Synthesis of 3-trifluoromethyl-substituted benzo[f]chromene derivatives in a one-pot reaction

Article abstract of DOI:10.1080/00397911.2012.748074

In the presence of 1,8-diazabicycolo[5.4.0]undec-7-ene (DBU) and concentrated H₂SO₄, 2-naphthol reacted smoothly with α,β-unsaturated trifluoromethyl ketones in CH₂Cl ₂ at room temperature, affording the 3-trifluoromethyl-substituted benzo[f]chromene derivatives in good to excellent yields in a one-pot reaction.

Full text of DOI:10.1080/00397911.2012.748074

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Synthesis of 3-trifluoromethyl Substituted
Benzo[F]chromene Derivatives by a One-Pot Reaction
Hua-Fang Fan a , Xiao-Wei Wang b , Jing-Wei Zhao b , Xin-Jin Li b , Jin-Ming Gao a & Shi-
Zheng Zhu b
a Shaanxi Engineering Center of Bioresource Chemistry and Sustainable Utilization, College
of Science, Northwest A & F University , Yangling , Shaanxi , China
b Key Laboratory of Organofluorine Chemistry , Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences , Shanghai , China
Accepted author version posted online: 31 May 2013.
To cite this article: Hua-Fang Fan , Xiao-Wei Wang , Jing-Wei Zhao , Xin-Jin Li , Jin-Ming Gao & Shi-Zheng Zhu (2013):
Synthesis of 3-trifluoromethyl Substituted Benzo[F]chromene Derivatives by a One-Pot Reaction, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, DOI:10.1080/00397911.2012.748074
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Synthesis of 3-trifluoromethyl substituted benzo[f]chromene derivatives by a
One-Pot Reaction
Hua-Fang Fan1, Xiao-Wei Wang2, Jing-Wei Zhao2, Xin-Jin Li2, Jin-Ming Gao1,
Shi-Zheng Zhu2
1Shaanxi Engineering Center of Bioresource Chemistry and Sustainable Utilization,
College of Science, Northwest A & F University, Yangling, Shaanxi, China, 2Key
Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai, China
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China Tel:
0086-21-54925185 Fax: 0086-21-64166128 E-mail: zhusz@mail.sioc.ac.cn
Abstract
In the presence of DBU and concentrated H2SO4, 2-naphthol reacted smoothly with α,
β-unsaturated trifluoromethyl ketones in CH2Cl2 at room temperature affording the
3-trifluoromethyl substituted benzo[f]chromene derivatives in good to excellent yields by
a one-pot reaction.
[Supplementary materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications® for the following free supplemental resource(s): Full
experimental and spectral details.]
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KEYWORDS: 2-naphthol, α,β-unsaturated trifluoromethyl ketone, benzo[f]chromene,
one pot reaction.
INTRODUCTION
One of tools used to combine economic aspects with the environmental ones is the
tandem reaction strategy, which process consists of two or more synthetic steps which are
carried out without isolation of any intermediate thus reducing time, saving money,
energy and raw materials. [1]
Benzo[f]chromene derivatives are an important class of compounds with excellent
photochromic properties, some of which are also structural motifs present in many
biologically active compounds.[2,3] Therefore, the synthesis of such compounds has
attracted strong interest.[4–8] In the past few decades, some studies have been reported on
the synthesis of Benzo[f]chromenes. Recently, Uemura group reported a
ruthenium-catalyzed cycloaddition reaction of propargylic alcohols with phenol
derivatives via allenylidene intermediates and obtained the product 1-phenyl-1H-naphtho
[2,1-b]pyran in a yield of 80% (Scheme 1).[9]
As is well known, one of the important methods to introduce the fluorine atom or the
fluoroalkyl group into the organic molecular is to use fluorine containing building block,
i.e. to prepare the suitable fluorinated compounds which are used to synthesize the target
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molecule. Due to this reaction process do not involve a C-F bond formation or broken,
this method generally is carried out with high selectivity and good yield of products.
As part of our current studies on the development of new routes to fluorinated
heterocycles, we report the tandem reaction of α,β-unsaturated trifluoromethyl ketones
with 2-naphthol catalyzed by DBU and concentrated H2SO4 affording the corresponding
benzo[f]chromene derivatives in high yields.
