Highly efficient iron(II) chloride/N-bromosuccinimide-mediated synthesis of imides and acylsulfonamides

Article abstract of DOI:10.1002/adsc.200800668

We have developed a general and highly efficient iron(II) chloride/N-bromosuccinimide (NBS)-mediated method for the synthesis of imides and acylsulfonamides via couplings of thioesters with carboxamides/sulfonamides, and the method is simple, economical and shows practical advantages.

Full text of DOI:10.1002/adsc.200800668

FULL PAPERS
DOI: 10.1002/adsc.200800668
Highly Efficient Iron(II) Chloride/N-Bromosuccinimide-Mediated
Synthesis of Imides and Acylsulfonamides
Feng Wang,a Hongxia Liu,b Hua Fu,a,* Yuyang Jiang,b,* and Yufen Zhaoa
a
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University, Beijing 100084, Peopleꢀs Republic of China
Fax : (+86)-10-62781695; e-mail: fuhua@mail.tsinghua.edu.cn
Key Laboratory of Chemical Biology (Guangdong Province), Graduate School of Shenzhen, Tsinghua University,
b
Shenzhen 518057, Peopleꢀs Republic of China
Received: October 30, 2008; Published online: January 12, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800668.
Abstract: We have developed a general and highly carboxamides/sulfonamides, and the method is
efficient
iron(II)
chloride/N-bromosuccinimide simple, economical and shows practical advantages.
(NBS)-mediated method for the synthesis of imides
and acylsulfonamides via couplings of thioesters with Keywords: acylsulfonamides; N-bromosuccinimide
(NBS); homogeneous catalysis; imides; iron
Introduction
mediates in organic synthesis, and they can be utilized
in transformations of a wide range of molecules,[8]
The imide moiety represents an important substruc- such as the synthesis of amides.[9] The coupling reac-
ture associated with certain natural products, such as tions usually use amines (strong nucleophic reagents)
fumaramidmycin,[1a,b] coniothyriomycin[1c] and SB- as the partners of the thioesters. However, to the best
253514,[1d] and it also acts as a key component in a va- of our knowledge, the coupling of various amides,
riety of reactions.[2] The acylsulfonamides are a class such as carboxamides and sulfonamides (weak nucleo-
of biologically active compounds of current therapeu- phic reagents), with thioesters has not yet been re-
tic interest,[3] for example they are used as HCV ported. Iron is one of the most abundant, inexpensive
NS5B polymerase allosteric inhibitors,[3a] as well as and environmentally friendly metals on earth.[10] Very
anti-inflammatory[3b] and antitumor agents.[3c] Some recently, we have developed an iron-catalyzed amida-
[11]
À
methods for the synthesis of imides and acylsulfona- tion of C H bonds in the presence of NBS. Herein,
mides have been reported. For example, coupling of we report a novel, simple and highly efficient FeCl2/
acyl chlorides with carboxamides is a common ap- NBS-mediated coupling of thioesters with carboxa-
proach to imides,[4a–c] and sometimes oxidation of N- mides and sulfonamides to provide imides and acyl-
alkylamides is used in the synthesis of imides.[4d,e] The sulfonamides.
usual methods for synthesis of acylsulfonamides are
the coupling of sulfonamides with anhydrides, active
esters or acyl chlorides[5a,b] and the direct condensa- Results and Discussion
tion of sulfonamides with carboxylic acids in the pres-
ence of coupling agents.[5c,d] Recently, the rhodium- Since N-halosuccinimides are effective N-halogena-
and ruthenium-catalyzed sulfamidation of aldehydes tion reagents,[11,12] they can be used in our studies. At
[6]
À
has been developed via a C H activation strategy.
first, ethyl acetate was used as the partner of benz-
ACHTUNGTRENNaUGN mide in the presence of FeCl2 and NBS, and N-ace-
The copper-catalyzed three-component coupling of
terminal alkynes, sulfonyl azides and water to form tylbenzamide was obtained in 15% yield. S-Ethyl thi-
acylsulfonamides has been reported.[7] Every method opropionate was chosen for its higher reactivity as
above has it advantages and disadvantages, therefore model substrate to optimize the reaction conditions as
it is still desirable to develop more convenient and ef- shown in Table 1. The coupling provided imide 3a in
ficient methods for the synthesis of imides and acyl- 42% yield using 0.1 equiv. of FeCl2 as the catalyst,
sulfonamides. Thioesters are importantly active inter- 0.4 equiv. of NBS as the N-halogenation reagent (rela-
246
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Highly Efficient Iron(II) Chloride/N-Bromosuccinimide-Mediated Synthesis of Imides
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Table 1. Metal/N-halosuccinimide-mediated coupling of S-ethyl thiopropionate with benzamide or benzenesulfonamide: opti-
mization of conditions.[a]
Entry
Amide
Catalyst [equiv.]
