COPPER(II) CHLORIDE

1

Copper(II) Chloride

CuCl

2

[7447-39-4]

CuCl

2

(MW 134.45)

InChI = 1/2ClH.Cu/h2*1H;/q;;+2/p-2/f2Cl.Cu/h2*1h;/q2*-1;m/

rCl2Cu/c1-3-2

InChIKey = ORTQZVOHEJQUHG-NFHYJNRTCJ
(·2H

2

O)

[10125-13-0]

Cl

2

CuH

4

O

2

(MW 170.48)

InChI = 1/2ClH.Cu.2H2O/h2*1H;;2*1H2/q;;+2;;/p-2/f2Cl.Cu.2H

2O/h2*1h;;;/q2*-1;m;;/rCl2Cu.2H2O/c1-3-2;;/h;2*1H2

InChIKey = MPTQRFCYZCXJFQ-FBUIOTBGCV

(chlorinating agent; oxidizing agent; Lewis acid)

Physical Data:

anhydrous: d 3.386 g cm

−3

; mp 620

◦

C (reported

mp of 498

◦

C actually describes a mixture of CuCl

2

and CuCl);

partially decomposes above 300

◦

C to CuCl and Cl

2

; dihydrate

d

2.51 g cm

−3

; mp 100

◦

C.

Solubility:

anhydrous: sol water, alcohol, and acetone; dihydrate:

sol water, methanol, ethanol; mod sol acetone, ethyl acetate; sl
sol Et

2

O.

Form Supplied in:

anhydrous: hygroscopic yellow to brown

microcrystalline powder; dihydrate: green to blue powder or
crystals; also supplied as reagent adsorbed on alumina (approx.
30 wt % CuCl

2

on alumina).

Analysis of Reagent Purity:

by iodometric titration.

70

Purification:

cryst from hot dil aq HCl (0.6 mL g

−1

) by cooling

in a CaCl

2

–ice bath.

71

Handling, Storage, and Precautions:

the anhydrous solid should

be stored in the absence of moisture, since the dihydrate is
formed in moist air. Irritating to skin and mucous membranes.

Original Commentary

Nicholas D. P. Cosford
SIBIA, La Jolla, CA, USA

Chlorination of Carbonyls.

Copper(II) chloride effects

the α-chlorination of various carbonyl functional groups.

1

The

reaction is usually performed in hot, polar solvents containing
Lithium Chloride, which enhances the reaction rate. For example,
butyraldehyde is α-chlorinated in DMF (97% conversion, eq 1)
while the same reaction in methanol leads to an 80% yield of the
corresponding α-chloro dimethyl acetal (eq 2).

2

H

O

H

O

Cl

CuCl

2

(1)

DMF, ∆

97%

H

O

OMe

OMe

Cl

CuCl

2

(2)

MeOH, ∆

80%

The process has been extended to carboxylic acids, anhydrides,

and acid chlorides by using an inert solvent such as sulfolane.

3

4-Oxo-4,5,6,7-tetrahydroindoles are selectively α-chlorinated,

allowing facile transformation to 4-hydroxyindoles (eq 3).

4

The

ability of the reaction to form α-chloro ketones selectively has
been further improved by the use of trimethylsilyl enol ethers
as substrates.

5

Recently, phase-transfer conditions have been

employed in a particularly difficult synthesis of RCH(Cl)C(O)Me
selectively from the parent ketones (eq 4).

6

N

O

N

O

Cl

R

R

CuCl

2

(3)

aq AcOH, ∆
R = Ts, 86%
R = Bn, 81%

CuCl

2

, H

2

O

EtNH

3

NO

3

(4)

R = Me(CH

2

)

n

, n = 2–5, 8

R

O

R

O

Cl

C

5

H

5

N(CH

2

)

15

MeCl

n

= 4, 70%

Chlorination of Aromatics. Aromatic systems may be chlori-

nated by the reagent. For example, 9-chloroanthracene is prepared
in high yield by heating anthracene and CuCl

2

in carbon tetrachlo-

ride (eq 5).

