A detailed study of the intramolecular hydroamination of N-(ortho-alkynyl)aryl-N′-substituted trifluoroacetamidines and bromodifluoroacetamidines

Article abstract of DOI:10.1039/c1ob06528a

The intramolecular hydroamination of N-(ortho-alkynyl)aryl-N′- substituted trifluoroacetamidines and bromodifluoroacetamidines is studied in detail. When the substituents on the alkyne fragment are aryl and alkyl groups, 5-endo-dig cyclization occurs utilizing NaAuCl₄·2H ₂O as a catalyst, while 6-exo-dig cyclization proceeds in the presence of K₂CO₃ as a base. Interestingly, the indole derivatives are afforded with good regioselectivity via a 5-endo-dig pathway catalyzed by Cu(OAc)₂ when ortho-ethynyl appears on the aryl substituent of the amidine. The electrophilic cyclization of the amidines also shows good regioselectivity under the I₂/NaHCO₃ system. At the end, a facile cascade synthesis of fluorinated quinazolones is described via hydroamination/ozonolysis from the corresponding amidine.

Full text of DOI:10.1039/c1ob06528a

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PAPER
A detailed study of the intramolecular hydroamination of
N-(ortho-alkynyl)aryl-N¢-substituted trifluoroacetamidines and
bromodifluoroacetamidines†
Jiangtao Zhu, Haibo Xie, Zixian Chen, Shan Li and Yongming Wu*
Received 6th September 2011, Accepted 3rd October 2011
DOI: 10.1039/c1ob06528a
The intramolecular hydroamination of N-(ortho-alkynyl)aryl-N¢-substituted trifluoroacetamidines and
bromodifluoroacetamidines is studied in detail. When the substituents on the alkyne fragment are aryl
and alkyl groups, 5-endo-dig cyclization occurs utilizing NaAuCl4·2H2O as a catalyst, while 6-exo-dig
cyclization proceeds in the presence of K2CO3 as a base. Interestingly, the indole derivatives are
afforded with good regioselectivity via a 5-endo-dig pathway catalyzed by Cu(OAc)2 when ortho-ethynyl
appears on the aryl substituent of the amidine. The electrophilic cyclization of the amidines also shows
good regioselectivity under the I2/NaHCO3 system. At the end, a facile cascade synthesis of fluorinated
quinazolones is described via hydroamination/ozonolysis from the corresponding amidine.
Introduction
The addition of a heteroatom–hydrogen bond across an unsat-
urated carbon–carbon bond is one of the most interesting and
intriguing subjects in organic synthesis, which can be performed
with 100% atom efficiency.1 In particular, the intramolecular
addition of alkynes toward heterocycles is a useful synthetic
protocol when the heteroatom nucleophile is in close proximity
to the triple bond.2 Over the past few years, the intramolecular
annulations of amines, amides, imines, carboxylic acids, alcohols,
phenols, esters, nitriles and phosphonic acid derivatives have
been developed,3 catalyzed by transition metal complexes, Lewis
acids and bases.4 The orientation of the reaction depends on the
nature of the substituents on the alkyne, the nucleophile and
catalyst. Since many reports have been focused on the synthesis
of indoles from 2-ethynylaniline derivatives,5 we predicted that N-
(ortho-alkynylaryl)amidine could serve as a good research object
for extending the intramolecular hydroamination substrates. As
shown in Scheme 1, the cyclization of the amidine 2 could
potentially give three products via different pathways in theory.6
If so, we could get many fluorinated azaheterocycles which are
Scheme 1 The different reaction pathways of the amidine 2.
frequently found in pharmaceuticals, drug candidates and other
molecular functional materials. During our research on the hy-
droamination of amidines, Ding and co-workers have developed a
mild and efficient synthesis of indole N-carboximidamides and N-
carboximidoates by Ag(I)-catalyzed regioselective intramolecular
cyclization of (2-alkynylphenyl)guanidine or (2-alkynylphenyl)-
isourea.7 Herein we would like to disclose our preliminary results
on the intramolecular hydroamination of fluorinated N-(ortho-
alkynylaryl)amidines under different conditions including Lewis
acids, base and iodine.
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai
200032, China; Fax: +86-21-64166128; Tel: +86-21-54925190
† Electronic supplementary information (ESI) available. CCDC reference
numbers 846077–846079. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1ob06528a
Results and discussion
The synthesis of the substrates 2 for cyclization was straight-
forward (Scheme 2).8 For example, the model substrate
2a was prepared by the treatment of benzylamine with
516 | Org. Biomol. Chem., 2012, 10, 516–523
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Table 1 Optimization of the cyclization by various Lewis acidsa
Entry
Catalyst
Solvent
T/◦C
Time (h)
Conversionb
3a : 4ac
1
2
3
4
5
6
7
8
CuI
CuI
CuSO4
Cu(OAc)2
AgNO3
AgNO3
Ag2SO4
AgOAc
AgBF4
AgClO4
AgOOCCF3
AgOTf
NaAuCl4·2H2O
NaAuCl4·2H2O
NaAuCl4·2H2O
NaAuCl4·2H2O
NaAuCl4·2H2O
NaAuCl4·2H2O
DMF
CH3CN
DMF
DMF
CH3CN
DMF
CH3CN
CH3CN
DMF
DMF
DMF
80
80
80
80
80
80
80
80
80
80
80
80
80
rt
2
2
2
3
2
2
2
1
1
1
1
1
0.5
1
1
1
2
2
35
20
—
—
100
100
17
100
100
100
100
100
100
100
100e
100
100
100
5 : 1
1 : 1
1 : 1
2 : 1
1 : 1
1.6 : 1
1.2 : 1
1.4 : 1
2.3 : 1
1.2 : 1
>95 : 5
>95 : 5
>95 : 5
>95 : 5
>95 : 5
>95 : 5
9
10
11
12
13
14
15d
16
17
18
DMF
toluene
toluene
toluene
CH2Cl2
CH3CN
THF
rt
rt
80
70
a Reaction conditions: 2a (0.2 mmol), catalyst (10 mol%), solvent (2 mL). b The conversion was determined by 19F NMR analysis with trifluoromethyl-
benzene as internal standard. c The ratio of the products 3a and 4a was also observed from 19F NMR spectroscopy. d NaAuCl4·2H2O (5 mol%). e The
isolated yield was 96%.
Scheme 2 Representative synthesis of the substrate 2a.
