Substitutive aromatic fluorination with chlorine pentafluoride

Journal of Fluorine Chemistry, 25 (1984)

435-446

435

Received: September30,1983;accepted: March24,1984

SUBSTITUTIVE AROMATIC FLUORINATION WITH CHLORINE PENTAFLUORIDE*

MAX M. BOUDAKIAN** AND GENE A. HYDE

Olin Chemicals, New Haven, Connecticut 06511 (U.S.A.)

SUMMARY

In contrast to limited substitutive fluorination of aromatics with halogen fluorides such as ClF, ClF3, BrF3 and IF5, fluorination is the predominant reaction path with ClF5. Under non-catalytic liquid phase conditions, benzene was converted to fluorobenzene (54% yield) and chlorobenzene (37% yield), respectively. For a heterocyclic substrate, i.e. 2,4,6-trifluoropyrimidine,substitutive fluorination predominated over chlorination. Three possible fluorinationmechanisms are discussed. A transition complex of ClF5 with benzene is favored. Enhanced exchange fluorination of Ccl& was effected with C1F5 (CF2C12>>CFC13>CF3C1)as compared with ClF3 (CFC13"CF$12).

INTRODUCTION

Growing applications for ring fluorinated aromatics [l] have created much interest in the development of new synthesis techniques. While early direct aromatic substitutionwith fluorine (F2) gave violent reactions involving ring scission, addition, coupling and polymerization,new fluorination techniques have been developed in recent years: molecular fluorine [2-51; xenon fluorides [6]; high valency metal fluorides such as silver difluoride [7,8] or cobaltic trifluoride [8]; organic hypofluorites

*

Based on an earlier presentation: 'Liquid Phase Aromatic Fluorination With Chlorine Pentafluoride,'162nd American Chemical Society Meeting, Washington, D.C.

September 1971. Paper No. 6 (Division of Fluorine

Chemistry) **

Rochester, New York 14611 (U.S.A.)

0022-1139/84/$3.00

OElsevier Sequoia/Printed in The Netherlands

436 such as CF30F 19,101 or CH3C02F [ll]; ionic hypofluorites such as CsS04F or RbS04F [12,13]; NFqBF41141; and, anodic fluorination by controlled potential electrolysis (151. With halogen fluorides such as ClF, ClF3, BrF3 and IF5, and aromatics, substitutive fluorination has been a minor reaction path (Table 1).

TABLE 1

Substitutive Aromatic Halogenation With Halogen Fluorides

Interhalogen

Substitution Product

Ref.

ccl4

C6H5C1

16

Solvent

Substrate

ClF

C6H6

C1F3

C6H6 'gHF5

BrF3

C6H6 'gHF5

ccl4

C6H5C1'C6H5F

17

HF

C6C1F5

18

CH3CN

C6H5BrF2

19

CFC12CF2C1;

C6BrF5

20

C6H51"C6H5F;

21

HF/S02C1F C6H6

IF5

C6H4FI 1,3,5-C3H3F3 'gHF5

Inert

22

Inert

22

Of the above halogen fluorides, C1F3 (or modifications) has been the most intensively studied reagent with aromatics. Ellis and Musgrave [17 a-c] established that substitutive chlorination predominated over fluorination when benzene was reacted with C1F3 (CC14 solvent) under catalytic (e.g. CoF2) or non-catalytic conditions in a steel reactor. (Side reactions such as ring addition, coupling and tar formation contributed to low yields). F

Cl

2.0

0 I

\

+ C1F3

,::,

L

6

>

4

(l)

/

(1)

(11)

431 A later modification discovery

of the ClF3-benzene

[23 a-c] that difluorochloronium

addition

of Lewis acids,

substitutive

fluorobenzene

ion, ClF2+

(generated

e.g. BF 3, to give ClF2+BF4-),

fluorination.

found that fluorinated

system was Pavlath's

In contrast,

aromatics,

Yakobson

by

enhanced

et al. [18,22] recently

e.g. 1,3,5_trifluorobenzene,

penta-

and 4-H-heptafluorotoluene,

do not undergo substitutive + aromatic fluorination with C1F2 + , BrF2+, BrF4+ and IF salts. 4 A major advance in recent halogen fluoride chemistry was the discovery of the new interhalogen, of alternate

synthesis

substitutive conditions

chlorine routes

halogenation

pentafluoride,

124-281.

patterns

and the rapid development

A study was undertaken

of ClF

5

with benzene

to assess

under 'liquid-phase'

[29].

