3
H), 4.74 (d, J = 5.9 Hz, 1H), 4.62 (dd, J = 7.0, 4.7 Hz, 1H),
.94 (dd, J = 10.5, 7.6 Hz, 1H), 3.50 (dd, J = 10.6, 4.5 Hz, 1H),
+
+
1
3
1
C H N SO [M+H] 359.1788, found 359.1785.
0
2
27
2
2
2.39 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ 144.7,
3
Ethyl 4-(5-phenyl-3-tosylimidazolidin-1-yl)benzoate (3ta).
White solid (70.1 mg, yield: 78 %); mp: 170-172︒C.
NMR (600 MHz, CDCl ): δ 7.72 (d, J = 8.8 Hz, 2H), 7.60 (d, J
8.2 Hz, 2H), 7.19-7.17 (m, 3H), 7.15 (d, J = 8.1 Hz, 2H),
.02-7.00 (m, 2H), 6.24 (d, J = 8.8 Hz, 1H), 4.94 (d, J = 6.4
Hz, 1H), 4.79 (d, J = 6.4 Hz, 1H), 4.48 (dd, J = 7.0, 5.3 Hz,
H), 4.21 (qd, J = 7.0, 1.3 Hz, 2H), 3.89 (dd, J = 10.7, 7.4 Hz,
H), 3.42 (dd, J = 10.7, 5.0 Hz, 1H), 2.31 (s, 3H), 1.25 (t, J =
7.1 Hz, 3H); C{ H} NMR (150 MHz, CDCl ): δ 166.6, 147.7,
144.6, 139.6, 132.6, 131.6, 131.1, 130.0, 129.1, 128.0, 127.8,
25.8, 119.7, 113.8, 111.9, 65.4, 61.1, 60.4, 55.6, 21.6, 14.4;
IR 2984, 1701, 1611, 1344, 1283, 1159, 1109, 770, 671, 554;
HRMS (ESI) m/z calcd for C H N SO [M+H] 451.1685,
found 451.1685.
144.5, 144.4, 132.8, 129.9, 129.3, 127.8, 126.3, 125.9, 125.8
1
1
1
18.7, 113.0, 65.9, 61.1, 55.2, 21.5; IR 2920, 2851, 1601,
506, 1325, 1163, 1067, 750, 665, 596; HRMS (ESI) m/z
H
3
+
+
calcd for C H F N SO [M+H] 447.1349, found 447.1347.
=
7
23 22
3
2
2
4-(4-Fluorophenyl)-3-phenyl-1-tosylimidazolidine
White solid (57.6 mg, yield: 70 %); mp: 168-170︒C.
NMR (600 MHz, CDCl ): δ 7.66 (d, J = 8.1 Hz, 2H), 7.22 (d, J
(3af).
1
H
1
1
3
=
8.0 Hz, 2H), 7.11 (t, J = 7.9 Hz, 2H), 7.09-7.04 (m, 2H),
6.90 (t, J = 8.6 Hz, 2H), 6.73 (t, J = 7.3 Hz, 1H), 6.35 (d, J =
.1 Hz, 2H), 5.03 (d, J = 5.8 Hz, 1H), 4.70 (d, J = 5.8 Hz, 1H),
4.56-4.48 (m, 1H), 3.87 (dd, J = 10.4, 7.4 Hz, 1H), 3.43 (dd, J
1
3
1
3
8
1
1
3
1
= 10.4, 4.8 Hz, 1H), 2.38 (s, 3H); C{ H} NMR (150 MHz,
CDCl ): δ 162.2 (d, J = 246.0 Hz), 144.5 (d, J = 16.7 Hz),
+
+
25
27
2
4
3
1
36.2 (d, J = 3.0 Hz), 132.7, 129.9, 129.2, 127.8, 127.6 (d, J =
3
-Phenyl-4-(p-tolyl)-1-tosylimidazolidine (3ab). White solid
8.2 Hz), 118.5, 115.8 (d, J = 21.6 Hz), 113.0, 65.9, 60.8, 55.6,
1
2
5
3
1.6; IR 3065, 2920, 1601, 1508, 1346, 1163, 1028, 829, 667,
(
63.0 mg, yield: 80 %); mp: 160-162︒C. H NMR (600 MHz,
CDCl ): δ 7.59 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 7.9 Hz, 2H),
.02 (t, J = 7.7 Hz, 2H), 6.96 (d, J = 7.7 Hz, 2H), 6.91 (d, J =
.8 Hz, 2H), 6.62 (t, J = 7.2 Hz, 1H), 6.28 (d, J = 8.0 Hz, 2H),
.92 (d, J = 5.8 Hz, 1H), 4.66 (d, J = 5.8 Hz, 1H), 4.40 (t, J =
.1 Hz, 1H), 3.84-3.77 (m, 1H), 3.34 (dd, J = 10.3, 5.2 Hz,
H), 2.30 (s, 3H), 2.21 (s, 3H); C{ H} NMR (150 MHz,
CDCl ): δ 144.9, 144.3, 137.4, 132.7, 129.9, 129.6, 129.1,
127.9, 125.9, 118.2, 113.0, 66.1, 61.3, 55.7, 21.6, 21.2; IR
1599, 1508, 1350, 1163, 1028, 812, 745, 667, 600, 550;
HRMS (ESI) m/z calcd for C H N SO [M+H] 393.1631,
+
+
50; HRMS (ESI) m/z calcd for C H FN SO [M+H]
22 22
2
2
3
97.1381, found 397.1380.