7

When the 9-position is blocked by a halogen, alkyl,

or aryl group, the corresponding 10-chloroanthracenes are formed
by heating the reactants in chlorobenzene.

8,9

Under similar condi-

tions, 9-acylanthracenes give 9-acyl-10-chloroanthracenes as the
predominant products.

10

Polymethylbenzenes are efficiently and

selectively converted to the nuclear chlorinated derivatives by
CuCl

2

/Alumina (eq 6).

11

H

R

Cl

R

(5)

R = H, Me, Ph, Ac

CuCl

2

∆

CuCl

2

, Al

2

O

3

(6)

Cl

PhCl, ∆

82%

Reactions with Alkoxy and Hydroxy Aromatics. Hydroxy

aromatics such as phenols and flavanones undergo aromatic
nuclear chlorination with copper(II) chloride.

12

Thus heating 3,

5-xylenol with a slight excess of the reagent in toluene at 90

◦

C

gave a 93% yield of 4-chloro-3,5-xylenol (eq 7).

13

2-Alkoxynaph-

thalenes are similarly halogenated at the 1-position.

14

Attempted

reaction of CuCl

2

with anisole at 100

◦

C for 5 h gave no prod-

ucts; in contrast, it was found that alkoxybenzenes were almost
exclusively para-chlorinated (92–95% para:0.5–3% ortho) using
CuCl

2

/Al

2

O

3

(eq 8).

15

Anisole reacts with benzyl sulfides in

the presence of equimolar CuCl

2

and Zinc Chloride to give

anisyl(phenyl)methanes (para:ortho = 2 : 1, eq 9).

16,17

Avoid Skin Contact with All Reagents

2

COPPER(II) CHLORIDE

OH

OH

(7)

Cl

CuCl

2

PhMe, ∆

93%

OEt

Cl

OEt

CuCl

2

, Al

2

O

3

OEt

(8)

Cl

94%

+

<0.5%

PhCl, ∆

OMe

Bn

OMe

CuCl

2

, ZnCl

2

OMe

Bn

(9)

2:1

+

BnSMe, ∆

53%

Reactions with Active Methylene-containing Compounds.

9-Alkoxy(or acyloxy)-10-methylanthracenes react with CuCl

2

to

give coupled products (eq 10), while the analogous 9-alkoxy(or
acyloxy)-10-benzyl(or ethyl)anthracenes react at the alkoxy or
acyloxy group to afford 10-benzylidene(or ethylidene)anthrones
(eq 11).

18

The reactions are believed to proceed via a radical

mechanism.

CuCl

2

OR

O

CH

2

OR

CH

2

(10)

R = Me, Ac

(11)

CuCl

2

OCH

2

R

CH

2

R

O

CHR

R = Me, Ph

Under similar conditions, 9-alkyl(and aryl)-10-halogeno-

anthracenes give products resulting from replacement of the
halogen, alkyl, or aryl groups with halogen from the CuCl

2

.

19

Boiling toluene reacts with CuCl

2

to yield a mixture of phenyl-

tolylmethanes.

20

Lithium enolates of ketones

21

and esters

22

undergo a coupling

reaction with copper(II) halides to afford the corresponding 1,4-
dicarbonyl compounds. Thus treating a 3:1 mixture of t-butyl
methyl ketone and acetophenone with Lithium Diisopropylamide
and CuCl

2

gives a 60% yield of the cross-coupled product (eq 12).

1. LDA

2. CuCl

2

O

Ph

O

O

Ph

O

+

3:1

60%

(12)

The intramolecular variant of this reaction producing carbo-

cyclic derivatives has been reported.

23

Copper(II) chloride

catalyzes the Knoevenagel condensation of 2,4-pentanedione
with aldehydes and tosylhydrazones (eq 13).

24

The reagent also

catalyzes the reaction of various 1,3-dicarbonyls with dithianes
such as benzaldehyde diethyl dithioacetal to give the correspond-
ing condensation products (eq 14).