N-(ortho-phenylethynyl)phenyl trifluoroacetimidoyl chloride 1a,
which was synthesized by one-pot reaction of 2-(phenyl-
ethynyl)aniline with trifluoroacetic acid under Uneyama’s
conditions.8a
toluene at room temperature for 1 h and the product 3a was
isolated in 96% yield (Table 1, entry 15).
With this optimized reaction condition, a series of N-(ortho-
alkynyl)phenyl-N¢-substituted bromodifluoro-acetamidines as
well as trifluoroacetamidines were synthesized using the procedure
described above to investigate the scope of this reaction. N¢-
Substituent groups (R2) such as alkyls (Table 2, entries 1, 3,
4, 8, 10–13, 15 and 17) and aryls bearing either electron-
withdrawing or electron-donating substitution (Table 2, entries
5–7, 9, 14 and 16) behaved the same and proceeded nicely for this
transformation. Notably, the hydroamination of N-(ortho-phenyl-
ethynyl)phenyltrifluoroacetamidine 2b led to the corresponding
indole 3b in an acceptable 73% yield. In addition, compounds with
alkyl and functionalised aryl substituents (R1) on the acetylene
terminal were also tested and the corresponding indole products
could also be obtained in high yields (Table 2, entries 8–9 and 15–
17). An X-ray crystal analysis confirmed the structure of the indole
3j in (Z)-imino form (Table 2, entry 10). Incidentally, when the
terminal substituent was H, regioisomers 3r and 4r were formed
With the model substrate 2a in hand, we decided to screen
various Lewis acids considered to have the high reactivities
towards the hydroamination reactions (Table 1). The substrate
2a was converted to the cyclized products 3a and 4a with a
modest yield using CuI as the catalyst, whereas Cu(OAc)2 and
CuSO4 were inactive (Table 1, entries 1–4). Silver salts except
for Ag2SO4 generally showed good activities, but the ratio of the
products 3a and 4a was ranging from 1 : 1 to 2.3 : 1 depending on
their counteranions (Table 1, entries 5–12). Much to our delight,
the hydroamination reaction took place efficiently with excellent
regioselectivity in the presence of NaAuCl4·2H2O in toluene at
80 ◦C for 30 min. Indole derivative 3a was the only detectable
product in the reaction system by 19F NMR spectroscopy. After
further studies of reaction conditions, we found out that the
reaction went to completion using 5 mol% NaAuCl4·2H2O in
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Table 3 Optimization of the substrate 2s under various Lewis acidsa
Table 2 Gold-catalyzed intramolecular hydroamination of the amidi-
nes 2a
Entry
Lewis acid
Ratio (4s : 3s)b
Yield (%)c
1
2
3
4
5
6
7
Ti(OBu)4
ZnCl2
BF3·Et2O
InCl3·3H2O
CuSO4
Cu(OTf)2
Cu(OAc)2
25 : 1
20 : 1
25 : 1
22 : 1
25 : 1
12 : 1
1 : 7
4s/30
4s/73
4s/70
4s/82
4s/73
4s/68
3s/67
Entry
RF
R1
R2
Yield (%)b
1
2
3
4
5
6
7
8
CF3
CF3
CF3
CF3
CF3
CF3
CF3
CF3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
p-ClC6H4
p-MeC6H4
Ph
Ph
Ph
Ph
Bn
H
Me
Cyclohexyl
p-OMeC6H4
p-ClC6H4
p-NO2C6H4
Bn
p-OMeC6H4
Bn
Bu
Cyclohexyl
Allyl
p-OMeC6H4
Bn
p-OMeC6H4
Bn
Bn
3a/96
3b/73
3c/90
3d/87
3e/89
3f/90
3g/94
3h/87
3i/95
3j/90
3k/93
3l/92
3m/91
3n/92
3o/91
3p/96
3q/94
a R◦eaction conditions: 2 (0.2 mmol), catalyst (10 mol%), toluene (2 mL),
80 C, 2 h. b The ratio was detected from the reaction mixture by 19F NMR.
c Isolated yield of the major product.
9
CF3
10
11
12
13
14
15
16
17
18
CF2Br
CF2Br
CF2Br
CF2Br
CF2Br
CF2Br
CF2Br
CF2Br
CF2Br
It should be noted that N-(ortho-ethynyl)phenylbromo-
difluoroacetamidine 2v was converted to the corresponding prod-
uct indole 3v in 82% yield.
Ph
Bu
Bu
During the study of the Lewis acid catalyzed hydroamination
of the amidines, we accidentally found out by 19F NMR that
the substrate 2j was converted exclusively to two unexpected
products by treatment with 2 equiv of K2CO3 in CH3CN at 80 ◦C
for 3 h. After removing the solvent, the residue was allowed to
sit at room temperature for 12 h and the 19F NMR revealed
that the ratio of the isomers altered from 3.8 : 1 to 70 : 1. The
structure of the product 4j¢ was confirmed by X-ray diffraction.
The reaction proceeded through a 6-exo-dig pathway and the
stereoisomers were produced under the base-catalyzed reaction.
Quinazoline 4j and 4j¢ tautomerized at room temperature and the
more thermodynamically stable 4j¢ predominated (eq 1, Scheme
4) when an equilibrium was reached. However, when the substrate
2e with PMP on nitrogen reacted under the same condition,
the isomerization of the two products also took place and the
quinazoline 4e was detected as the major product which was also
determined by X-ray diffraction (eq 2, Scheme 4).
p-OMeC6H4
H
c
—
a Reaction conditions: 2 (0.5 mmol), NaAuCl4·2H2O (5 mol%), toluene
(5 mL), at room temperature for 1 h. b Yield of the isolated product. c The
ratio of 3r and 4r was 1 : 1 by 19F NMR.
in a ratio of 1 : 1 (Table 2, entry 18). This phenomenon gave us
an incentive to study the influence of different Lewis acids on the
substrate with an ethynyl substituent.
Subsequently, the substrate 2s was subjected to an array of
Lewis acids in toluene at 80 ◦C for 2 h (Table 3). Almost all
Lewis acid catalysts showed good catalytic activities except for
Ti(OBu)4, which made 2s rapidly decompose. The quinazoline
4s was identified as the major product under these conditions.
To our delight, the reaction proceeded by a different pathway
and provided indole 3s as the major product in the presence of
Cu(OAc)2 as catalyst (Table 3, entry 7). So we then employed
some substrates with N¢-substituent groups (R2) to investigate the
scope under the catalyst Cu(OAc)2. The indoles 3 were obtained in
good yields no matter what the substituent was on the N-position
under these conditions (Scheme 3).9
Scheme 3 Copper-catalyzed intramolecular hydroamination of the sub-
strate 2 with ethynyl substituent.