RESULTS AND DISCUSSION

Substitutive

Fluorination

Substitutive non-catalytic

of Benzene With Chlorine

halogenation

Pentafluoride

studies with benzene

were conducted

under

in CC14 solvent at low and high C1F5

conditions

concentrations. At -low C1F5 concentrations nearly arising

from aromatic

over chlorination fluorobenzene

substitution

as evidenced

+

In contrast negligible

evidence

C1F5

showed no evidence

are reminiscent exchange substrate

between

Fluorination

(Table III).

3N2 17 cc14 O0

f

C1F3-benzene

examination

CC14),

predominated yields of

(I), respectively.

for side reactions

Infrared

N2:16.8

for as products

by 53.8% and 36.5% corrected

to the corresponding

polymerization.

C6H6:3.0

benzene was accounted

(II) and chlorobenzene

2.75

-134')

(1.0 C1F5:2.75

all (97%) of the consumed

arising

(II) >

system

1171, there was

from addition,

of the cold traps

of chlorofluoromethanes.

of Ellis and Musgrave's

findings

(2)

(I)

coupling

or

c-15', -78' and

(The latter observations 117 a,b] that halogen

Ccl4 and C1F3 did not occur if a more easily halogenated

such as benzene was present).

438 Attempts

failed

concentrations' benzene

to enhance

(1.0 ClF5:1.3

was consumed,

products

the maximum

products.

fluorination

CC14).

higher

to the absence

to further

competitive

fluorinate

fluorobenzene

was completely

consumed

catalyst/Ccl4

solvent),

were

Likewise,

the reaction

formed.

in complete

were found.

conversion

(Similar inability

liquid phase conditions

Grakauskas:

product

that

to non-volatile at low C1F5

Ccl4 exchange

polymer

formation

distribution

Substitutive

of p-difluorobenzene

fluorine

stoichiometry,

products

and C1F3

no substitution

to effect poly-substitutive

products

fluorination

(F2) were noted by

appreciable

was noted; at higher molar

was reversed

Fluorination

with C1F3 (CoF2 and addition

of the substrate;

with molecular

at low F2/benzene

to give polyfluoro-

117 bl found that, while

upon reaction

only R-chlorofluorobenzene

and minor

represented

of (II) suggests

by conversion

Ellis and Musgrave

is not surprising.

fluorobenzene

under

While all of the for as substitution

of chlorofluoromethanes

C1F5 levels effected

ClF5

to give CC13F and CC12F2).

The inability

resulted

at h&$

(5.2% yield)

The absence

of the latter was followed

(In contrast

concentrations,

N2:8.4

g- and/or P-Difluorobenzene

degree of fluorination.

generation

benzenes

C6H6:Z.O

fluorination

only 32.4% could be accounted

(Table IV).

in-situ --

substitutive

substitution

ratios,

this

[2]).

of 2,4,6-Trifluoropyrimidine

With Chlorine

Pentafluoride In contrast exhibit

slightly

sluggish

different

fluorination

pyrimidine

benzenes,

behavior

evidenced

toward halogen

(33.9% conversion)

(fluorination

path:

again predominating)

of the perfluorocyclic by quantitative

heterocyclics

fluorides.

For example,

was noted when 2,4,6-trifluoro-

2,4,5,6_tetrafluoropyrimidine

5-chloro-2,4,6_trifluoropyrimidine cleavage

fluorinated

was reacted with C1F5 in FLUORINERW

halogenation reaction

to fluorinated

Liquid

FC-75.

represented

Substitutive

a minor

(IV), 14.8% yield

(V), 8.7% yield

(corrected).

(corrected); (Ring

ether solvent by C1F5 is not possible

recovery

as

of FC-75 and C1F5 after 120 hours at 25').

F 7 ,I\ 'N

+

ClF5 c;;60

)

FaF

>

F&F

(3)

F

(III)

F

Cl

(IV)

QJ)

439

Mechanism

At least three potential fluorination paths could be considered.

