Manganese(III) Acetate-Promoted Cross-Coupling Reaction of Benzothiazole/Thiazole Derivatives with Organophosphorus Compounds under Ball-Milling Conditions

Article abstract of DOI:10.1021/acs.joc.6b00786

The first solvent-free manganese(III) acetate-promoted reaction of benzothiazole/thiazole derivatives with organophosphorus compounds including phosphine oxides, phosphinate ester, and phosphonate diester has been efficiently developed under ball-milling conditions, providing a highly efficient and green protocol to structurally diverse C2-phosphonylated benzothiazole/thiazole derivatives with remarkable functional group tolerance and excellent yields.

Full text of DOI:10.1021/acs.joc.6b00786

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Article
Manganese(III) Acetate-Promoted Cross-Coupling
Reaction of Benzothiazole/Thiazole Derivatives with
Organophosphorus Compounds under Ball-Milling Conditions
Liang Li, Jun-Jie Wang, and Guan-Wu Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00786 • Publication Date (Web): 01 Jun 2016
Downloaded from http://pubs.acs.org on June 6, 2016
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Manganese(III) Acetate-Promoted Cross-Coupling Reaction of
Benzothiazole/Thiazole Derivatives with Organophosphorus
Compounds under Ball-Milling Conditions
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Liang Li, JunꢀJie Wang, and GuanꢀWu Wang*
CAS Key Laboratory of Soft Matter Chemistry, iChEM (Collaborative
Innovation Center of Chemistry for Energy Materials), Hefei National Laboratory for
Physical Sciences at Microscale, and Department of Chemistry, University of Science
and Technology of China, Hefei, Anhui 230026, P. R. China
Fax: (+86)551ꢀ360ꢀ7864; Eꢀmail: gwang@ustc.edu.cn
ABSTRACT
The first solventꢀfree manganese(III) acetateꢀpromoted reaction of
benzothiazole/thiazole derivatives with organophosphorus compounds including
phosphine oxides, phosphinate ester, and phosphonate diester has been efficiently
developed under ballꢀmilling conditions, providing a highly efficient and green
protocol to structurally diverse C2ꢀphosphonylated benzothiazole/thiazole derivatives
with remarkable functional group tolerance and excellent yields.
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INTRODUCTION
Aromatic organophosphorus compounds, an important class of chemical
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building blocks, have been widely applied in medicinal chemistry,
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3
phosphineꢀcontaining ligands and materials science. Since the pioneering work
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of the Hirao group in 1981, the transitionꢀmetalꢀcatalyzed coupling reactions have
2
5
become practical methods to construct C(sp )−P bonds (Scheme 1a). However,
these coupling reactions were limited to functionalized (hetero)arenes (e.g.,
halogenated and boronꢀcontaining reagents) and would generate a large quantity of
wastes, thus leading to low atom and step economy. In order to avoid the
preꢀfunctionalization of reactants, the dehydrogenative crossꢀcoupling reaction of
(
hetero)arenes with organophosphorus compounds containing P(O)−H moiety
under oxidative conditions would become an efficient and promising strategy for
2
6
the formation of C(sp )−P bonds. In 2006, Ishii and coꢀworkers reported an
elegant radical phosphonylation of arenes with dialkyl phosphites to afford dialkyl
7
a
arylphosphonates by using a Mn(OAc)
2
/Co(OAc)
2 2
/O redox couple. Later, Zou
and coꢀworkers developed a similar Mn(OAc)
3
ꢀpromoted radical phosphonylation
7
b,7c
of (hetero)aromatic compounds.
Subsequently, the Montchamp group reported
2
2
a general intermolecular C(sp )−H to C(sp )−P transformation for (hetero)arenes
with phosphinate esters, phosphonate diesters and diphenylphosphine oxide using
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d
2 2
the Mn(OAc) /MnO system. Notably, these radical methods required aliphatic
acids as solvents, which could not be applied to acidꢀsensitive substrates. In 2012,
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the first palladiumꢀcatalyzed direct phosphonylation of benzothiazoles and
benzoxazoles with dialkyl phosphites was discovered by the Li group (Scheme
1
2 2 8
b), which required proline or 2,2´ꢀbipyridine as a ligand and K S O as the
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oxidant to achieve the optimal results. Meanwhile, the Huang group disclosed a
silverꢀcatalyzed dehydrogenative crossꢀcoupling reaction of dialkyl phosphites
with substituted furans, thiophenes, thiazoles, pyrroles and pyridines in the
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presence of K
2
S
2
O
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. Chen et al. recently realized the direct C2ꢀphosphonylation
of benzothiazoles by the reaction with dialkyl phosphites in the presence of
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0
diꢀtertꢀbutyl peroxide. Very recently, Zhang, et al revealed a silver
Scheme 1. Comparison of Previous Works with This Work
Classical methods
catalyst
ligand
O
O
R
R
a)
X
+
H
PR'2
PR'2
base, solvent
X = I, Br, Cl, B(OH) etc.
2
requirement for pre-functionalization
generation of waste
Dehydrogenative cross-coupling strategy
Previous works
Pd(OAc)2
proline or bpy
O
O
X
N
X
N
b)
R
H + H P(OR')2
R
P(OR')2
K S O
8
2
2
o
CH CN, 100 C, 24 h
3
X = O, S
O
S
N
O
S
N
AgNO3
c)
R
H + H PAr2
R
PAr2
o
CH CN, 90 C, 24 h
3
Ar
This work
O
O
S
N
S
N
Mn(OAc) —2H O
3
2
d)
R
H + H PR'2
R
PR'2
ball milling, 1.5 h
under air
- solvent-free
-
-
-
ligand-free
without external heating
short reaction time
- up to 97% yield
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nitrateꢀmediated phosphonylation of benzothiazoles and thiazoles with
1
1
diarylphosphine oxides without additional oxidants (Scheme 1c). It was believed
that this process involved nucleophilic addition of the diarylphosphine oxide to the
thiazole ring, which was activated through the coordination of the nitrogen atom
with the Ag(I) salt rather than a phosphoryl radical path. Unfortunately, this
reaction system had disadvantage of poor functional group tolerance, especially for
paraꢀhalogen atom substituents on the phenyl ring of diarylphosphine oxides. In
addition, the reaction conditions also had some drawbacks including the need for
inert atmosphere, high temperature, long reaction time, and the involvement of
toxic solvent.