Scheme 4 Base-catalyzed intramolecular hydroamination of the amidi-
nes 2.
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Table 4 The cascade synthesis of 2-polyfluoroalkyl quinazolonesa
(100 MHz) spectrometer. IR spectra were obtained with a Nicolet
AV-360 spectrophotometer. Elemental analysis was performed by
the Analytical Laboratory of Shanghai Institute of Organic Chem-
istry. Mass spectra were recorded by EI methods. HRMS (EI)
was measured on a Waters Micromass GCT Premier mass spec-
trometer. Solvents and reagents were purchased from commercial
sources and used as received. Flash column chromatography was
carried out using 300–400 mesh silica gel at increased pressure and
petroleum ether/ethyl acetate combination was used as the eluent.
Entry
RF
R1
R2
Yield (%)b
1
2
3
4
CF3
CF3
CF2Br
CF2Br
Ph
Ph
Ph
Ph
Bn
6a/82
6b/76
6c/64
6d/69
p-OMeC6H4
Bn
p-OMeC6H4
General procedure for NaAuCl4·2H2O catalyzed intramolecular
hydroamination of the amidines 2
a Reaction conditions: the amidines 2 (0.5 mmol), potassium carbonate
(1.0 mmol), acetonitrile (10 mL). b Overall isolated yield of the product.
To a solution of the amidines 2 (0.5 mmol) in toluene (5 mL),
NaAuCl4·2H2O (10 mg, 0.025 mmol) was added. The reaction
mixture was stirred at room temperature for 1 h and then filtrated.
The solvents were evaporated under reduced pressure. The crude
product was chromatographed by column chromatography on
silica gel (petroleum ether/ethyl acetate (20 : 1)) to give the
products 3.
In order to explore this reaction and prove the transforma-
tion of the stereoisomers, we developed a tandem hydroami-
nation/ozonolysis process from the substrate 2 to synthesize
quinazolone 6 without separating the intermediate quinazoline
4.10 Using this methodology, 2-polyfluoroalkyl substituted quina-
zolones 6 were easily prepared in high yields (Table 4).
Finally, we showed that the substrate 2 underwent electrophilic
cyclization in the presence of I2.11 3-Iodo substituted indoles
were obtained exclusively under the optimized conditions and
three substrates including benzyl, butyl, p-methoxyphenyl on the
nitrogen provided the corresponding indoles in excellent yields
(Scheme 5).
(Z)-1-Phenyl-N-(2,2,2-trifluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)methanamine (3a)
White solid, mp: 87–88 ◦C; 1H NMR (300 MHz, CDCl3): d 7.72–
7.67 (m, 1H), 7.42–7.09 (m, 13H), 6.84 (s, 1H), 4.68–4.51 (m,
2H); 13C NMR (100 MHz, CDCl3): d 143.7 (q, J = 38.6 Hz),
140.2, 136.7, 136.4, 131.4, 128.9, 128.8, 128.5, 127.7, 127.4, 127.4,
123.7, 122.1, 121.2, 117.9 (q, J = 280.2 Hz), 110.4, 105.3, 55.4;
MS (EI): m/z (%): 378 (36.49) [M+], 91 (100.00); Anal. Calcd. for
C23H17F3N2: C, 73.01; H, 4.53; N, 7.40; Found: C, 72.97; H, 4.69;
N, 7.51; IR (film): n 3044, 1682, 1452, 1345, 1270, 1154, 928 cm-1.
2,2,2-Trifluoro-1-(2-phenyl-1H-indol-1-yl)ethanimine (3b)
1H NMR (300 MHz, CDCl3): d 10.94 (brs, 0.39H), 10.24 (brs,
0.60H), 7.62 (d, J = 7.0 Hz, 1H), 7.54–7.19 (m, 8H), 6.74 (s, 1H);
MS (EI): m/z (%): 288 (100.00) [M+]; HRMS (EI) Calcd. for
C16H11F3N2: 288.0874, Found: 288.0869; IR (film): n 3254, 3064,
1661, 1455, 1391, 1287, 1188, 1158 cm-1.
Scheme 5 Iodine mediated cyclization of the amidines 2.
(Z)-N-(2,2,2-Trifluoro-1-(2-phenyl-1H-indol-1-
Conclusions
yl)ethylidene)methanamine (3c)
White solid, mp: 72–74 ◦C; 1H NMR (300 MHz, CDCl3): d 7.67 (d,
In conclusion, a detailed study of the intramolecular hydroami-
nation of the fluorinated (ortho-alkynylaryl)amidines under Lewis
acid, base and iodine was presented. A facile and mild way for
the synthesis of the fluorinated quinazolones was developed via
hydroamination/ozonolysis from the amidines. Further trans-
formation of the bromodifluoro group in the product indole
derivatives and synthesis of other heterocycles by applying this
methodology are in progress in our laboratory.
J = 7.3 Hz, 1H), 7.47–7.06 (m, 8H), 6.80 (s, 1H), 3.29 (s, 3H); 13
C
NMR (100 MHz, CDCl3): d 144.9 (q, J = 38.4 Hz), 140.0, 136.5,
131.5, 128.9, 128.7, 128.5, 127.2, 123.6, 122.0, 121.1, 119.2, 117.9
(d, J = 279.7 Hz), 110.2, 105.2, 39.2; MS (EI): m/z (%): 302 (79.30)
[M+], 110 (100.00); Anal. Calcd. for C17H13F3N2: C, 67.54; H, 4.33;
N, 9.27; Found: C, 67.23; H, 4.54; N, 9.12; IR (film): n 3077, 2974,
2923, 1738, 1686, 1453, 1275, 1204, 1145, 926, 751 cm-1.
(Z)-N-(2,2,2-Trifluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)cyclohexanamine (3d)
Experimental section
General experimental
White solid, mp: 76–77 ◦C; 1H NMR (300 MHz, CDCl3): d 7.69–
7.63 (m, 1H), 7.49–7.33 (m, 5H), 7.28–7.16 (m, 3H), 6.79 (s, 1H),
3.13–2.99 (m, 1H), 1.66–0.69 (m, 10H); 13C NMR (100 MHz,
CDCl3): d 140.5, 140.3 (q, J = 38.3 Hz), 137.5, 131.3, 128.7 128.5,
128.4, 128.0, 123.4, 121.7, 120.8, 118.2 (q, J = 280.0 Hz), 110.4,
Melting points were measured on a Melt-Temp apparatus and
uncorrected. 1H NMR spectra were recorded in CDCl3 on a
Bruker AM-300 spectrometer (300 MHz) with TMS as internal
standard. 13C NMR spectra were taken on a Bruker AM-400
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104.7, 60.3, 32.9, 31.5, 25.1, 23.6, 23.4; MS (EI): m/z (%): 370
(27.33) [M+], 193 (100.00); HRMS (EI) Calcd. for C22H21F3N2:
370.1657; Found: 370.1663; IR (film): n 3063, 2935, 2858, 1669,
1455, 1204, 1142, 936 cm-1.
