One-Pot Methylenation-Cyclization Employing Two Molecules of CO2 with Arylamines and Enaminones

Article abstract of DOI:10.1021/acs.joc.9b02858

One-pot methylenation-cyclization employing two molecules of CO₂ with enaminones and primary aromatic amines was discussed for the first time to access cyclized products. This 1,5,7-triazabicyclo[4.4.0]dec-5-ene and ZnCl₂-catalyzed p

Full text of DOI:10.1021/acs.joc.9b02858

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Article
One-pot Methylenation-Cyclization Employing Two
Molecules of CO2 with Arylamines and Enaminones
Yulei Zhao, Xu Liu, Lijun Zheng, Yulan Du, Xinrui Shi, Yunlin
Liu, Zhengquan Yan, Jinmao You, and Yuan-Ye Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02858 • Publication Date (Web): 06 Dec 2019
Downloaded from pubs.acs.org on December 8, 2019
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Page 1 of 32
The Journal of Organic Chemistry
One-pot Methylenation-Cyclization Employing Two Molecules of CO2 with
1
2
3
4
5
Arylamines and Enaminones
6
7
8
,
Yulei Zhao*,† Xu Liu,† Lijun Zheng,† Yulan Du,† Xinrui Shi,† Yunlin Liu,‡ Zhengquan Yan*,† Jinmao You*,† § and
9
Yuanye Jiang*,†
10
11
12
† School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, 273165, China.
‡ School of Chemistry and Chemical Engineering, Guangzhou University, Guangzhou, 510006, China.
§ Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, 810001, China.
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O
R2
R3
R1
N
ZnCl2
Nu
Nu
TBD
Nu
CO
2
+
+
2
H2C
CH2
N
R4
Hydrosilane
Abstract: One-pot methylenation-cyclization employing two molecules of CO2 with enaminones and
primary aromatic amines was discussed for the first time to access cyclized products. This 1,5,7-
triazabicyclo[4.4.0]dec-5-ene (TBD) and ZnCl2 catalyzed procedure was characterized by the selective
conversion of two molecules of CO2 into methylene groups in a multi-component cyclization reaction.
According to the computational study and control experiments, the reaction might proceed through the
generation of bis(silyl)acetal, condensation of arylamine and aza-Diels-Alder processes. Moreover, the
resulting products will probably be potential organic building-ins with adjustable photophysical
properties.
■ INTRODUCTION
Carbon dioxide (CO2) refers to a very abundant, renewable and nontoxic one-carbon (C1) source
when compared with other C1 sources for producing chemicals.1 However, the current application of
CO2 primarily emphasizes the transformation of its single molecule during a reaction. Developing
effective strategies to employ bi- or multi-molecules of CO2 during a reaction will be favorable for the
CO2 reuse. Recently, the reductive functionalization of CO2 has aroused ever-increasing attention
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worldwide. These reductive processes can achieve the formylation,2 methylenation,3 methylation,4 etc.5
of nucleophiles in a controllable manner. The oxidation state of carbon in CO2 can reduce to +II, 0 or -II
valence state via 2-, 4- or 6-electron reduction, respectively.6 However, given that the reduction of the
C0 species (i.g., formaldehyde) to C-II species (i.g., methylamine, methanol) is usually more rapid than
that of C+II (i.g., formamide, formic acid) to C0 species, it is challenging to isolate or trap the C0
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species.6a,7
a) By Cantat's group, He's group and Han's group
H2
R1
H
R1
R1
Hydrosilanes
C
N
R2
CO2
+
2
N
N
Glycine betaine or TBD
R2 R2
b) By Klankermayer's group
H2
C
Co(BF4)2/Triphos, H2
HNTf2, THF
2 MeOH
c) By Xi's group
CO2
Me
R
Me
CO2
+
O
O
H2
C
NaBH4 / I2
+
2 R-SH
R
S
S
1,4-dioxane
d) Previous Strategy
CO2
H2
C
Reductant
+
2
Nu
Nu
Nu
e) This work
Nu
H2C
Nu
CH2
Reductant
Nu
CO
2
Nu
+
Nu
+
2
Nu
Scheme 1. CO2 methylenation reactions
In recent years, great effort has been devoted to the conversion of CO2 for methylenation chemicals.
Employing hydrosilane as reductant and CO2 as C1 feedstock, Oestreich,8 Piers,9 and Berke10 identified
the formation of active bis(silyl)acetal C0 species. In 2015, Cantat6a et al. reported an elegant 4-electron
reduction of CO2 in the presence of secondary aromatic amines to access aminals (C0) (Scheme 1a).
He7b and Han11 converted CO2 with amines to furnish formamides, aminals or methylamines
controllably by tactfully using the naturally occurring glycine betaine (GB) as catalyst. In 2015, Sabo-
Etienne and Bontemps’s group6d reported a significant iron-catalyzed reduction of CO2 into methylene
group. In 2017, Klankermayer12 et al. built an efficacious tailor-made molecular cobalt catalyst system
to convert CO2 into dialkoxymethane ethers (C0) (Scheme 1b). Furthermore, CO2 was also adopted as
C1 source for the methylenation to handily achieve olefination of phosphorus ylides13 (Xia’s group), the
synthesis of spiro-indolepyrrolidines14 (Xia’s group) and dithioacetals15 (Xi’s group, under distinctive
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NaBH4/I2 System, Scheme 1c). In all the above studies, CO2 was converted into methylene in a highly
selective manner, whereas these CO2 methylenation reactions almost focused on the application of
single molecule of CO2 during a reaction (Scheme 1d).
1
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3
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5
6
7
8
9
To our best knowledge, despite the mentioned achievements, the reductive methylenation reaction
involving bi- or multi-molecules of CO2 has not been reported. Accordingly, it is required to formulate
feasible methylenation strategies to employ two molecules or multi-molecules of CO2 for the formation
of value-added fine chemicals. Based on our research on one-pot or tandem reactions,16 we thought that
to introduce 1,1- and asymmetric 1,3-dinucleophilic reagents may be feasible to capture two molecules
of CO2 in a cyclization reaction (Scheme 1e). Here, we wish to report our efforts in developing such an
unprecedented tandem bimolecular CO2 methylenation cyclization sequence to synthesize
tetrahydropyrimidine derivatives17, which often exhibit unique therapeutic properties (i.g. anti-
inflammatory activity18, muscarinic agonist activity19 and antiviral activity20).
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■ RESULTS AND DISCUSSION
Enaminone, exhibiting high N-21, C-22 and O-nucleophilicity23, shows a wide range of synthetic
6b
applications.24 Hydrosilane reductant exhibits a kinetic advantage over H2 and it can be effectively
activated by metal-free Lewis bases or Lewis acids.25 Thus, with 1,5,7-triazabicyclo[4.4.0]dec-5-ene
(TBD) as the catalyst and phenylsilane as the reductant, aniline and enaminone 1a were taken as the
nucleophiles to implement our one-pot tandem reaction strategy (Scheme 1e).
When toluene, 1,4-dioxane or tetrahydrofuran was adopted as the solvent, the initial trials did not
yield any desired product as required. It is noteworthy that when acetonitrile was used as the solvent,
tetrahydropyrimidine derivative (2aa) could be isolated in 52% yield (Table 1, entry 1: using 1.5 eq. of
aniline). This initial result verified the feasibility of our hypothesis and laid a basis for the study of
methylenation-cyclization reaction involving two molecules of CO2. Then, the amount of aniline was
screened (entries 2-4). When 2 eq. of aniline was employed, the yield of 2aa was up-regulated to 83%
(entry 2). When the amount further rose to 2.5 and 3 eq., 88% and 92%
Table 1. Optimization of the Reaction Conditionsa
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O
NHPh
1a
(0.125 mmol)
Cat.2, (0.5 eq.)
Temp.2 = 100 oC, 12 h (t2)
O
Cat.1 (0.5 eq.)
Silane
Ph
1
2
3
Ph
Ph
N
(y eq.)
2 CO2
+
PhNH2
(x eq.)
H2C
2aa
CH2
MeCN, Temp.1
6 h (t1)
N
Ph
Temp.1 (oC)
4
Entry
x
Silane (y eq.)
Cat.1
Cat.2
Yieldb (%)
5
6
7
8
1
1.5
2.0
2.5
3.0
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (5)
PhSiH3 (4)
Ph2SiH2 (6)
Ph3SiH (6)
Et3SiH (6)
EtO3SiH (6)
PMHS (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
PhSiH3 (6)
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
TBD
-
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
-
52
83
88
92
68
55
55
ND
ND
ND
11
44
96
66c
63d
30
ND
99
97
58
77
ND
89
7
100
100
100
100
100
100
100
100
100
100
100
80
2
3
4
9
5
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27
115
115
115
115
115
115
115
115
115
115
115
115
115
115
AlCl3
ZnCl2
BF3·Et2O
HOTf
AgNO2
ZnCl2
GB
ZnCl2
DABCO
DBU
Cs2CO3
ZnCl2
ZnCl2
26
92
98e
ZnCl2
TBD (0.2 eq.) ZnCl2 (0.2 eq.)