25

O

O

O

O

CuCl2

THF, 25 °C

R

O

R

NNHTs

R

+

or

(13)

R = alkyl, aryl

48–95%

R

O

O

R

O

O

Ph

CuCl

2

THF, 25 °C

R = Me, 65%

R = OEt, 46%

+

(14)

Ph

SEt

SEt

Catalyst for Conjugate Additions. The catalytic effect of

copper(II)

chloride

on

the

1,4-addition

of

β

-dicarbonyl

compounds to (arylazo)alkenes

26,27

and aminocarbonylazo-

alkenes

28,29

has been studied in some detail. The reactions pro-

ceed at ambient temperature in THF and afford the corres-
ponding pyrrole derivatives (eq 15). This mild method requires
no other catalyst and succeeds with β-diketones, β-ketoesters, and
β

-ketoamides. Copper(II) chloride also catalyzes the addition of

water, alcohols, phenol, and aromatic amines to arylazoalkenes
(eq 16).

30

X

O

O

CuCl

2

THF, 25 °C

+

(15)

R

1

N

N

R

3

R

2

N

NHR

1

R

3

R

2

O

X

X = alkyl, aryl, OR, NHR
R

1

= Ar, ArNHCO

R

2

, R

3

= alkyl, aryl, CO

2

R

ArNH

2

+

R

1

N

N

R

3

R

2

CuCl

2

THF, 25 °C

R

1

N

H

N

NHAr

R

2

R

3

(16)

R

1

, R

2

, R

3

= Ar

Oxidation and Coupling of Phenolic Derivatives.

In the

presence of oxygen, copper(II) chloride converts phenol deriva-
tives to various oxidation products. Depending on the reaction
conditions, quinones and/or coupled compounds are formed.

31

Several groups have examined different sets of conditions
employing CuCl

2

to favor either of these products. Thus

2,3,6-trimethylphenol was selectively oxidized to trimethyl-p-
benzoquinone with CuCl

2

/amine/O

2

as the catalyst (eq 17),

32

while 2,4,6-trimethylphenol was converted to 3,5-dimethyl-4-
hydroxybenzaldehyde using a catalytic system employing either
acetone oxime or amine (eq 18).

33,34

A list of General Abbreviations appears on the front Endpapers

COPPER(II) CHLORIDE

3

OH

O

O

76.7%

+

0.9% coupled product

CuCl

2

, O

2

Et

2

NH

(17)

ROH, 25 °C

OH

O

O

(18)

OH

CuCl

2

, O

2

Me

2

CNOH

ROH, 25 °C

CHO

+

85.6%

6.1%

The oxidation of alkoxyphenols to the corresponding quinones

has been studied,

35

and even benzoxazole derivatives are oxi-

dized by a mixture of copper(II) chloride and Iron(III) Chloride
(eq 19).

36

A CuCl

2

/O

2

/alcohol catalytic system has been used for

the oxidative coupling of monophenols.

37

O

N

O

N

Et

Et

CuCl

2

, FeCl

3

HCl, H

2

O, EtOH

(19)

O

HO

O

OH

∆

94%

Copper(II) amine complexes are very effective catalysts

for the oxidative coupling of 2-naphthols to give symmetri-
cal 1,1

′

-binaphthalene-2,2

′

-diols.

38

Recent work has extended

this methodology to the cross-coupling of various substituted
2-naphthols.

39,40

For example, 2-naphthol and 3-methoxy-

carbonyl-2-naphthol are coupled under strictly anaerobic condi-
tions using CuCl

2

/tert-Butylamine in methanol to give the un-

symmetrical binaphthol in 86% yield (eq 20).

CuCl

2

, t-BuNH

2

MeOH, ∆

(20)

OH

OH

CO

2

Me

OH

OH

CO

2

Me

+

86%

Other ligands such as methoxide are also effective; a mecha-

nistic study indicates that the selectivity for cross- rather than
homo-coupling is dependent upon the copper:ligand ratio.

41

A 1:1

mixture of 2-naphthol and 2-naphthylamine is cross-coupled with
CuCl

2

/benzylamine to give 2-amino-2

′

-hydroxy-1,1

′

-binaphthyl

(68% yield, eq 21).