(Z)-4-Methoxy-N-(2,2,2-trifluoro-1-(2-p-tolyl-1H-indol-
1-yl)ethylidene)aniline (3i)
White solid, mp: 74 ◦C; 1H NMR (400 MHz, CDCl3): d 7.62–7.49
(m, 1H), 7.21–6.89 (m, 7H), 6.62 (s, 1H), 6.51 (s, 4H), 3.61 (s, 3H),
2.24 (s, 3H); 13C NMR (101 MHz, CDCl3): d 159.9, 139.7, 138.2,
137.1 (q, J = 38.9 Hz), 136.1, 135.8 129.2, 129.1, 128.5, 127.2,
126.2, 123.4, 122.0, 120.8, 118.4 (q, J = 219.2 Hz), 114.1, 111.0,
105.5, 55.3, 21.1; MS (MALDI): m/z: 409 [M + H+]; Anal. Calcd.
for C24H19F3N2: C, 70.58, H, 4.69; N, 6.86; Found: C, 70.48; H,
4.84; N, 6.70.
(Z)-4-Methoxy-N-(2,2,2-trifluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)aniline (3e)
White solid, mp: 74–75 ◦C; 1H NMR (300 MHz, CDCl3): d 7.68–
7.62 (m, 1H), 7.30–7.13 (m, 8H), 6.73 (s, 1H), 6.62–6.50 (m, 4H),
3.71 (s, 3H); 13C NMR (100 MHz, CDCl3): d 159.9, 139.5, 137.2
(q, J = 38.8 Hz), 136.2, 135.7, 131.3, 129.0, 128.5, 128.2, 127.3,
126.1, 123.7, 122.1, 121.0, 120.2 (q, J = 278.1 Hz), 114.1, 111.0,
106.0, 55.1; MS (EI): m/z (%): 394 (38.47) [M+], 202 (100.00);
Anal. Calcd. for C23H17F3N2O: C, 70.04; H, 4.34; N, 7.10; Found:
C, 69.80; H, 4.50; N, 7.10; IR (film): n 3013, 2969, 1649, 1595,
1502, 1454, 1246, 1197, 1142, 1028, 751 cm-1.
(Z)-N-(2-Bromo-2,2-difluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)-1-phenylmethanamine (3j)
◦
1
White solid, mp: 113–114 C; H NMR (300 MHz, CDCl3): d
7.73–7.63 (m, 1H), 7.44–7.09 (m, 13H), 6.81 (s, 1H), 4.84–4.15
(m, 2H); 13C NMR (100 MHz, CDCl3): d 147.7 (t, J = 27.6 Hz),
140.1, 137.0, 136.7, 131.9, 128.9, 128.8, 128.6, 128.5, 127.7, 127.5,
127.4, 123.6, 122.1, 121.2, 113.8 (t, J = 308.2 Hz), 110.7, 105.4,
55.5; MS (EI): m/z (%): 438 (9.52) [M+], 91 (100.00); Anal. Calcd.
for C23H17BrF2N2: C, 62.88; H, 3.90; N, 6.38; Found: C, 62.77; H,
4.25; N, 6.36; IR (film): n 3044, 1680, 1453, 1338, 1157, 954 cm-1.
(Z)-4-Chloro-N-(2,2,2-trifluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)aniline (3f)
White solid, mp: 67–68 ◦C; 1H NMR (300 MHz, CDCl3): d 7.63
(d, J = 7.8 Hz, 1H), 7.43–7.20 (m, 6H), 7.07–6.90 (m, 4H), 6.66
(s, 1H), 6.14 (d, J = 8.3 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 141.4, 140.9 (q, J = 39.1 Hz), 139.6, 136.9, 133.3, 130.8, 128.8,
128.7, 128.5, 128.2, 127.3, 124.0, 123.6, 122.4, 121.1, 118.5 (q, J =
279.7 Hz), 111.1 (q, J = 2.2 Hz), 106.8; MS (EI): m/z (%): 398
(58.72) [M+], 206 (100.00); HRMS (EI) Calcd. for C22H14ClF3N2:
398.0798; Found: 398.0791; IR (film): n 3062, 2926, 1738, 1658,
1485, 1455, 1217, 1199, 1150, 951 cm-1.
(Z)-N-(2-Bromo-2,2-difluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)butan-1-amine (3k)
White solid, mp: 46–48 ◦C; 1H NMR (300 MHz, CDCl3): d 7.66
(d, J = 7.3 Hz, 1H), 7.40–7.12 (m, 8H), 6.79 (s, 1H), 3.57–3.33 (m,
2H), 1.83–1.60 (m, 2H), 1.46–1.27 (m, 2H), 0.90 (t, J = 7.3 Hz,
3H); 13C NMR (100 MHz, CDCl3): d 146.8 (t, J = 27.5 Hz), 139.9,
136.9, 132.0, 128.8, 128.6, 128.4, 127.3, 123.4, 121.8, 121.0, 113.9
(t, J = 307.4 Hz), 111.0, 105.0, 52.0, 31.8, 20.6, 13.8; MS (EI): m/z
(%): 404 (6.15) [M+], 57 (100.00); Anal. Calcd. for C20H19BrF2N2:
C, 59.27; H, 4.73; N, 6.91; Found: C, 59.36; H, 4.64; N, 6.88; IR
(film): n 3062, 2929, 1658, 1454, 1340, 1154, 959 cm-1.