7
7
4
6
1
4-(3-Fluorophenyl)-3-phenyl-1-tosylimidazolidine
White solid (61.7 mg, yield: 75 %); mp: 165-166︒C.
(3ag).
1
H
NMR (600 MHz, CDCl ): δ 7.58 (d, J = 8.1 Hz, 2H), 7.17-
3
1
3
1
7
.13 (m, 3H), 7.05 (t, J = 7.9 Hz, 2H), 6.85-6.80 (m, 2H), 6.67
3
(t, J = 7.3 Hz, 1H), 6.62 (d, J = 9.5 Hz, 1H), 6.28 (d, J = 8.1
Hz, 2H), 4.97 (d, J = 6.0 Hz, 1H), 4.64 (d, J = 6.0 Hz, 1H),
4
.53-4.35 (m, 1H), 3.84 (dd, J = 10.5, 7.6 Hz, 1H), 3.39 (dd, J
+
+
13 1
23
25
2
2
= 10.6, 4.8 Hz, 1H), 2.31 (s, 3H); C{ H} NMR (150 MHz,
found 393.1631.
CDCl ): δ 163.1 (d, J = 247.0 Hz), 144.6, 143.4 (d, J = 6.5 Hz),
3
3-Phenyl-4-(m-tolyl)-1-tosylimidazolidine (3ac). White sol-
id (64.2 mg, yield: 82 %); mp: 158-160︒C. H NMR (600
MHz, CDCl ): δ 7.59 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 8.1 Hz,
H), 7.06-7.00 (m, 3H), 6.98-6.89 (m, 2H), 6.87-6.80 (m, 1H),
.64 (t, J = 6.1 Hz, 1H), 6.35-6.17 (m, 2H), 4.93 (dd, J = 8.6,
.9 Hz, 1H), 4.66 (d, J = 5.9 Hz, 1H), 4.43-4.35 (m, 1H), 3.81
dd, J = 10.3, 7.5 Hz, 1H), 3.40-3.30 (m, 1H), 2.30 (s, 3H),
.20 (d, J = 15.4 Hz, 3H); C{ H} NMR (150 MHz, CDCl ): δ
132.7, 130.5 (d, J = 8.2 Hz), 129.9, 129.2, 127.8, 121.6 (d, J =
1
2
2
1
.7 Hz), 118.6, 114.7 (d, J = 21.2 Hz), 113.1, 112.80 (d, J =
2.3 Hz), 66.0, 61.1 (d, J = 1.3 Hz), 55.3, 21.6; IR 2924, 1603,
508, 1346, 1159, 1028, 750, 667, 590, 552; HRMS (ESI) m/z
3
2
6
5
(
2
1
+
+
calcd for C H FN SO [M+H] 397.1381, found 397.1380.
22 22
2
2
4-(4-Chlorophenyl)-3-phenyl-1-tosylimidazolidine
Yellow solid (58.1 mg, yield: 71 %); mp: 174-177︒C. H
(3ah).