42

The cross-coupled products from these

reactions are important in view of their use as chiral ligands for
asymmetric synthesis.

(21)

NH

2

OH

NH

2

OH

+

CuCl

2

, t-BuNH

2

MeOH, ∆

68%

Dioxygenation of 1,2-Diones. 1,2-Cyclohexanedione deriva-

tives have been converted to the corresponding 1,5-dicarbonyl
compounds by oxidation with O

2

employing copper(II) chloride

as the catalyst.

43

More recently, CuCl

2

–Hydrogen Peroxide has

been used to prepare terminal dicarboxylic acids in high yield.

44

While 1,2-cyclohexanedione afforded α-chloroadipic acid in 85%
yield, 1,2-cyclododecanedione was converted to 1,12-dodecane-
dioic acid in 47% yield under identical conditions (eq 22).

O

O

HO

2

C

CO

2

H

1. CuCl

2

, H

2

O

2

MeOH, H

2

O, 20 °C

47%

( )

10

(22)

2. H

2

SO

4

Addition of Sulfonyl Chlorides to Unsaturated Bonds. The

addition of alkyl and aryl sulfonyl chlorides across double and
triple bonds is catalyzed by copper(II) chloride.

45

–

51

The reac-

tion appears to be quite general and proceeds via a radical chain
mechanism. The 2-chloroethyl sulfones produced in the reac-
tion with alkenes undergo base-induced elimination to give vinyl
sulfones (eq 23).

45

–

48

1,3-Dienes similarly react, yielding 1,4-

addition products (eq 24) which may be dehydrohalogenated to
1,3-unsaturated sulfones.

45,49

+

PhSO

2

Cl

(23)

Ph

Ph

SO

2

Ph

1. CuCl

2

, MeCN, ∆

87%

2. NEt

3

PhSO

2

Cl

Cl

SO

2

Ph

CuCl

2

(24)

+

100 °C

62%

The stereoselectivity of the addition to alkynes can be con-

trolled by varying the solvent or additive, and thus favoring either
the cis or trans β-chlorovinyl sulfone.

50,51

For example (eq 25),

when benzenesulfonyl chloride is reacted with phenylacetylene in
acetonitrile with added triethylamine hydrochloride, the trans:cis
ratio is 92:8, while the same reaction performed in CS

2

without

additive favors the cis isomer (16:84).

Ph

Cl

SO

2

Ph

Ph

Ph

SO

2

Ph

Cl

(a) or (b)

+

PhSO

2

Cl

(25)

+

(a) = CuCl

2

, NEt

3

HCl, MeCN

(b) = CuCl

2

, CS

2

trans:cis = 92:8
trans:cis = 16:84

trans

cis

100 °C

Acylation Catalyst. N-Trimethylsilyl derivatives of (+)-bor-

nane-2,10-sultam (Oppolzer’s chiral sultam) and chiral 2-oxazoli-
dinones (the Evans chiral auxiliaries) are N-acylated with a
number of acyl chlorides including acryloyl chloride in reflux-
ing benzene in the presence of CuCl

2

.

52

The N-acylated products

were prepared in high yields; the method does not require an aque-
ous workup, making it advantageous for large-scale preparations.

Avoid Skin Contact with All Reagents

4

COPPER(II) CHLORIDE

Racemization Suppression in Peptide Couplings. A mixture

of copper(II) chloride and Triethylamine catalyzes the forma-
tion of peptide bonds.

53

Furthermore, when used as an addi-

tive, CuCl

2

suppresses racemization in both the carbodiimide

54

and mixed anhydride

55

peptide coupling methods. Recently it

was shown that a combination of 1-Hydroxybenzotriazole and
CuCl

2

gives improved yields of peptides while eliminating

racemization.

56,57

Reaction with Palladium Complexes.

π

-Allylpalladium

complexes undergo oxidative cleavage with copper(II) chloride
to form allyl chlorides with the concomitant release of PdCl

2

(eq 26).

58

Pd

CuCl

2

Cl

Cl

2

(26)

EtOH

85%

This methodology has been used in the dimerization of allenes

to 2,3-bis(chloromethyl)butadienes.