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On the other hand, environmental concerns have given rise to increasing
attention due to the requirement of sustainable development in recent years. More
and more chemists are dedicated to the development of more environmentally
friendly and efficient organic reactions. To overcome the aforementioned
problems, an attractive alternative is to carry out the reactions under solventꢀfree
conditions. Solventꢀfree reactions, which avoid the use of toxic organic solvents,
shorten the reaction time, simplify the separation procedure, and supply
highꢀyielding organic products, have been drawing increasing attention in the field
of organic synthesis. One of the protocols applied to solventꢀfree reactions is the
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2
13,14
ballꢀmilling technique. In light of our previous studies in this field,
herein we
report a solventꢀfree and highly efficient Mn(OAc) ꢀpromoted crossꢀcoupling
3
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reaction of benzothiazole or thiazole derivatives with organophosphorus
compounds under ballꢀmilling conditions. To the best of our knowledge, this is the
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first example of C(sp )−P bond construction under ballꢀmilling conditions.
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RESULTS AND DISCUSSION
At the outset of our study, we chose benzothiazole (1a) and
diphenylphosphine oxide (2a) as the model substrates to screen the optimal
reaction conditions. It was encouraging to find that the solventꢀfree reaction of 1a
(
0.3 mmol) with 2a (2 equiv) for 2 h afforded the desired 2ꢀdiphenylphosphinyl
benzothiazole (3aa) in 33% yield in the presence of Mn(OAc) •2H O (1 equiv)
3
2
under ballꢀmilling conditions (Table 1, entry 1). Then, the effect of the additive
loadings on the product yield was investigated. Increasing the amount of
Mn(OAc)
3 2
•2H O to 2 equiv improved the product yield to 67% (Table 1, entry 2).
To our delight, when 3 equiv of Mn(OAc) •2H O was used, the yield of 3aa was
3
2
increased to 91% (Table 1, entry 3). The influence of the amount of 2a on the
product yield was also examined. Further increasing the amount of 2a to 3 equiv
led to a lower yield of 78% (Table 1, entry 4). Meanwhile, decreasing the amount
of 2a to 1 equiv, the yield of 3aa sharply dropped to 54% (Table 1, entry 5). To
our surprise, keeping the 1a:2a:Mn(OAc) •2H O ratio as 1:2:3 and shortening the
3
2
reaction time to 1.5 h, no decrease of the product yield was observed (Table 1,
entry 3 vs entry 6), while continuing to shorten the reaction time to 1 h would
reduce the product yield to 76% (Table 1, entry 7). The efforts to replace
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Mn(OAc)
FeCl •6H
use of Ce(NH
3
•2H
O (Table 1, entries 8ꢀ12) failed to provide the desired product, while the
(NO (CAN) afforded 3aa in only 9% yield (Table 1, entry 13).
2 3 2 2 2 2
O with AgNO , AgOAc, Cu(OAc) •2H O, CuCl •2H O or
3
2
4
)
2
3 6
)
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A reason that the silver salt was effective in solution, but not under solventꢀfree
ballꢀmilling conditions remains unclear now. In addition, we also carried out the
reaction in solution phase. Acetonitrile and acetic acid are known to be the most
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b,7c,15
widely used solvents in Mn(OAc)
3
ꢀpromoted reactions.
When the reaction
o
was performed in acetonitrile at 90 C for 24 h, the yield of 3aa was 19% (Table 1,
entry 14). While the reaction was performed in acetic acid, a lower yield (6%) was
obtained (Table 1, entry 15). Neither of the results turned out to be efficient
compared with the present solventꢀfree mechanical milling procedure,
demonstrating the advantages of the solventꢀfree mechanochemical reaction over
the liquidꢀphase reaction. Thus, this reaction was most efficient when the molar
ratio of 1a:2a:Mn(OAc) •2H O was 1:2:3 under the solventꢀfree and mechanical
3
2
milling conditions for 1.5 h.
Table 1. Optimization of the Mn(OAc) -Promoted Reaction of Benzothiazole (1a)
3
a
with Diphenylphosphine Oxide (2a) under Ball-Milling Conditions
b
entry
1
additive
Mn(OAc) •2H
molar ratio yield (%)
3
2
O
1:2:1
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Mn(OAc)
Mn(OAc)
Mn(OAc)
3
3
3
•2H
•2H
•2H
2
2
2
O
O
O
1:2:2
1:2:3
1:3:3
1:1:3
1:2:3
1:2:3
1:2:3
67
91
78
54
91
76
0
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Mn(OAc) •2H O
3
2
c
6
Mn(OAc) •2H O
3 2
d
7
Mn(OAc)
AgNO
AgOAc
3 2
•2H O
8
3
9
1:2:3
1:2:3
1:2:3
1:2:3
1:2:3
1:2:3
1:2:3
0
0
10
Cu(OAc)
2
•2H
2
O
1
1
12
13
CuCl
FeCl
CAN
Mn(OAc) •2H
Mn(OAc) •2H O
2
•2H
2
O
0
3
•6H
2
O
0
9
e
14
3
2
O
19
6
f
15
3
2
a
All reactions were carried out in Spex SamplePrep 5100 Mixer Mill for 2 h
b
c
unless otherwise stated. Molar ratio refers to 1a:2a:additive. The reaction time was
d
e
1
.5 h. The reaction time was 1 h. The reaction was performed in acetonitrile (2 mL)
o
f
o
at 90 C for 24 h. The reaction was performed in acetic acid (2 mL) at 90 C for 24 h.