(a) Fluorination via ClF, Dissociation -I Fluorination could arise from ClF5 dissociation products at O":

O0

ClF5

ClF3 +

/

F2

(4)

(5)

However, the negligible rate of ClF5 dissociation up to 200' (16 hours) reported by Bauer and Sheehan [30] does not support this mechanism.

(b) Self-Ionizationof C1F5 Self-ionizationof ClF5 to generate ClF4* as the active fluorinating species represents another reaction path: 2ClF5

ClF4+ +

+

ClF6-

(6)

This sequence does not appear likely. Meinert and Gross established the following order of decreasing self-ionizationwithin the halogen fluorides: BrF3>IF5>BrF5>C1F3>ClF51311. Moreover, the use of CC14 solvent, a medium of low dielectric constant employed in the substitutive fluorination of benzene, would not favor self-ionizationof ClF,.

(c) Transition Complex A transition complex with the aromatic ring was proposed by Musgrave for the non-catalyzed reaction of ClF3 and benzene 117 cl.

o+ oH .

U I

,

+

C1F3

-

0

_.F--C1F2 *

F

I

I' -

0

+HF+C:I

440 ClF would then erve as a chlorinating agent, in agreement with the likely ci5apolarization, Cl-F, to give chlorobenzene,as previously demonstrated by Gambaretto, et al. [16]. (A potential intermediate in Musgrave's transition complex mechanism could be C6H5C1F2. Nesmeyanov, et

[19] formed

phenylbromosodifluoride,C6H5BrF2, from benzene and BrF3/acetonitrile). A modified transition complex mechanism proceeding via an arenium cation could be envisaged for the correspondingnon-catalyzed ClF5-benzene system: + (I

a-

ClF3 generated from the above sequence would then participate by the Musgrave transition complex path with benzene depicted in equation (7) [17 c] 1321.

,Reaction of Chlorine Fluorides With Carbon Tetrachloride

ClF5 effected exchange fluorination of CC14 (absence of aromatic substrate) to give a mixture of chlorofluoromethanes: CF2C12>>CECL3 >CE3Cl (Table 2). The corresponding study by Ellis and Musgrave for C1F3 and CC14 gave chlorofluoromethanesof a lesser degree of fluorimation: CFC13>>CF2C12 117 b].

TABLE 2

Reaction of Chlorine Fluorides With CC14

Chlorine Fluoride

Ref.

ClF5

This Study

C1F3

117 b]

Molar Ratio CIFx CC14 N? 1.0

Temp.

Time (hr)

00

1.5

13.2

3.0

1.0

11.0

3.4

O"

6.8

1.0

10.7 4.1

25'

8.4

Molar Ratio CF,Cl CF2C12 CFC13_ 1.0

7.5

1.3

(--)

(--)

1.0

(--)

1.0

7.0

441

EXPERIMENTAL

Reagents

ClF5 Benzene,

(IR assay, > 99%) was prepared Baker & Adamson

Mallinckrodt prepared

(A.R. Grade).

FC-75, mainly

was obtained

15% Igepal CO880-Chromosorb

temp., 210°; detector

and

from 3M Co.

W (80/100 mesh);

75-250" at lO'/min.;

injection

temp., 210'; flow rate, 7 sec./l0

2,4,6_trifluoropyrimidine:

temp., 160'; flow rate, 6.3 sec./l0

column, port

cc.

15% SE30-Chromosorb

3 m., l/4 in.; column temp., 60"; injection

detector

[34].

perfluoro-(2-g-butyltetrahydrofuran)

2 m., l/4 in. i.d.; column temp.,

column,

(gc, 99.9%) was

Chromatography

ClF5 with benzene:

C1F5 with

tetrachloride,

and KF in sulfolane

perfluoro-(2-z-propyltetrahydropyran),

Gas Liquid

Carbon

2,4,6_Trifluoropyrimidine

from 2,4,6_trichloropyrimidine

FLUORINER'I@ Liquid

from KC1 and F2 [28 a,b].

(Reagent ACS Grade).

W (SO/l00 mesh);

port temp., 150";

cc.