115
N
N
N
O
N
N
N
N
N
O
H
TBD
DBU
DABCO
GB
a ZnCl2 (0.5 mol/L in THF) was used for the corresponding reactions (entries 18 and 22-26). b
Isolated yield, ND = no detected. c Temp.2 = 80 oC. d Temp.2 = 120 oC. e t1 = 12 h, t2 = 24 h.
yields were achieved, separately (entries 3 and 4). According to these results (entries 1-4), the excess
(>2.0 eq.) amine could facilitate this reaction. Thus, 2.5 eq. of aniline was ascertained to use for
subsequent investigations. Subsequently, the amount of phenylsilane was investigated. When the
amount of phenylsilane dropped from 6 eq. to 5 or 4 eq., the yield of 2aa was down-regulated
significantly (entries 5 and 6). Other silanes (i.g. Ph2SiH2, Ph3SiH, Et3SiH, EtO3SiH and
polymethylhydrosiloxane (PMHS)), were also investigated, whereas no better results were achieved
(entries 7-11). The reaction temperature was found to be susceptible for the reaction. When the
temperature of the first step was lowered to 80 ℃, the yield of 2aa declined to 44% (entry 12). When
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the reaction temperature was risen to 115 ℃, a better yield was obtained (entry 13, 96%). However, for
the temperature of the second step, whether it rose or lowered, the yields of 2aa would be down-
regulated observably (entries 14 and 15). Note that without FeCl3, only 30% yield of 2aa was obtained
(entry 16). This result suggested that a Lewis acid catalyst might be critical for the cyclization process.
Accordingly, different Lewis or Brønsted acid catalysts were investigated (entries, 17-21). ZnCl2 was
found as the optimal catalyst to prepare the desired 2aa in a near-quantitative yield (entry 18, 99%). An
excellent yield of 2aa (97%) could also be provided by using BF3·Et2O (entry 19). Lastly, the catalyst
for the first step was investigated. No 2aa was detected without TBD, revealing that a proper catalyst is
vital (entry 22). Other catalysts (i.g. glycine betaine (GB), DABCO, DBU and Cs2CO3) were also
investigated, whereas no better results were achieved (entries, 23-26). It is worth noting that when the
amount of TBD and ZnCl2 dropped from 0.5 eq. to 0.2 eq. (TBD: 3.5 mg), 2aa could also be obtained in
98% yield (entry 27: it will take longer, t1 = 12 h, t2 = 24 h).
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Under the optimal reaction conditions ascertained (Table 1, entry 18), the substrate scope was then
examined (Table 2). This method was found to be applicable to a wide substituted enaminone and
aromatic amine. First, the electronic effect of the substituent R1 was investigated (2aa-2ah). The
substrates with electron-donating (e.g., 2ab, R1 = 3,4,5-trimethoxyphenyl, 95%; 2ac, R1 = p-OMePh,
99%) or electron-withdrawing (e.g., 2ah, R1 = p-NO2Ph, 94%) groups were all tolerable to furnish
corresponding products in excellent yields. When R1 was heteroaryl substituent (e.g., 2-furanyl) the
corresponding 2ai was formed in 94% yield. 2-Naphthyl and sterically hindered 1-naphthyl were also
well tolerated to afford 2aj and 2ak in excellent yields. It is noteworthy that when R1 was ethoxy, the
corresponding product 2al could be obtained in 65% yield, and exhibits obvious fluorescent
properties26. 2al could also be hydrolyzed to generate the corresponding carboxylic acid 2al' in 75%
yield (for the details, see Experimental Section). Besides, alkyl substituent (i.g. n-pentyl) also fitted the
standard reaction conditions, furnishing 2am in 72% yield. Next, the R2 substituents were examined
(2an-2aq). Good yields of the corresponding tetrahydropyrimidines could be isolated irrespective of the
presence of electron-donating (2an, R2 = p-MeOC6H4, 82%) or electron-withdrawing (2ap, R2 = p-
ClC6H4, 75%)
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Table 2. The scope of the reactiona
1
2
3
4
5
6
7
O
R2
O
NHR3
R2
R3
1
TBD (0.5 eq.)
PhSiH
R1
N
3 (6 eq.) R1
(0.125 mmol)
+
R4NH2
2 CO2
H2C
2
CH2
MeCN, 115 oC
6 h (t1)
ZnCl2 (0.5 eq.), 100 oC
12 h (t2)
N
R4
(2.5 eq.)
8
9
O
O
O
CH2
Ph
MeO
Ph
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
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30
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32
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Ph
N
N
N
H2C
CH2
H2C
CH2
H2C
CH2
N
MeO
N
MeO
N
Ph
OMe
Ph
Ph
2aa
2ab
2ac
, 99%
, 95%
, 99%
CH2
X-ray of
O
2aa
O
O
Ph
Ph
O
N
N
Ph
t
2ad
2ae
, R = Bu, 99%
N
H2C
CH2
H2C
CH2
, R = F, 99%
, R = Cl, 91%
O2N
N
H2C
CH2
N
R
N
2af
2ag
Ph
Ph
2ah
, 94%
2ai
, 94%
Ph
2ad-2ag
, R = Br, 93%
O
O
O
Ph
Ph
Ph
N
N
O
N
H2C
CH2
H2C
CH2
H2C
CH2
N
N
N
Ph
Ph
Ph
2ak
2aj
, 93%
2al
, 65%
R
, 94%
Fluorescent imagesd
2al
OMe
of
in THF
O
O
O
O
Ph
N
Ph
Ph
Ph
Ph
N
Ph
N
Ph
N
H2C
CH2
H2C
CH2
H2C
CH2
N
H2C
CH2
N
N
N
Ph
Ph
Ph
c
Ph
2ao
2ap
2am
, R = H, 87%
, 72%
c
2aq
, 67%
b
b
2an
, 82%
, R = Cl, 75%
R
O
Ph
2at
X-ray of
O
O
Ph
Ph
N
CH2
Ph
N
N
H2C
CH2
N
H2C
CH2
H2C
CH2
N
O2N
N
Ph
Ph
Ph
c
2ar
, R = OMe, 85%
b
b
2au
, 50%
2at
, 60%
c
2as
, R = Cl, 82%
CH2
R
O
Ph
N
PMP = p-methoxyphenyl
O
2bc
2bd
2be
, R = OMe, 80%
c
PMP
2av
, R = OMe, 89%
Ph
N
t
c
Ph
N
, R = Bu, 90%
t
c
2aw
, R = Bu, 86%
H2C
CH2
H2C
CH2
, R = Et, 97%
, R = Me, 99%
c
2ax
2ay
2az
, R = Et, 86%
N
R
2bf
c
, R = Me, 89%
2bg
2bh
, R = F, 88%
, R = Cl, 83%
c
, R = F, 87%
c
c
2ba
, R = Cl, 83%
, R = Br, 78%
2av 2bb
-
c
2bc 2bi
-
2bi
, R = Br, 87%
c
R
2bb
a Yields are of isolated products. b t1 = 6 h, t2 = 24 h. c t1 = 12 h, t2 = 24 h. d The wavelength of 360 nm
2al
and 254 nm meaning
lamp, respectively
in THF under excited lights at 365 nm and 254 nm using a portable ultraviolet
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groups on the benzene ring. When alkyl (such as R2 = n-butyl) instead of aryl was used, the
corresponding product 2aq could be generated in 67% yield. Then, the electronic effect of R3 was
investigated. Substrates with both p-OMePh and p-ClPh groups were suitable for the reaction, offering
the desired tetrahydropyrimidines in good yields (2ar, 85%; 2as, 82%). When R3 were alkyl
substituents (i.g. benzyl and n-butyl group), the corresponding N-alkyl product 2at and 2au were
formed in moderate yields. For substituents R4, the substituted phenyls bearing p-OMe, p-tBu, p-Et, p-
Me, p-F, p-Cl and p-Br were all well tolerated (2av-2bb, 78-89%). In addition, regardless of the
presence of electron-withdrawing or electron-donating groups on the aryl ring, when R3 = R4, good to
excellent yields of the corresponding tetrahydropyrimidines could be obtained (2bc-2bi, 83-99%). It is
worth noting that this reaction is specific to the use of primary aromatic amine. Primary alkylamine and
secondary amine were not suitable for the reaction. The structure of the products was ascertained by
NMR analysis and further confirmed by X-ray analysis of 2aa and 2at.27
1
2
3
4
5
6
7
8
9
10
11
12
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To understand the reaction mechanism, several control experiments were performed. The reaction of
CO2, 1a and aniline provided 2aa in 99% yield under the optimal conditions. Without CO2, no 2aa was
formed (Scheme 2a), suggesting that CO2 might be the C1 source for the methylenation-cyclization
reaction. When CO2 and 2,6-diisopropylaniline were subjected to the standard conditions, the
corresponding imine 3 was produced in 74% NMR yield (Scheme 2b), revealing that formaldehyde or
formaldehyde equivalent might be formed as the intermediate in the reaction.17b To further verify this
speculation, formaldehyde instead of CO2 and phenylsilane was directly adopted, and it was found that
2aa could be isolated in 89% yield (Scheme 2c; even without TBD, 2aa could also be obtained in 28%
yield).
O
O
NHPh
a)
2 CO2
1a
(0.125 mmol)
ZnCI2 (0.5 eq.), 100 oC, 12 h
TBD (0.5 eq.)
PhSiH
Ph
Ph
N
3 (6 eq.)
MeCN, 115 oC, 6 h
Ph
+
PhNH2
H2C
CH2
N
(2.5 eq.)
2aa
Ph
99%
without CO2: 0%
iPr
iPr
b)
TBD (0.2 eq.)
PhSiH
N
NH2
iPr
CH2
3 (2.0 eq.)
MeCN, 100 oC, 2 h
CO2
+
iPr
3
, NMR yield: 74%
(0.2 mmol)
O
Ph
c)
Ph
N
CH2O
H2C
CH2
O
NHPh
+
TBD (0.5 eq.), ZnCl2 (0.5 eq.)
