Perfluoroalkylation of thiols. Evidence for a radical chain process

Journal of Fluorine Chemistry, 24

191

(1984)19l--203

Received: March14,1983;accepted: May 8,1983

PERFLUOROALKYLATION OF THIOLS. PROCESS

EVIDENCE FOR A RADICAL CHAIN

ANDREW E. FEIRING Central Research & Development Department, E. I. du Pont de Nemours & Company, Experimental Station, Wilmington, Delaware 19898 (U.S.A.) SUMMARY Perfluoroalkyl sulfides are formed from primary or secondary perfluoroalkyl iodides and aromatic or aliphatic thiolates without UV irradiation.

Perfluoroalkyl radicals are

intermediates as demonstrated by inhibition and trapping studies. INTRODUCTION The perfluoroalkylation of aromatic, heteroaromatic,and aliphatic thiols by perfluoroalkyl iodides has been described in a series of papers tl].

The reactions were generally conducted

in liquid ammonia under UV irradiation.

Although the yields

were generally quite good, the somewhat inconvenient experimental procedure prompted this study of the perfluoroalkylation reaction under different reaction conditions including the use of phase transfer procedures.

After completing this work,a

separate report appeared on the phase transfer catalyzed perfluoroalkylation of thiols [21.

In contrast to the earlier re-

ports, I find that the perfluoroalkylation reactions proceed satisfactorily in organic solvents or under phase transfer conditions without UV irradiation.

I also describe radical trap-

ping studies which support a radical chain mechanism for this process. 0022-1139/83/$3.00

OElsevier Sequoia/Printed inTheNetherlands

192

RESULTS

The perfluoroalkyl of the perfluoroalkyl zene or c-butane Alternatively,

sulfides

iodides

thiol

&e-k%

in DMF under

the same sulfides

stirring

a solution

ammonium

hydroxide

with

+

with

the sodium

normal

-

by reaction salt of ben-

laboratory

prepared

or methylene

Results

RS-M+

prepared

lighting.

by vigorously

in 40% aqueous

a benzene

iodide.

were

2 were

of the thiols

of the perfluoroalkyl Rf1

&-e

tetrabutyl

chloride

are summarized

solution

in Table

1.

RfSR R = Ph, Rf="--C6F13

&

Rf = "-CsF15

&

R = Ph

&I

&

Rf = "_C8Fl,

&

R = "-C4H9

&I, R = Ph, Rf="-C8F17

;tr;Rf = i-C3F,

R = Ph, Rf=i-C3F.,

&f

&!I R = fl-C4Hg,Rf="CSF17 Using &

either

and ,$k could

(entries much

2,5).

better

as cosolvent sulfide

using

be achieved

give better

(entries

modest

results

sulfide

procedure.

procedure

(entries

of the alkyl substantial

higher

chloride

perfluoroalkyl amounts

of

isolated

appeared

to

8,9).

benzenethiol. with

gave

than methylene

Here the DMF conditions

and the unsaturated

gave consistently

rather

sulfides

to UV irradiation

and di-_n-butyldisulfide

of the secondary

together

resorting

lower with iodide

of the aryl

catalyzed

Yields

1,2).

procedure.

only with yield

without

benzene

distinctly

Reactions studied

using

perfluoroalkyl

either

good yields

The phase-transfer

results

,@ were

unreacted

procedure,

perfluoroalkyl The product

substantial sulfide

yields

,I,_% were

Jr; was obtained

amounts

,$,. Again

iodide

in

of diphenyldithe DMF procedure

of 2% than the phase

transfer

193

(CP3)2c~1

+

PhS-

B

(CF3)2CFSPh

+

(PhS), L

+

% CF3CF=CFSPh % Addition of three equivalents of styrene to the reaction of the primary iodides with benzenethiolate in DMF or under phase transfer conditions resulted in complete inhibition of the perfluoroalkylation process.

Both the perfluoroalkyl

iodide and styrene could be recovered unchanged.

In contrast,

addition of norbornene to the reaction resulted in the formation of the 2-iodo-3-perfluoroalkylnorbornane to the normal product 2.

2% in addition

A control experiment established

that 2 was not formed from & and norbornene under the reaction conditions in the absence of thiolate.

