PhPOCl2as a potent catalyst for chlorination reaction of phenols with PCl5

Article abstract of DOI:10.1080/00397911.2016.1218897

Phenols are easily converted to the corresponding aryl chlorides by using phosphorus pentachloride (PCl₅) and a catalytic amount of phenylphosphonic dichloride (PhPOCl₂), which is a new efficient method for synthesis of aryl chloride in good yields.

Full text of DOI:10.1080/00397911.2016.1218897

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
PhPOCl2 as a Potent Catalyst for Chlorination
Reaction of Phenols with PCl5
Jiang Wu, Junpeng Zhou, Yalei Shi & Jintao Zhu
To cite this article: Jiang Wu, Junpeng Zhou, Yalei Shi & Jintao Zhu (2016): PhPOCl2 as a Potent
Catalyst for Chlorination Reaction of Phenols with PCl5, Synthetic Communications, DOI:
10.1080/00397911.2016.1218897
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1218897
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Date: 01 September 2016, At: 15:25

PhPOCl2 as A Potent Catalyst for Chlorination Reaction of Phenols with PCl5
Jiang Wu, Junpeng Zhou, Yalei Shi, Jintao Zhu
1Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou , China
Address correspondence to: Jintao Zhu Department of Chemistry, Zhejiang Sci-Tech
University, Hangzhou 310018, China, E-mail: zhujintao1968@163.com
Abstract
Phenols are easily converted to the corresponding aryl chlorides by using phosphorus
pentachloride (PCl5) and the catalytic amount of phenylphosphonic dichloride (PhPOCl2) ,
which is a new efficient method for synthesis of aryl chloride in good yields.
GRAPHICAL ABSTRACT:
KEYWORDS: chlorination reaction; phenols; aryl chloride; phosphorus pentachloride;
phenylp-hosphonic dichloride
1

INTRODUCTION
A series of chlorinated aromatic hydrocarbons are important intermediates for synthesis
of organic fine chemicals, such as dyes, drugs, and pesticides [1].They have versatile
applications in carbon-carbon bond-forming reactions, such as cross-coupling reaction
with organic boranes[2-4] and Grignard reaction with carbonyl compounds[5-7]. Very few
methods have been reported in the literature for converting phenols directly into
arylhalides. Bestmann’s team[8] have observed that chlorobenzene can be obtained from
phenol via a phenylchloroformate intermediate which produced by reaction with
phosgene. This intermediate can be treated with triphenylphosphine , producing
chlorobenzene in 67% yield by elimination of carbon dioxide. Moreover, Wiley[9] and
Heinz[10] have found that halogenated benzene could be prepared from phenol by using
triphenyl-phosphine dihalide. Recently, Bay and coworkers[11] have a discovery that
phenylphosphorus tetrachloride (PPTC) is an excellent reagent for converting phenol into
chlorobenzene. But in these above cases, expensive stoichiometric phosphorus-based
halogenating agents are used, which reduce their atom efficiency and complicate the
purification process. Since the generation of phenylphosphine oxides as a stoichiometric
by-product is inevitable in the process, the development of a more efficient protocol still
remains highly important and challenging. Now in our work, we have developed a novel
system for chlorination to increase atom efficiency which is applicable to a wide range of
phenols. In the process, PCl5 is used as chlorination reagent under the catalysis of
PhPOCl2 to afford the target product. The amount of the PhPOCl2 is around 10 mol% of
the substrate. The reactions were described in Scheme 1.
2

RESULTS AND DISCUSSION
We began our study with 2-methoxyphenol as a model substrate. POCl3, SOCl2, PCl5 or
PhPOCl2 was used as chlorination reagents which were cheap and generally available in
laboratory, but the results showed that 2-chloroanisole was obtained in very poor yield.
While Ph3PCl2, Ph3PCl4, Ph3P/CCl4 were used in this reaction, complex mixtures were
formed in most cases. In the course of our trial, we were lucky enough to find 2-
methoxyphenol could be converted 2-chloroanisole by treatment with the mixture of PCl5
and PhPOCl2. Moreover, in the late of our work we were surprised to find that a high
yield for the chlorination of 2-methoxyphenol (Table 1) could be maintained when
decreasing the molar ratio of the mixed reagent (PhPOCl2/PCl5), and the optimal catalyst
loading was 10 mmol%. It seemed that the PhPOCl2 plays a role as catalyst in the
reacting system.
To validate this assumption, 2-Methoxyphenol was treated with PCl5 alone (Table 1,
entry 2), nothing was happened. When it was treated with PhPOCl2 only (Table 1, entry
1), no target product was found, and yet a new substance appeared. The compound could
then be isolated and proven to be phenylphosphonic acid diphenylester (PhPO(OPhOMe-
o)2). To our surprised, 2-chloroanisole was isolated in high yield while PhPO (OphOMe-
o)2 was heated with PCl5. Base on the above experiments, a mechanism was proposed for
the reaction of phenols with PCl5 and PhPOCl2 (Scheme 2). The PhPOCl2 reacted with
phenols to give phenyl phosphate diester(A), A was then reacted with PCl5 to form the
intermediate B, which can decomposed to yield the desired aryl chloride and
3