RESULTS AND DISCUSSION
As a test reaction, the reaction of (E)-1,1,1-trifluoro-4-phenylbut-3-en-2-one 1a and
2-naphthol was initially studied with several different bases as catalysts and different
acids as dehydrating agent in CH2Cl2 at room temperature (Table 1). The reaction
proceeded well at room temperature in CH2Cl2 with Et3N to furnish a Friedel-Craft type
addition intermediate 3 in 24 hours. Then compound 3 was dehydrated with a catalytic
amount of concentrated H2SO4 in a one-pot fashion after completion of the Friedel-Craft
type addition step, which provided the benzo[f]chromene derivative 4a in a yield of 80%.
If the base was changed from DMAP to DIPEA or TMEDA, the yield was slightly
decreased (Table 1 entries 2-4) and a bit high yield was obtained when Piperdine or
DABCO was used (Table 1 entries 5, 7). While strong bases, such as DBU, were used to
replace the weak bases, the yield can increase to 97% (Table 1 entry 6). On the contrary,
no expected product was monitored by 19F NMR when Na2CO3 was used (Table 1 entry
8). When PPA or TsOH was used as dehydrating agent, no better result was observed
(Table 1 entries 9, 10).
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Next, we examined the influence of solvent and the results were summarized in Table 2.
When CH2Cl2 was used, the reaction was almost completed after 10 hours monitored by
TLC and the product was isolated in a yield of 97%. Slightly lower yield was obtained
with the use of CHCl3 or DCE (Table 2 entries 2, 3). When we changed the solvent into
ether, such as THF and Et2O, the yields were around 85% (Table 2 entries 5, 6). However,
PhCF3 or n-hexane as a solvent, the reaction gave a moderate or a lower yield,
respectively, even through longer reaction time was necessary. According to the results,
CH2Cl2 was proved to be the most efficient solvent (Table 2 entry 1).
The reaction of a series of trifluoromethyl ketones with 2-naphthol derivatives in the
presence of DBU and concentrated H2SO4 in CH2Cl2 at room temperature were also
studied (Table 3). According to the results, we found that the CF3 substituted
benzo[f]chromene derivatives were obtained in good to excellent yields when the group
R1 of compound 1 was substituted by phenyl derivatives. However, when R1 was alkyl,
such as Me or Et, the reaction was complicated and no expected product was monitored
by 19F NMR. On the other hand, we also got the affording products in good yields when
R2 was 8-Br, 9-Br or 9-OMe, respectively.
All new CF3 substituted benzo[f]chromene derivatives were confirmed by the NMR, IR
and MS. For example, in the 13C NMR of 4a, the quartet at 119.6 ppm (q, J = 270 Hz)
and two quartets at 107.7 ppm and 138.2 ppm were assigned to CF3 and two sp2 carbon
atoms closed to CF3, respectively. The singlet at -72.1 ppm in 19F NMR spectrum was
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assigned to the trifluoroacetyl group. And the mass spectrum of 4a showed a molecular
ion peak at m/z = 326 [M] +.
CONCLUSION
In conclusion, a series of 3-trifluoromethyl substituted benzo[f]chromene derivatives
were prepared using α, β-unsaturated trifluoromethyl ketones and 2-naphthalenol in
present of DBU and concentrated H2SO4 at room temperature in CH2Cl2 by tandem
reaction. Further research and applications of the reaction are in progress in our
laboratories.
EXPERIMENTAL
Melting points were measured in Temp-Melt apparatus and uncorrected. 1H and 19F NMR
spectra were recorded in CDCl3 on Bruker AM-300 instruments with Me4Si and CFCl3
(with upfield negative) as the internal and external standards, respectively. IR spectra
were obtained with a Nicolet AV-360 spectrophotometer. Lower resolution mass spectra
or high-resolution mass spectra (HRMS) were obtained on a FinniganMAT-8430
instrument using the electron impact ionization technique (70ev). All reaction as well as
column chromatography were monitored routinely with the aid of TLC or 19F NMR
spectroscopy.
General Procedure For The Preparation Of
Trifluoromethyl-1H-Benzo[F]Chromene (4)
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A solution of compound 1 (0.15 mmol), 2 (0.1 mmol) and DBU (0.02 mmol) in DCM
(1.0 mL) was reacted at room temperature for 10 hours (monitored by TLC). Then a drop
of concentrated H2SO4 (98%) was added directly and stirring was continued for 2 hours
at room temperature. The crude reaction mixture was directly purified by column
chromatography on silica gel using an eluent gradient of petroleum ether to afford the
corresponding products.