With the optimized reaction conditions in hand (Table 1, entry 6), we next turned
our attention to explore various benzothiazole and thiazole derivatives 1 in this
reaction. As is apparent from Table 2, the benzothiazoles bearing either an
electronꢀdonating or electronꢀwithdrawing substituent at the 6ꢀposition of the
aromatic moiety (1b–h) underwent coupling efficiently, generating the corresponding
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adducts (3ba–ha) in good to excellent yields of 75ꢀ90% (Table 1). It is worthy
pointing out that a wide range of functional groups, such as chloro (1e), bromo (1f),
ester (1g), and cyano (1h), were adopted well under the reaction conditions. These
functional groups could be transformed easily and offered versatile synthetic handle
for further elaboration. In addition, the reactivity was increased when the substituents
were on other positions of the phenyl ring. 4ꢀMethyl and 5ꢀchloroꢀsubstituted
benzothiazoles (1i and 1j) reacted smoothly with 2a to afford comparable high yields
of 96% and 95%, respectively. Interestingly, 4,5ꢀdimethylthiazole (1k) and ethyl
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ꢀmethyl thiazoleꢀ5ꢀcarboxylate (1l) also proved to be excellent substrates to afford
products 3ka and 3la in high yields of 94% and 97%, respectively. However, when
the simplest thiazole (1m) was treated with diphenylphosphine oxide, the desired
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product 3ma was isolated in a poor yield of 37% due to the formation of byproducts.
Benzoxazole and 1ꢀmethylbenzimidazole were also utilized to replace benzothiazole
under the same conditions. Disappointedly, no desired phosphonylated products were
observed.
Table
2.
Mn(OAc) -Promoted
Cross-Coupling
Reaction
of
3
Benzothiazole/Thiazole Derivatives (1b–m) with Diphenylphosphine Oxide (2a)
a
under Ball-Milling Conditions
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O
S
N
O
PPh2
S
N
Mn(OAc) •2H O
3
2
R
H + H PPh2
R
ball milling, 1.5 h
under air
1
2a
3
O
P Ph
Ph
MeO
Br
O
P Ph
Ph
F
O
S
S
N
S
N
P Ph
Ph
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N
3ba: 79%
3ca: 90%
3da: 87%
Cl
O
P Ph
Ph
O
P Ph
Ph
EtO C
O
S
N
S
N
2
S
N
P Ph
Ph
3ea: 85%
3fa: 83%
3ga: 80%
NC
O
P Ph
Ph
O
P Ph
Ph
O
S
N
S
N
S
N
P Ph
Ph
Cl
3
ha: 75%
3ia: 96%
3ja: 95%
O
O
P Ph
Ph
O
S
S
N
S
N
P Ph
Ph
P Ph
Ph
N
EtOOC
3
ka: 94%
3la: 97%
3ma: 37%
a
Unless otherwise specified, the reaction mixture of 1 (0.3 mmol), 2a (0.6 mmol) and additive
(
0.9 mmol) was milled for 1.5 h.
Various diarylphosphine oxides were explored as well to examine their
substrate scope, and the results are illustrated in Table 3. Satisfactorily, substrates
bearing methyl groups at the paraꢀposition or metaꢀposition of the phenyl ring (2b
and 2c) reacted with benzothiazole (1a) to give the desired products 3ab and 3ac
in 93% and 87% yields, respectively (Table 3). Gratifyingly, substrates containing
halogen atoms including fluoro (2d) and bromo (2e), which had poor reactivity
1
1
under Zhang’s conditions, performed well under our reaction conditions, and the
corresponding products 3ad and 3ae were isolated in 94% and 81% yields,
respectively. When di(naphthalenꢀ2ꢀyl)phosphine oxide (2f) was introduced as the
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reactant, the desired product 3af was obtained in moderate yield (58%). In
addition, we have also examined the reactions of dialkylphosphine oxides with 1a.
To our delight, when dicyclohexylphosphine oxide (2g) and dibutylphosphine
oxide (2h) were chosen as the coupling partners, both of them were successfully
transformed into the desired phosphonylated products 3ag and 3ah in comparable
yields (66% and 73%). Furthermore, other organophosphorus compounds could
also be employed. Ethyl phenylphosphinate (2i) could react with 1a under the
standard conditions to afford the desired product 3ai in 40% yield. It is worth
mentioning that diethyl phosphonate (2j) exhibited less reactivity under the
standard conditions, with only 22% yield of 3aj perhaps due to the unstable nature
caused by more oxygen atoms connected to the phosphoryl radical intermediate.
Treatment of 4,5ꢀdimethylthiazole 1k with di(4ꢀfluorophenyl)phosphine oxide (2d)
and di(naphthalenꢀ2ꢀyl)phosphine oxide (2f) gave the corresponding
phosphonylated products 3kd and 3kf in 95% and 71% yields, respectively.
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2
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4
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6
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9
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2
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5
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9
0
3
Table 3. Mn(OAc) -Promoted Cross-Coupling Reaction of Benzothiazole
(1a)/4,5-Dimethylthiazole (1k) with Organophosphorus Compounds (2b–j) under
a
Ball-Milling Conditions
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O
O
PR'2
S
S
Mn(OAc) •2H O
3
2
H + H PR'2
ball milling, 1.5 h
under air
N
N
1
a,1k
2
3
O
P
O
P
O
P
S
S
N
S
N
F
10
11
12
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N
F
3
S
ab: 93%
3ac: 87%
3ad: 94%
O
P
O
P
S
O
S
P
N
Br
N
N
Br
3
S
N
ae: 81%
3af: 58%
3ag: 66%
O
P
O
P O
O
S
N
S
N
P O
O
3ah: 73%
3ai: 40%
3aj: 22%
O
P
O
P
S
N
S
N
F
F
3kd: 95%
3kf: 71%
To demonstrate the practical application of the present protocol, a gramꢀscale
experiment was carried out for the reaction of benzothiazole (1a, 0.81 g) with
diphenylphosphine oxide (2a, 2.43 g) under the optimal reaction conditions
(Scheme 2). The coupling product 3aa was obtained in 95% yield (1.90 g), which
showed that the present method could be easily adopted for the largeꢀscale
preparation.
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Scheme 2. Gram-Scale Synthesis of 3aa
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0
To understand the reaction mechanism, control experiments were carried out, as
shown in Scheme 3. The radical scavenging experiment was investigated by adding
2
,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy (TEMPO) to the reaction mixture of 1a and 2a
under the standard conditions. It was found that 3 equiv of TEMPO suppressed the
reaction completely, and the TEMPO−P(O)Ph adduct (4) was isolated in 47% yield.