Apparatus

The reactor was an adaptation [35] for gas-liquid

reactions

gauze 'micro-bubble' avoids

a high speed

The design

stirrer.

high spots and permits

of a type described

featuring

rapid mixing

features

by Miller,

et al

(3500 rpm) wire

of this apparatus

of the gaseous

and liquid

phases.

General

Fluorination

The substrate brought

Procedure

was mixed with

up to speed

(15 min.) and ClF5 flow started Cold traps reactor.

(-lS", -78O and -134O,

(15 min.),

to warm

in the individual

to 25".

(0') and the stirrer

(after nitrogen respectively)

At the end of the fluorination,

with nitrogen allowed

the solvent

The system was flushed with nitrogen

(3500 rpm).

flow had stabilized). were attached

the ice-bath

removed

and the reactor

The reaction

mixture

was processed

experiments.

to the

the system was again flushed contents

as described

442 Reaction

of Benzene with ClF5

(a) ClF5

Low ClF, Concentration J (0.0575 Mol, 7.50 g) was fed at a rate of 7.5 g/hr diluted

with nitrogen 65 standard

(C1F5 flow rate:

cc/min)

12.34 g) dissolved reactor.

in CC14

The reaction

100 ml of saturated

determined

TABLE

of benzene

(162 g) was successively

sodium bicarbonate

sulfate.

identical

ccfmin; N2 flow rate:

(0') solution

(0.964 Mol, 159.5 g) contained

mixture

aqueous

dried over magnesium productshad

21.5 standard

into a cooled

infrared

1:3

(0.1580 Mel, in a glass

treated with

(2 x), water

(3x) and

(The crude and treated reaction Product

spectra).

by GLC and mass spectroscopy

composition

was

(Table 3).

3

Low ClF5 Concentration:

Fluorination

of Benzene by C1F5

Starting Materials C1F5

0.0575

(moles)

Benzene cc14

(moles)

0.1580

(ml)

Molar Ratio Benzene

100 (Benzene/ClF5)

Consumed

2.7511

(moles)

0.0842

Moles

Corrected Yield

Fluorobenzene

0.0453

53.8%

R-Chlorofluorobenzene

0.0034

4.0%

-o-Chlorofluorobenzene

0.0022

2.6%

Chlorobenzene

0.0307

36.5%

C6H4F2,

Traces

--_

Products

Moles

C6H3F3 and C6H3C1F2

(Out)

0.0816

% Accountability (Based on benzene

96.9%

consumed)

443 IR spectroscopy no evidence Fractionation

showed significant

2:4 with nitrogen 60 standard

rate:

gave 1.23 g (0.0118 Mol) of SiF

(ClF5 flow rate:

cc/min)

4'

etching.

High ClF, Concentration -I (0.1795 Mol, 23.41 g) was fed at an average

C1F5 diluted

(combined wt, 6.58 g) showed

CF2C12 or CFC13; only CC14, C6H6 and SiF4 were present.

(-40°) of the trap contents

The glass reactor

(b)

of the cold trap contents

of CF3C1,

into a cooled

rate of 15.6 g/hr

45 standard

(0') solution

c∈

N2 flow

of benzene

(0.2338 Mol, 18.26 g) dissolved

in Ccl4

(1.50 Mol, 233.0 g) contained

The reaction

mixture

(231 g) was treated with potassium

a copper reactor. fluoride

(17 g) to remove HF.

assay identified compounds

the components

were also present

A combination

of mass spectral

listed in Table 4.

in trace quantities;

in

and GLC

At least 17 other

benzene

accountability

was only 32.4%.