NBS [equiv.]
Temperature [8C]//time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
4a
4a
4a
4a
FeCl2
FeCl2
FeCl2
FeCl2
–
NBS (0.4)
NBS (0.4)
NBS (1)
–
21/12
45/12
45/12
45/16
45/16
45/12
45/12
45/12
45/12
45/12
45/12
45/8
42
65
80
0
–
0
–
NBS (1)
NBS (1)
NBS (1)
NBS (1)
NBS (1)
NCS (1)
NBS (1)
NBS (0.4)
–
46
78
36
76
59
72
98
92
0
FeCl3
FeACTHNGUTRENU(NG acac)3
9
CuBr
CuCl2
FeCl2
FeCl2
FeCl2
FeCl2
–
10
11
12
13
14
15
45/12
45/12
45/12
NBS (0.4)
45
[a]
Reaction conditions: catalyst (0.1 mmol), benzamide or benzenesulfonamide (1 mmol), S-ethyl thiopropionate (1.2 mmol),
CH3CN (3 mL). The reaction was performed without exclusion of air.
Isolated yield.
[b]
tive to amount of benzamide) and acetonitrile with carboxamides or sulfonamides were carried out
(CH3CN) as the solvent at 218C for 12 h (entry 1), under our standard conditions: 10 mol% FeCl2 and
and yield of 3a rose to 65% when temperature was in- 0.4–1 equiv. of NBS (relative to carboxamide/sulfon-
creased to 458C (entry 2). The coupling provided an
ACHTUNGTERNNaUNG mide) as the mediating reagents and CH3CN as the
80% yield when 1 equiv. of NBS was used (entry 3). solvent. As shown in Table 2, the coupling reactions
The coupling reaction could not be performed in the of primary aromatic amides with aliphatic thioesters
absence of NBS or FeCl2/NBS (entries 4 and 5), and a provided good to excellent yields, and aromatic
46% yield of product was obtained without the addi- amides containing electron-withdrawing groups
tion of FeCl2 (entry 6). We attempted to use other showed higher reactivity than those containing elec-
metal salts, FeCl3, FeACHTNUGTRNEUNG(acac)3, CuBr, and CuCl2, and tron-donating groups. Primary aromatic carboxamides
they showed weaker catalytic activity than FeCl2 (en- were better substrates relative to secondary ones (en-
tries 7–10). The coupling gave 3a in 72% yield when tries 14 and 15), and aliphatic thioesters exhibited
NCS replaced NBS as the N-halogenation reagent higher activity than S-ethyl thiobenzoate (entry 16).
(entry 11). We also attempted to couple of S-ethyl Methyl thioester 2b (entries 6–9) displayed higher ac-
thiopropionate with benzenesulfonamide, and the re- tivity than ethyl thioester 2a. Interestingly, couplings
action provided acylsulfonamide 5a in 98% yield of sulfonamides with various thioesters gave good to
within 8 h (entry 12). Interestingly, 0.4 equiv. of NBS excellent yields as shown in Table 3, and electronic
(relative to sulfonamide) was also effective for the variation in the sulfonamides and thioesters did not
coupling reaction (entry 13). The coupling of S-ethyl obviously affect the efficiency of the reactions. Sulfon-
thiopropionate with benzenesulfonamide showed sim-
ACHTUNGTRENaNGNU mides and thioesters with functional groups such as
ilar results to entries 4 and 6 in the absence of NBS ester (entry 8), amide (entry 9), nitro (entry 7),
or FeCl2 (see entries 14 and 15). Investigation of the carbon-halogen bonds on aryl ring (entries 3, 10, 13,
starting material stoichiometry revealed that a slight 14), and sulfur- or nitrogen-containing heterocycles
excess of S-ethyl thiopropionate (1.2 equiv.) was nec- (entries 10 and 14) coupled well with thioesters. Sec-
essary to improve the yield of the products.
ondary sulfonamides were weaker substrates relative
After the optimization process for metal salts and to primary ones (entry 11).