MeCN, 115 oC, N2, 12 h
(4.0 eq.)
N
2aa
Ph
Ph
PhNH2
89%
without TBD: 28%
1a
(0.125 mmol)
(2.5 eq.)
Scheme 2. Control experiments
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To gain more insights into the detailed reaction mechanism, density functional theory (DFT)
calculations were conducted (Figure 1 and see Supporting Information for details). The addition of
phenylsilane and CO2 to generate bis(silyl)acetal 4 has been previously reported.28 This TBD-catalyzed
process is thermodynamically favorable with an energy decrease of 13.0 kcal/mol. At the outset, the
nucleophilic substitution of 4 with 1a or aniline was considered, but the corresponding calculations
always led to elimination processes. This phenomenon revealed that direct formation of formaldehyde
from 4 (via TS1) is more likely and is also in line with our control experiment (Scheme 2b and 2c).
Formaldehyde can further undergo condensation with aniline to generate imine 8. The condensation in
the presence of TBD (via TS2 and TS3) is kinetically favorable than that catalyzed by ZnCl2 (see Fig.
S1 for the calculation results of ZnCl2-catalyzed condensation process). In view of the equilibrium
between formaldehyde and imine 8, they were both considered for the following addition with
enaminone 1a. The two processes are both feasible with energy barriers around 10 kcal/mol, while the
addition of imine 8 (via TS4 and TS5) is slightly superior (see Fig. S2 for the details of formaldehyde
addition). Finally, we found that the elimination of 11 (via TS6 and TS7) to afford aza-diene 14
followed by an aza-Diels-Alder reaction with 8 (via TS16) is remarkably kinetically favored.
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H
PhH2Si
(a)
H
O
1
2
3
4
H2Si
Ph
TS1
12.1
O
N
N
5
6
7
8
2 PhSiH3
+
CO2
H
H
H
O(SiH2Ph)2
O
N
N
N
H
5
H
N
O
H
N
0.0
Ph
TS3
-6.0
H
H
H
N
Ph
TS2
-10.9
9
H
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N
N
H
H
H
N
H
N
PhNH2
TBD
O
H2O
TBD
N
H
-13.0
PhH2SiO OSiH2Ph
H
N
O
H
N
H
O
Ph
7
H
N
4
PhNCH2
8
-23.0
H
Ph
H
H
-21.8
6
-22.1
-24.1
O
(b)
Ph
Ph
N
H
O
Ph
Ph
H
N
H
N
O
O
N
H
N
Ph ZnCl2
Ph
Ph
N
N
ZnCl2
Ph
NH
N
Ph
TS5
N
H
O
H
Ph
H
8.7
NHPh
Ph
N
O
Ph
1a
ZnCl2
TS4
4.6
9
4.0
N
N
Zn
Cl2
N
Ph
TS8
2.3
Ph
Ph
N
H
N
O
H
N
0.0
PhNCH2 ( )
Ph ZnCl2
TS6
-2.4
Ph
Ph
N
H
ZnCl2
TS7
-4.7
Ph ZnCl2
8
8
10
13
-6.9
N
14
-9.3
Ph
O
12
-17.8
TBD
Ph
O
NHPh
Ph
N
11
-20.1
N
H
N
14
Ph
H
O
2aa
-23.7
1a
Ph
N
N
N
H
O
Ph
N
Ph
N
ZnCl
Ph
H
H
N
Ph
12
N
11
N
H
H
Ph ZnCl2
N
13
TBD
Ph ZnCl2
Figure 1. Calculated solution-phase Gibbs free energy changes of the cascade reaction of PhSiH3, CO2,
PhNH2 and enaminone 1a via the nucleophilic addition of 1a towards 8 (in kcal/mol).
Based on the above results, the following mechanism was proposed for this reaction (Figure 2).
Initially, TBD-catalyzed reduction of CO2 led to the production of bis(silyl)acetal 4 (C0 species).28
Formaldehyde might be formed via the elimination of bis(silyl)acetal species. Subsequently, the
condensation of aniline with in situ generated bis(silyl)acetal 4 or formaldehyde led to the generation of
imine 8. The subsequent nucleophilic attack of enaminone 1a to 8 occurred to furnish 11’. After the
elimination, aza-diene 14 was generated. Finally, an aza-Diels-Alder process between 14 and additional
8 proceed to form the final product 2aa. This mechanism shows that two molecules of imine 8 are
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utilized in this reaction, which can reasonably explain why excess (>2.0 eq.) amine is conducive (Table
1, entries 1-4).
1
2
3
4
5
6
7
H
H
C
Si
Si
TBD
H
O
O
4
bis(silyl)acetal ( )
or
CO2
Si
+
CH2O
NH2
Ph
8
9
NH2
Ph
CH2
8
N
10
11
12
13
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O
NHPh
Ph
TBD
ZnCl2
Ph
CH2
1a
N
O
8
Ph
Ph
Ph
N
O
H2C
CH2
H
aza-
N
Ph
Diels-Alder
Ph
N
2aa
Ph
H2C
11'
O
NH
Ph
Ph
Ph
N
CH2
14
NH2
Ph
Figure 2. Proposed reaction mechanism
To interpret the relationship between photophysical properties and the molecular structures, UV-vis
and fluorescent spectra of the target compounds were recorded. Figure 3a, Figure S4a and Table S2
obviously show that 2aa in dilute THF solution (1.0×10−5 mol/L) possesses a strong absorption peak at
335 nm with a molar absorptivity (ε) of 4360 L∙mol−1∙cm−1. When the H atom in double bond of 2aa
was replaced by phenyl ring (2ao), the maximal absorption peak (λmax) red shifted to 355 nm, attributed
to its enlarged π-conjugated system. However, some further substituent groups on phenyl rings did not
affect the resulting absorption profiles with only negligible changes happened in absorption peaks or
intensities. As shown in Figure S4 and Table S2, introducing different substituted groups in phenyl rings,
λmax for 2aa derivatives just alters from 333 nm to 340 nm with ε between 2820 L∙mol−1∙cm−1 and 4360
L∙mol−1∙cm−1 and λmax for 2ao derivatives from 352 nm to 358 nm with ε between 1180 L∙mol−1∙cm−1
and 1840 L∙mol−1∙cm−1 respectively, demonstrating compounds 2aa and 2ao are two typical kinds of
optical-function organic molecules. Once one of the phenyl ring in 2aa or 2ao was substituted by
strongly electron-deficient group (2ah and 2at), electron-rich heteroaryl group (2ai), ethoxy (2al) or
non-conjugated group (2am and 2au), either absorption peak, intensity or its absorption profile would
obviously change accordingly, i.e., λmax ranges from 300 nm to 358 nm with ε between 570
L∙mol−1∙cm−1 and 5270 L∙mol−1∙cm−1.
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The Journal of Organic Chemistry
The same regularity for the fluorescent spectra was observed from three typical compounds 2aa, 2ao
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5
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7
8
9
and 2al as examples in THF (1.0×10−5 mol/L). As shown in Figure 3b and Table S3, both 2aa and 2ao
exhibit moderate fluorescent intensity at 381 nm and 408 nm with normal Stokes shifts (46 nm and 53
nm), respectively. While for 2al, multifold growth in fluorescent intensity was obtained, i.e., from 196.2
a.u. for 2aa and 185.1 a.u. for 2ao increasing to 470.6 a.u. for 2al. Accordingly, photophysical
behaviors of the target compounds could be efficiently controlled by designing the molecular structures.
All the results suggested that some more organic materials with desirable optical properties could be
derivatized from the typical compounds 2aa and 2ao in the future.
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Figure 3. a) UV-vis absorption spectra and b) Fluorescent spectra of representative 2aa, 2ao and 2al
excited at λmax in THF (1.0×10−5 mol/L; Insert: The colors of 2aa, 2ao and 2al under excited lights at
365 nm using a portable ultraviolet lamp)
■ CONCLUSION
In summary, we have developed a tandem methylenation-cyclization reaction involving two
molecules of CO2 to access tetrahydropyrimidines. Control experiments and DFT studies revealed that
this TBD and ZnCl2 catalyzed reaction might proceed through the generation of bis(silyl)acetal,
condensation of arylamine and aza-Diels-Alder processes. Potential photophysical behaviors were
preliminarily investigated by UV-vis and fluorescent spectral analyses. This method realized the
selective conversion of two molecules of CO2 into methylene groups in a one-pot multi-component
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cyclization reaction and effectively made the reuse of CO2 diversified. Further investigations on the
detailed reaction mechanism and potential application are in progress.
■ EXPERIMENTAL SECTION
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8
9
General Methods. All reactions were carried out in carbon dioxide except noted. The ZnCl2 (0.5 mol/L
in THF) was purchased from Sun Chemical Technology (Shanghai) Co., Ltd. Anhydrous acetonitrile
were prepared by distillation from CaH2. Anhydrous toluene, 1,4-dioxane and tetrahydrofuran was
distilled from sodium and benzophenone. Commercially, available reagents were used without further
purification. Reactions were monitored by thin layer chromatography using UV light to visualize the
course of reaction. Purification of reaction products was carried out by flash chromatography on silica
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1
13
gel (300~400 mesh). H NMR spectra were recorded at 500 MHz, C NMR spectra were recorded at
1
125 MHz, and in CDCl3 or (CD3)2SO (containing 0.03% TMS) solutions. H NMR spectra were
13
recorded with Me4Si (δ = 0.00) as the internal reference and C NMR spectra were recorded with
CDCl3 (δ = 77.00) or DMSO-d6 (δ = 39.52) as the internal reference. High-resolution mass spectra were
obtained using a Bruker Maxis Impact mass spectrometer with a TOF (for ESI) analyzer. Single crystal
X-ray diffraction data was collected in Bruker SMARTAPEX diffractiometers with molybdenum
cathodes. The enaminones 1 were prepared according to the literature methods29 and the spectroscopic
data are in agreement with that previously reported.