(Z)-4-Nitro-N-(2,2,2-trifluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)aniline (3g)
◦
1
Yellow solid, mp: 108 C; H NMR (300 MHz, CDCl3): d 7.85–
7.45 (m, 4H), 7.42–7.22 (m, 5H), 6.95 (d, J = 6.8 Hz, 2H), 6.63
(s, 1H), 6.11 (d, J = 8.2 Hz, 2H); 13C NMR (101 MHz, CDCl3): d
148.6, 145.7, 143.6 (q, J = 39.5 Hz), 139.6, 137.5, 130.4, 128.7,
128.5, 127.3, 124.4, 124.0, 122.8, 121.6, 121.3, 118.3 (q, J =
280.0 Hz), 111.1 (q, J = 2.8 Hz), 107.6; MS (EI): m/z (%): 409
(97.54) [M+], 217 (100.00); Anal. Calcd. for C22H14F3N2O2: C,
64.55; H, 3.45; N, 10.26; Found: C, 64.58; H, 3.66; N, 10.17; IR
(film): n 3063, 1668, 1603, 1517, 1455, 1347, 1200, 1153, 1109,
944 cm-1.
(Z)-N-(2-Bromo-2,2-difluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)cyclohexanamine (3l)
White solid, mp: 118–120 ◦C; 1H NMR (300 MHz, CDCl3): d 7.65
(d, J = 6.9 Hz, 1H), 7.52–7.16 (m, 8H), 6.80 (s, 1H), 3.32–3.15 (m,
1H), 1.74–0.96 (m, 10H); 13C NMR (100 MHz, CDCl3): d 144.5
(t, J = 28.3 Hz), 140.3, 137.6, 131.6, 128.6, 128.5, 127.9, 123.2,
121.7, 120.8, 114.7 (t, J = 309.0 Hz), 111.1, 104.9, 60.3, 32.8,
31.7, 25.2, 23.6, 23.5; MS (EI): m/z (%): 430 (10.72) [M+], 193
(100.00); HRMS (EI) Calcd. for C22H21BrF2N2: 430.0856; Found:
430.0867; IR (film): n 3050, 2932, 2856, 1663, 1454, 1341, 1157,
1144, 973 cm-1.
(Z)-N-(1-(2-(4-Chlorophenyl)-1H-indol-1-
yl)-2,2,2-trifluoroethylidene)-1-phenylmethanamine (3h)
(Z)-N-(2-Bromo-2,2-difluoro-1-(2-phenyl-1H-indol-1-
yl)ethylidene)prop-2-en-1-amine (3m)
White solid, mp: 83–84 ◦C; 1H NMR (300 MHz, CDCl3): d 7.73–
7.66 (m, 1H), 7.36–7.06 (m, 12H), 6.82 (s, 1H), 4.72–4.54 (m, 2H);
13C NMR (100 MHz, CDCl3): d 143.5 (q, J = 38.7 Hz), 138.9,
136.9, 136.2, 134.7, 129.9, 129.2, 128.7, 128.6, 128.6, 127.7, 127.5,
124.0, 122.3, 121.3, 117.9 (q, J = 280.2 Hz), 110.4, 105.8, 55.5; MS
(MALDI): m/z: 413 [M + H+]; Anal. Calcd. for C23H16ClF3N2:
C, 66.91, H, 3.91; N, 6.79; Found: C, 66.97; H, 4.07; N, 6.67; IR
(film): n 3063, 3031, 1665, 1611, 1503, 1453, 1336, 1248, 1157,
1031 cm-1.
1H NMR (300 MHz, CDCl3): d 7.66 (d, J = 7.8 Hz, 1H), 7.42–
7.20 (m, 7H), 7.12 (d, J = 8.2 Hz, 1H), 6.79 (s, 1H), 6.16–6.01 (m,
1H), 5.28–5.22 (m, 2H), 4.25–4.16 (m, 2H); 13C NMR (100 MHz,
CDCl3): d 147.5 (t, J = 26.8 Hz), 139.9, 137.0, 132.7, 131.9,
128.9, 128.7, 128.5, 127.3, 123.4, 122.0, 121.1, 116.6, 113.5 (t,
J = 310.4 Hz), 111.0, 105.2, 54.7; MS (EI): m/z (%): 388 (49.58)
[M+], 165 (100.00); Anal. Calcd. for C19H15BrF2N2: C, 58.63; H,
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3.88; N, 7.20; Found: C, 58.40; H, 4.42; N, 7.21; IR (film): n 3062,
filtrated. The solvents were evaporated under reduced pressure.
The crude product was purified by column chromatography
(petroleum ether/ethyl acetate (20 : 1)) on silica gel to provide the
desired product.
3030, 2914, 1738, 1671, 1454, 1340, 1158, 990 cm-1.
(Z)-N-(2-Bromo-2,2-difluoro-1-(2-phenyl-1H-indol-
1-yl)ethylidene)-4-methoxyaniline (3n)
(Z)-N-(2-Bromo-2,2-difluoro-1-(1H-indol-1-yl)ethylidene)butan-
1-amine (3r)
White solid, mp: 84–85 ◦C; 1H NMR (300 MHz, CDCl3): d 7.66–
7.61 (m, 1H), 7.32–7.13 (m, 8H), 6.81 (s, 1H), 6.78 (d, J = 9.2 Hz,
2H); 6.65 (d, J = 9.2 Hz, 2H), 3.71 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 160.2, 139.2 (t, J = 26.8 Hz), 135.8, 135.6, 131.9,
129.0, 128.7, 128.3, 127.2, 126.7, 123.5, 121.9, 120.9, 112.5 (t, J =
308.4 Hz), 114.3, 111.7, 105.8, 55.3; MS (EI): m/z (%): 454 (42.27)
[M+], 262 (100.00); Anal. Calcd. for C23H17BrF2N2O: C, 60.67; H,
3.76; N, 6.15; Found: C, 60.81; H, 3.88; N, 6.17; IR (film): n 3056,
2931, 1738, 1651, 1589, 1502, 1453, 1335, 1258 cm-1.
1H NMR (300 MHz, CDCl3): d 7.78–7.65 (m, 1H), 7.44–7.03 (m,
4H), 6.72 (d, J = 3.4 Hz, 1H), 3.23 (s, 2H), 1.69–1.55 (m, 2H),
1.34–1.17 (m, 2H), 0.84 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 145.1 (t, J = 21.6 Hz), 136.1, 128.0, 125.8, 123.4, 121.5,
121.4, 113.8 (t, J = 246.0 Hz), 110.9, 105.6, 51.6, 31.8, 20.3, 13.5;
MS (EI): m/z (%): 328 (28.41) [M+], 57 (100.00); HRMS (EI)
Calcd. for C14H15BrF2N2: 328.0385; Found: 328.0386; IR (film):
n 2959, 2933, 2873, 1670, 1609, 1519, 1453, 1323, 1189, 1155,
963 cm-1.