59

1,5-Bismethylenecyclo-

octane was transformed into the bridgehead-substituted bicyclo
[3.3.1]nonane system using CuCl

2

/HOAc/NaOAc, while the same

substrate produced bicyclo[4.3.1]decane derivatives (eq 27) with
a Palladium(II) Chloride/CuCl

2

catalytic system.

60

(27)

CuCl

2

HOAc

NaOAc

PdCl

2

, CuCl

2

LiCl, O

2

, HOAc

X

X

X

X = Cl, OAc

While reaction of a steroidal π-allylpalladium complex with

AcOK yields the allyl acetate arising from trans attack, treatment
of a steroidal alkene with PdCl

2

/CuCl

2

/AcOK/AcOH gave the

allyl acetate arising from cis attack.

61

Reoxidant in Catalytic Palladium Reactions.

Copper(II)

chloride has been used extensively in catalytic palladium chem-
istry for the regeneration of Pd

II

in the catalytic cycle. In particu-

lar, the reagent has found widespread use in the carbonylation of
alkenes,

62

–

64

alkynes,

65

and allenes

66,67

to give carboxylic acids

and esters using PdCl

2

/CuCl

2

/CO/HCl/ROH, and in the oxida-

tion of alkenes to ketones with a catalytic PdCl

2

/CuCl

2

/O

2

system

(the Wacker reaction).

68

The PdCl

2

/CuCl

2

/CO/NaOAc catalytic

system has been used in a mild method for the carbonylation of
β

-aminoethanols, diols, and diol amines (eq 28).

69

O

R

1

N

O

R

2

OH

R

2

R

1

HN

PdCl

2

, CuCl

2

(28)

CO, NaOAc

Cyclopropanation with CuCl

2

2

2

–Cu(OAc)

2

2

2

Catalyst. Ethyl

Cyanoacetate reacts with alkenes under CuCl

2

–Copper(II)

Acetate catalysis to give cyclopropanes.

72

Thus heating cyclo-

hexene in DMF (110

◦

C, 5 h) with this reagent combination gives

a 53% yield of the isomeric cyclopropanes. The reaction also pro-
ceeds with styrene, 1-decene, and isobutene. Byproducts formed
from the addition to the alkene are removed with Potassium Per-
manganate.

First Update

Pauline Pei Li
Hong Kong Polytechnic University, Kowloon Hong Kong,
P. R. China

Copper(II) Chloride-catalyzed Oxidation of Hydrocarbons

with Molecular Oxygen.

Oxidation of Hydrocarbons to Alcohols and Ketones. A com-

bination of CuCl

2

and a crown ether is an efficient catalytic

system for the aerobic oxidation of alkanes in the presence of
acetaldehyde.

73,74

For example, oxidation of cyclohexane in the

presence of CuCl

2

(2.5 × 10

−4

mol %), 18-crown-6 (2.5 ×

10

−4

mol %), and acetaldehyde (10 mol %) at 70

◦

C under O

2

at 1 atmosphere gave cyclohexanone (61% yield based on ac-
etaldehyde) and cyclohexanol (10%). This catalytic system has
high turnover number of 1.62 × 10

4

for the aerobic oxidation of

cyclohexane (eq 29). The presence of crown ether forms a com-
plex with copper ions which enhances the catalytic activity of the
copper chloride. Thus, the CuCl

2

-18-crown-6 complexes catalyze

oxidation of acetaldehyde with molecular oxygen to give peracid.
The reaction of copper complexes with peracid then gives the
oxo-copper intermediate. Hydrogen abstraction of alkane by the
oxo-copper complex, followed by oxygen transfer yields the cor-
responding alcohol. The alcohol suffers further oxidation to the
corresponding ketone under the reaction conditions.

+

CH

3

CHO, O

2

(1 atm)

CuCl

2

, CH

2

Cl

2

, 70 °C

18-crown-6

O

OH

61%

10%

(29)

A highly catalytic bimetallic system for the low temperature

selective oxidation of methane, ethane, and butane with oxygen
as the oxidant has been reported.