Computational details. Density functional theory (DFT) study was performed using Gaussian
program.30 Geometry optimization, frequency analysis and intrinsic reaction coordinates (IRC)
analysis31 were performed with B3LYP method32, 6-31G(d) basis set and ‘ultrafine’ grid.33 Based on
optimized structures (no imaginary frequency for energetic minimum and only one imaginary frequency
for transition states), solution-phase single point energies were calculated with B3LYP-D3(BJ)
method34, 6-311++g(d,p) basis set, SMD solvation model35 (solvent = acetonitrile) and ‘ultrafine’ grid.
1.9 kcal/mol was added to the Gibbs free energies of every species to account for the change of standard
state from 1 atm to 1 M at 298.15 K.36 Thermodynamic correction obtained from frequency analysis was
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The Journal of Organic Chemistry
added by solution-phase single point energy and 1.9 kcal/mol to get the solution-phase Gibbs free
energy used for mechanistic discussion.
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3
4
5
6
Synthesis and characterization of 2
7
8
9
Method A: To a well-dried 25 mL seal tube containing a magnetic stirring bar was added TBD (8.7
mg, 0.0625mmol). Then, the vessel was evacuated and refilled with CO2 for five times. Under a stream
of CO2, to this vessel were added arylamine (0.3125 mmol), acetonitrile (1.5 mL) and PhSiH3 (91 μL,
0.75 mmol). Then the vessel was sealed at atmospheric pressure of CO2 (1 atm) and the resulting
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o
mixture was stirred in a 115 C oil bath for 6 h (t1). After cooling the reaction mixture to ambient
temperature, 1 (0.125 mmol) and ZnCl2 (125 μL, 0.5 mol/L in THF, 0.0625 mmol) were added under a
o
stream of CO2. Subsequently, the vessel was sealed and heated in a 100 C oil bath for 12 h (t2). The
reaction could be monitored by TLC analysis. The resulting mixture was concentrated under reduced
pressure and subjected to column chromatography for purification directly, using petroleum ether/ethyl
acetate (3:1-15:1) as the eluent.
Method B: t1 = 6 h, t2 = 24 h; Method C: t1 = 12 h, t2 = 24 h.
(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2aa). Compound 2aa was
prepared in 99% yield (42 mg) according to the general procedure (Method A). Yellow solid; mp 134-
137 oC; 1H NMR (500 MHz, CDCl3): δ 7.56-7.52 (m, 3H), 7.46-7.43 (m, 1H), 7.41-7.38 (m, 2H), 7.36-
7.32 (m, 2H), 7.24-7.22 (m, 2H), 7.15-7.12 (m, 1H), 6.99 (d, J = 7.9 Hz, 2H), 6.95-6.90 (m, 3H), 5.16
13
(s, 2H), 4.51 (s, 2H); C{1H} NMR (125 MHz, CDCl3): δ 193.4, 148.4, 146.0, 143.9, 139.5, 130.3,
129.8, 129.3, 128.4, 128.2, 124.5, 121.2, 118.5, 117.8, 110.8, 65.5, 47.1; IR (KBr): 3059, 2924, 1566,
1494, 1407, 1257, 998, 695 cm-1; HRMS (ESI) calcd for C23H21N2O [M+H]+: 341.1648, found:
341.1653.
(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(3,4,5-trimethoxyphenyl)methanone
(2ab).
Compound 2ab was prepared in 95% yield (51 mg) according to the general procedure (Method A).
Yellow solid; mp 107-109 oC; 1H NMR (500 MHz, CDCl3): δ 7.60 (s, 1H), 7.37-7.34 (m, 2H) 7.24-7.23
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(m, 2H), 7.16-7.13 (m, 1H), 6.99 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 7.8 Hz, 2H), 6.93-6.90 (m, 1H), 6.80
1
2
3
13
(s, 2H), 5.16 (s, 2H), 4.49 (s, 2H), 3.87 (s, 3H), 3.86 (s, 6H); C{1H} NMR (125 MHz, CDCl3): δ
4
5
6
7
8
9
192.6, 152.9, 148.4, 145.6, 143.8, 140.0, 135.0, 129.9, 129.3, 124.6, 121.2, 118.4, 117.8, 110.5, 105.9,
65.4, 60.9, 56.3, 47.1; IR (KBr): 2936, 1654, 1494, 1460, 1410, 1237, 764, 696, 632 cm-1; HRMS (ESI)
calcd for C26H27N2O4 [M+H]+: 431.1965, found: 431.1960.
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(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(4-methoxyphenyl)methanone (2ac). Compound 2ac
was prepared in 99% yield (46 mg) according to the general procedure (Method A). Yellow solid; mp
o
1
119-121 C; H NMR (500 MHz, CDCl3): δ 7.57-7.53 (m, 3H), 7.35-7.32 (m, 2H), 7.24-7.21 (m, 2H),
7.14-7.11 (m, 1H), 6.98 (d, J = 7.9 Hz, 2H), 6.94 (d, J = 7.8 Hz, 2H), 6.91-6.88 (m, 3H), 5.15 (s, 2H),
4.49 (s, 2H), 3.83 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 192.5, 161.5, 148.5, 145.0, 144.0, 132.0,
130.5, 129.8, 129.3, 124.2, 121.1, 118.4, 117.8, 113.4, 110.9, 65.4, 55.3, 47.2; IR (KBr): 2988, 2971,
2901, 1580, 1406, 1250, 1066, 761, 702 cm-1; HRMS (ESI) calcd for C24H23N2O2 [M+H]+: 371.1754,
found: 371.1748.
(4-(tert-butyl)phenyl)(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)methanone (2ad). Compound
2ad was prepared in 99% yield (49 mg) according to the general procedure (Method A). Yellow solid;
mp 144-147 oC; 1H NMR (500 MHz, CDCl3): δ 7.56 (s, 1H), 7.51 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.3
Hz, 2H), 7.36-7.33 (m, 2H), 7.24-7.21 (m, 2H), 7.14-7.11 (m, 1H), 6.99-6.95 (m, 4H), 6.91-6.88 (m,
13
1H), 5.15 (s, 2H), 4.49 (s, 2H), 1.32 (s, 9H); C{1H} NMR (125 MHz, CDCl3): δ 193.2, 153.7, 148.5,
145.5, 144.1, 136.7, 129.8, 129.3, 128.4, 125.1, 124.4, 121.1, 118.7, 117.8, 110.9, 65.5, 47.1, 34.8, 31.2;
IR (KBr): 2971, 2901, 1571, 1496, 1405, 1255, 1066, 884, 759, 703 cm-1;HRMS (ESI) calcd for
C27H29N2O [M+H]+: 397.2274, found: 397.2272.
(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(4-fluorophenyl)methanone (2ae). Compound 2ae
was prepared in 99% yield (44 mg) according to the general procedure (Method A). Yellow solid; mp
o
1
123-127 C; H NMR (500 MHz, CDCl3): δ 7.58-7.55 (m, 2H), 7.48 (s, 1H), 7.37-7.34 (m, 2H), 7.26-
7.22 (m, 2H), 7.16-7.13 (m, 1H), 7.09-7.06 (m, 2H), 6.99-6.90 (m, 5H), 5.16 (s, 2H), 4.49 (s, 2H);
13C{1H} NMR (125 MHz, CDCl3): δ 191.9, 164.0 (d, JC-F = 248.9 Hz), 148.4, 145.8, 143.9, 135.6 (d, JC-
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F = 3.2 Hz), 130.6 (d, JC-F = 8.5 Hz), 129.9, 129.3, 124.6, 121.2, 118.5, 117.8, 115.2 (d, JC-F = 21.4 Hz),
110.7, 65.5, 47.1; IR (KBr): 2924, 2852, 1578, 1496, 1258, 759, 696 cm-1; HRMS (ESI) calcd for
C23H20FN2O [M+H]+: 359.1554, found: 359.1555.
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8
9
(4-chlorophenyl)(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)methanone (2af). Compound 2af was
prepared in 91% yield (43 mg) according to the general procedure (Method A). Yellow solid; mp 138-
141 oC; 1H NMR (500 MHz, CDCl3): δ 7.50-7.46 (m, 3H), 7.37-7.33 (m, 4H), 7.22 (d, J = 7.6 Hz, 2H),
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7.16-7.13 (m, 1H), 6.98-6.89 (m, 5H), 5.15 (s, 2H), 4.48 (s, 2H); C{1H} NMR (125 MHz, CDCl3): δ
191.8, 148.3, 145.9, 143.8, 137.8, 136.4, 129.9, 129.8, 129.3, 128.4, 124.7, 121.2, 118.6, 117.8, 110.6,
65.5, 47.0; IR (KBr): 2914, 1572, 1498, 1396, 1090, 884, 758, 693 cm-1; HRMS (ESI) calcd for
C23H20ClN2O [M+H]+: 375.1259, found: 375.1254.