Similarly, reaction of

the secondary iodide ,+I; with benzenethiolate gave JK!, $,and the norbornene adduct ?k.

2%Rf

= n-CSF17

V? Rf = i-C3F7

To compare these results with my earlier work on the perfluoroalkylation of the 2-nitropropyl anion 171,

perfluoro-

octyl iodide (,&) was allowed to react with an excess equimolar mixture of sodium benzenethiolate and lithium 2-nitropropanide in DMF.

The product mixture was the perfluorooctyl phenyl sul-

fide (JQ) plus a small amount of the unreacted iodide J-Q. No 2-perfluorooctyl-2-nitropropane

(6) was detected.

PhS No

PhS No

C6F131 (0.02)

C8F171 (0.02)

DMF DMF

C8F171 (0.02) PhS Na(0.031)

C8F171 (0.02) PhS Na(0.025)

C8F171 (0.02) C4H9S N(Bu)~(O.O~~)C~H~/H,O

DMF

C8F171 (0.02) PhS Na(0.025)

(0.02) C6H6/H20

(0.02) C6H6/H20

(0.02) C6H6/H20

PhS No

C6F131 (0.02)

Solvent

PhS N(Bu)4 (0.02) CH2C12/H20

Thiolate(mole)

C6F131 (0.02)

Entry RfI(mole)

Reaction of PerfluoroalkylIodides with Thiolates

Table 1.

25"C/2.5 hr

4O"C/4 hr

25'C/4 hr

Norbornene(O.1) 25"C/17 hr

Styrene (0.075) 25'C/17 hr

25"C/17 hr

Norbornene(O.1) 25'C/5 hr

Styrene (0.06) 25“C/17 hr

-

Additive(mole) Conditions

(7)

C8F171 (47)

(C4HgSj2 (35)

C8F17SC4Hg (12)

C8F171 (16)

2-Iodo-3-Perfluorooctylnorbornane (6)

PhSC8F17 (77)

NO REACTION

C8F171 (5)

PhSC8F17 (92) [90]

C8F171 (46)

2-Iodo-3-Perfluorooctylnorbornane (7)

(W2

PhSC8F17 (30)

NO REACTION

PhSC6F13 1761

C6F131 (41)

(PhS)2 (11)

PhSC6F13 (48) 1441

Product (gc yield)[isolatedyield]

25'C/17 hr

PhS Na(0.024) DMF

14

N02Li(0.024)

(cH3)2c=

Norbornene(O.1) 25'C/17 hr

(CF3)2CFI(0.025) PhS Na(0.025) DMF

13

(C8F171 (0.010)

25"C/17 hr

(CF3)2CFI(0.025) PhS Na(0.025) DMF

12

25"C/4 hr

(CF3)2CFI(O.O25) PhS.N(Bu)4(0.025)C6H6/H20 Norbornene(O.1) 25'C/4 hr

-

25'C/17 hr

11

c~H~/H~~

DMF

(CF~)~CFI (0.025) Phs ~(~~)4(0.025)

C8Fl71 (0.04) C4HyS Na(0.046)

10

9

02Nc(cH3)2c8F17 LO1

PhSC8F17 [891

2-Iodo-3-(perfluoroisopropyl)norbornane (24)

CF3CF=CFSPh (16)

(PhS)2 (31)

PhSCF(CF3)2 (27)

CF3CF=CFSPh (6)

(PhS)2 (16)

PhSCF(CF3)2 (76) [401

2-Iodo-3-(perfluoroisopropyl)norbornane (30)

CF3CF=CFSPh (10)

(PhS)2 (57)

PhSCF(CF3)2 (3)

CF3CF=CFSPh (15)

(PhS)2 (71)

PhSCF(CF3)2 (14)

c8F171 (47)

(c4HyS)2 (15)

c8F17Sc4Hy (36) [351

196

DISCUSSION The perfluoroalkylation nucleophilic

displacement

[31 to be quite

reaction

resistant

here

itiated

is described

fluoroalkyl

a new anion

transfer

radical

radical.

considered

is likely

chain

of the anion

which

adds

Electron

iodide

perfluoroalkyl

anion

radical

RfF

+

gives

to pro-

[4] as ap-

process

from the thiolate

to the perfluoroalkyl iodide

This

1.