1-Phenyl-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4a
Yield: 97%; yellowish solid; mp: 88-89 oC; IR (CH2Cl2, film): 1601, 1518, 1454, 1311,
1269, 1128, 1035, 950, 869, 699 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.79-7.73 (m,
2H), 7.65-7.61 (m, 1H), 7.36-7.17 (m, 8H), 5.88 (s, 1H), 5.27 (s, 1H); 13C NMR (100
MHz, CDCl3): 148.5, 144.3, 138.2 (q, J = 37.4 Hz), 131.5, 131.4, 129.6, 129.1, 128.6,
127.7, 127.1, 126.9, 124.7, 123.6, 119.6 (q, J = 269.8 Hz), 117.5, 113.4, 107.7 (q, J = 3.6
Hz), 38.2; 19F NMR (282 MHz, CDCl3): δ = -72.1 (s, 3F); MS (EI) (m/z): 249 (100), 326
(M+, 20%), 152 (17), 250 (16), 151 (12), 257 (8), 129 (8), 199 (7); HRMS calcd for
C20H13F3O: 326.0918, found: 326.0918.
1-(4-Chlorophenyl)-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4b
Yield: 93%; yellowish oil; IR (CH2Cl2, film): 1601, 1518, 1437, 1310, 1270, 1141, 1034,
951, 854, 695 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.82-7.76 (m, 2H), 7.59-7.56 (m,
1H), 7.39-7.26 (m, 5H), 7.12 (d, J = 8.1 Hz, 2H), 5.86 (d, J = 5.1 Hz, 1H), 5.28 (d, J =
4.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): 148.5, 142.7, 138.5 (q, J = 33.5 Hz), 133.0,
131.5, 131.1, 129.9, 129.3, 129.0, 128.7, 127.1, 124.9, 123.4, 119.5 (q, J = 269.7 Hz),
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117.5, 112.8, 107.2 (q, J = 3.6 Hz), 37.5; 19F NMR (282 MHz, CDCl3): δ = -72.6 (s, 3F);
MS (EI) (m/z): 249 (100), 360 (M+, 20%), 152 (17), 250 (16), 291 (13), 151 (12), 293 (8),
146 (8); HRMS calcd for C20H12ClF3O: 360.0529, found: 360.0532.
1-(2-Methoxyphenyl)-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4c
Yield: 92%; yellowish solid; mp: 132-133 oC; IR (CH2Cl2, film): 1602, 1516, 1464, 1307,
1269, 1120, 1028, 948, 874, 721 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.78 (d, J = 8.4
Hz, 2H), 7.54 (d, J = 6.0 Hz, 1H), 7.38-7.28 (m, 3H), 7.19-7.13 (m, 1H), 6.93 (d, J = 8.7
Hz, 1H), 6.76-6.67 (m, 2H), 5.96 (d, J = 5.1 Hz, 1H), 5.75 (d, J = 4.8 Hz, 1H), 4.01 (s,
3H); 13C NMR (100 MHz, CDCl3): 155.5, 149.2, 138.7 (q, J = 36.6 Hz), 132.0, 131.4,
131.3, 129.6, 129.2, 128.4, 128.0, 126.9, 124.6, 123.6, 121.3, 119.8 (q, J = 269.8 Hz),
117.4, 113.6, 110.4, 108.9 (q, J = 3.7 Hz), 55.6, 30.9; 19F NMR (282 MHz, CDCl3): δ =
-72.6 (s, 3F); MS (EI) (m/z): 249 (100), 356 (M+, 46%), 287 (37), 152 (22), 151 (22), 250
(17), 325 (16), 357 (10); HRMS calcd for C21H15F3O2: 356.1024, found: 356.1029.