(4-bromophenyl)(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)methanone (2ag). Compound 2ag
was prepared in 93% yield (49 mg) according to the general procedure (Method A). Yellow solid; mp
127-130 oC; 1H NMR (500 MHz, CDCl3): δ 7.53 (d, J = 8.4 Hz, 2H), 7.46 (s, 1H), 7.42 (d, J = 8.4 Hz,
2H), 7.37-7.34 (m, 2H), 7.25-7.22 (m, 2H), 7.17-7.14 (m, 1H), 6.98-6.90 (m, 5H), 5.15 (s, 2H), 4.48 (s,
2H); 13C{1H} NMR (125 MHz, CDCl3): δ 191.9, 148.3, 146.0, 143.8, 138.3, 131.4, 130.0, 129.9, 129.3,
124.8, 124.7, 121.3, 118.6, 117.8, 110.6, 65.5, 47.0; IR (KBr): 3062, 2910, 1569, 1498, 1406, 1257,
1146, 877, 763, 695 cm-1; HRMS (ESI) calcd for C23H20BrN2O [M+H]+: 419.0754, found: 419.0749.
(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(4-nitrophenyl)methanone (2ah). Compound 2ah was
prepared in 94% yield (45 mg) according to the general procedure (Method A). Yellow solid; mp 152-
155 oC; 1H NMR (500 MHz, CDCl3): δ 8.25 (d, J = 8.7 Hz, 2H), 7.68-7.67 (m, 2H), 7.39 (s, 1H), 7.38-
7.34 (m, 2H), 7.27-7.24 (m, 2H), 7.20-7.17 (m, 1H), 6.98-6.92 (m, 5H), 5.18 (s, 2H), 4.51 (s, 2H);
13C{1H} NMR (125 MHz, CDCl3): δ 190.6, 148.7, 148.2, 146.8, 145.4, 143.6, 130.0, 129.4, 129.2,
125.3, 123.5, 121.5, 118.9, 117.8, 110.5, 65.8, 46.8; IR (KBr): 3070, 2909, 1561, 1498, 1346, 847, 757,
693 cm-1; HRMS (ESI) calcd for C23H19N3NaO3 [M+Na]+: 408.1319, found: 408.1322.
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(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(furan-2-yl)methanone (2ai). Compound 2ai was
prepared in 94% yield (39 mg) according to the general procedure (Method A). Yellow solid; mp 104-
107 oC; 1H NMR (500 MHz, CDCl3): δ 8.38 (s, 1H), 7.51 (s, 1H), 7.42-7.38 (m, 2H), 7.23-7.17 (m, 3H),
7.09-7.06 (m, 3H), 6.97 (d, J = 8.0 Hz, 2H), 6.90-6.87 (m, 1H), 6.48 (dd, J = 3.4, 1.7 Hz, 1H), 5.16 (s,
2H), 4.48 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3): δ 177.9, 153.6, 148.4, 144.6, 144.4, 144.2, 129.8,
129.3, 124.6, 121.2, 118.7, 117.9, 115.9, 111.5, 110.0, 65.6, 46.9; IR (KBr): 2926, 1577, 1497, 1468,
850, 753, 693 cm-1; HRMS (ESI) calcd for C21H18N2NaO2 [M+Na]+: 353.1260, found: 353.1265.
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(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(naphthalen-2-yl)methanone (2aj). Compound 2aj
was prepared in 94% yield (46 mg) according to the general procedure (Method A). Yellow solid; mp
o
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142-144 C; H NMR (500 MHz, CDCl3): δ 8.02 (s, 1H), 7.88-7.85 (m, 3H), 7.67 (dd, J = 8.5, 1.5 Hz,
1H), 7.58 (s, 1H), 7.55-7.49 (m, 2H), 7.31-7.30 (m, 2H), 7.27-7.24 (m, 2H), 7.11-7.08 (m, 1H), 7.01 (d,
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J = 8.0 Hz, 2H), 6.94-6.91 (m, 3H), 5.18 (s, 2H), 4.56 (s, 2H); C{1H} NMR (125 MHz, CDCl3): δ
193.3, 148.5, 146.0, 143.9, 136.9, 134.2, 132.5, 129.8, 129.4, 128.8, 128.4, 128.1, 127.7, 127.2, 126.5,
125.7, 124.5, 121.2, 118.5, 117.8, 111.1, 65.5, 47.1; IR (KBr): 2924, 1576, 1561, 1494, 1239, 757, 695
cm-1; HRMS (ESI) calcd for C27H23N2O [M+H]+: 391.1805, found: 391.1801.
(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(naphthalen-1-yl)methanone (2ak). Compound 2ak
was prepared in 93% yield (45 mg) according to the general procedure (Method A). Yellow solid; mp
o
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140-142 C; H NMR (500 MHz, CDCl3): δ 7.89-7.87 (m, 1H), 7.79-7.75 (m, 2H), 7.40-7.35 (m, 4H),
7.21-7.14 (m, 5H), 7.00-6.94 (m, 3H), 6.88-6.85 (m, 1H), 6.72 (d, J = 7.7 Hz, 2H), 5.07 (s, 2H), 4.54 (s,
2H); 13C{1H} NMR (125 MHz, CDCl3): δ 194.0, 148.3, 146.7, 143.6, 137.4, 133.7, 131.0, 129.7, 129.4,
129.3, 128.1, 126.7, 126.2, 125.8, 125.4, 124.7, 124.5, 121.2, 118.7, 117.8, 112.4, 65.7, 46.7; IR (KBr):
2919, 1618, 1572, 1492, 1405, 1249, 1202, 759, 695 cm-1; HRMS (ESI) calcd for C27H23N2O [M+H]+:
391.1805, found: 391.1799.
ethyl 1,3-diphenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (2al). Compound 2al was prepared in
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65% yield (25 mg) according to the general procedure (Method A). Yellow solid; mp 73-75 C; H
NMR (500 MHz, CDCl3): δ 7.83 (s, 1H), 7.37-7.34 (m, 2H), 7.23-7.19 (m, 2H), 7.12-7.09 (m, 1H), 7.01
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(d, J = 7.9 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.90-6.87 (m, 1H), 5.04 (s, 2H), 4.26 (s, 2H), 4.20 (q, J =
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7.1 Hz, 2H), 1.29 (t, J = 7.1 Hz, 3H); C{1H} NMR (125 MHz, CDCl3): δ 166.8, 148.7, 144.2, 140.2,
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129.7, 129.2, 123.5, 121.0, 117.8, 117.7, 100.0, 64.4, 59.6, 47.5, 14.5; IR (KBr): 3062, 2976, 1623,
1594, 1494, 1394, 1244, 748, 696 cm-1; HRMS (ESI) calcd for C19H21N2O2 [M+H]+: 309.1598, found:
309.1592.
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(1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)hexan-1-one (2am). Compound 2am was prepared in
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72% yield (30 mg) according to the general procedure (Method A). Yellow oil; H NMR (500 MHz,
CDCl3): δ 7.73 (s, 1H), 7.41-7.38 (m, 2H), 7.22-7.19 (m, 2H), 7.18-7.15 (m, 1H), 7.04 (d, J = 7.8 Hz,
2H), 6.92 (d, J = 8.0 Hz, 2H), 6.89-6.86 (m, 1H), 5.07 (s, 2H), 4.31 (s, 2H), 2.52 (t, J = 7.6 Hz, 2H),
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1.67-1.62 (m, 2H), 1.33-1.28 (m, 4H), 0.88 (t, J = 6.8 Hz, 3H); C{1H} NMR (125 MHz, CDCl3): δ
196.8, 148.5, 144.2, 141.2, 129.8, 129.2, 124.2, 121.0, 118.4, 117.7, 111.6, 65.0, 46.9, 36.0, 31.7, 25.4,
22.5, 14.0; IR (KBr): 2924, 2853, 1654, 1618, 1493, 1257, 759, 695 cm-1; HRMS (ESI) calcd for
C22H27N2O [M+H]+: 335.2118, found: 335.2121.
(6-(4-methoxyphenyl)-1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone
(2an).
Compound 2an was prepared in 82% yield (46 mg) according to the general procedure (Method B).
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Yellow solid; mp 126-128 C; H NMR (500 MHz, CDCl3): δ 7.45-7.43 (m, 2H), 7.18-7.15 (m, 2H),
7.11-7.08 (m, 1H), 7.07-6.97 (m, 6H), 6.93-6.90 (m, 1H), 6.86-6.78 (m, 5H), 6.33 (d, J = 8.7 Hz, 2H),
5.12 (s, 2H), 4.46 (s, 2H), 3.53 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 197.0, 160.0, 154.4, 147.9,
146.5, 140.3, 132.6, 130.4, 129.1, 128.9, 128.7, 128.0, 127.3, 125.9, 124.4, 119.7, 116.0, 115.9, 113.1,
70.1, 55.0, 49.5; IR (KBr): 2969, 2923, 1601, 1571, 1492, 1254, 752, 697 cm-1; HRMS (ESI) calcd for
C30H27N2O2 [M+H]+: 447.2067, found: 447.2070.
phenyl(1,3,6-triphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)methanone (2ao). Compound 2ao was
prepared in 87% yield (45 mg) according to the general procedure (Method C). Yellow solid; mp 131-
135 oC; 1H NMR (500 MHz, CDCl3): δ 7.45 (d, J = 7.5 Hz, 2H), 7.19-7.16 (m, 2H), 7.10-6.99 (m, 7H),
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6.91-6.87 (m, 3H), 6.82-6.80 (m, 6H), 5.14 (s, 2H), 4.49 (s, 2H); C{1H} NMR (125 MHz, CDCl3): δ
197.0, 154.0, 147.9, 146.3, 140.1, 135.5, 131.1, 130.6, 129.1, 128.9, 128.9, 128.7, 127.6, 127.3, 125.9,
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124.5, 119.8, 116.6, 116.1, 70.3, 49.5; IR (KBr): 2970, 2923, 1615, 1567, 1490, 1210, 747, 695 cm-1;
HRMS (ESI) calcd for C29H25N2O [M+H]+: 417.1961, found: 417.1965.