Decomposjtion

iodide.

ates a perfluoroalkyl giving

on a substrate

a facile

The SRRl process

11,21. in Scheme

by one electron

involving

to such processes,

ceed by an SRN 1 mechanism plied

of thiols,

is in-

to the per-

radical

qener-

to the thiolate

transfer

from this

the product

and a new

to continue

anion species

a chain

process.

RfI

+

RfI-

PhS-----+

Rf

+

RfI

+

Scheme

PhS-

Rf.

+

I-

p>

RfSPh'

RfSPh= -----+

RfI;

+

RfSPh

1

The involvement the substitution

of primary

process

clearly

supported

Styrene

inhibits

the process

radicals

sulting

radical

benzyl

an iodine

atom

perfluoroalkyl

radicals

of the 1-iodoperfluoroalkanes

by the results

perfluoroalkyl

stract

PhS'

with

added

by efficiently

formed

olefins

S is not sufficiently

is (Scheme

scavenging

in the initiation

2).

the

step.

reactive

in

The reto ab-

from RfI or add to RS- to continue

an

197

efficient chain process.

Norbornene addition of the per-

fluoroalkyl radical to the olefin generates a reactive secondary alkyl radical Q,. This species can abstract an iodine atom from RF1 to form 2 and a new perfluoroalkyl radical.

Addition

of RF1 to norbornene is known to proceed readily using traditional radical initiators 151.

It is interesting to note that

the overall reaction of RfI with benzenethiolate in the presence of norbornene involves two simultaneous chain processes, one involving electron transfer, the second involving atom transfer in the chain carrying steps.

With the primary per-

fluoroalkyl iodide,the sulfide 2 is the major product even in the presence of excess norbornene.

Thus the primary radical

prefers pathway a rather than pathway c in Scheme 2.

INITIATION:

RfI

+

RS-

->

Rf*

+

RS'

+

PROPAGATION:

Rf1 >

RfSRY

RfSR

+

Rf.

/y, R' f

RfCH26HPh PhCH=CH2

-sqp

7 % C

norbornene

‘\,

RfI 1111 I Rf

Scheme 2

Rf

I-

198

The chemistry

The secondary

more complex.

gave

the primary

relatively iodide.

more

from the secondary

product

suggests

react

[6] with

vinyl

sulfide

experiments detected

generate

>

as a by-

of the latter intermediate,

which

to give

(CF312C@

could

Loss

3).

poor material iodide

secondary

detected

(Scheme

anion

loss of the very volatile

PhS-

2

di-

2 than did

hexafluoropropene

the secondary

gave more

adduct

Formation

anion

$,. The relatively

(CF3) 2CFI

$ was

of an ionic

the benzenethiolate

with

in general

sulfide

the involvement

ion would

,& is somewhat

of norbornene,the

iodide.

the perfluoroisopropyl

fluoride

iodide

of the norbornene

The vinyl

product

namely

iodide

In the presence

phenyldisulfide. iodide

of the secondary

of

is known

to

the observed

balances

in the

be due to the un-

hexafluoropropene.

PhS+

CF3CF=CF2

-----+

4 %

2 Scheme

3

The mechanism

of formation

tion.

A direct

iodine

atom of the substrate

iodide. sulfide

SN2 displacement

The latter with

excess

an intermediate

PhSNa.

radical

generate

would

certainly

Alternatively,

of the anion

radical

is certainly

of ?r; and ?Q. Whether

the formation

by thiolate

would

perfluoroalkyl

perfluoroisopropyl formation

compound

of 2 is an interesting anion

ques-

on the

2 and phenylsulfenyl give

diphenyldi-

electron

could

transfer

be involved.

an intermediate

The in the

it is also an intermediate

2 has not been

determined.

to

in

199

It is interesting to compare these results to the earlier work [71 on reactions of the 2-nitropropanide ion with perfluoroalkyl iodides.

In DMF solution,&Q reacts with lithium 2-nitro-

propanide giving 2-perfluorooctyl-2-nitropropane inhibits the process.

($1.

Styrene

The secondary iodide ,& gave only the

nitronate diner ,@, and volatile fluorocarbons.

No product cor-

responding to fiwas detected.