2
This result indicates that the reaction may take place through a radical pathway, which
1
1
might be different from Zhang’s work. In addition, the reaction of 1a with 2a under
argon atmosphere gave product 3aa in 89% yield (Scheme 3b), which was pretty
close to that (91%) in the presence of air, suggesting that air had little effect on the
reaction and that the Mn(III) species was likely the only oxidant.
Scheme 3. Control Experiments
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On the basis of the above results and the previous literature, a plausible
mechanism is depicted in Scheme 4. We believe that in this work, the first step
3 2
involves the reaction of Mn(OAc) •2H O with organophosphorus compounds 2 to
10
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afford the phosphoryl radical A. Then, A attacks the thiazole ring at the C2ꢀposition
of 1 to give the radical intermediate B. Subsequently, the final phosphonylation
products 3 are obtained via oxidation by a Mn(III) species to regain the aromaticity of
the thiazole ring. Although only 1 equiv of 2 and 2 equiv of Mn(OAc)
3
are required
for the formation of 3, a molar ratio of 1:2:Mn(OAc)
3
as 1:2:3 was used to achieve the
highest product yield.
Scheme 3. Proposed Reaction Pathway for the Formation of Products 3
CONCLUSION
In summary, we have developed the first example of direct phosphonylation of
benzothiazole and thiazole derivatives with organophosphorus compounds including
phosphine oxides, phosphinate ester, and phosphonate diester promoted by
Mn(OAc)
3
•2H
2
O using a ballꢀmilling technique. This process provides a highly
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6
efficient and environmentally friendly solventꢀfree synthesis method for the
construction of diverse C2ꢀphosphonylated benzothiazole and thiazole derivatives
with remarkable functional group tolerance and up to 97% yield. Further usage of a
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ballꢀmilling technique to construct C(sp )−P bonds are ongoing in our laboratory.
EXPERIMENTAL SECTION
General Procedure for the Synthesis of 3 under Ball-Milling Conditions. A
mixture of benzothiazole/thiazole derivatives (1, 0.3 mmol), organophosphorus
compounds (2, 0.6 mmol) along with Mn(OAc) •2H O (0.9 mmol) was added to a
3
2
stainlessꢀsteel jar (5 mL) containing two stainlessꢀsteel balls (6 mm). The vessel was
o
milled in a Spex SamplePrep 5100 Mixer Mill at room temperature (~25 C) for 1.5 h.
After the reaction was complete, the reaction mixture was slightly sticky solid, and
o
the temperature of the reaction mixture was raised to about 50 C. The same reaction
was repeated again. Then, the combined reaction mixtures were dissolved in ethyl
acetate. The solution was filtered and then evaporated in vacuo to remove the solvent.
Finally, the residue was purified by silica gel column chromatography using a
petroleum ether/ethyl acetate mixture [from 5:1 to 1:1 (v/v)] as the eluent to give
products 3.
1
13
The new products (3ga, 3ha, 3la, 3ag, 3kd) were characterized by H NMR, C
31
NMR, P NMR and ESIꢀMS spectra. Other products are known compounds, and
1
13
characterized by H NMR and C NMR spectra, which were consistent with those
10,11
described in the literature.
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1
Benzo[d]thiazol-2-yldiphenylphosphine Oxide (3aa). White solid, 91% yield
1
(
91.1 mg). Mp: 162–164 °C. H NMR (400MHz, CDCl
3
) δ 8.20 (d, J = 8.0 Hz, 1H),
) δ 166.8 (d,
13
8
.05–7.92 (m, 5H), 7.61–7.45 (m, 8H); C{1H}NMR (100 MHz, CDCl
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
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32
33
34
35
36
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39
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42
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51
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53
54
55
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57
58
59
60
J = 127.1 Hz), 155.4 (d, J = 21.7 Hz), 136.8 (s), 132.7 (d, J = 2.8 Hz), 132.0 (d, J =
0.3 Hz), 131.0 (d, J = 109.1 Hz), 128.7 (d, J = 12.9 Hz), 126.73 (s), 126.68 (s), 124.8
s), 122.1 (s).
1
(
11
(
6-Methylbenzo[d]thiazol-2-yl)diphenylphosphine Oxide (3ba). White solid,
1
7
9% yield (82.9 mg). Mp: 153–154 °C. H NMR (400MHz, CDCl
3
) δ 8.06 (d, J = 8.6
Hz, 1H), 8.01–7.91 (m, 4H), 7.79 (s, 1H), 7.60–7.53 (m, 2H), 7.52–7.45 (m, 4H), 7.35
13
(
d, J = 8.6 Hz, 1H), 2.50 (s, 3H); C{1H}NMR (100 MHz, CDCl
3
) δ 165.4 (d, J =
128.3 Hz), 153.7 (d, J = 21.8 Hz), 137.2 (s), 132.6 (d, J = 2.8 Hz), 132.0 (d, J = 10.2
Hz), 131.3 (d, J = 108.7 Hz), 128.7 (d, J = 12.8 Hz), 128.6 (s), 124.3 (s), 121.7 (s),
21.7 (s).
11
(
6-Methoxybenzo[d]thiazol-2-yl)diphenylphosphine Oxide (3ca). Yellow
1
solid, 90% yield (98.9 mg). Mp: 151–152 °C. H NMR (400 MHz, CDCl
3
) δ 8.05 (d,
J = 9.1 Hz, 1H), 8.00–7.90 (m, 4H), 7.59–7.53 (m, 2H), 7.52–7.45 (m, 4 H), 7.40 (d, J
13
= 2.5 Hz, 1H), 7.14 (dd, J = 9.1, 2.5 Hz, 1H), 3.87 (s, 3H); C{1H}NMR (100 MHz,
CDCl ) δ 163.3 (d, J = 129.8 Hz), 158.8 (s), 150.1 (d, J = 21.9 Hz), 138.6 (s), 132.5 (d,
J = 2.7 Hz), 131.8 (d, J = 10.3 Hz), 131.2 (d, J = 109.6 Hz), 128.6 (d, J = 12.7 Hz),
3
1
25.2 (s), 117.1 (s), 103.4 (s), 55.8 (s).