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(6-(4-chlorophenyl)-1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone
(2ap).
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Compound 2ap was prepared in 75% yield (42 mg) according to the general procedure (Method B).
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Yellow solid; mp 141-143 C; H NMR (500 MHz, CDCl3): δ 7.44 (d, J =7.4 Hz, 2H), 7.19-7.15 (m,
3H), 7.07-7.03 (m, 4H), 7.00 (d, J =8.4 Hz, 2H), 6.95-6.92 (m, 1H), 6.86 (d, J =8.1 Hz, 2H), 6.82-6.78
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(m, 5H), 5.12 (s, 2H), 4.47 (s, 2H); C{1H} NMR (125 MHz, CDCl3): δ 196.8, 152.5, 147.7, 146.0,
139.9, 134.8, 134.1, 132.2, 130.9, 129.2, 128.9, 128.9, 127.9, 127.5, 125.9, 124.8, 120.0, 117.3, 116.2,
70.4, 49.5; IR (KBr): 2923, 2847, 1599, 1490, 1375, 1200, 722, 694 cm-1; HRMS (ESI) calcd for
C29H24ClN2O [M+H]+: 451.1572, found: 451.1568.
(6-butyl-1,3-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2aq). Compound 2aq
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was prepared in 67% yield (33 mg) according to the general procedure (Method C). Yellow oil; H
NMR (500 MHz, CDCl3): δ 7.67-7.66 (m, 2H), 7.47-7.39 (m, 3H), 7.34-7.31 (m, 2H), 7.25-7.21 (m,
3H), 7.03 (d, J = 7.4 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.89-6.86 (m, 1H), 4.89 (s, 2H), 4.32 (s, 2H),
2.10 (t, J = 8.0 Hz, 2H), 1.14-1.08 (m, 2H), 0.75-0.68 (m, 2H), 0.45 (t, J = 7.3 Hz, 3H); 13C{1H} NMR
(125 MHz, CDCl3): δ 196.2, 156.9, 148.2, 144.5, 142.4, 130.7, 129.3, 129.1, 128.3, 127.9, 127.3, 126.6,
120.5, 117.2, 109.3, 70.5, 49.8, 30.6, 30.6, 22.2, 13.2; IR (KBr): 2958, 2870, 1625, 1598, 1495, 1264,
754, 698 cm-1; HRMS (ESI) calcd for C27H29N2O [M+H]+: 397.2274, found: 397.2279.
(1-(4-methoxyphenyl)-3,6-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone
(2ar).
Compound 2ar was prepared in 85% yield (47 mg) according to the general procedure (Method C).
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Yellow solid; mp 126-128 C; H NMR (500 MHz, CDCl3): δ 7.43-7.42 (m, 2H), 7.21-7.18 (m, 2H),
7.09-7.04 (m, 3H), 7.01-6.98 (m, 2H), 6.90 (d, J = 7.9 Hz, 2H), 6.82-6.80 (m, 4H), 6.75-6.72 (m, 2H),
6.58-6.55 (m, 2H), 5.06 (s, 2H), 4.48 (s, 2H), 3.64 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 197.0,
156.6, 155.1, 148.0, 140.4, 139.5, 135.6, 131.2, 130.4, 129.2, 128.9, 128.8, 127.5, 127.4, 127.3, 119.9,
116.2, 115.7, 113.9, 70.7, 55.2, 49.4; IR (KBr): 2928, 1600, 1562, 1509, 1373, 1249, 771, 693 cm-1;
HRMS (ESI) calcd for C30H27N2O2 [M+H]+: 447.2067, found: 447.2070.
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(1-(4-chlorophenyl)-3,6-diphenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone
(2as).
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Compound 2as was prepared in 82% yield (46 mg) according to the general procedure (Method C).
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Yellow solid; mp 148-152 C; H NMR (500 MHz, CDCl3): δ 7.47 (d, J = 7.3 Hz, 2H), 7.20-7.17 (m,
2H), 7.12-7.09 (m, 1H), 7.06-6.98 (m, 6H), 6.88-6.81 (m, 6H), 6.71 (d, J = 8.7 Hz, 2H), 5.10 (s, 2H),
4.48 (s, 2H); C{1H} NMR (125 MHz, CDCl3): δ 197.0, 153.0, 147.7, 145.1, 139.7, 135.3, 131.0,
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130.8, 129.8, 129.2, 129.1, 128.9, 128.8, 127.8, 127.4, 127.0, 120.2, 117.4, 116.3, 70.6, 49.5; IR (KBr):
2925, 1581, 1566, 1490, 1417, 1279, 761, 699 cm-1; HRMS (ESI) calcd for C29H24ClN2O [M+H]+:
451.1572, found: 451.1575.
(1-benzyl-3-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(4-nitrophenyl)methanone (2at). Compound 2at
was prepared in 60% yield (30 mg) according to the general procedure (Method B). Yellow solid; mp
128-131 oC; 1H NMR (500 MHz, CDCl3): δ 8.21 (d, J =8.3 Hz, 2H), 7.61 (d, J =8.3 Hz, 2H), 7.31-7.30
(m, 3H), 7.23-7.20 (m, 2H), 7.11 (s, 1H), 7.07-7.06 (m, 2H), 6.93-6.90 (m, 1H), 6.87 (d, J = 8.0 Hz,
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2H), 4.61 (s, 2H), 4.35 (s, 2H), 4.31 (s, 2H); C{1H} NMR (125 MHz, CDCl3): δ 189.3, 151.3, 148.3,
148.2, 146.0, 134.7, 129.2, 129.0, 129.0, 128.4, 127.4, 123.3, 121.2, 117.7, 106.7, 65.2, 58.2, 45.2; IR
(KBr): 2926, 2799, 1627, 1560, 1519, 1344, 1238, 750, 703 cm-1; HRMS (ESI) calcd for C24H22N3O3
[M+H]+: 400.1656, found: 400.1661.
(1-butyl-3-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2au). Compound 2au was
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prepared in 50% yield (20 mg) according to the general procedure (Method B). Yellow oil; H NMR
(500 MHz, CDCl3): δ 7.49-7.47 (m, 2H), 7.41-7.36 (m, 3H), 7.30-7.27 (m, 2H), 7.03 (d, J = 9.5 Hz,
3H), 6.94-9.91 (m, 1H), 4.64 (s, 2H), 4.35 (s, 2H), 3.09 (t, J = 7.1 Hz, 2H), 1.45-1.39 (m, 2H), 1.20-1.13
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(m, 2H), 0.83 (t, J = 7.3 Hz, 3H); C{1H} NMR (125 MHz, CDCl3): δ 191.8, 151.1, 148.7, 140.2,
129.6, 129.2, 128.3, 128.0, 121.1, 118.0, 105.7, 65.6, 54.2, 45.6, 30.9, 19.5, 13.5; IR (KBr): 2928, 1655,
1599, 1553, 1496, 1133, 757, 699 cm-1; HRMS (ESI) calcd for C21H25N2O [M+H]+: 321.1961, found:
321.1963.
(1,3-bis(4-methoxyphenyl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone
(2av).
Compound 2av was prepared in 89% yield (53 mg) according to the general procedure (Method C).
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o
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Yellow solid; mp 138-140 C; H NMR (500 MHz, CDCl3): δ 7.41-7.40 (m, 2H), 7.07-6.96 (m, 5H),
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2H), 4.44 (s, 2H), 3.73 (s, 3H), 3.62 (s, 3H); C{1H} NMR (125 MHz, CDCl3): δ 197.0, 156.5, 154.8,
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154.0, 142.1, 140.5, 139.5, 135.6, 131.2, 130.2, 128.8, 128.7, 127.5, 127.4, 127.2, 118.7, 115.1, 114.5,
113.8, 72.4, 55.5, 55.1, 50.3; IR (KBr): 2933, 2835, 1620, 1491, 1443, 1364, 1037, 769, 695 cm-1;
HRMS (ESI) calcd for C31H29N2O3 [M+H]+: 477.2173, found: 477.2169.
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(4-(tert-butyl)phenyl)-1-(4-methoxyphenyl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-5-
yl)(phenyl)methanone (2aw). Compound 2aw was prepared in 86% yield (54 mg) according to the
general procedure (Method C). Yellow solid; mp 154-156 oC; 1H NMR (500 MHz, CDCl3): δ 7.42 (d, J
= 7.4 Hz, 2H), 7.22 (d, J = 8.6 Hz, 2H), 7.08-7.05 (m, 3H), 7.00-6.97 (m, 2H), 6.85 (d, J = 8.6 Hz, 2H),
6.81-6.80 (m, 3H), 6.72 (d, J = 8.8 Hz, 2H), 6.54 (d, J = 8.8 Hz, 2H), 5.02 (s, 2H), 4.46 (s, 2H), 3.63 (s,
3H), 1.26 (s, 9H); 13C{1H} NMR (125 MHz, CDCl3): δ 197.1, 156.5, 155.1, 145.6, 142.8, 140.4, 139.6,
135.7, 131.2, 130.4, 128.9, 128.8, 127.5, 127.5, 127.3, 125.9, 116.1, 115.9, 113.8, 71.2, 55.2, 49.6, 33.9,
31.4; IR (KBr): 2953, 2925, 2854, 1561, 1508, 1390, 1039, 769, 694 cm-1; HRMS (ESI) calcd for
C34H35N2O2 [M+H]+: 503.2693, found: 503.2695.