(Z)-N-(2-Bromo-1-(2-butyl-1H-indol-1-yl)-2,2-
difluoroethylidene)-1-phenylmethanamine (3o)
(Z)-N-(2-Bromo-2,2-difluoro-1-(1H-indol-1-yl)ethylidene)-1-
phenylmethanamine (3s)
1H NMR (300 MHz, CDCl3): d 7.60–7.55 (m, 1H), 7.30–7.10 (m,
8H), 6.46 (s, 1H), 4.46–4.24 (m, 2H), 2.76–2.29 (m, 2H), 1.81–
1.58 (m, 2H), 1.46–1.21 (m, 2H), 0.89 (t, J = 7.3 Hz, 3H); 13C
NMR (100 MHz, CDCl3): d 147.5 (t, J = 29.1 Hz), 140.7, 136.6,
135.9, 128.7, 128.5, 127.6, 127.4, 122.4, 121.3, 120.3, 114.4 (t,
J = 309.2 Hz), 110.4, 102.5, 55.2, 30.0, 26.6, 22.4, 13.7; MS (EI):
m/z (%): 418 (7.11) [M+], 91 (100.00); HRMS (EI) Calcd. for
C21H21BrF2N2: 418.0856; Found: 418.0854; IR (film): n 3062, 3031,
2958, 2932, 2872, 1667, 1556, 1455, 1321, 1163, 995 cm-1.
1H NMR (300 MHz, CDCl3): d 7.85–7.61 (m, 1H), 7.41–7.01 (m,
9H), 6.74 (d, J = 3.2 Hz, 1H), 4.42 (brs, 2H); 13C NMR (100 MHz,
CDCl3): d 145.6 (t, J = 26.8 Hz), 136.9, 136.0, 128.5, 128.2, 127.6,
127.4, 125.7, 123.6, 121.7, 121.5, 113.8 (t, J = 308.2 Hz), 111.0,
106.0, 55.3; MS (EI): m/z (%): 362 (1.29) [M+], 91 (100.00); HRMS
(EI) Calcd. for C17H13BrF2N2: 362.0230, Found: 362.0231; IR
(film): n 3057, 3030, 2927, 1670, 1518, 1453, 1324, 1186, 1155,
980 cm-1.
(Z)-N-(2-Bromo-1-(2-butyl-1H-indol-1-yl)-2,2-
difluoroethylidene)-4-methoxyaniline (3p)
(Z)-N-(2-Bromo-2,2-difluoro-1-(1H-indol-1-yl)ethylidene)-
cyclohexanamine (3t)
1H NMR (300 MHz, CDCl3): d 7.60–7.46 (m, 1H), 7.30–7.10 (m,
3H), 6.71–6.50 (m, 4H), 6.42 (s, 1H), 3.71 (s, 3H), 2.67–2.06 (m,
2H), 1.68–1.36 (m, 2H), 1.35–1.18 (m, 2H), 0.85 (t, J = 7.3 Hz,
3H); 13C NMR (100 MHz, CDCl3): d 160.0, 140.7 (t, J = 28.6 Hz),
140.0, 135.5, 135.4, 128.9, 126.2, 122.4, 121.3, 120.1 115.2 (t,
J = 309.3 Hz), 114.2, 111.0, 103.2, 55.2, 29.9, 26.4, 22.3, 13.7;
MS (EI): m/z (%): 434 (25.42) [M+], 262 (100.00); HRMS (EI)
Calcd. for C21H21BrF2N2O: 434.0805; Found: 434.0802; IR (film):
n 3053, 2940, 2872, 1715, 1648, 1594, 1455, 1380, 1323, 1255, 1169,
985 cm-1.
1H NMR (300 MHz, CDCl3): d 7.66 (d, J = 7.8 Hz, 1H), 7.33–7.04
(m, 4H), 6.70 (d, J = 3.3 Hz, 1H), 3.21–2.77 (m, 1H), 1.84–0.71 (m,
10H); 13C NMR (100 MHz, CDCl3): d 145.1 (t, J = 26.8 Hz), 136.3,
127.9, 126.4, 123.4, 121.3, 121.2, 114.0 (t, J = 308.2 Hz), 110.5,
105.3, 59.8, 32.9, 25.1, 23.6; MS (EI): m/z (%): 354 (3.57) [M+], 117
(100.00); HRMS (EI) Calcd. for C16H17BrF2N2: 354.0543, Found:
354.0536; IR (film): n 2933, 2856, 1669, 1518, 1452, 1323, 1188,
1148, 973 cm-1.
(Z)-N-(2-Bromo-2,2-difluoro-1-(1H-indol-1-yl)ethylidene)prop-
(Z)-N-(2-Bromo-2,2-difluoro-1-(2-(4-methoxyphenyl)-1H-indol-
2-en-1-amine (3u)
1-yl)ethylidene)-1-phenylmethanamine (3q)
1H NMR (300 MHz, CDCl3): d 7.68 (d, J = 7.2 Hz, 1H), 7.42–7.02
(m, 4H), 6.72 (d, J = 3.3 Hz, 1H), 6.12–5.76 (m, 1H), 5.24–5.01
(m, 2H), 3.86 (s, 2H); 19F NMR (282 MHz, CDCl3): -54.89 (s,
3F); 13C NMR (100 MHz, CDCl3): d 145.7 (t, J = 27.5 Hz), 135.9,
133.0, 128.1, 125.7, 123.5, 123.5, 121.6, 121.4, 117.2, 113.7 (t, J =
308.2 Hz), 111.0, 54.2; MS (EI): m/z (%): 312 (14.95) [M+], 116
(100.00); HRMS (EI) Calcd. for C13H11BrF2N2: 312.0074, Found:
312.0072; IR (film): n 3077, 2922, 2842, 1673, 1517, 1453, 1324,
1189, 1156, 926 cm-1.
◦
1
White solid, mp: 98–101 C; H NMR (300 MHz, CDCl3): d
7.73–7.60 (m, 1H), 7.42–7.06 (m, 10H), 6.93–6.82 (m, 2H), 6.74
(s, 1H), 4.82–4.64 (m, 2H), 3.82 (s, 3H); 13C NMR (101 MHz,
CDCl3): d 159.8, 147.9 (t, J = 29.3 Hz), 139.9, 136.7, 128.9, 128.7,
128.6, 127.6, 127.3, 124.2, 123.2, 121.9, 120.9, 114.3, 110.9, 104.4,
55.4, 55.2; MS (MALDI): m/z: 469 [M + H+]; Anal. Calcd. for
C24H19BrF2N2O: C, 61.42; H, 4.08; N, 5.97; Found: C, 61.36; H,
4.24; N, 5.80; IR (film): n 3063, 3031, 1665, 1611, 1503, 1453, 1336,
1248, 1157, 1031 cm-1.