1-(3-Methoxyphenyl)-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4d
Yield: 95%; yellowish oil; IR (CH2Cl2, film): 1600, 1517, 1465, 1313, 1262, 1137, 1053,
855, 721 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.92 (d, J = 8.7 Hz, 2H), 7.83-7.77 (m,
1H), 7.51-7.48 (m, 2H), 7.45-7.42 (m, 1H), 7.33 (t, J = 7.8 Hz, 1H), 6.93 (d, J = 7.2 Hz,
1H), 6.85 (d, J = 6.6 Hz, 1H), 6.02 (d, J = 4.8 Hz, 1H), 5.40 (d, J = 4.8 Hz, 1H), 3.85 (s,
3H); 13C NMR (100 MHz, CDCl3): 160.2, 148.2, 145.9, 138.3 (q, J = 36.3 Hz), 131.5,
131.4, 131.1, 130.1, 129.7, 128.5, 126.9, 124.7, 123.6, 120.1, 119.5 (q, J = 269.8 Hz),
117.5, 114.0, 113.2, 111.9, 107.6 (q, J = 3.5 Hz), 55.2, 38.1; 19F NMR (282 MHz,
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CDCl3): δ = -72.6 (s, 3F); MS (EI) (m/z): 249 (100), 356 (M+, 22%), 250 (15), 152 (15),
151 (11), 199 (7), 287 (7), 201 (5); HRMS calcd for C21H15F3O2: 356.1024, found:
356.1026.
1-(4-Methoxyphenyl)-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4e
Yield: 97%; yellowish solid; mp: 97-98 oC; IR (CH2Cl2, film): 16014, 1515, 1465, 1308,
1261, 1128, 1049, 951, 853, 721 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.82-7.76 (m,
2H), 7.68-7.64 (m, 1H), 7.37-7.28 (m, 3H), 7.12 (d, J = 8.1 Hz, 2H), 6.80 (d, J = 8.4 Hz,
2H), 5.87 (d, J = 4.8 Hz, 1H), 5.25 (d, J = 4.5 Hz, 1H), 3.73 (s, 3H); 13C NMR (100 MHz,
CDCl3): 156.5, 148.4, 138.0 (q, J = 35.7 Hz), 136.6, 131.5, 131.4, 129.5, 128.7, 128.5,
126.8, 124.7, 123.6, 119.6 (q, J = 269.8 Hz), 117.5, 114.5, 113.7, 107.9 (q, J = 2.9 Hz),
55.2, 37.2; 19F NMR (282 MHz, CDCl3): δ = -71.9 (s, 3F); MS (EI) (m/z): 287 (100), 249
(85), 356 (M+, 25%), 288 (22), 152 (20), 157 (18), 151 (14), 144 (13); HRMS calcd for
C21H15F3O2: 356.1024, found: 356.1028.
1-(4-Bromophenyl)-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4f
Yield: 92%; yellowish oil; IR (CH2Cl2, film): 1601, 1518, 1437, 1309, 1270, 1141, 1034,
951, 859, 682 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.82 (d, J = 8.7 Hz, 2H), 7.62-7.56
(m, 1H), 7.44-7.28 (m, 5H), 7.08 (d, J = 7.8 Hz, 2H), 5.86 (d, J = 4.8 Hz, 1H), 5.29 (d, J
= 3.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): 148.5, 143.2, 138.5 (q, J = 36.9 Hz), 132.3,
131.5, 131.1, 129.9, 129.4, 128.7, 127.1, 124.9, 123.4, 121.0, 119.5 (q, J = 269.7 Hz),
117.5, 112.7, 107.1 (q, J = 3.7 Hz), 37.6; 19F NMR (282 MHz, CDCl3): δ = -72.0 (s, 3F);
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MS (EI) (m/z): 249 (100), 152 (17), 250 (16), 151 (10), 406 (9), 404 (M+, 9%), 271 (7),
199 (7); HRMS calcd for C20H12BrF3O: 404.0024, found: 404.0021.
1-(4-Ethylphenyl)-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4g
Yield: 87%; yellowish oil; IR (CH2Cl2, film): 1601, 1517, 1437, 1311, 1270, 1139, 1034,
951, 854, 628 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.83-7.75 (m, 2H), 7.68-7.65 (m,
1H), 7.37-7.28 (m, 3H), 7.13-7.07 (m, 4H), 5.89 (d, J = 4.8 Hz, 1H), 5.25 (d, J = 4.2 Hz,
1H), 2.56 (q, J = 7.8 Hz, 2H), 1.17 (t, J = 7.8 Hz, 3H), ; 13C NMR (100 MHz, CDCl3):
148.5, 143.0, 141.5, 138.1 (q, J = 37.2 Hz), 131.5, 131.4, 129.5, 128.6, 127.7, 126.9,
124.7, 123.7, 119.7 (q, J = 269.7 Hz), 117.5, 113.7, 107.9 (q, J = 3.7 Hz), 37.7, 28.4, 15.3;
19F NMR (282 MHz, CDCl3): δ = -72.5 (s, 3F); MS (EI) (m/z): 249 (100), 285 (26), 340
(M+, 22%), 152 (18), 250 (16), 151 (11), 199 (8), 286 (7); HRMS calcd for C22H17F3O:
354.1232, found: 354.1235.