11
(6-Fluorobenzo[d]thiazol-2-yl)diphenylphosphine Oxide (3da). White solid,
1
8
7% yield (92.6 mg). Mp: 181–182 °C. H NMR (400 MHz, CDCl
3
) δ 8.14 (dd, J =
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.0, 4.6 Hz, 1H), 8.01ꢀ7.91 (m, 4H), 7.68 (dd, J = 7.8, 2.2 Hz, 1H), 7.62–7.55 (m, 2H),
1
3
.54–7.46 (m, 4H), 7.29 (td, J = 8.8, 2.4 Hz, 1H); C{1H}NMR (100 MHz, CDCl
3
) δ
66.9 (dd, J = 126.3, 3.5 Hz), 161.4 (d, J = 249.1 Hz), 152.2 (d, J = 22.3 Hz), 138.1 (d,
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J = 11.5 Hz), 132.8 (d, J = 2.8 Hz), 132.0 (d, J = 10.3 Hz), 130.9 (d, J = 109.1 Hz),
28.8 (d, J = 12.9 Hz), 126.0 (d, J = 9.7 Hz), 116.0 (d, J = 25.3 Hz), 108.1 (d, J = 26.6
Hz).
1
10
(
6-Chlorobenzo[d]thiazol-2-yl)diphenylphosphine Oxide (3ea).
Light
) δ
1
yellow solid, 85% yield (94.5 mg). Mp: 121–122 °C. H NMR (400 MHz, CDCl
3
8
.09 (d, J = 8.8 Hz, 1H), 8.01–7.91 (m, 5H), 7.62–7.55 (m, 2H), 7.55ꢀ7.46 (m, 5H);
13
3
C{1H}NMR (100 MHz, CDCl ) δ 167.8 (d, J = 124.9 Hz), 154.0 (d, J = 21.6 Hz),
138.1 (s), 133.0 (s), 132.8 (d, J = 2.8 Hz), 132.0 (d, J = 10.3 Hz), 130.8 (d, J = 108.7
Hz), 128.8 (d, J = 13.0 Hz), 127.8 (s), 125.5 (s), 121.7 (s).
11
(6-Bromobenzo[d]thiazol-2-yl)diphenylphosphine Oxide (3fa). Yellow solid,
1
8
3% yield (103.1 mg). Mp: 128–130 °C. H NMR (400 MHz, CDCl ) δ 8.15 (d, J =
3
1.5 Hz, 1H), 8.03 (d, J = 8.8 Hz, 1H), 8.00–7.92 (m, 4H), 7.63 (dd, J = 8.8, 1.5 Hz,
13
1
H), 7.61–7.55 (m, 2H), 7.54–7.46 (m, 4H); C{1H}NMR (100 MHz, CDCl
3
) δ
167.8 (d, J = 124.8 Hz), 154.2 (d, J = 21.5 Hz), 138.5 (s), 132.9 (d, J = 2.8 Hz), 132.0
d, J = 10.4 Hz), 130.7 (d, J = 109.3 Hz), 130.4 (s), 128.8 (d, J = 13.0 Hz), 125.8 (s),
124.7 (s), 120.9 (s).
Ethyl 2-(Diphenylphosphoryl)benzo[d]thiazole-6-carboxylate (3ga). Yellow
(
1
solid, 80% yield (97.9 mg). Mp: 171–172 °C. H NMR (400 MHz, CDCl
3
) δ 8.75 (s,
1
H), 8.22 (s, 2H), 8.03–7.93 (m, 4H), 7.63–7.56 (m, 2H), 7.55–7.48 (m, 4H), 4.43 (q,
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3
J = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H); C{1H}NMR (100 MHz, CDCl
3
) δ 170.9 (d,
J = 123.4 Hz), 165.9 (s), 157.9 (d, J = 21.2 Hz), 136.7 (s), 132.9 (d, J = 2.7 Hz), 132.0
(
d, J = 10.3 Hz), 130.6 (d, J = 109.1 Hz), 128.8 (d, J = 13.0 Hz), 128.7 (s), 127.7 (s),
10
11
12
13
14
15
16
17
18
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57
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59
60
3
1
1
24.5 (s), 124.4 (s), 61.6 (s), 14.4 (s); P NMR (162 MHz, CDCl ) δ 19.92 (s);
3
+
HRMS (+ESI) calcd for C22
H
19NO
3
SP [M + H] : 408.0818; found: 408.0813.
2
-(Diphenylphosphoryl)benzo[d]thiazole-6-carbonitrile (3ha). Pale yellow
1
solid, 75% yield (81.4 mg). Mp: 175–176 °C. H NMR (400 MHz, CDCl
3
) δ 8.39 (d,
J = 1.3 Hz, 1H), 8.27 (d, J = 8.7 Hz, 1H), 8.02–7.93 (m, 4H), 7.79 (dd, J = 8.7, 1.3 Hz,
1
3
1
1
H), 7.64–7.58 (m, 2H), 7.57–7.49 (m, 4H); C{1H}NMR (100 MHz, CDCl ) δ
3
72.6 (d, J = 120.4 Hz), 157.3 (d, J = 20.8 Hz), 137.2 (s), 133.1 (d, J = 2.8 Hz), 132.0
(d, J = 10.4 Hz), 130.2 (d, J = 109.5 Hz), 129.6 (s), 128.9 (d, J = 13.1 Hz), 127.4 (s),
31
1
25.7 (s), 118.3 (s), 110.3 (s); P NMR (162 MHz, CDCl
3
) δ 19.98 (s); HRꢀMS (+ESI)
+
calcd for C20
H
14
N
2
OSP [M + 1] : 361.0559; found: 361.0558.
10
(
4-Methylbenzo[d]thiazol-2-yl)diphenylphosphine Oxide (3ia). White solid,
1
96% yield (100.3 mg). Mp: 203–204 °C. H NMR (400 MHz, CDCl
3
) δ 8.05–7.96 (m,
4
H), 7.81 (d, J = 7.6 Hz, 1H), 7.59–7.53 (m, 2H), 7.52–7.45 (m, 4H), 7.40–7.30 (m,
13
2H), 2.78 (s, 3H); C{1H}NMR (100 MHz, CDCl
d, J = 21.2 Hz), 136.7 (s), 134.9 (s), 132.5 (d, J = 2.7 Hz), 131.9 (d, J = 10.1 Hz),
131.4 (d, J = 108.5 Hz), 128.6 (d, J = 12.9 Hz), 127.0 (s), 126.7 (s), 119.4 (s), 18.4
s).