2-Bromo-2,2-difluoro-1-(1H-indol-1-yl)ethanimine (3v)
General procedure for Cu(OAc)2 catalyzed annulations of the
amidines 2 with a ethynyl group
1H NMR (300 MHz, CDCl3): d 9.29 (s, 1H), 8.62 (d, J = 8.1 Hz,
1H), 7.62–7.22 (m, 4H), 6.70 (d, J = 3.9 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 153.7 (t, J = 28.5 Hz), 136.5, 130.0, 125.4
(t, J = 5.1 Hz), 124.8, 123.5, 120.8, 117.1, 109.9 (t, J = 306.5 Hz),
A mixture of the amidine 2 (0.5 mmol), Cu(OAc)2 (10 mg,
0.05 mmol), and toluene (5 mL) was stirred at 80 ◦C for 1 h, then
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108.4; MS (EI): m/z (%): 272 (68.09) [M+], 117 (100.00); HRMS
(EI) Calcd. for C10H7BrF2N2: 271.9761, Found: 271.9760; IR
(film): n 3331, 3054, 2927, 2847, 1638, 1541, 1455, 1368, 1258,
1153, 1055 cm-1.
3-(4-Methoxyphenyl)-2-(trifluoromethyl)quinazolin-4(3H)-one
(6b)
◦
1
White solid, mp: 153–154 C; H NMR (300 MHz, CDCl3): d
8.34 (d, J = 7.6 Hz, 1H), 7.89 (s, 2H), 7.75–7.60 (m, 1H), 7.21
(d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H); 13C
NMR (100 MHz, CDCl3): d 161.9, 160.4, 145.1, 142.5 (q, J =
35.3 Hz), 135.0, 130.0, 129.3, 128.6, 127.3, 127.0, 122.0, 117.8 (q,
J = 277.5 Hz), 114.4, 55.4; MS (MALDI): m/z: 322 [M + H+];
Anal. Calcd. for C16H11F3N2O2: C, 60.00; H, 3.46; N, 8.75; Found:
C, 60.20; H, 3.66; N, 8.63; IR (film): 3081, 2969, 2844, 1699, 1609,
1506, 1465, 1376, 1220, 1138, 781 cm-1.
General procedure for the synthesis of quinazolines 4 and
quinazolones 6
A 25 mL flask equipped with a magnetic stirring bar was charged
with the amidine 2 (0.5 mmol), acetonitrile (10 mL) and potassium
carbonate (138 mg, 1.0 mmol). The reaction mixture was stirred
◦
at 80 C for 1 h until the amidine was completely consumed by
monitoring with TLC. The resulting solution was cooled to room
temperature and filtered, and the solvent of filtrate was removed
in vacuo. The residue was placed for 12 h, and recrystallized from
hexane to give yellow crystals of 4.
The residue was directly dissolved in 10 mL of CH2Cl2, Ozone
was slowly ventilated for 10 min, then 10 mL of water was added.
The resulting mixture was extracted by CH2Cl2 (2 ¥ 10 mL). and
thecombinedextractwasdriedwithanhydrousmagnesiumsulfate.
Solvent was removed, and the residue was separated by column
chromatography to give the pure product 6.
3-Benzyl-2-(bromodifluoromethyl)quinazolin-4(3H)-one (6c)
White solid, mp: 79–82 ◦C; 1H NMR (300 MHz, CDCl3): d 8.33 (d,
J = 8.0 Hz, 1H), 7.86 (d, J = 3.4 Hz, 2H), 7.69–7.51 (m, 1H), 7.42–
7.00 (m, 5H), 5.57 (s, 2H); 13C NMR (100 MHz, CDCl3): d 161.7,
146.3 (t, J = 27.7 Hz), 144.9, 135.5, 135.0, 129.2, 128.5, 127.4,
127.3, 126.0, 121.5, 111.5 (t, J = 308.5 Hz), 48.2; MS (EI): m/z (%):
364 (35.76) [M+], 91 (100.00); Anal. Calcd. for C16H11BrF2N2O:
C, 52.62; H, 3.04; N, 7.67; Found: C, 52.70; H, 3.40; N, 7.65; IR
(film): n 3068, 3030, 1696, 1600, 1455, 1386, 1231, 1163, 1115, 896,
773 cm-1.
(Z)-3-Benzyl-4-benzylidene-2-(bromodifluoromethyl)-3,4-
dihydroquinazoline (4j¢)
◦
2-(Bromodifluoromethyl)-3-(4-methoxyphenyl)quinazolin-
1
Yellow solid, mp: 122–123 C; H NMR (300 MHz, CDCl3): d
7.66–7.23 (m, 9H), 7.20–6.95 (m, 3H), 6.82 (d, J = 6.2 Hz, 2H),
6.30 (s, 1H), 4.76 (s, 2H); 13C NMR (100 MHz, CDCl3): d 150.3 (t,
J = 24.8 Hz), 139.7, 135.7, 135.1, 129.3, 128.7, 128.5, 128.3, 127.9,
127.5, 127.2, 126.8, 126.6, 126.5, 121.6, 113.4 (t, J = 305.0 Hz),
112.1, 54.4 (t, J = 3.6 Hz); 19F NMR (282 MHz, CDCl3) d -48.89
(s, 2F); MS (EI): m/z (%): 438 (38.63) [M+], 91 (100.00); Anal.
Calcd. for C23H17BrF2N2: C, 62.88; H, 3.90; N, 6.38; Found: C,
63.30; H, 4.16; N, 6.13; IR (KBr): n 3072, 3025, 2064, 1632, 1581,
1457, 1387, 1152, 1135, 995 cm-1.
4(3H)-one (6d)
White solid, mp: 178–180 ◦C; 1H NMR (300 MHz, CDCl3): d 8.32
(d, J = 7.6 Hz, 1H), 8.01–6.77 (m, 8H), 3.87 (s, 3H); 13C NMR
(100 MHz, CDCl3): d 162.3, 160.3, 146.3 (t, J = 24.7 Hz), 145.0,
135.1, 130.7, 129.2, 128.6, 127.4, 127.1, 121.7, 114.2, 111.5 (t, J =
308.5 Hz), 55.4; MS (MALDI): m/z: 382 [M + H+]; Anal. Calcd.
for C16H11BrF2N2O2: C, 50.42; H, 2.91; N, 7.35; Found: C, 50.47;
H, 3.10; N, 7.14; IR (film): n 2969, 2919, 2838, 1693, 1609, 1597,
1510, 1255, 1150, 1124, 990, 900, 778 cm-1.