C8F17C (CH3) 2N02 fi

Hf'GF17 Rfl

+

(CH3)2C=N02Li

DMF /

With both the primary and secondary iodides &

and ,&,reaction

with the nitronate salt in the presence of excess norbornene gave the norbornene adducts &

or ZQ plus k or ,$Q 181.

How-

ever, the yields of the norbornene adducts were substantially higher with the nitronate compared to the thiolate.

Thus under

conditions of experiment 7 using lithium 2-nitropropanide instead of sodium benzenethiolate,the product mixture was 78% norbornene adduct 2% and 23% nitropropane k.

With the second-

ary iodide ,&,, a 55% yield of the norbornene adduct 2Q was isolated.

The higher yields of the norbornene adducts in the

nitronate reactions areconsistent with the competition experiment, described above, where thiolate was found to be a better trap than nitronate for perfluorooctyl radical.

200

7,8,91.

The electron transfer processes can be initiated spon-

taneously or be catalyzed by UV light as has been observed in non-fluorinated cases [4].

The ultimate fate of the radical

depends on the nature of the radical, the nucleophile, solvent [7],and the presence or absence of other radical traps in a finely balanced and not yet fully understood way.

Studies

along these lines are continuing.

EXPERIMENTAL Benzenethiol, butanethiol,and styrene were commercial samples, freshly distilled and stored under argon. was used as received.

Norbornene

The sodium thiolate salts were either

prepared as dried solids [lo] or generated -in situ by dropwise addition of the thiol to a suspension of sodium hydride in DMF. The tetrabutylammonium thiolates were generated by addition of the thiol to a carefully deoxygenated solution of commercial 40% tetrabutylammonium hydroxide in water.

The perfluoroalkyl

iodides were obtained from the Chemicals & Pigments Department, E. I. du Pont de Nemours & Company, or from.PCR, Inc.

The

iodides were washed with dilute aqueous sodium thiosulfate to remove traces of iodine, dried over MgSO 4,and stored in the dark. Proton NMR spectra were obtained on an IBM NR-80 spectrometer at 80 MHz using TMS as internal standard.

Fluorine

NMR spectra were obtained on a Varian XL-100 spectrometer at 84.1 MHz using fluorotrichloromethane as internal standard. Negative chemical shift values are upfield from the standard.

a4

a?

22

(m)

l.O-2.5(9H,m); -183.96 (lF,heptet) -73.66 (3F,dq) 4.50(1H,m) -72.55 (3F,dq)

Calcd for C15H10F17(M-1)+ m/e=513.0510 found m/e=513.0461

m/e=240

-68.11(3F,dd,J=11,22Hz) -120.25(1F,dq,J=146,11Hz) -155.88(1F,dq,J=146,22Hz)

l.O-2.5(9H,m); -81.6(31); -126.7(2F); -123.2(21) -122.3(4F) 4.31(1H,m) -121.5(2F); -117.7( ZF,AB quartet,J=280 Hz)

Calcd for C 2HgF17S: m/e=508.0153 found m/e=508.0092

m/e=278

found m/e=427.9861

m/e=427.9904

Calcd for C 2H5SF13

Mass Spectrum

-81.5(3F); -126.7(2F); -123.2(2F); -122.3(4F) -121.5(2F) -120.23(21); -87.96(2F)

-74.4(6F,d); -157.5(1F,heptet)

mp 40-42"

0.93(3H,t); l.l-1.9(4H,m); 2.93(2H,t)

7.1-7.7

-81.7(3F); -126.7(2F); -123.1(2F); -122.2(4F); -121.9(2F); -119.5(2F); -87.1(2F)

(m>

7.1-7.7

7.1-7.7 (m)

(20 mm)

(0.4 mm)

-81.6(3F); -126.7(2F); -123.1(2F); -121.7(2F) -119.0(2F); -87.6(2F)

Fluorine NMR

7.1-7.7 (m)

Proton NMR

oil

92-94"

65-67'

103-105°(20mm)

bp

oil "01 CF(CF3j2

%lF17

‘-#,I

CF3CF=CFSPh

a

nBuSC8Fl7 -

2%

PhSCF(CF3)2

f?k

PhSC8F1,

28

PhSC6Fl3

Structure

Product Properties

Table 2.