N-halosuccinimides, couplings of various thioesters
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Feng Wang et al.
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Table 2. FeCl2/NBS-mediated couplings of carboxamides with thioesters.[a]
Entry
1
1
2
Time [h]
12
Product (Yield[b] [%])
2
3
4
5
6
7
8
2a
2a
2a
2a
8
12
12
10
8
1a
1c
1d
1e
2b
2b
2b
2b
8
8
9
8
10
16
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Highly Efficient Iron(II) Chloride/N-Bromosuccinimide-Mediated Synthesis of Imides
Table 2. (Continued)
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Entry
1
2
Time [h]
Product (Yield[b] [%])
11
2b
20
12
2b
20
13
14
15
16
2b
2b
2a
20
16
12
1j
1c
16
16
17
[a]
Reaction conditions: carboxamide (1 mmol), thioester (1.2 mmol), FeCl2 (0.1 mmol), NBS (1 mmol), CH3CN (3 mL).
Isolated yield.
[b]
Conclusions
Experimental Section
We have developed a general and highly efficient General Experimental Procedure for the Preparation
FeCl2/NBS-mediated method for couplings of thioest- of Compounds 3a–q and 5a–r
ers with carboxamides and sulfonamides in the pres-
A 10-mL round-bottom flask was charged with a magnetic
ence of NBS, and the corresponding imides and acyl-
stirrer, carboxamide or sulfonamide (1 mmol), N-bromosuc-
sulfonamides were obtained in good to excellent
cinimide (NBS) (1 mmol, 178 mg for the synthesis of imides;
yields. The protocol uses inexpensive and environ-
0.4 to 1 mmol for synthesis of acylsulfonamides), FeCl2
mentally friendly FeCl2 as the catalyst, and no addi-
(0.1 mmol, 13 mg) and 3 mL of acetonitrile (CH3CN) were
tional ligand and additive were required. Therefore,
added to the flask at room temperature, After stirring for
our procedure may find widespread use in organic
chemistry and medicinal chemistry. Further investiga-
tions in this direction are in progress.
1 min, thioester (1.2 mmol) was added to the solution. The
mixture was stirred at 458C for a time as shown in Table 2
and Table 3. The resulting solution was concentrated by the
rotary evaporator, and the residue was purified by column
chromatography on silica gel using petroleum ether/ethyl
acetate as eluent to give the desired product.
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Feng Wang et al.
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Table 3. FeCl2/NBS-mediated couplings of sulfonamides with thioesters.[a]
Entry
1
4
2
NBS [equiv]/Time [h]
0.4/8
Product (Yield[b] [%])
2
3
4
5
2a
2a
0.4/8
0.4/8
0.8/6
0.4/8
4a
4b
2b
2b
2b
6
7
4c
1/8
0.8/10
8
9
2b
0.8/10
2b
2b
1/12
1/8
10
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Highly Efficient Iron(II) Chloride/N-Bromosuccinimide-Mediated Synthesis of Imides
Table 3. (Continued)
FULL PAPERS
Entry
4
2
NBS [equiv]/Time [h]
Product (Yield[b] [%])
11
2b
1/8
12
13
14
15
4b
4b
4b
4b
1/8
1/10
1/10
0.4/10
1/8
16
17
2c
2b
2f
1/8
1/8
18
4j
[a]
Reaction conditions: sulfonamide (1 mmol), thioester (1.2 mmol), FeCl2 (0.1 mmol), NBS (0.4 to 1 mmol), CH3CN
(3 mL).
Isolated yield.
[b]
References
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This work was supported by the National Natural Science
Foundation of China (Grants 20672065, 20732004), the Min-
istry of Science and Technology of China (Grant Nos.
2007AA02Z160, 2006DFA43030), Programs for New Centu-
ry Excellent Talents in University (NCET-05–0062) and
Changjiang Scholars and innovative Research Team in Uni-
versity (PCSIRT) (No. IRT0404) in China and the Key Sub-
ject Foundation from Beijing Department of Education
(XK100030514).
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