1
13
1
3
NMR (600 MHz, CDCl ): δ 7.55 (d, J = 8.2 Hz, 2H), 7.13-
3
44.9, 144.9, 144.3, 140.5, 138.6, 137.4, 137.4, 132.7, 129.9,
7
.06 (m, 4H), 7.02 (t, J = 7.9 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H),
ACS Paragon Plus Environment

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The Journal of Organic Chemistry
.64 (t, J = 7.3 Hz, 1H), 6.24 (d, J = 8.1 Hz, 2H), 4.93 (d, J =
6
NMR (600 MHz, CDCl ): δ 7.90 (d, J = 8.2 Hz, 2H), 7.65 (d, J
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
5.9 Hz, 1H), 4.61 (d, J = 5.9 Hz, 1H), 4.42 (dd, J = 7.1, 4.8 Hz,
1H), 3.79 (dd, J = 10.5, 7.5 Hz, 1H), 3.40-3.29 (m, 1H), 2.29
= 8.2 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.2 Hz,
2H), 7.12 (t, J = 8.0 Hz, 2H), 6.74 (t, J = 7.3 Hz, 1H), 6.34 (d,
J = 8.1 Hz, 2H), 5.06 (d, J = 6.0 Hz, 1H), 4.75 (d, J = 6.0 Hz,
1H), 4.59 (dd, J = 7.3, 5.0 Hz, 1H), 3.95 (dd, J = 10.6, 7.6 Hz,
1
3
1
(s, 3H); C{ H} NMR (150 MHz, CDCl ): δ 144.5, 144.5,
3
1
1
8
39.1, 133.3, 132.8, 129.9, 129.3, 129.0, 127.8, 127.4, 118.5,
13.0, 65.9, 60.8, 55.4, 21.6; IR 1601, 1506, 1344, 1159, 1088,
20, 750, 667, 600, 550; HRMS (ESI) m/z calcd for
1
3
1
1H), 3.90 (s, 3H), 3.55-3.43 (m, 1H), 2.39 (s, 3H); C{ H}
NMR (150 MHz, CDCl ): δ 166.7, 145.7, 144.5, 144.5, 132.8,
3
+
+
C H ClN SO [M+H] 413.1085, found 413.1085. I
130.2, 129.9, 129.9, 129.6, 129.3, 127.8, 125.9, 118.6, 113.0,
2
2
22
2
2
6
6.0, 61.3, 55.2, 52.2, 21.6; IR 2924, 1724, 1508, 1350, 1283,
4
-(3-Chlorophenyl)-3-phenyl-1-tosylimidazolidine
(3ai).
1
1161, 1028, 667, 600, 550; HRMS (ESI) m/z calcd for
White solid (57.7 mg, yield: 70 %); mp: 169-170︒C.
H
+
+
C H N SO [M+H] 437.1530, found 437.1529.
24
25
2
4
NMR (600 MHz, CDCl ): δ 7.59 (d, J = 8.2 Hz, 2H), 7.17-
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7
(
.08 (m, 4H), 7.06 (dd, J = 8.5, 7.5 Hz, 2H), 6.97 (s, 1H), 6.94
d, J = 6.9 Hz, 1H), 6.68 (t, J = 7.3 Hz, 1H), 6.28 (d, J = 8.0
Hz, 2H), 4.97 (d, J = 6.0 Hz, 1H), 4.64 (d, J = 6.0 Hz, 1H),
3-Phenyl-1-tosyl-4-vinylimidazolidine (3an). White solid
1
(52.0 mg, yield: 79 %); mp: 157-158︒C. H NMR (600 MHz,
CDCl ): δ 7.61 (d, J = 8.2 Hz, 2H), 7.15 (d, J = 8.1 Hz, 2H),
3
4
3
.41 (dd, J = 7.4, 5.0 Hz, 1H), 3.82 (dd, J = 10.6, 7.5 Hz, 1H),
.38 (dd, J = 10.6, 4.9 Hz, 1H), 2.32 (s, 3H); C{ H} NMR
7.08 (dd, J = 8.3, 7.6 Hz, 2H), 6.65 (t, J = 7.3 Hz, 1H), 6.36 (d,
J = 8.0 Hz, 2H), 5.46 (ddd, J = 17.0, 10.2, 6.7 Hz, 1H), 5.03
(dd, J = 33.1, 13.7 Hz, 2H), 4.67 (d, J = 5.7 Hz, 1H), 4.48 (d, J
= 5.7 Hz, 1H), 3.96 (dd, J = 11.1, 6.8 Hz, 1H), 3.53 (dd, J =
10.2, 7.2 Hz, 1H), 3.31 (dd, J = 10.3, 4.2 Hz, 1H), 2.28 (s, 3H);
1
3
1
(150 MHz, CDCl ): δ 144.5, 144.5, 142.8, 134.8, 132.6, 130.3,
3
129.9, 129.3, 128.0, 127.8, 126.0, 124.2, 118.6, 113.1, 66.0,
61.1, 55.3, 21.6; IR 1601, 1508, 1385, 1348, 1163, 1090, 748,
+
13
1
6
[
89, 667, 552; HRMS (ESI) m/z calcd for C H ClN SO
C{ H} NMR (150 MHz, CDCl ): δ 144.8, 144.4, 136.0,
22 22
2
2
3
+
M+H] 413.1085, found 413.1085.
