NH4I/EtOCS2K promoted synthesis of substituted benzils from diphenylacetylene derivatives

Article abstract of DOI:10.1016/j.tetlet.2018.06.053

A facile protocol is described for the synthesis of benzil derivatives from readily accessible diarylacetylene derivatives using the NH₄I/EtOCS₂K system. This novel protocol results in excellent chemoselectivity and provided good to excellent yields. A control experiment indicated that the reaction proceeds via NH₄I promoted EtOCS₂K dimerization to give the corresponding dixanthogen and subsequent dixanthogen assisted oxidation.

Full text of DOI:10.1016/j.tetlet.2018.06.053

Accepted Manuscript
NH4I/EtOCS2K promoted synthesis of substituted benzils from diphenylacety-
lene derivatives
Shaohua Jiang, Yibiao Li, Xianglin Luo, Guoling Huang, Yan Shao, Dongli Li,
Bin Li
PII:
S0040-4039(18)30819-0
https://doi.org/10.1016/j.tetlet.2018.06.053
TETL 50091
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
21 April 2018
19 June 2018
21 June 2018
Please cite this article as: Jiang, S., Li, Y., Luo, X., Huang, G., Shao, Y., Li, D., Li, B., NH4I/EtOCS2K promoted
synthesis of substituted benzils from diphenylacetylene derivatives, Tetrahedron Letters (2018), doi: https://doi.org/
10.1016/j.tetlet.2018.06.053
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Tetrahedron Letters
NH4I/EtOCS2K promoted synthesis of substituted benzils from diphenylacetylene
derivatives
Shaohua Jiang a, Yibiao Lia,*, Xianglin Luoa , Guoling Huanga , Yan Shaoa , Dongli Lia,* and Bin Lia
a School of Chemical & Environmental Engineering, Wuyi University, Jiangmen, Guangdong Province, 529090, China
Phone (Fax): +86-0750 3299391; e-mail: leeyib2668@126.com; wyuchemldl@126.com
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A facile protocol is described for the synthesis of benzil derivatives from readily accessible
diarylacetylene derivatives using the NH4I/EtOCS2K system. This novel protocol results in
excellent chemoselectivity and provided good to excellent yields. A control experiment
indicated that the reaction proceeds via NH4I promoted EtOCS2K dimerization to give the
corresponding dixanthogen and subsequent dixanthogen assisted oxidation.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Benzil
Oxidation
Transition-metal-free
Radical
Dixanthogen
Introduction
The development of practical alkyne oxidation strategies has received considerable attention because as one of the most useful
transformations in organic synthesis, the process offers low-cost and straightforward access to highly synthetically valued building
blocks from commercially available starting materials.1 Among the various methods for the stoichiometric oxidation of C(sp)-C(sp)
triple bonds, the use of KMnO4,2 TlNO3,3 OsO4,4 H3PO5,4 dioxiranes,6 organic peracids7 and transition-metal-catalyzed conditions8
has been widely developed. Despite remarkable progress in this area, examples of environmentally friendly methods are still under
underexplored; these established methods require the use of expensive transition-metal catalysts, high temperatures, or toxic
reaction conditions.
Recently, catalytic systems for the oxidation of 1,2-diarylalkynes to benzils have been widely developed. Among them, the
transition-metal complexes containing Pd,9 Cu,10 Fe,11 Ru,12 Au,13 Hg,14 and Mn15 have proven to be useful for this transformation.
However, these transition-metal reagents still have drawbacks, such as high price, generation of toxic waste, and the need for air
sensitive or expensive ligands. From an economical and environmentally friendly viewpoint, it would be advantageous to develop
transition-metal-free systems for the synthesis of benzils from 1,2-diarylalkynes. The use of a stoichiometric amount of inorganic
oxidants, such as sulfur trioxide (SO3),16 Oxone,17 CH3SO3H18 and CAN,19 as well as photo-oxidation,20 is essential for such
reactions. Among the various transition-metal-free syntheses of 1,2-diarylalkynes from benzils, I2/DMSO21 and its variants are the
most popular choices. At high temperatures, carbon-carbon double bonds are not affected. As shown in Scheme 1, NIS22 and
hypervalent iodine species,23 were used as inexpensive and efficient oxidants. Although the mechanism for the oxidation of
diarylalkynes by I2, NIS and hypervalent iodine species has not been fully determined, it is reasonable to propose an iodonium ion is
generated as the key intermediate. There have been no literature reports that the oxidation reaction can be initiated by an iodide
anion or iodine radical initiation. Herein, we report that the NH4I/EtOCS2K system can efficiently oxidize diarylacetylene to benzil
compounds as well as mechanistic studies that indicate that the reaction is likely triggered by radical initiated iodooxidation.