3
) δ 165.0 (d, J = 129.1 Hz), 155.0
(
(
11
(5-Chlorobenzo[d]thiazol-2-yl)diphenylphosphine Oxide (3ja). Pale brown
1
solid, 95% yield (105.3 mg). Mp: 152–153 °C. H NMR (400 MHz, CDCl
3
) δ 8.18 (d,
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2
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2
2
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J = 1.6 Hz, 1H), 8.00–7.93 (m, 4H), 7.92 (d, J = 8.8 Hz, 1H), 7.61–7.55 (m, 2H),
13
7
3
.54–7.48 (m, 4H), 7.46 (dd, J = 8.8, 1.6 Hz, 1H); C{1H}NMR (100 MHz, CDCl )
δ 169.3 (d, J = 124.3 Hz), 156.2 (d, J = 21.4 Hz), 135.1 (s), 132.9 (s), 132.8 (d, J = 2.9
Hz), 131.9 (d, J = 10.3 Hz), 130.7 (d, J = 109.2 Hz), 128.8 (d, J = 12.9 Hz), 127.3 (s),
0
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2
3
4
5
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7
8
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0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
24.4 (s), 122.9 (s).
11
(
4,5-Dimethylthiazol-2-yl)diphenylphosphine Oxide (3ka). White solid, 94%
1
yield (88.5 mg). Mp: 154–156 °C. H NMR (400 MHz, CDCl
3
) δ 7.93–7.84 (m, 4H),
13
7
.57–7.51 (m, 2H), 7.50–7.42 (m, 4H), 2.42 (s, 3H), 2.41 (s, 3H); C{1H}NMR (100
MHz, CDCl ) δ 158.9 (d, J = 137.0 Hz), 153.5 (d, J = 19.9 Hz), 133.7 (s), 132.3 (d, J
3
=
2.8 Hz), 132.0 (d, J = 109.1 Hz), 131.9 (d, J = 10.2 Hz), 128.6 (d, J = 12.7 Hz), 15.1
(s), 11.7 (s).
Ethyl 2-(Diphenylphosphoryl)-5-methylthiazole-4-carboxylate (3la). White
1
solid, 97% yield (108.1 mg). Mp: 133–134 °C. H NMR (400 MHz, CDCl
3
) δ
7
.87–7.77 (m, 4H), 7.52–7.44 (m, 2H), 7.44–7.35 (m, 4H), 4.25 (q, J = 6.9 Hz, 2H),
13
2.71 (s, 3H), 1.26 (t, J = 7.0 Hz, 3H); C{1H}NMR (100 MHz, CDCl
3
) δ 166.6 (d, J
=
125.9 Hz), 162.0 (d, J = 19.0 Hz), 160.7 (s), 131.7 (d, J = 2.8 Hz), 130.9 (d, J =
10.2 Hz), 129.8 (d, J = 109.4 Hz), 127.7 (d, J = 12.8 Hz), 126.5 (s), 60.7 (s), 16.6 (s),
31
1
3.3 (s); P NMR (162 MHz, CDCl
3
) δ 18.64 (s); HRꢀMS (+ESI) calcd for
+
C H NO SP [M + H] : 372.0823; found: 372.0826.
19
19
3
11
Diphenyl(thiazol-2-yl)phosphine Oxide (3ma). Beige solid, 37% yield (31.8
1
mg). Mp: 105–106 °C. H NMR (400 MHz, CDCl
3
) δ 8.18 (d, J = 1.6 Hz, 1H),
7
.95–7.85 (m, 4H), 7.74 (s, 1H), 7.60–7.53 (m, 2H), 7.53–7.44 (m, 4H);
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C{1H}NMR (100 MHz, CDCl ) δ 165.3 (d, J = 131.9 Hz), 146.6 (d, J = 21.3 Hz),
1
32.6 (d, J = 2.8 Hz), 131.9 (d, J = 10.3 Hz), 131.5 (d, J = 109.5 Hz), 128.7 (d, J =
1
2.7 Hz), 125.0 (s).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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28
29
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1
1
Benzo[d]thiazol-2-yldi-p-tolylphosphine Oxide (3ab). Yellow liquid, 93%
1
yield (101.1 mg). H NMR (400 MHz, CDCl
3
) δ 8.18 (d, J = 8.0 Hz, 1H), 8.00 (d, J =
7
7
1
.6 Hz, 1H), 7.89–7.77 (m, 4H), 7.53 (t, J = 7.4 Hz, 1H), 7.47 (t, J = 7.4 Hz, 1H),
1
3
.33–7.26 (m, 4H), 2.39 (s, 6H); C{1H}NMR (100 MHz, CDCl
3
) δ 167.5 (d, J =
26.3 Hz), 155.4 (d, J = 21.4 Hz), 143.3 (d, J = 2.6 Hz), 136.9 (s), 132.1 (d, J = 10.5
Hz), 129.5 (d, J = 13.2 Hz), 127.9 (d, J = 111.6 Hz), 126.7 (s), 126.6 (s), 124.8 (s),
22.1 (s), 21.8 (s).
1
11
Benzo[d]thiazol-2-ylbis(3,5-dimethylphenyl)phosphine Oxide (3ac). Yellow
1
solid, 87% yield (101.7 mg). Mp: 167–168 °C. H NMR (400 MHz, CDCl
3
) δ 8.22 (d,
J = 8.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.59–7.52 (m, 5H), 7.48 (t, J = 7.4 Hz, 1H),
13
7
.18 (s, 2H), 2.33 (s, 12H); C{1H}NMR (100 MHz, CDCl ) δ 167.5 (d, J = 124.9
3
Hz), 155.4 (d, J = 21.3 Hz), 138.4 (d, J = 13.4 Hz), 136.9 (s), 134.5 (d, J = 2.8 Hz),
30.7 (d, J = 107.8 Hz), 129.4 (d, J = 10.3 Hz), 126.5 (s), 126.4 (s), 124.8 (s), 122.1
(s), 21.3 (s).