1-(P-Tolyl)-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4h
Yield: 92%; yellowish solid; mp: 97-98 oC; IR (CH2Cl2, film): 1599, 1511, 1465, 1310,
1268, 1105, 1026, 948, 860, 727 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.80-7.77 (m,
2H), 7.68-7.65 (m, 1H), 7.37-7.29 (m, 3H), 7.11-7.06 (m, 4H), 5.88 (d, J = 5.1 Hz, 1H),
5.27 (d, J = 5.4 Hz, 1H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3): 148.4, 141.4, 138.0
(q, J = 36.6 Hz), 136.7, 131.4, 131.3, 129.8, 129.5, 128.5, 127.6, 126.9, 123.6, 119.6 (q, J
= 269.8 Hz), 117.5, 113.6, 107.9 (q, J = 3.7 Hz), 37.7, 21.0; 19F NMR (282 MHz, CDCl3):
δ = -72.0 (s, 3F); MS (EI) (m/z): 249 (100), 340 (M+, 32%), 271 (31), 152 (17), 250 (15),
151 (11), 136 (10), 199 (8); HRMS calcd for C21H15F3O: 340.1075, found: 340.1074.
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9-Methoxy-1-Phenyl-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4i
Yield: 87%; yellowish solid; mp: 125-126 oC; IR (CH2Cl2, film): 1604, 1515, 1454, 1309,
1272, 1136, 1030, 923, 837, 701 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.69 (d, J = 9.0
Hz, 2H), 7.31-7.17 (m, 6H), 7.02-6.98 (m, 1H), 6.89-6.88 (m, 1H), 5.87 (d, J = 5.1 Hz,
1H), 5.19 (d, J = 4.2 Hz, 1H), 3.65 (s, 3H); 13C NMR (100 MHz, CDCl3): 158.4, 149.0,
144.3, 138.1 (q, J = 36.9 Hz), 132.8, 130.0, 129.2, 129.1, 127.8, 127.1, 126.6, 119.6 (q, J
= 269.9 Hz), 116.8, 114.9, 112.4, 107.5 (q, J = 3.5 Hz), 103.3, 55.1, 38.6; 19F NMR (282
MHz, CDCl3): δ = -72.0 (s, 3F); MS (EI) (m/z): 279 (100), 356 (M+, 29%), 236 (24), 280
(16), 139 (11), 144 (11), 287 (9), 357 (7); HRMS calcd for C21H15F3O2: 356.1024, found:
356.1022.
9-Bromo-1-Phenyl-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4j
Yield: 85%; yellowish solid; mp: 111-112 oC; IR (CH2Cl2, film): 1599, 1500, 1447, 1307,
1266, 1133, 1039, 963, 854, 700 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.80 (s, 2H),
7.73 (d, J = 9.0 Hz, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.44-7.41 (m, 1H), 7.32-7.28 (m, 3H),
7.23-7.19 (m, 3H), 5.90 (d, J = 5.1 Hz, 1H), 5.19 (d, J = 4.2 Hz, 1H); 13C NMR (100
MHz, CDCl3): 149.0, 143.7, 138.1 (q, J = 37.3 Hz), 132.7, 130.1, 129.9, 129.5, 129.3,
128.2, 127.7, 127.4, 126.1, 121.5, 119.5 (q, J = 269.7 Hz), 118.0, 112.9, 107.5 (q, J = 3.5
Hz), 38.0; 19F NMR (282 MHz, CDCl3): δ = -71.8 (s, 3F); MS (EI) (m/z): 329 (100), 327
(98), 151 (31), 249 (25), 406 (24), 404 (M+, 23%), 150 (21), 328 (19); HRMS calcd for
C20H12BrF3O: 404.0024, found: 404.0020.