TABLE

4

High C1F5 Concentration:

Starting C1F5

Fluorination

of Benzene

Materials 0.1795

(moles)

Benzene Ccl4

0.2338

(moles)

150

(ml)

Molar Ratio Benzene

by C1F5

1.30/l

(Benzene/C1F5)

Consumed

0.2338

(moles)

Moles

Products

___

Fluorobenzene

Corrected Yield

_--

-o- and/or pDifluorobenzene

0.0121

5.2%

pChlorofluorobenzene

0.0127

12.7%

g-Chlorofluorobenzene

0.0090

3.9%

Chlorobenzene

0.0298

5.4%

Dichlorobenzene

0.0121

5.2%

Moles

0.0757

(Out)

32.4%

% Accountability (Based on benzene

consumed)

444 IR spectroscopy showed

of the cold trap contents

the presence

contained

of 2,4,6_Trifluoropyrimidine

C1F5

(0.0519 Mol,

cc/min)

treated with

into a glass reactor

fluoropyrimidine

14.8%;

of Carbon

Chlorine

reactor. CC14.

a solution

(containing

dispersed

assayed

(0.0772 Mol,

1:3 with nitrogen

(c h aracteristic

Mol;

and

FLUORINERT@

(C1F5 flow rate:

of initial

19 standard

mixture

cc/min)

to 0' in a glass

(147 g) indicated

99.8 Mel %

(combined wt, 9.64 g)

(CF2C12>CFC13>CF3C1), along with trace amounts -1 bands at 732 and 786 cm ). IR and mass spectroscopy

product CF3C1,

Liquid

120 hr/25'

volatiles

8.7%.

identical

gave the following 0.00995

2,4,5,6-tetre-

10.07 g) was fed at a rate of

GLC assay of the -40°, -134O and -196O traps

of C1F5

2,4,6-tri-

Pentafluoride

(1.0195 Mol, 157 g) cooled

VPC assay of the reaction

Liquid

solids) was

by GLC:

yields:

With Chlorine

1:3

60

(O") of

20.16 g) and FLUORINERT@

33.9%; corrected

Tetrachloride

tetrachloride

were qualitatively

after

containing

5-chloro-2,4,6_trifluoropyrimidine,

pentafluoride

6.7 g/hr diluted into carbon

mixture

cc/ruin; N2 flow rate:

KF and the solution

conversion,

fluoropyrimidine,

Reaction

(0.150 Mol,

The reaction

anhydrous

KF.

6.77 g) was fed at a rate of 6.7 g/hr diluted

2,4,6_trifluoropyrimidine (538 g).

with anhydrous

With ClF5

(C1F5 flow rate: 19 standard

with nitrogen

FC-75

The trap contents

HF (5.10 g, 0.2549 Mol) based on treatment

Reaction

standard

(combined wt, 26.01 g)

of CC14, CC13F and CC12F2.

distribution:

CF2C12,

0.0587 Mol; CFC13,

0.00785 Mol. FC-75 was inert

in a KEL-F@

gave quantitative

reactor. recovery

to C1F5 Vacuum

of C1F5.

charge) was found by IR spectroscopy

(3.1/l molar

transfer

ratio)

(O") of the

The residual

liquid

to be identical

(98%

to FC-75.

REFERENCE8

1

M. M. Boudakian, Encyclopedia New York,

2

of Chemical

and D. Eckroth

Technology,

1980,CFluorinated

V. Grakauskas, therein.

in M. Grayson

Aromatic

J. Org. Chem., 35

(Editors),

Kirk-Othmer:

Vol. 10, 3rd edn, J. Wiley, ComPounds,'p.

901.

(1971) 723 and references

cited

445 3

N. B. Kaz'mina

L. S. German,

Akad. Nauk SSSR, 194 4

S. Misaki,

I. D. Rubin and I. L. Knunyants,

Dokl,

(1970) 1329.

J. Fluorine

Chem., -21 (1982) 191 and references

cited

therein. 5

F. Cacace,

6

R. Filler,

P. Giacomello

and A. P. Wolf, J. Am. Chem. Sot., -101 (1980)

3511. Israel .I. Chem., 17

H. Schroeder, 8

(1978) 71.

J. Am. Chem. Sot., -82 (1960) 4115.

A. Zweig, R. G. Fischer

and .I. E. Lancaster,

J. Org. Chem., g

(1980)

3597. 9 10

R. Hesse,

Israel J. Chem., 17

J. Kollonitsch, 92

L. Barash

(1978) 60.

and G. A. Doldouras,

J. Am. Chem. Sot.,

(1970) 7494.

0. Lerman,

Y. Tor and S. Rosen,

12

S. Stavber

and M. Zupan, J. Chem. Sot. Chem. Commun.