75

The catalytic system con-

sists of a mixture of copper chloride and metallic palladium in
a 3:1 mixture (v/v) of trifluoroacetic acid-water in the presence
of oxygen and carbon monoxide. For example, methane can be
selectively converted to methanol at 80–85

◦

C for 20 h in a bomb

(eq 30), pressurized to 200 psi with carbon monoxide, 1200 psi
with methane, then 1300 psi with oxygen. An increase in reac-
tion temperature significantly increases the rate of methane to
methanol conversion. The rate of formation of methanol is ca.
65 × 10

−4

M min

−1

at 145–150

◦

C.

CH

4

CH

3

OH

CuCl

2

(0.1 mmol)

5% Pd on carbon

H

2

O/CF

3

CO

2

H

CO/O

2

80–85 °C, 20 h

(30)

A list of General Abbreviations appears on the front Endpapers

COPPER(II) CHLORIDE

5

For oxidation of ethane and n-butane under similar oxidation

conditions, products derived from C–C bond cleavage compete
with or dominate those derived from C–H bond cleavage on a
per bond basis. The overall transformation encompasses three
catalytic steps: (1) Pd-catalyzed reaction between CO and H

2

O to

form CO

2

and H

2

; (2) Combination of H

2

and O

2

to yield hydrogen

peroxide; and (3) Cu-catalyzed oxidation of the alkane by hydro-
gen peroxide. This catalytic system shows interesting synergism,
in that the principle role of metallic Pd is to generate hydrogen
peroxide in situ, and the CuCl

2

activates hydrogen peroxide for

oxidation of the substrates.

This catalytic system has been extended to the hydroxylation

of remote primary C–H bonds of various acids, alcohols, and
aliphatic halides.

76

For example, propionic acid can be converted

to 3-hydroxypropionic acid in 22% yield (eq 31). This catalytic
system exhibits two important features: (1) Reactions are very
specific, and only hydroxylation is observed; further oxidation
to aldehyde and carboxylic acid does not occur; (2) C–C bond
cleavage and overoxidation can be minimized under suitable
conditions.

CuCl

2

/Pd on carbon

CO/N

2

/O

2

(200 psi/800 psi/100 psi)

CF

3

COOH/H

2

O

75 °C, 18 h

CH

3

CH

2

C

O

OH

HO CH

2

CH

2

C

O

OH

(31)

Copper(II) Chloride-catalyzed Oxidation of Hydrocarbons

with tert-Butyl Hydroperoxide.

Oxidation of Allylic Compounds. Allylic oxidation reaction of

various types steroids have been preformed in the presence
of t-butyl hydroperoxide (t-BuOOH) catalyzed by copper(I),(II)
or copper metal.

77

For example, allylic oxidation of the 

5

-3β-

acetoxy steroid (1) was catalyzed with CuCl

2

in the presence of

t

-BuOOH at 50–55

◦

C for 20 h to give 81% yield of 2 (eq 32). No

oxidation is detected in the absence of copper catalyst.

O

AcO

AcO

O

O

t

-BuOOH/CuCl

2

CH

3

CN/N

2

50–55 °C

(32)

1

2

Oxidation of Alkynes to α

α

α

,β

β

β

-Acetylenic Ketones.

Various

alkynes have been converted to the corresponding α,β-acetylenic
ketones by oxidation with oxygen and t-BuOOH using copper(II)
chloride as the catalyst (eq 33).

78

The catalytic system gives

both high conversion and selectivity in the formation of the α,β-
acetylenic ketones. This selectivity results from rapid oxidation of
the intermediate acetylenic alcohol, RC=CCH(OH)R

′

, to ketone

under the reaction conditions. The resulting acetylenic ketone is
deactivated from further oxidation.