Benzo[d]thiazol-2-ylbis(4-fluorophenyl)phosphine Oxide (3ad).
1
11
Light
1
yellow solid, 94% yield (104.9 mg). Mp: 115–117 °C. H NMR (400 MHz, CDCl ) δ
3
8
.20 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 7.6 Hz, 1H), 8.02–7.93 (m, 4H), 7.58 (t, J = 7.2
13
Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 7.20 (td, J = 8.6, 2.3 Hz, 4H); C{1H}NMR (100
MHz, CDCl
3
) δ 166.2 (d, J = 130.1 Hz), 165.6 (dd, J = 255.1, 3.5 Hz), 155.3 (d, J =
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1.8 Hz), 136.7 (s), 134.5 (dd, J = 11.7, 9.2 Hz), 126.9 (s), 126.8 (dd, J = 112.9, 3.2
Hz), 124.8 (s), 122.2 (s), 116.3 (dd, J = 21.7, 14.1 Hz).
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Benzo[d]thiazol-2-ylbis(4-bromophenyl)phosphine Oxide (3ae). Beige solid,
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1% yield (119.0 mg). Mp: 140–142 °C. H NMR (400 MHz, CDCl ) δ 8.20 (d, J =
3
8
.4 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.87–7.78 (m, 4H), 7.69–7.62 (m, 4H), 7.58 (t,
13
J = 7.2 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H); C{1H}NMR (100 MHz, CDCl
J = 130.7 Hz), 155.4 (d, J = 22.0 Hz), 136.8 (s), 133.4 (d, J = 11.1 Hz), 132.2 (d, J =
3.3 Hz), 129.7 (d, J = 110.5 Hz), 128.4 (d, J = 3.6 Hz), 127.1 (s), 124.9 (s), 122.3 (s).
3
) δ 165.6 (d,
1
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Benzo[d]thiazol-2-yldi(naphthalen-2-yl)phosphine Oxide (3af). Light red
1
solid, 58% yield (76.2 mg). Mp: 202–204 °C. H NMR (400 MHz, CDCl
3
) δ 8.61 (s,
1H), 8.57 (s, 1H), 8.22 (d, J = 8.0, 1H), 8.06–7.83 (m, 9H), 7.63–7.46 (m, 6H);
13
3
C{1H}NMR (100 MHz, CDCl ) δ 166.9 (d, J = 127.6 Hz), 155.5 (d, J = 21.6 Hz),
136.9 (s), 135.2 (d, J = 2.3 Hz), 134.3 (d, J = 9.9 Hz), 132.5 (d, J = 14.3 Hz), 129.2
s), 128.71 (s), 128.70 (d, J = 12.5 Hz), 128.1 (d, J = 109.6 Hz), 128.0 (s), 127.2 (s),
(
126.8 (d, J = 3.8 Hz), 126.7 (s), 126.5 (s), 124.9 (s), 122.2 (s).
Benzo[d]thiazol-2-yldicyclohexylphosphine Oxide (3ag). Beige solid, 66%
1
yield (68.5 mg). Mp: 161–162 °C. H NMR (400 MHz, CDCl
3
) δ 8.20 (d, J = 8.0 Hz,
1
H), 8.04 (d, J = 8.0 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.4 Hz, 1H),
2.40–2.23 (m, 2H), 2.20–2.09 (m, 2H), 1.90–1.53 (m, 10H), 1.46–1.14 (m, 8H);
13
3
C{1H}NMR (100 MHz, CDCl ) δ 167.0 (d, J = 99.0 Hz), 155.3 (d, J = 18.5 Hz),
136.9 (s), 126.5 (s), 126.3 (s), 124.4 (s), 122.2 (s), 36.3 (d, J = 67.0 Hz), 26.4 (d, J =
5
.4 Hz), 26.2 (d, J = 5.6 Hz), 25.8 (d, J = 0.9 Hz), 25.2 (d, J = 3.2 Hz), 24.7 (d, J =
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.2 Hz); P NMR (162 MHz, CDCl ) δ 47.03 (s); HRꢀMS (+ESI) calcd for
+
C
19
H
27NOSP [M + H] : 348.1546; found: 348.1545.
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Benzo[d]thiazol-2-yldibutylphosphine Oxide (3ah). White solid, 73% yield
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60
1
(
64.7 mg). Mp: 86–87 °C. H NMR (400 MHz, CDCl ) δ 8.18 (d, J = 8.0 Hz, 1H),
3
8
.05 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 7.2 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 2.23–2.11
(
m, 4H), 1.80–1.66 (m, 2H), 1.59–1.46 (m, 2H), 1.46–1.36 (m, 4H), 0.89 (t, J = 7.2
1
3
Hz, 6H); C{1H}NMR (100 MHz, CDCl
3
) δ 167.7 (d, J = 108.8 Hz), 155.1 (d, J =
0.1 Hz), 137.0 (s), 126.8 (s), 126.5 (s), 124.4 (s), 122.4 (s), 29.9 (d, J = 69.5 Hz),
4.1 (d, J = 15.2 Hz), 23.5 (d, J = 4.8 Hz), 13.7 (s).
2
2
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Ethyl Benzo[d]thiazol-2-yl(phenyl)phosphinate (3ai). Yellow liquid, 40%
1
yield (36.8 mg). H NMR (400 MHz, CDCl
3
) δ 8.21 (d, J = 8.4 Hz, 1H), 8.10–8.02 (m,
2
H), 8.00 (d, J = 8.0 Hz, 1H), 7.62–7.47 (m, 5H), 4.40–4.22 (m, 2H), 1.45 (t, J = 7.0
1
3
Hz, 3H); C{1H}NMR (100 MHz, CDCl
3
) δ 164.2 (d, J = 167.1 Hz), 155.1 (d, J =
2
4.0 Hz), 136.9 (s), 133.3 (d, J = 2.7 Hz), 132.3 (d, J = 10.4 Hz), 129.2 (d, J = 149.1
Hz), 128.8 (d, J = 14.2 Hz), 127.0 (s), 126.9 (s), 125.0 (s), 122.1 (s), 63.0 (d, J = 6.2
Hz), 16.6 (d, J = 6.4 Hz).