3
Scheme 1. Synthesis of benzils from diarylalkyne oxidation.
Results and Discussion
Initially, 1,2-diphenylethyne, NH4I and DMSO were selected as model substrates for optimization of the reaction conditions.
Initial attempts in the presence of NH4I (2.0 equiv.) at 130 oC using DMSO/H2O (3.0 mL) as the solvent only gave benzil 2a in trace
amounts (Table 1, entry 1). The reaction efficiency did not change in the presence of EtOCS2K (1.2 equiv.) at 130 oC (Table 1, entry
2). When using NH4I (1.0 equiv.) and EtOCS2K (0.5 equiv.), benzil 2a was not obtained and only trace 1,2-diphenylethene was
detected by GC-MS. Conversely, moderate yields of benzil 2a were obtained using NH4I (1.0 equiv.) and EtOCS2K (1.2 equiv.)
(Table 1, entries 3-5). It was found that the reaction of NH4I (2.0 equiv.) and EtOCS2K (1.2 equiv.) at 130 oC for 12 h gave benzil
2a in 91% yield (Table 1, entries 6-7). In is noteworthy that ammonium iodide plays an important role in the reaction. No reaction
was observed when similar ammonium salts such as Et4NI, NH4Br and ICl were used (Table 1, entries 9-11). In addition, screening
other solvents such as DMF, NMP, DMAc, and 1,4-dioxane did not provide better results (Table 1, entries 12-14). It was found that
o
lower reaction temperatures (120 C) led to only a 37% yield, and prolonged reaction times did not improve the reaction (Table 1,
entry 15). Finally, no product 2a was detected when the chemistry was performed in the presence of the radical scavenger butylated
hydroxytoluene (BHT) or 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) (Table 1, entries 16 and 17). These results suggested that
the iodooxidation reaction presumably proceeded through a radical pathway. Under a nitrogen atmosphere, the yield did not
improve significantly (Table 1, entry 18).
Table 1. Optimization of the reaction conditions.a
Yield
EtOCS2K
(mmol)
Entry Halide (mmol)
Solvent
2a
(%)b
1
2
NH4I (2)
-
-
DMSO/H2O (2:1)
DMSO/H2O (2:1)
DMSO/H2O (2:1)
DMSO/H2O (2:1)
DMSO/H2O (2:1)
DMSO/H2O (2:1)
DMSO/H2O (2:1)
DMSO/H2O (3:0)
DMSO/H2O (2:1)
DMSO/H2O (2:1)
DMSO/H2O (2:1)
NMP/H2O (2:1)
DMAc/H2O (2:1)
DMF/H2O (2:1)
DMSO/H2O (2:1)
-
-
1.2
0.5
1.2
0.5
1.2
2
3
NH4I (1)
NH4I (1)
NH4I (2)
NH4I (2)
NH4I (2)
NH4I (2)
Et4NI (2)
NH4Br (2)
ICl (2)
<5
45
35
93 (91)
87
68
-
4
5
6
7
8
2
9
1.2
1.2
1.2
1.2
1.2
1.2
1.2
10
11
12
13
14
15c
-
<5
<5
<5
<5
37
NH4I (2)
NH4I (2)
NH4I (2)
NH4I (2)