R

1

C C C R

2

H

H

CuCl

2

·2H

2

O

R

1

C C C

O

R

2

t

–BuOOH/t–BuOH

70 °C, O

2

(33)

R

1

=H, aliphatic, or aromatic group

R

2

=aliphatic group

Copper(II) chloride not only catalyzes the decomposition of

t

-BuOOH, but also plays a key role in converting the acetylenic

alcohol intermediates to α,β-acetylenic ketones. To obtain both
high conversion and selectivity towards α,β-acetylenic ketones,
optimal reaction conditions are determined to be CuCl

2

·2H

2

O:

alkyne:t-BuOOH in a 1:25:50 ratio in t-BuOH at 70

◦

C under an

oxgen atmosphere. The reaction has broad substrate applicability,
where R and R

′

can be a variety of aliphatic or aromatic groups

(Table 1).

The oxidation to the α,β-acetylenic ketone proceeds with both

high conversion and selectivity. The only major side-product
after 24 h is the acetylenic alcohol. If a longer reaction time is
employed, this side-product is completely converted to the α,β-
acetylenic ketone. Alkyne reactivities correlate with the ease of
C–H atom abstraction. Symmetric internal aliphatic alkynes, such
as 3-hexyne, 4-octyne, and 5-decyne, give excellent conversion
and selectivity for ketone formation. The aliphatic chain length
has little effect on the reactivity and selectivity. Unsymmetrical
internal aliphatic alkynes, such as 3-heptyne and 4-nonyne,
afford a pair of acetylenic ketones with approximately equal
distribution, indicating that the system cannot distinguish between
the two chemically similar α-CH

2

groups of the substrate.

However, the oxidation of 2-decyne is regiospecific, yield-
ing 2-decyn-3-one in 70% yield with no C–H abstrac-
tion from the C-1 methyl group. Terminal acetylenes also
yield acetylenic ketones although the substrate reactivity is
diminished. Besides the aliphatic alkynes, aromatic alkynes
such as 1-phenyl-1-pentyne can be oxidized to the corres-
ponding conjugated acetylenic ketone in good yield. The reac-
tion conditions can also be employed for oxidation of other related
substrates, such as cis-cyclooctene, which yields 3-cyclooctenone
with lower selectivity. Adjacent carboxylate groups severely
inhibit the alkyne reactivity. No apparent substrate oxidation
is observed for methyl-2-octynoate or 2-octynoic acid after
24 h. By contrast, 3-hexyn-2,5-diol is rapidly converted to
3-hexyn-2-ol-5-one in high yield with some further oxida-
tion to 3-hexyn-2,5-dione. Acetylenic alcohols, while not
typically as reactive as 3-hexyn-2,5-diol, are still activated
for further reaction to acetylenic ketones. However, like acetylenic
esters or acids, the acetylenic ketones are strongly deactivated.

Avoid Skin Contact with All Reagents

6

COPPER(II) CHLORIDE

Table 1

Oxidation of alkynes catalyzed by CuCl

2

·2H

2

O/t-BuOOH under oxygen

a

Substrate

Conv.

b

(%)

Product

Yield

c

(%)

CH

3

CH

2

C≡CCH

2

CH

3

91

CH

3

C(O)C≡CCH

2

CH

3

59

3-hexyne

CH

3

(CH

2

)

2

C≡C(CH

2

)

2

CH

3

99

CH

3

CH

2

C(O)C≡C(CH

2

)

2

CH

3

74

4-octyne

CH

3

(CH

2

)

3

C≡C(CH

2

)

3

CH

3

95

CH

3

(CH

2

)

2

C(O)C≡C(CH

2

)

3

CH

3

66

5-decyne

CH

3

CH

2

C≡CCH

2

CH

2

CH

3

100

CH

3

C(O)C≡CCH

2

CH

2

CH

3

37

3-heptyne

CH

3

CH

2

C≡CC(O)CH

2

CH

3

31

CH

3

(CH

2

)

2

C≡C(CH

2

)

3

CH

3

99

CH

3

CH

2

C(O)C≡C(CH

2

)

3

CH

3

39

4-nonyne

(CH

2

)

2

C≡C(O)(CH

2

)

2

CH

3

37

CH

3

C≡C(CH

2

)

6

CH

3

84

CH

3

C≡CC(O)(CH

2

)

5

CH

3

70

2-decyne

HC≡C(CH

2

)