(4-ethylphenyl)-1-(4-methoxyphenyl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone
(2ax). Compound 2ax was prepared in 86% yield (51 mg) according to the general procedure (Method
o
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C). Yellow solid; mp 146-147 C; H NMR (500 MHz, CDCl3): δ 7.42 (d, J = 7.2 Hz, 2H), 7.08-6.97
(m, 7H), 6.85-6.79 (m, 5H), 6.71 (d, J = 8.9 Hz, 2H), 6.55 (d, J = 8.9 Hz, 2H), 5.02 (s, 2H), 4.46 (s, 2H),
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3.64 (s, 3H), 2.54 (q, J = 7.6 Hz, 2H), 1.17 (t, J = 7.6 Hz, 3H); C{1H} NMR (125 MHz, CDCl3): δ
197.0, 156.5, 155.0, 145.9, 140.4, 139.6, 136.0, 135.7, 131.2, 130.3, 128.9, 128.8, 128.5, 127.5, 127.2,
116.6, 115.7, 113.8, 71.3, 55.2, 49.7, 27.9, 15.9; IR (KBr): 2960, 2926, 1617, 1561, 1507, 1364, 1246,
771, 696 cm-1; HRMS (ESI) calcd for C32H31N2O2 [M+H]+: 475.2380, found: 475.2386.
(4-methoxyphenyl)-6-phenyl-3-(p-tolyl)-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2ay).
Compound 2ay was prepared in 89% yield (51 mg) according to the general procedure (Method C).
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Yellow solid; mp 139-143 C; H NMR (500 MHz, CDCl3): δ 7.42-7.40 (m, 2H), 7.07-6.97 (m, 7H),
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6.83-6.78 (m, 5H), 6.73-6.70 (m, 2H), 6.56-6.53 (m, 2H), 5.01 (s, 2H), 4.45 (s, 2H), 3.63 (s, 3H), 2.23
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(s, 3H); C{1H} NMR (125 MHz, CDCl3): δ 197.0, 156.5, 155.0, 145.7, 140.5, 139.5, 135.7, 131.2,
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130.3, 129.6, 129.4, 128.9, 128.7, 127.5, 127.4, 127.2, 116.6, 115.6, 113.8, 71.2, 55.1, 49.7, 20.4; IR
(KBr): 3059, 2918, 2836, 1602, 1491, 1365, 1243, 773, 694 cm-1; HRMS (ESI) calcd for C31H29N2O2
[M+H]+: 461.2224, found: 461.2227.
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(3-(4-fluorophenyl)-1-(4-methoxyphenyl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-5-
yl)(phenyl)methanone (2az). Compound 2az was prepared in 87% yield (50 mg) according to the
general procedure (Method C). Yellow solid; mp 126-129 oC; 1H NMR (500 MHz, CDCl3): δ 7.42-7.41
(m, 2H), 7.08-6.97 (m, 5H), 6.89-6.87 (m, 4H), 6.81-6.78 (m, 3H), 6.67-6.65 (m, 2H), 6.55-6.53 (m,
2H), 5.01 (s, 2H), 4.45 (s, 2H), 3.62 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 197.0, 157.3 (d, JC-F
=
237.8 Hz), 156.6, 154.8, 144.5 (d, JC-F = 2.2 Hz), 140.3, 139.4, 135.5, 131.2, 130.4, 128.9, 128.8, 127.5,
127.4, 127.2, 118.3 (d, JC-F = 7.6 Hz), 115.6 (d, JC-F = 22.1 Hz), 115.0, 113.9, 71.9, 55.2, 55.1; IR
(KBr): 2924, 2853, 1599, 1512, 1366, 1247, 772, 694 cm-1; HRMS (ESI) calcd for C30H26FN2O2
[M+H]+: 465.1973, found: 465.1968.
(4-chlorophenyl)-1-(4-methoxyphenyl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone
(2ba). Compound 2ba was prepared in 83% yield (50 mg) according to the general procedure (Method
C). Yellow solid; mp 124-127 oC; 1H NMR (500 MHz, CDCl3): δ 7.42 (d, J = 7.2 Hz, 2H), 7.12 (d, J =
8.9 Hz, 2H), 7.09-6.97 (m, 5H), 6.81-6.78 (m, 5H), 6.71 (d, J = 8.9 Hz, 2H), 6.56 (d, J = 8.9 Hz, 2H),
5.03 (s, 2H), 4.46 (s, 2H), 3.63 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 196.9, 156.7, 155.0, 146.6,
140.2, 139.3, 135.4, 131.2, 130.4, 129.0, 128.9, 128.9, 127.5, 127.3, 127.3, 124.6, 117.4, 115.3, 114.0,
70.5, 55.2, 49.5; IR (KBr): 2926, 1595, 1555, 1508, 1366, 1245, 1095, 771, 694 cm-1; HRMS (ESI)
calcd for C30H26ClN2O2 [M+H]+: 481.1677, found: 481.1671.
(3-(4-bromophenyl)-1-(4-methoxyphenyl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-5-
yl)(phenyl)methanone (2bb). Compound 2bb was prepared in 78% yield (51 mg) according to the
general procedure (Method C). Yellow solid; mp 139-142 oC; 1H NMR (500 MHz, CDCl3): δ 7.42 (d, J
= 7.3 Hz, 2H), 7.27-7.25 (m, 2H), 7.09-6.98 (m, 5H), 6.82-6.79 (m, 3H), 6.75-6.71 (m, 4H), 6.57 (d, J =
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8.9 Hz, 2H), 5.03 (s, 2H), 4.45 (s, 2H), 3.64 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 196.9, 156.7,
155.2, 147.2, 140.2, 139.3, 135.4, 131.9, 131.2, 130.5, 128.9, 128.9, 127.5, 127.3, 127.3, 117.7, 115.4,
114.0, 111.8, 70.3, 55.2, 49.4; IR (KBr): 2834, 1589, 1562, 1508, 1493, 1377, 1247, 1032, 769, 723,
694 cm-1;HRMS (ESI) calcd for C30H26BrN2O2 [M+H]+: 525.1172, found: 525.1177.
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(1,3-bis(4-methoxyphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2bc). Compound
2bc was prepared in 80% yield (40 mg) according to the general procedure (Method A). Yellow solid;
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mp 147-149 C; H NMR (500 MHz, CDCl3): δ 7.54-7.53 (m, 2H), 7.44-7.37 (m, 4H), 6.97-6.94 (m,
2H), 6.87-6.83 (m, 4H), 6.81-6.79 (m, 2H), 5.01 (s, 2H), 4.41 (s, 2H), 3.77 (s, 3H), 3.75 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3): δ 193.1, 157.0, 154.5, 146.9, 142.3, 139.8, 137.6, 130.1, 128.4,
128.1, 121.0, 119.8, 114.9, 114.5, 109.5, 67.5, 55.5, 55.5, 47.4; IR (KBr): 2928, 2833, 1562, 1509,
1441, 1245, 1034, 872, 702 cm-1; HRMS (ESI) calcd for C25H25N2O3 [M+H]+: 401.1860, found:
401.1863.
(1,3-bis(4-(tert-butyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2bd). Compound
2bd was prepared in 90% yield (51 mg) according to the general procedure (Method C). Yellow solid;
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mp 144-146 C; H NMR (500 MHz, CDCl3): δ 7.54-7.50 (m, 3H), 7.43-7.34 (m, 6H), 7.25-7.24 (m,
1H), 6.93 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 5.10 (s, 2H), 4.46 (s, 2H), 1.29 (s, 9H), 1.27 (s,
9H); 13C{1H} NMR (125 MHz, CDCl3): δ 193.2, 147.6, 146.3, 146.1, 143.9, 141.3, 139.7, 130.1, 128.4,
128.1, 126.6, 126.1, 118.3, 117.6, 110.4, 65.6, 47.1, 34.4, 34.0, 31.4, 31.3; IR (KBr): 2960, 2866, 1591,
1568, 1517, 1364, 1257, 1147, 878, 828, 699 cm-1; HRMS (ESI) calcd for C31H37N2O [M+H]+:
453.2900, found: 453.2906.
(1,3-bis(4-ethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2be). Compound 2be
was prepared in 97% yield (48 mg) according to the general procedure (Method A). Yellow solid; mp
128-129 oC; 1H NMR (500 MHz, CDCl3): δ 7.54-7.52 (m, 2H), 7.48 (s, 1H), 7.44-7.36 (m, 3H), 7.15 (d,
J = 8.4 Hz, 2H), 7.07 (d, J = 8.5 Hz, 2H), 6.92 (d, J = 8.6 Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 5.09 (s,
2H), 4.46 (s, 2H), 2.61 (q, J = 7.6 Hz, 2H), 2.56 (q, J = 7.6 Hz, 2H), 1.21 (t, J = 7.6 Hz, 3H), 1.19 (t, J =
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7.6 Hz, 3H); C{1H} NMR (125 MHz, CDCl3): δ 193.3, 146.5, 146.4, 141.8, 140.8, 139.7, 137.1,
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130.1, 129.1, 128.6, 128.4, 128.1, 118.8, 118.0, 110.2, 65.9, 47.2, 28.1, 27.9, 15.6, 15.5; IR (KBr):
2961, 2924, 1567, 1513, 1368, 1254, 972, 867, 719 cm-1; HRMS (ESI) calcd for C27H29N2O [M+H]+:
397.2274, found: 397.2280.