4
16d
17e
18f
NH4I (2)
NH4I (2)
NH4I (2)
1.2
1.2
1.2
DMSO/H2O (2:1)
DMSO/H2O (2:1)
DMSO/H2O (2:1)
<5
<5
86
a Reagents and conditions: diphenylacetylene 1a (1.0 mmol), halide, EtOCS2K, solvent (v/v) (3.0 mL), 130 oC, 12 h; b Yield determined by GC-MS analysis;
c Reaction was carried out at 120 oC for 18 h; d TEMPO (1.0 mmol); e BHT (1.0 mmol); f Under a N2 atmosphere.
With the optimized reaction conditions in hand, we next examined the substrate scope for the synthesis of substituted benzil
derivatives (Scheme 2). By varying the R1 and R2 substituents of alkynes 3, it was shown that both electron-donating as well as
electron-withdrawing substituents on the aromatic rings could be introduced and gave the benzil products in moderate to good
yields. The reaction tolerated a range of substituents including: -OMe, -CN, -CHO, -COOEt, -F, -Cl, -Br, -Me, -NMe2 and
thiophenyl groups. The use of diphenylethyne derivatives with electron-donating substituents afforded the corresponding products
in higher yields (Scheme 2, 2b, 2k and 2l). The steric hindrance associated with the diphenylethyne derivatives also affected the
reaction, as the introduction of a 2-F group onto the aromatic ring lowered the yield of the corresponding benzils (Scheme 2, 2n). It
was noteworthy that the reaction of sulphur-containing heterocycles such as 2-(2-phenylethynyl)thiophene and 2-(2-(thiophen-3-
yl)ethynyl)thiophene proceeded well and afforded benzils 2p-q in good yields. Finally, the reaction of 1,4-bis(2-
phenylethynyl)benzene gave 1,4-bisbenzil 2r in 89% yield. Unfortunately, the reactions with 1-aryl-2-alkyl-acetylenes (prop-1-yne-
1,3-diyldibenzene, cyclohexylethynyl)benzene, non-1-yn-1-ylbenzene), 1,2-dialkyl-acetylenes (4-octyne) and phenylacetylene,
were unsuccessful under the current reaction conditions.
Scheme 2. Synthesis of benzils from alkynes.a,b
a Reagents and conditions: alkyne 1 (1.0 mmol), NH4I (2.0 mmol), EtOCS2K (1.3 mmol), DMSO/H2O (2/1) (3.0 mL), 130 oC, 12 h; b Isolated yield.

5
This synthetic method can also be used for the direct synthesis of heterocyclic compounds via cyclization. During the course of
these studies, we discovered that the one-pot synthesis of 2,3-diphenylquinoxaline proceeded in 71% yield, which is potentially
useful for the pharmaceutical industry.23, 24
NH2
N
NH2
NH4I, EtOCS2K
DMSO, H2O, 130 o
2a
N
C
K3PO4 (1 equiv)
100 oC, 8 h
3a, 71%
Scheme 3. One-pot synthesis of quinoxaline 3a from 1,2-diphenylethyne.
Although the mechanism of this reaction is not clear, we were able to gain insight from control experiments. We used I2-
catalyzed potassium xanthate to synthesise dixanthogen,25 then diphenylacetylene and dixanthogen in the absence of EtOCS2K give
the benzil product in 83% yield. Wang and co-workers reported a similar thiyl radical catalyzed oxidation of diarylalkynes to α-
diketones using 4,4'-dinitrodiphenyldisulfide as the radical source.26
Scheme 4. Synthesis of benzil 2a from dixanthogen 4a.
Conclusion
In conclusion, we have developed a transition-metal-free NH4I/EtOCS2K (EtOCS2K, 25g/$10) system for the reaction of 1,2-
diarylalkynes to give the corresponding benzil products in moderate to good yields. This novel protocol proceeds with excellent
chemoselectivity and high functional group tolerance. A control experiment indicated that the reaction proceeds via NH4I promoted
EtOCS2K dimerization to give the corresponding dixanthogen and subsequent dixanthogen assisted oxidation. The further
applications of this general methodology to other reactions is the subject of ongoing investigations.
Acknowledgements
We thank the National Natural Science Foundation of China (21302146, 1702148), the Foundation of the Department of Education
of Guangdong Province (2016KTSCX144, 2016KCXTD005) and Science Foundation for Young Teachers of Wuyi University
(2015td01), Chemical Industry Collaborative Innovation Center of Yueshan Town 2017(368) the Foundation of Department of
Education of Guangdong Province (YQ2015162) for financial support.
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7
Synthesis benzils from easily accessible diarylacetylene derivatives
Mild conditions, good functional groups tolerance and good yield was obtained
Proceeded smoothly through a dixanthogen assisted thiyl radical catalyzed oxidation
Transformation of diarylalkynes leading to the quinoxalines via cyclization

8
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NH4I/EtOCS2K promoted synthesis of
substituted benzils from diphenylacetylene
derivatives
Shaohua Jiang a, Yibiao Li a,*, Xianglin Luo a , Guoling Huang a , Yan Shao a , Dongli Li a,* and Bin Li
a
School of Chemical & Environmental Engineering, Wuyi University, Jiangmen 529020, Guangdong Province, P.R. China