4-(2-Chlorophenyl)-3-phenyl-1-tosylimidazolidine
White solid (52.1 mg, yield: 63 %); mp: 110-111︒C.
NMR (600 MHz, CDCl ): δ 7.58 (d, J = 8.2 Hz, 2H), 7.28 (d, J
132.7, 129.9, 129.2, 127.9, 118.2, 117.6, 113.0, 65.0 59.7,
2.8, 21.6; IR 2826, 1510, 1385, 1350, 1159, 932, 747, 665,
5
(3aj).
+
+
1
600, 550; HRMS (ESI) m/z calcd for C H N SO [M+H]
18 21 2 2
H
3
29.1318, found 329.1318;
1,5-Diphenylimidazolidine (3ap). Pink oil (16.1 mg, yield:
3
=
7.5 Hz, 1H), 7.14-7.07 (m, 3H), 7.04 (t, J = 7.9 Hz, 2H),
1
6
1
.95 (t, J = 7.4 Hz, 1H), 6.93-6.89 (m, 1H), 6.66 (t, J = 7.3 Hz,
H), 6.19 (d, J = 8.1 Hz, 2H), 5.00 (d, J = 6.0 Hz, 1H), 4.75
36 %). H NMR (600 MHz, CDCl ): δ 7.44-7.30 (m, 3H), 7.21
3
(d, J = 6.5 Hz, 2H), 7.10 (t, J = 7.8 Hz, 2H), 6.71 (t, J = 7.3 Hz,
1H), 6.57 (d, J = 7.9 Hz, 2H), 4.95 (dd, J = 14.5, 5.2 Hz, 1H),
4.73 (t, J = 8.3 Hz, 1H), 4.46 (t, J = 8.9 Hz, 1H), 4.19 (dd, J =
(dd, J = 7.4, 4.3 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 3.91 (dd, J
=
10.8, 7.6 Hz, 1H), 3.46 (dd, J = 10.8, 4.3 Hz, 1H), 2.29 (s,
13
1
13
1
3
1
H); C{ H} NMR (150 MHz, CDCl ): δ 144.4, 1144.3,
37.4, 132.6, 132.2, 129.9, 129.7, 129.3, 128.9, 127.8, 127.4,
14.6, 7.5 Hz, 1H), 4.10 (s, 1H), 4.02-3.91 (m, 1H); C{ H}
NMR (150 MHz, CDCl ): δ 157.3, 144.2, 136.4, 128.5, 128.4,
3
3
127.3, 118.4, 112.7, 65.8, 58.8, 53.9, 21.6; IR 1603, 1508,
1391, 1348, 1159, 1032, 758, 667, 604, 550; HRMS (ESI) m/z
126.0, 117.9, 112.3, 69.1, 57.6, 50.9; IR 3412, 1732, 1653,
1603, 1495, 1215, 814, 748, 692, 505; HRMS (ESI) m/z calcd
+
+
+
+
calcd for C H ClN SO [M+H] 413.1085, found 413.1087.
for C15H N [M+H] 225.1386, found 225.1385.
17 2
2
2
22
2
2
4-(4-Bromophenyl)-3-phenyl-1-tosylimidazolidine
White solid (66.8 mg, yield: 73 %); mp: 170-171︒C.
(3ak).