5

CH

3

61

HC≡CC(O)(CH

2

)

4

CH

3

51

1-octyne

C

6

H

5

C≡C(CH

2

)

2

CH

3

85

C

6

H

5

C≡C(O)CH

2

CH

3

78

1-phenyl-1-pentyne

C

5

H

11

C≡CCOOCH

3

No reaction

Methyl-2-octynoate

C

5

H

11

C≡C-COOH

No reaction

2-Octynoic acid

97

O

42

cis

-Cyclooctene

CH

3

CH(OH)C≡CCH(OH)CH

3

d

100

CH

3

C(O)C≡CCH(OH)CH

3

65

3-hexyn-2,5-diol

CH

3

C(O)C≡C(O)CH

3

15

a

Reaction conditions: CuCl

2

·2H

2

O:substrate:t-BuOOH = 1:25:50 (molar ratio). Reaction was carried out at 70

◦

C under O2.

b

Conversion was determined by GC analysis using an internal standard, t-butylbenzene. By-products were mainly acetylenic alcohol.

c

Isolated yield.

d

10 h reaction.

Oxidation of Poly(Methyl styrene).

Anionic or cationic

poly(methyl styrene) (PMS) latex particles can be functionalized
via oxidation of the benzylic methyl group to the corresponding
aldehyde and carboxylic acid in water. The oxidation of PMS
latex dispersion has been achieved using t-butyl hydroperoxide
as an oxidant catalyzed by a small amount of copper(II) chloride
under air (Scheme 1).

79

–

83

The oxidation mechanism involves

initial copper(II) chloride-catalyzed decomposition of t-BuOOH
to both t-BuO

·

and t-BuOO. radicals. These reactive radicals

abstract benzylic hydrogens to generate benzylic radicals, which
are oxidized to the corresponding aldehyde groups under air. Since
the aldehyde groups are easily oxidized to the carboxylic acid
under the oxidative conditions, a mixture of aldehyde and car-
boxylic acid functionalities result. The distribution of these two
functional groups can be controlled by varying reaction con-
ditions such as concentration of t-BuOOH, type of surfactant,
reaction temperature, and time. Since the CuCl

2

/t-BuOOH/O

2

is an effective system for benzylic C–H oxidation in aqueous

CH

3

C

12

H

25

SO

3

−

Na

+

CH

3

H

3

C

H

2

C

CH

3

H

3

C

CH

3

H

3

C

CH

3

CHO

H

3

C

H

3

C

CHO

COOH

H

3

C

COOH

H

3

C

CuCl

2

/t

–BuOOH

H

2

O, 60 °C, air

CuCl

2

/t

–BuOOH

H

2

O/t–BuOH

60 °C, air

AIBN/CTAB

60 °C

K

2

S

2

O

8

, 80 °C

V–50, 70 °C

emulsion polymerization

Scheme 1

A list of General Abbreviations appears on the front Endpapers

COPPER(II) CHLORIDE

7

media, it is environmentally benign. This aqueous functionaliza-
tion method for opens up a new route to the preparation of a
potentially large class of functionalized latex particles, which may
find useful applications in various fields.

Related Reagents. Chlorine; N-Chlorosuccinimide; Cop-

per(I) Chloride; Copper(II) Chloride–Copper(II) Oxide; Iodine–
Copper(II) Chloride Copper(I) Chloride–Oxygen; Copper(I)
Chloride-Tetrabutylammonium Chloride Copper(I) Chloride–
Sulfur Dioxide Iodine– Aluminum(III) Chloride–Copper(II)
Chloride;

Iodine–Copper(I)

Chloride–Copper(II)

Chloride;

Methylmagnesium Iodide– Copper(I) Chloride; Palladium(II)
Chloride–Copper(I) Chloride; Palladium(II) Chloride–Copper(II)
Chloride; Phenyl Selenocyanate–Copper(II) Chloride; Vinyl-
magnesium

Chloride–Copper(I)

Chloride;

Zinc–Copper(I)

Chloride

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Avoid Skin Contact with All Reagents

8

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A list of General Abbreviations appears on the front Endpapers