phenylphosphineoxid(C). Finally, PhPOCl2 was reformed from compound C by reaction
with PCl5. Meanwhile, we investigated the effects of the amount of chlorinating agent
based on the above reaction mechanism. Taking 2-methoxyphenol as a model substrate,
the results were showed in Table 2. The yield didn’t improve dramatically by increasing
the amount of chlorinateing agents. As a consequence, the optimal molar ratio for
substrate/PCl5/PhOPOCl2 is (1 : 1.1 : 0.11).
Reaction condition: 2-methoxyphenol (100 mmol), Reaction temperature: 160℃, reaction
time: 5h; b n1 : n2 : n3= n(Substrate) : n ( PCl5) : n (PhPOCl2)
Then the optimized reaction conditions were tested on a variety of substrates, and our
results showed that the substituted phenols readily undergone hydroxyl displacement.
These data were recorded in Table 3.
Reaction condition: Substrate (100 mmol); Reaction temperature: 160℃, reaction time:
5h; The Molar ratio of Substrate/ PhPOCl2 /PCl5 is (1.0:0.11:1.1); a the molar ratio of
Substrate/ PhPOCl2 /PCl5 is (1.0:0.33:3.3).
Phenols containing electron-withdrawing groups or electron-donating groups could be
converted into the corresponding aryl chloride in high yield by our methods(entries 1-5).
And the hydroxyl of pyridine derivatives (entries 8,9,10,11) were also effectively
replaced by chloride group. In addition, the carboxyl group on the aromatic ring (entries
6,7,10,11) was easily converted into trichloromethyl group in the meantime, which were
4

consistent with the results of H. B. Chen and Y.B. LIN’s work in terms of carboxyl
group[12]
.
CONCLUSION
In conclusion, the present investigation has demonstrated that the use of PhPOCl2 /PCl5
offers a simple, novel, efficient and convenient method for the conversion of phenols to
their corresponding aryl chlorides.
EXPERIMENTAL
The 1HNMR spectra were recorded on AVANCE AV (400MHz) FTNMR Digital
spectrometer with CDCl3 as the solvent, TMS as the internal standard; the IR spectra
were measured on a Nicolet Vatar 370 spectrometer with KBr film; the mass spectra were
obtained with Agilent GC: 6890N/MS:5973I. All the chemicals were of analytical grade
or chemically pure. Products (a-j) are known compounds and their spectral data can be
found in the literature[13-21]
.
General Procedure (Taking The Synthesis Of Compound I As An Example)
A mixture of 2-Hydroxypyridine-3-carboxylic acid (100.0 mmol), phenylphosphonic
dichlo-ride (33.0 mmol) and phosphorus pentachloride (330.0 mmol) was slowly heated
to 160 °C while distilled the by-product (POCl3). Then the mixture was stirred at the
same temperature for 5 hours. TLC analysis showed the reaction had been finished. The
POCl3 was evaporated in vacuum and the residue was poured into ice water, and it was
5

neutralized with saturated aqueous sodium carbonate solution, and extracted with acetic
ether. The organic layer was washed with water, dried over anhydrous sodium sulfate,
and then concentrated under reduced pressure , the obtained crude product was distilled
or purified with silica gel chromatograph.
2-Chloro-3-Trichloromethylpyridine (Compound I)
R=COOH, X=N, yield:72.0%.1HNMR (400 MHz, CDCl3) δ: 8.51 (t, J = 6.6 Hz, 2H),
7.39 (dd, J = 7.9, 4.8 Hz, 1H). IR (KBr) ,ν,cm-1: 1564.0 (C=C), 1074.6 (C-Cl). 759.6 (-C-
Cl3). GC-MS, m/z: 231.0 [M]+, 194.0 [M- Cl]+, 159.1[M-2Cl]+ , 124.1 [M-3Cl]+, 97.1[M-
4Cl]+ .
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7

Table 1. Effect of Phenylphosphonic dichloride on the reaction to aryl chlorides a
Entry
Substrate
molar ratio e
0.0:1.0 b
1.0:0.0 c
1.0:0.05 d
1.0:0.1 d
1.0:0.2 d
1.0:0.5 d
1.0:1.0 d
yield %
0.0%
1
2
3
4
5
6
7
2-Methoxyphenol
2-Methoxyphenol
2-Methoxyphenol
2-Methoxyphenol
2-Methoxyphenol
2-Methoxyphenol
2-Methoxyphenol
0.0%
42.1%
73.0%
72.7%
73.5%
72.8%
a Reaction condition: 2-methoxyphenol (100 mmol ), reaction temperature: 160℃,
reaction time: 5h; b PCl5(0 mmol) , PhPOCl2 (125 mmol ); c PCl5(125 mmol) , PhPOCl2 (0
mmol); d PCl5(125 mmol); e Molar ratio is PCl5/ PhPOCl2 .
8

Table 2 Effect of chlorinating agent on the reaction
b
n1 : n2 : n3
1:0.8:0.08
60.3
1:0.9:0.09
72.9
1:1:0.1
74.4
1:1.1:0.11
73.3
1:1.2:0.12
72.5
Yield/%
9

Table 3 Substrate Scope
Entry Starting
material
Product
yield %
75.4
76.3
1
2
73.3
79.4
76.3
3
4
5
6
64.9 a
7
54.6 a
96.5
8
94.6
9
72.0 a
70.5 a
10
11
CCl
3
Cl
N
10

Scheme 1. Synthesis of chloroaromatics from phenols catalyzed by PhPOCl2.
11

Scheme 2. Possible mechanism of phosphorus-based catalytic reaction
12