5,13

n.c.

6

n.c.

1,12

n-c.

11

Reference

=:

202 GLPC data was obtained using peak

on a Hewlett-Packard

a 6 ft x l/8 in 10% SP-2100 areas were

obtained

5700A

instrument

Retention

column.

from a HP 3390A

digital

times

and

recording

integrator. PROCEDURE Reactions alkyl

iodide

in DMF were

in one portion

thiolate

salt and olefin,

solution

immediately

times

indicated

several

volumes

of ether.

several

times with

In some cases,the the ether

duced

water, products

solution

if used,

under

bright

DMF solution

1, the solutions

dried

After were

solutions

over MgS04,and

were

isolated

and distillation

of the

The colorless

argon.

yellow.

The ether

the perfluoro-

stirring

diluted were

for

with

washed

analyzed

by

by concentration

GLPC. of

of the residue

under

re-

were

by adding

pressure. The phase

transfer

a deoxygenated

benzene

perfluoroalkyl

iodide

thiolate

solution.

stirred

by magnetic

Table

by adding

to a stirred

turned

in Table

conducted

or methylene and olefin,

The bright stirring

1, then worked Product

reactions

chloride if used,

yellow

bars

solution

of the

to the aqueous

solutions

for the times

up and analyzed

properties

conducted

were

vigorously

indicated

in

as above.

are summarized

in Table

2.

REFERENCES 1

V. N. Boiko,

G. M., Shchupak

and L, M, Yagupolskii,

Chem USSR (Engl. Transl.)l3 972(1977); %%' Boiko, N. V. Kondratenko, V. P. Sambur J. Org.

Chem

USSR

(Engl.Transl.1

T. A. Dashevskaya, Org. 2

v. I. Popov, Chem,

G. M. Shchupak

Chem USSR,(Engl.Transl.) v. N. Boiko

Q,, 365(1982).

J. Org.

V. I. Popov,

V. N.

and L. M. Yagupolskii,

&z, 1985(1977);

V. N. Boiko,

and L. M. Yagupolskii,

J. -

&$,347(1979).

and L. M. Yagupolskii,

J. Fluorine

203 3

New York

4

'Fluorine

R. D. Chambers,

Angew

N. Kornblum, Bunnett,

Act.

Pure Appl.

38, 1453

Int Ed Engl

J. Org. Chem.

&7,

3027(1962).

J. Gen. Chem.

USSR

(1968).

A. E. Feiring,

unpublished

Reactions

J. F.

G. A. Russell,

and A. M. Aleksandrov,

J. Org.

nucleophiles

$t,

Chem.,

iodides

have been

and R. Doume,

1365(1977);

described

polskii,J.Org.Chem

J. Org. Chem

N. Kornblum,

electron

(D. Cantacuzene,

Sot. Perkins

V. I. Popov,

V.N.

I,

V. N. Boiko

(Engl.Transl.)&&

Boiko

and L.M.Yagu-

USSR(Engl.Transl.)~~,l866(1977); N.V.

G. I. Matyuschecheva,

Yagupolskii,

other

J. Org. Chem USSR

V.G. Volaschchuk,

2086(1977);

with

J. Chem.

N. V. Kondratenko,

and L. M. Yagupolskii,

347(1983).

work.

of perfluoroalkyl

C. Wakselman

Boiko,

Wiley,

&!$, 734(1975);

Res. ,$l_,413(1978);

A. E. Feiring,

donor

Chemistry',

,$,,67(1971).

L. M. Yagupolskii

Z%

Chem

Chem.

Chem.

N. 0. Brace,

10

in Organic

1973, p. 98-99.

USSR

S. D. Boyd

Pavlenko

L.M. and V.N.

(Engl.Transl.)@,,l4(1982)). and N. Ono, J. Am. Chem.

Sot.

96 2580(1974).

v-b 11

L. M. Yagupolskii, and V. V. Orda,

12

T. Nguyen,

I. I. Maletina,

Synthesis

M. Rubinstein

N. V. Kondratenko

835(1978). and C. Wakselman,

46, 1938(1981).

v-b 13

N. 0. Brace,

J. Org. Chem.

23, 2429(1972).

J. Org.

Chem.