1-(Methylsulfonyl)-3,4-diphenylimidazolidine (3aq). Light
1
1
H
red solid (50.2 mg, yield: 83%); mp: 135-136︒C. H NMR
NMR (600 MHz, CDCl ): δ 7.64 (d, J = 7.8 Hz, 2H), 7.32 (d, J
(600 MHz, CDCl ): δ 7.24 (d, J = 7.2 Hz, 2H), 7.19 (dd, J =
3
3
= 8.0 Hz, 2H), 7.20 (d, J = 7.7 Hz, 2H), 7.12 (t, J = 7.5 Hz,
7.7, 3.9 Hz, 3H), 7.08 (dd, J = 8.6, 7.4 Hz, 2H), 6.69 (t, J = 7.3
Hz, 1H), 6.43 (d, J = 7.9 Hz, 2H), 5.01 (d, J = 6.3 Hz, 1H),
4.79 (dd, J = 7.2, 5.2 Hz, 1H), 4.75 (d, J = 6.3 Hz, 1H), 4.01
(dd, J = 10.9, 7.5 Hz, 1H), 3.49 (dd, J = 10.9, 5.0 Hz, 1H),
2
H), 6.95 (d, J = 8.0 Hz, 2H), 6.73 (t, J = 7.1 Hz, 1H), 6.34 (d,
J = 7.9 Hz, 2H), 5.02 (s, 1H), 4.71 (d, J = 5.7 Hz, 1H), 4.53-
4
3
1
6
7
.47 (m, 1H), 3.93-3.85 (m, 1H), 3.48-3.41 (m, 1H), 2.39 (s,
1
3
1
13
1
H); C{ H} NMR (150 MHz, CDCl ): δ 144.5, 144.5, 139.6,
2.68 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ 143.6,
3
3
32.8, 132.0, 129.9, 129.3, 127.8, 127.7, 121.5, 118.6, 113.0,
5.9, 60.9, 55.3, 21.7; IR 1601, 1506, 1344, 1159, 1030, 816,
48, 667, 600, 550; HRMS (ESI) m/z calcd for
139.3, 128.3, 128.0, 126.9, 125.0, 117.6, 112.4, 64.7, 60.6,
54.5, 35.3; IR 1601, 1508, 1329, 1221, 1153, 1034, 955, 748,
+
+
698, 525; HRMS (ESI) m/z calcd for C16
303.1162, found 303.1160.
H N O S [M+H]
19 2 2
+
+
C H BrN SO [M+H] 457.0580, found 457.0580.
2
2
22
2
2
4
-(2-Bromophenyl)-3-phenyl-1-tosylimidazolidine
(3al).
1-Benzyl-3,4-diphenylimidazolidine (3ar). White solid
1
1
White solid (59.4 mg, yield: 65 %); mp: 175-176︒C.
H
(47.8mg, yield: 76% ); mp 100-101︒C. H NMR (600 MHz,
NMR (600 MHz, CDCl ): δ 7.67 (d, J = 8.2 Hz, 2H), 7.54 (dd,
CDCl ): δ 7.35-7.27 (m, 9H), 7.27-7.20 (m, 2H), 7.15 (d, J =
3
3
J = 7.5, 1.4 Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.15-7.05 (m,
8.8 Hz, 2H), 6.26 (d, J = 8.9 Hz, 2H), 4.67 (dd, J = 6.5, 5.2 Hz,
1H), 4.39 (d, J = 4.6 Hz, 1H), 4.05 (d, J = 4.6 Hz, 1H), 3.71 (q,
J = 13.0 Hz, 2H), 3.29 (dd, J = 9.2, 7.2 Hz, 1H), 2.89 (dd, J =
4
H), 6.99 (dd, J = 7.3, 1.9 Hz, 1H), 6.73 (t, J = 7.3 Hz, 1H),
6.25 (d, J = 8.0 Hz, 2H), 5.09 (d, J = 6.1 Hz, 1H), 4.78 (dd, J =
7.4, 4.4 Hz, 1H), 4.74 (d, J = 6.1 Hz, 1H), 4.00 (dd, J = 10.8,
7.6 Hz, 1H), 3.52 (dd, J = 10.9, 4.4 Hz, 1H), 2.37 (s, 3H);
1
3
1
9.4, 4.9 Hz, 1H); C{ H} NMR (150 MHz, CDCl ): δ 145.0,
3
142.2, 138.1, 131.7, 128.8, 128.7, 128.6, 127.5, 127.4, 126.3,
114.1, 108.8, 72.0, 62.4, 62.3, 58.3; IR 3030, 2872, 1599,
1508, 1452, 1368, 1219, 1186, 748, 692; HRMS (ESI) m/z
1
3
1
C{ H} NMR (150 MHz, CDCl ): δ 144.4, 144.2, 138.9,
3
1
1
1
33.0, 132.7, 129.9, 129.3, 129.2, 128.0, 127.8, 127.5, 122.1,
18.4, 112.7, 66.0 61.1, 54.0, 21.6; IR·1601, 1510, 1387, 1352,
159, 1034, 818, 747, 665, 550; HRMS (ESI) m/z calcd for
+
+
calcd for C22
-([1,1'-Biphenyl]-4-yl)-4-phenyl-1-tosylimidazolidine (4).