13

D. P. Ip, C. D. Arthur,

11

Chem. Sot., 103

J. Org. Chem., 66

R. B. Winans

(1981) 4629.

C. J. Schack and K. 0. Christe,

J. Fluorine

15

A. N. Rozhkov,

and I. L. Knunyants,

A. V. Bukhtiarov

Nauk SSSR, Ser. Khim., 16

G. P. Gambaretto

17

a.

(1972) 1130.

and M. Napoli,

J. Fluorine

Chem., 1 (1976) 569.

b.

J. F. Ellis and W. K. R. Musgrave,

ibid (1953) 1063.

c.

W. K. R. Musgrave,

Advances

in Fluorine

(1950) 3608.

Chem., 1 (1960) 21.

G. G. Furin and G. G. Yakobson,

J. Fluorine

Chem.,

(1983) 67.

A. N. Nesmeyanov,

A. N. Vanchikov,

and T. P. Tolstaya, 20

(1981) 363. Isv. Akad.

J. Chem. Sot.,

23 19

Chem., s

J. F. Ellis and W. K. R. Musgrave,

V. V. Bardin,

J. Am.

(1981) 1964.

14

18

(1981) 148.

and E. H. Appelman,

T. W. Bastock, J. Fluorine

I. N. Lisichkina,

Dokl. Akad. Nauk SSSR, 254

M. E. Harley,

N. S. Khruscheva

(1980) 652.

A. E. Pedler and J. C. Tatlow,

Chem., 5 (1975) 331.

21

0. Ruff and R. Heim, 2. anorg. allgem.

22

V. V. Bardin,

Chem., -201 (1931) 245.

G. G. Furin and G. G. Yakobson,

Zh. Org. Khim., -16

(1980) 1256. 23

a. b.

C.

A. E. Pavlath,

(1961).

A. E. Pavlath

and A. J. Leffler,

Aromatic

ACS Monograph

No. 155, Reinhold,

N.Y., 1962.

A. E. Pavlath, Division

24

U.S. Pat. 2,993,937

Abstracts,

of Organic

Fluorine

133rd ACS Meeting,

Chemistry.

Compounds,

p. 7. San Francisco.

April 1958, Paper No. 99.

D. F. Smith, Science, -141 (1963) 1039.

446 25

R. Gatti, R. L. Krieger,

J. E. Sicre and H. J. Schumacher,

J. Inorg.

Nucl. Chem., -28 (1966) 655. 26

G. Pilipovich,

27

W. Maya and H. F. Bauer, U.S. Pat. 3,354,646

28

G. A. Hyde and M. Boudakian

29

ual,

Inorg. Chem., 6 (1967) 1918.

1 (1968) 2648.

a.

Inorg. Chem.,

b.

U.S. Pat. 3,388,970

The term, 'liquid-phase' may be a misnomer. 2

(1968). fluorination,

(See J. M. Tedder,

(1961) 112 for interpretation

F2 with organic aromatics:

F 2 solubility

an essentially

'heterogeneous

interface

the gaseous

solution."

makes

process'

reagent

system Chem.,

in Fluorine

fluorination

of

for recent studies with 'liquid phase' fluorination occurring

is bubbled

at the gas-liquid

through

the substrate

151

30

H. Bauer and D. F. Sheehan,

31

H. Meinert

and U. Gross, J. Fluorine

32

Generation

of difluorochloronium

agent

for the ClF5-benzene Advances

of 'liquid-phase' Likewise

substrates).

"....low

when

(1967).

Inorg. Chem., 5 (1967) 1736.

[23], from by-products

fluorination

path.

Chem., 2 (1972/73) 381. + , an aromatic fluorinating

ion, C1F2

HF and C1F3, represents

Hyman,

et,

+HF

ah

another

1331 have reported

the following

equilibrium: C1F3 33

T. Surles, L. A. Quaterman

34

M. M. Boudakian

35

W. T. Miller,

(1973174)

C1F2+

+

HF2

and H. H. Hyman, J. Fluorine

Chem., 2

293. and C. W. Kaufman,

J. 0. Stoffer,

sot., -86 (1964) 51.

U.S. Pat. 3 314 955 (1967).

G. Fuller

and A. G. Currie,

J. Am. Chem.