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8-Bromo-1-Phenyl-3-(Trifluoromethyl)-1H-Benzo[F]Chromene 4k
Yield: 85%; yellowish solid; mp: 138-139 oC; IR (CH2Cl2, film): 1590, 1500, 1453, 1306,
1267, 1134, 1037, 947, 862, 699 cm-1; 1H NMR (300 MHz, DCl3): δ = 7.92 (d, J = 1.8
Hz, 1H), 7.68 (d, J = 9.0 Hz, 1H), 7.49 (d, J = 9.0 Hz, 1H), 7.41-7.38 (m, 1H), 7.38-7.24
(m, 3H), 7.22-7.16 (m, 3H), 5.89 (d, J = 5.4 Hz, 1H), 5.24 (d, J = 4.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3): 148.6, 143.9, 138.1 (q, J = 37.0 Hz), 132.6, 130.5, 130.2, 129.9,
129.9, 129.2, 128.7, 127.7, 127.3, 125.4, 119.5 (q, J = 270.0 Hz), 118.7, 118.6, 113.7,
107.6 (q, J = 3.6 Hz), 38.1; 19F NMR (282 MHz, CDCl3): δ = -72.6 (s, 3F); MS (EI)
(m/z): 327 (100), 329 (96), 157 (31), 406 (29), 151 (27), 404 (M+, 27%), 287 (22), 249
(22); HRMS calcd for C20H12BrF3O: 404.0024, found: 404.0022.
Complete experimental and spectral details are available online in the Supplementary
Materials.
ACKNOWLEDGEMENTS
This research was supported by the National Natural Science Foundation of China
(No.21032006, 20172064), the QT Program, Shanghai Natural Science Council.
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5. Ballini, R.; Bosica, G.; Conforti, M. L.; Maggi, R.; Mazzacani, A.; Righi, P.; Sartori, G.
Three-component process for the synthesis of 2-amino-2-chromenes in aqueous media.
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Table 1. Optimization of the tandem reaction[a]
Entry
Base
Acid
t/h
24
24
24
24
24
10
10
-
Yield (%)[b]
1
Et3N
H2SO4 (98%)
H2SO4 (98%)
H2SO4 (98%)
H2SO4 (98%)
H2SO4 (98%)
H2SO4 (98%)
H2SO4 (98%)
H2SO4 (98%)
TsOH
80
71
75
72
86
97
90
-
2
DMAP
DIPEA
TMEDA
Piperdine
DBU
3
4
5
6
7
DABCO
Na2CO3
DBU
8
9
10
10
85
72
10
DBU
PPA
[a] The reaction was carried out with 1a (0.15 mmol) and 2a (0.1 mmol) and base (0.02
mmol) at room temperature in DCM (1.0 mL) .
[b] Yield of the isolated product after column chromatography on silica gel.
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Table 2. Screening of solvent[a]
Entry
Solvent
DCM
t/h
10
10
12
10
10
10
10
15
48
Yield(%)[b]
1
2
3
4
5
6
7
8
9
97
93
92
77
85
88
72
70
45
CHCl3
DCE
EtOAc
Et2O
THF
DMF
PhCF3
n-hexane
[a] The reaction was carried out with 1a (0.15 mmol) and 2a (0.1 mmol) and base (0.02
mmol) at room temperature in solvent (1.0 mL) .
[b] Isolated yield of the product after column chromatography on silica gel.
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Table 3. Synthesis of 3-trifluoromethyl substituted benzo[f]chromenes [a]
Entry
R1
R2
t/h
10
10
10
10
10
10
10
10
12
12
12
Product
4a
Yield(%)[b]
1
Ph
H
97
93
92
95
90
92
87
92
87
85
85
2
4-ClC6H4
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
4-BrC6H4
4-EtC6H4
4-MeC6H4
Ph
H
4b
4c
3
H
4
H
4d
4e
5
H
6
H
4f
7
H
4g
8
H
4h
4i
9
9-OMe
9-Br
8-Br
10
11
Ph
4j
Ph
4k
[a] The reaction was carried out with 1 (0.15 mmol) and 2 (0.1 mmol) and base (0.02
mmol ) at room temperature in solvent (1.0 mL) .
[b] Isolated yield of the product after column chromatography on silica gel.
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Scheme 1
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