(E)-4-Benzylidene-3-(4-methoxyphenyl)-2-(trifluoromethyl)-3,4-
dihydroquinazoline (4e)
General procedure for iodocyclization of the amidines 2
A mixture of the amidine 2 (0.5 mmol), I2 (254 mg, 1.0 mmol),
and NaHCO3 (84 mg, 1.0 mmol) in CH3CN (10 mL) was stirred at
rt for 1h. The excess I2 was removed by washing with a saturated
aqueous solution of Na2S2O3. The solution was extracted with
ethyl acetate (3 ¥ 10 mL), and the combined extract was dried
with anhydrous magnesium sulfate. Solvent was removed, and
the residue was separated by column chromatography (petroleum
ether/ethyl acetate (20 : 1)) to give the pure product.
◦
1
Yellow solid, mp: 162–164 C; H NMR (300 MHz, CDCl3): d
7.45–6.86 (m, 13H), 5.31 (s, 1H), 3.88 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 160.0, 143.4 (q, J = 32.8 Hz), 141.6, 138.1, 137.4, 131.5,
130.3, 129.6, 129.1, 128.7, 128.5, 127.3, 127.2, 126.9, 126.4, 122.5,
118.2 (q, J = 275.6 Hz), 115.0, 107.8, 55.4; MS (EI): m/z (%): 394
(18.40) [M+], 197 (100.00); HRMS (EI) Calcd. for C23H17F3N2O:
394.1293, Found: 394.1295; IR (KBr): n 3094, 2837, 1624, 1608,
1589, 1506, 1458, 1303, 1247, 1224, 1207, 1145, 1022 cm-1.
3-Benzyl-2-(trifluoromethyl)quinazolin-4(3H)-one (6a)
(Z)-N-(2-Bromo-2,2-difluoro-1-(3-iodo-2-phenyl-1H-indol-1-
yl)ethylidene)-1-phenylmethanamine (3w)
White solid, mp: 92–94 ◦C; 1H NMR (300 MHz, CDCl3): d 8.34
(d, J = 8.1 Hz, 1H), 7.86 (d, J = 3.6 Hz, 2H), 7.74–7.52 (m, 1H),
7.46–6.99 (m, 5H), 5.45 (s, 2H); 13C NMR (100 MHz, CDCl3): d
161.4, 144.9, 142.3 (q, J = 35.8 Hz), 135.4, 135.0, 129.3, 128.5,
128.5, 127.5, 127.2, 126.2, 121.8, 118.1 (q, J = 277.5 Hz), 47.7 (q,
J = 3.4 Hz); MS (EI): m/z (%): 304 (46.36) [M+], 91 (100.00); Anal.
Calcd. for C16H11F3N2O2: C, 63.16; H, 3.64; N, 9.21; Found: C,
63.50; H, 3.92; N, 9.00; IR (film): n 3073, 3030, 1697, 1608, 1456,
1398, 1310, 1208, 1134, 973, 774 cm-1.
1H NMR (400 MHz, CDCl3): d 7.58–7.54 (m, 1H), 7.40–7.22 (m,
12H), 7.12–7.06 (m, 1H), 4.78–4.62 (m, 2H); 13C NMR (100 MHz,
CDCl3): d 146.7 (t, J = 28.5 Hz), 139.4, 136.5, 136.2, 131.2, 130.4,
129.8, 129.4, 128.6, 127.5, 127.4, 124.9, 122.7, 122.4, 113.4 (t, J =
309.2 Hz), 111.0, 65.2, 55.4; MS (EI): m/z (%): 564 (2.67) [M+], 91
(100.00); HRMS (EI) Calcd. for C23H16BrF2IN2: 563.9510, Found:
563.9507; IR (film): n 3058, 3035, 2922, 2847, 1671, 1451, 1333,
1166, 1089, 992 cm-1.
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(Z)-N-(2-Bromo-2,2-difluoro-1-(3-iodo-2-phenyl-1H-indol-1-
yl)ethylidene)butan-1-amine (3x)
Gruit, D. Michalik, A. Tillack and M. Beller, Angew. Chem., Int. Ed.,
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1H NMR (400 MHz, CDCl3): d 7.58–7.52 (m, 1H), 7.50–7.27 (m,
7H), 7.12 (d, J = 7.6 Hz, 1H), 3.54–3.04 (m, 2H), 1.83–1.58 (m, 2H),
1.46–1.29 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 145.6 (t, J = 28.5 Hz), 139.4, 136.2, 131.0, 130.6, 129.8,
129.4, 128.5, 124.7, 122.5, 122.3, 113.6 (t, J = 308.4 Hz), 111.0,
64.9, 52.1, 31.7, 20.6, 13.7; MS (EI): m/z (%): 530 (1.96) [M+], 57
(100.00); HRMS (EI) Calcd. for C20H18BrF2IN2: 529.9666, Found:
529.9669; IR (film): n 3054, 2957, 2870, 1669, 1450, 1332, 1167,
1085, 988 cm-1.
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(Z)-N-(2-Bromo-2,2-difluoro-1-(3-iodo-2-phenyl-1H-indol-1-
yl)ethylidene)-4-methoxyaniline (3y)
1H NMR (400 MHz, CDCl3): d 7.54 (d, J = 6.8 Hz, 1H), 7.36–7.22
(m, 7H), 7.15 (d, J = 7.2 Hz, 1H), 6.72–6.65 (m, 4H), 3.69 (s, 3H);
13C NMR (100 MHz, CDCl3): d 160.4, 139.3 (t, J = 29.2 Hz),
138.6, 135.4, 135.2, 131.4, 130.4, 129.6, 129.1, 128.3, 126.8, 124.8,
122.7, 122.2, 114.5, 114.4 (t, J = 307.7 Hz), 111.7, 65.3, 55.3;
MS (EI): m/z (%): 580 (8.09) [M+], 262 (100.00); HRMS (EI)
Calcd. for C23H16BrF2IN2O: 579.9459, Found: 579.9468; IR (film):
n 3058, 2930, 2838, 1647, 1591, 1503, 1450, 1332, 1301, 1255, 1170,
1143 cm-1.
Acknowledgements
Support of our work by the National Natural Science Foundation
of China No. 21172239 is gratefully acknowledged.
Notes and references
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