To a solution of 3ak (200 mg, 0.630 mmol) in toluene (10 mL)
under a nitrogen atmosphere was added Pd(P(Ph) (73 mg,
.063 mmol). After stirring 30 min, a solution of phenyl-
H N [M+H] 315.1856, found 315.1856.
23 2
3
+
+
C H BrN SO [M+H] 457.0580, found 457.0580.
2
2
22
2
2
Methyl 4-(3-phenyl-1-tosylimidazolidin-4-yl)benzoate (3am).
)
3 4
1
0
White solid (52.4 mg, yield: 60 %); mp: 170-171︒C.
H
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 10
boronic acid in ethanol (5mL) and saturated NaHCO (3mL)
was added. Then mixture was heated to reflux for 24 h. After
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI:
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
cooling to room temperature, the mixture was added saturated
aqueous NaCl solution and extracted with ethyl acetate. The
organic layer was combined, washed with saturated brine,
dried with anhydrous Na SO , and concentrated. The residue
1
13
Copies of H, C NMR spectra data for all compounds (PDF)
2
4
■ AUTHOR INFORMATION
was chromatographed on silica gel to give the desired product
1
Corresponding Authors
4
as a white solid (180 mg, yield: 62 %). mp: 135-136︒C; H
*
*
E-mail: zhysh@mail.scuec.edu.cn (Y.-S.Z.)
E-mail: liujikai@mail.scuec.edu.cn (J.-K.L.)
NMR (600 MHz, CDCl ): δ 7.68 (d, J = 8.2 Hz, 2H), 7.46 (d, J
3
=
6
7.4 Hz, 2H), 7.38-7.32 (m, 4H), 7.23 (dd, J = 19.7, 7.6 Hz,
H), 7.12 (d, J = 6.5 Hz, 2H), 6.42 (d, J = 8.7 Hz, 2H), 5.05 (d,
J = 6.0 Hz, 1H), 4.80 (d, J = 6.0 Hz, 1H), 4.61-4.49 (m, 1H),
.93 (dd, J = 10.4, 7.4 Hz, 1H), 3.46 (dd, J = 10.5, 5.2 Hz, 1H),
Author Contributions
⊥
These authors contributed equally.
Notes
0
1
2
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7
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9
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7
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9
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3
1
3
1
2.37 (s, 3H); C{ H} NMR (150 MHz, CDCl ): δ 144.4, 144.2,
3
The authors declare no competing financial interest
140.8, 140.3, 132.7, 131.1, 130.0, 129.0, 128.8, 128.7, 127.9,
127.8, 127.8, 126.4, 126.4, 126.0, 113.4, 66.1, 61.6, 55.6, 21.6;
IR 2918, 1614, 1526, 1489, 1346, 1161, 818, 760, 669, 548;
■
ACKNOWLEDGMENT
+
+
HRMS (ESI) m/z calcd for C H N SO [M+H] 455.1788,
We are grateful to the National Natural Science Foundation of
China (no. 81773590, 31801789, 21502239, 81561148013,
28 27
2
2
found 455.1787.
8
1872762, 31870513, 31560010) and “the Fundamental Research
1
-(4-Bromophenyl)-5-phenylimidazolidine (5). To a solution
Funds for the Central Universities”, the South-Central University
for Nationalities (no. CZQ19013) for support of this research.
of 3ak (200 mg, 0.438 mmol) in MeOH (20 mL) were added
Mg turnings (105 mg, 4.38 mmol), the resulting mixture was
refluxed until confirmed to be complete by TLC. The mixture
was added 1 N HCl to remove excess Mg, then NaOH was
added to adjust pH of aqueous to pH = 10. The aqueous layer
was extracted with ethyl acetate. The organic layer was com-
bined, washed with saturated brine, dried with anhydrous
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.88 (d, J = 8.1 Hz, 1H), 7.64 (td, J = 8.1, 1.5 Hz, 1H), 7.44-
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2
22
2
■
ASSOCIATED CONTENT
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