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Diethyl Benzo[d]thiazol-2-ylphosphonate (3aj). Yellow liquid, 22% yield
1
(
18.1 mg). H NMR (400 MHz, CDCl
3
) δ 8.26 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 8.0 Hz,
1H), 7.59 (t, J = 7.0 Hz, 1H), 7.54 (t, J = 7.4 Hz, 1H), 4.42–4.26 (m, 4H), 1.40 (t, J =
13
7
.0 Hz, 6H); C{1H}NMR (100 MHz, CDCl
3
) δ 160.1 (d, J = 238.6 Hz), 154.7 (d, J
= 28.5 Hz), 136.5 (s), 127.2 (s), 127.0 (s), 125.1 (s), 122.1 (s), 64.3 (d, J = 5.8 Hz),
6.4 (d, J = 6.4 Hz).
1
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(
4,5-Dimethylthiazol-2-yl)bis(4-fluorophenyl)phosphine Oxide (3kd). Light
1
yellow solid, 95% yield (99.8 mg). Mp: 129–130 °C. H NMR (400 MHz, CDCl
3
) δ
7
.93–7.84 (m, 4H), 7.16 (td, J = 8.7, 2.1 Hz, 4H), 2.44 (s, 3H), 2.42 (s, 3H);
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C{1H}NMR (100 MHz, CDCl ) δ 165.4 (dd, J = 254.3, 3.3 Hz), 158.4 (d, J = 140.1
3
Hz), 153.7 (d, J = 20.3 Hz), 134.4 (dd, J = 11.7, 9.0 Hz), 134.1 (s), 127.9 (dd, J =
3
1
1
12.9, 3.2 Hz), 116.1 (dd, J = 21.6, 13.9 Hz), 15.1 (s), 11.7 (s); P NMR (162 MHz,
+
CDCl
3 2
) δ 17.09 (s); HRꢀMS (+ESI) calcd for C17H15NOF SP [M + H] : 350.0580;
found: 350.0576.
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(4,5-Dimethylthiazol-2-yl)di(naphthalen-2-yl)phosphine Oxide (3kf). Pale
1
yellow solid, 71% yield (88.2 mg). Mp: 136–137 °C. H NMR (400 MHz, CDCl
3
) δ
8.54 (s, 1H), 8.50 (s, 1H), 7.95–7.88 (m, 6H), 7.86 (d, J = 8.0 Hz, 2H), 7.61–7.50 (m,
13
4
H), 2.43 (s, 6H); C{1H}NMR (100 MHz, CDCl
3
) δ 158.9 (d, J = 137.6 Hz), 153.6
(d, J = 20.0 Hz), 135.0 (d, J = 2.2 Hz), 134.0 (d, J = 9.6 Hz), 133.9 (s), 132.5 (d, J =
4.0 Hz), 129.1 (s), 129.0 (d, J = 109.4 Hz), 128.5 (s), 128.4 (d, J = 12.5 Hz), 127.9
1
(s), 127.0 (s), 126.6 (d, J = 11.1 Hz), 15.1 (s), 11.7 (s).
Typical Procedure for the Synthesis of 3aa in Acetonitrile or Acetic acid.
Benzothiazole (1a, 40.6 mg, 0.3 mmol), diphenylphosphine oxide (2a, 121.3 mg, 0.6
3 2
mmol), Mn(OAc) •2H O (241.3 mg, 0.9 mmol), and acetonitrile or acetic acid (2 mL)
were sequentially added at room temperature. The reaction mixture was heated with
stirring at 90 °C for 24 h. The reaction solution was concentrated in vacuo, and then
20 mL of saturated sodium bicarbonate solution was added, and the resultant solution
was extracted with ethyl acetate (3 × 15 mL). The combined organic layer was dried
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over MgSO
4
, filtered, and concentrated in vacuo. The residue was purified by silica
gel column chromatography using a petroleum ether/ethyl acetate mixture [from 5:1
to 1:1 (v/v)] as the eluent to give product 3aa.
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Typical Procedure for the Gram-Scale Synthesis of 3aa under Ball-Milling
Conditions. By following the general procedure for the synthesis of compound 3, the
reaction of 1a (0.81 g, 6 mmol), 2a (2.43 g, 12 mmol) with Mn(OAc)
8 mmol) under ballꢀmilling conditions for 1.5 h produced 3aa (1.90 g, 95%).
Scavenging Experiment with TEMPO under Ball-Milling Conditions. By
following the general procedure for the synthesis of compound 3, the reaction of 1a
40.6 mg, 0.3 mmol), 2a (121.3 mg, 0.6 mmol) with Mn(OAc) •2H O (241.3 mg, 0.9
3 2
•2H O (4.83 g,
1
(
3
2
mmol) in the presence of TEMPO (140.6 mg, 0.9 mmol) under ballꢀmilling conditions
for 1.5 h produced 4 (101.5 mg, 47%).
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2,2,6,6-Tetramethylpiperidin-1-yl diphenylphosphinate (4). Light yellow
1
solid, 47% yield (101.5 mg). Mp: 110–112 °C. H NMR (400 MHz, CDCl ) δ
3
1
3
7.89–7.82 (m, 4H), 7.50–7.39 (m, 6H), 1.36–0.80 (m, 18H); C{1H}NMR (100 MHz,
CDCl ) δ 134.0 (d, J = 135.3 Hz), 131.8 (d, J = 9.4 Hz), 131.7 (d, J = 2.5 Hz), 128.4
(d, J = 13.0 Hz), 61.7 (d, J = 2.5 Hz), 40.3 (s), 17.0(s); P NMR (162 MHz, CDCl
3.58 (s).
3
31
3
) δ
3
ACKNOWLEDGMENTS
We are grateful for financial support from the National Natural Science
Foundation of China (21372211).
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Supporting Information
The Supporting Information is available free of charge on the ACS Publications
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website at DOI: 10.1021/acs.joc.
NMR Spectra of Compounds 3aa-ma, 3ab-aj, 3kd, 3kf, 4 (PDF)
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