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(1,3-di-p-tolyl-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2bf). Compound 2bf was
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prepared in 99% yield (46 mg) according to the general procedure (Method A). Yellow solid; mp 125-
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127 C; H NMR (500 MHz, CDCl3): δ 7.54-7.52 (m, 2H), 7.46 (s, 1H), 7.42-7.41 (m, 1H), 7.39-7.36
(m, 2H), 7.12 (d, J = 8.2 Hz, 2H), 7.04 (d, J = 8.3 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 6.83 (d, J = 8.4 Hz,
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2H), 5.08 (s, 2H), 4.46 (s, 2H), 2.31 (s, 3H), 2.25 (s, 3H); C{1H} NMR (125 MHz, CDCl3): δ 193.2,
146.4, 146.1, 141.6, 139.7, 134.4, 130.6, 130.3, 130.1, 129.8, 128.4, 128.1, 118.8, 118.0, 110.1, 66.0,
47.1, 20.7, 20.4; IR (KBr): 3027, 2920, 1586, 1569, 1512, 1257, 1133, 998, 806, 722 cm-1; HRMS (ESI)
calcd for C25H25N2O [M+H]+: 369.1961, found: 369.1956.
(1,3-bis(4-fluorophenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2bg). Compound 2bg
was prepared in 88% yield (41 mg) according to the general procedure (Method A). Yellow solid; mp
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118-120 C; H NMR (500 MHz, CDCl3): δ 7.55-7.54 (m, 2H), 7.47-7.39 (m, 4H), 7.04-7.01 (m, 2H),
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6.94 (d, J = 6.4 Hz, 4H), 6.89-6.86 (m, 2H), 5.05 (s, 2H), 4.43 (s, 2H); C{1H} NMR (125 MHz,
CDCl3): δ 193.3, 159.8 (d, JC-F = 243.9 Hz), 157.8 (d, JC-F = 239.4 Hz), 146.1, 144.7 (d, JC-F = 2.4 Hz),
140.4 (d, JC-F = 2.7 Hz), 139.3, 130.4, 128.4, 128.2, 120.8 (d, JC-F = 8.2 Hz), 119.7 (d, JC-F = 7.8 Hz),
116.6 (d, JC-F = 22.7 Hz), 115.8 (d, JC-F = 22.2 Hz), 110.4, 67.0, 47.3; IR (KBr): 2974, 2900, 1564,
1509, 1406, 1382, 1050, 880 cm-1; HRMS (ESI) calcd for C23H19F2N2O [M+H]+: 377.1460, found:
377.1467.
(1,3-bis(4-chlorophenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2bh). Compound 2bh
was prepared in 83% yield (42 mg) according to the general procedure (Method C). Yellow solid; mp
120-122 oC; 1H NMR (500 MHz, CDCl3): δ 7.54 (d, J = 7.3 Hz, 2H), 7.47-7.39 (m, 4H), 7.30 (d, J = 8.6
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Hz, 2H), 7.18 (d, J = 8.8 Hz, 2H), 6.88-6.83 (m, 4H), 5.08 (s, 2H), 4.46 (s, 2H); C{1H} NMR (125
MHz, CDCl3): δ 193.3, 146.9, 145.1, 142.4, 139.1, 130.6, 130.0, 129.9, 129.3, 128.4, 128.3, 126.3,
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119.6, 119.1, 111.1, 65.6, 47.0; IR (KBr): 2972, 2901, 1630, 1556, 1497, 1407, 1255, 1066, 879, 703
cm-1; HRMS (ESI) calcd for C23H19Cl2N2O [M+H]+: 409.0869, found: 409.0874.
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(1,3-bis(4-bromophenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)(phenyl)methanone (2bi). Compound 2bi
was prepared in 87% yield (54 mg) according to the general procedure (Method C). Yellow solid; mp
135-137 oC; 1H NMR (500 MHz, CDCl3): δ 7.54 (d, J = 7.1 Hz, 2H), 7.46-7.39 (m, 6H), 7.32 (d, J = 8.9
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Hz, 2H), 6.82-6.77 (m, 4H), 5.08 (s, 2H), 4.45 (s, 2H); C{1H} NMR (125 MHz, CDCl3): δ 193.3,
147.3, 145.0, 142.9, 139.1, 132.9, 132.2, 130.6, 128.4, 128.3, 119.9, 119.4, 117.5, 113.7, 111.3, 65.4,
47.0; IR (KBr): 2924, 2853, 1610, 1582, 1493, 1265, 1207, 1142, 822, 698 cm-1; HRMS (ESI) calcd for
C23H19Br2N2O [M+H]+: 496.9859, found: 496.9865.
Synthesis and characterization of 2al’
To a 25 mL Schlenk tube containing a magnetic stirring bar was added 2al (80 mg, 0.26 mmol),
ethanol (3 mL, 95%), NaOH (31.2 mg, 0.78 mmol), H2O (9.5 μL, 0.52 mmol). The mixture was stirred
in an 80 oC oil bath for about 8 h until 2al had disappeared by TLC analysis. Then, the resulting mixture
was cooled to room temperature and quenched with by saturated solution of ammonium chloride, and
extracted with ethyl acetate (20 mL × 3). The combined organic layers were washed with brine and
dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by flash
chromatography on silica gel with dichloromethane/ethyl acetate = 1:2 as the eluent afforded the
corresponding acid 2al'.
1,3-diphenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid (2al'). White solid; 75% yield (55 mg);
mp 142-144 oC; 1H NMR (500 MHz, DMSO-d6): δ 11.61 (s, 1H), 7.74 (s, 1H), 7.38-7.35 (m, 2H), 7.20-
7.14 (m, 4H), 7.09-7.06 (m, 1H), 6.93 (d, J = 8.1 Hz, 2H), 6.83-6.81 (m, 1H), 5.15 (s, 2H), 4.16 (s, 2H);
13C{1H} NMR (125 MHz, DMSO-d6): δ 167.5, 148.6, 143.6, 139.1, 129.7, 129.1, 122.9, 120.3, 117.2,
116.9, 99.8, 63.3, 46.7; IR (KBr): 2868, 1640, 1594, 1495, 1404, 1243, 758, 690 cm-1; HRMS (ESI)
calcd for C17H17N2O2 [M+H]+: 281.1285, found: 281.1288.
Observation of imine intermediate 3 under the standard conditions
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According to General Method A, to a well-dried 25 mL seal tube containing a magnetic stirring bar
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was added TBD (5.6 mg, 0.04mmol). Then, the vessel was evacuated and refilled with CO2 for five
times. Under a stream of CO2, to this vessel were added 2,6-diisopropylaniline (0.2 mmol), acetonitrile
(1.0 mL) and PhSiH3 (49 μL, 0.4 mmol). Then the vessel was sealed at atmospheric pressure of CO2 (1
atm) and the resulting mixture was stirred in a 100 oC oil bath for 4 h. The mixture was cooled to room
temperature and internal standard 1,1,2,2-tetrachloroethane (0.2 mmol, 21uL) was added. N-(2,6-
Diisopropylphenyl) methanimine 3 was obtained in 74% NMR yield. 1H NMR (500 MHz, DMSO-d6): δ
7.77 (d, J = 17.7 Hz, 1H), 7.39 (d, J = 17.7 Hz, 1H), 7.16-6.95 (m, 3H), 2.92-2.87 (m, 2H), 1.14 (d, J =
6.9 Hz, 12H).37
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Gram-Scale Preparation (for 2aa):
To a well-dried 500 mL seal tube containing a magnetic stirring bar was added TBD (208.8 mg, 1.5
mmol). Then, the vessel was evacuated and refilled with CO2 for five times. Under a stream of CO2, to
this vessel were added aniline (0.68 mL, 7.5 mmol), acetonitrile (40 mL) and PhSiH3 (2.2 mL, 18
mmol). Then the vessel was sealed at atmospheric pressure of CO2 (1 atm) and the resulting mixture
was stirred in a 115 oC oil bath for 10 h. After cooling the reaction mixture to ambient temperature, 1a
(0.67 g, 3 mmol) and ZnCl2 (3 mL, 0.5 mol/L in THF, 1.5 mmol) were added under a stream of CO2.
o
Subsequently, the vessel was sealed and heated in a 100 C oil bath for 16 h. The reaction could be
monitored by TLC analysis. The resulting mixture was concentrated under reduced pressure. The
resulting residue was subjected to column chromatography for purification (petroleum ether/ethyl
acetate = 5:1) to give pure 2aa (0.95 g, 93%).
■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
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1H and 13C NMR spectra for compounds 2 and 3, calculated energy profile of less favored pathways,
the UV-vis absorption spectra and spectral properties of compounds 2, fluorescent spectral properties of
representative 2aa, 2ao and 2al (PDF)
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Crystallographic details for compounds 2aa and 2at (CIF)
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■ AUTHOR INFORMATION
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Corresponding Author
*(Yulei Zhao) E-mail: zhaoyulei86@126.com
*(Zhengquan Yan) E-mail: yanzhq2008@163.com
*(Jinmao You) E-mail: jmyou6304@163.com.
*(Yuanye Jiang) E-mail: qfnu_yuanyejiang@163.com
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENTS
This work was financially supported by NSFC (No. 21702119) and the Natural Science Foundation of
Shandong Province (Nos. ZR2018BB026, ZR2017QB001)
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