Stereochemistry of nucleophilic additions to hexafluoro-2-butyne

Journal of Fluorine Chemistry. 25 (1984) 41-56

STEREOCHEMISTRY

RICHARD

OF NUCZEOPHILIC

D. CHAMBERS,

47

ADDITIONS

COLIN G.P. JONES,

TO HEXAFLUORO-2-BUTYNE

MICHAEL

J. SILVESTER

and

DAVID B. SPEIQ1T.

Departmant Durham,

of Chemistry,

DHl 3IE

University

Science

Laboratories,

South Road,

(U.K.)

s UMMARY

Base-catalysed products

of trans-addition

additions addition

of alcohols

sulphur

to F-2-butyne

cis-addition

is very dependent Stepwise

(1) give mainly

predominates

and concerted

for these observations.

in uncatalysed

The stereochemistry

on the solvent

of

used and cis- or

mechanisms

Nucleophilic

to (1) gives F-tetramethylthiophene

are

addition

(68%) and hydration

of

gives

(91%).

AND DISCUSSION

Although established

nucleophilic

the influence

products

Where

Base-catalysed

additions

of addition

of alcohols

with

0022-l 139/84/$3.00

larger steric

affecting

has been investigated,

Here, however,

of the nucleophile

we probe

and effects

of

(Scheme 1).

to hexaflmro-2-butyne

and results of a series of reactions

In all cases -ca. 90% trans-addition that almhols

the stereochemistry

on the stereochemistry

(1) are well

about the factors

(3) are described.

of steric requirements

and solvent

to hexaflmro-2-butyne

little is known

of addition.

mainly trans-addition

very readily

additions

[1,2], relatively

stereochemistry

charge

while

may predominate.

to account

CF~CR~COCF~

RESULTS

of alcohols

carried out in a diluent.

of diethylamine

trans-addition advanced

additions

is described

(1) proceed in Table

1.

occurs but there is some indication

requirements

give more _cis-product

(5).

0 ElsevierSequoia/Printedin The Netherlands

48 CF

CF3 \c,cD +A Nut-H ,p CF3CZCCF

H+ (kL) L CF


Transfer Nut

(2)

'CF

3

+ NucH

3

3

(3)

(1)

Scheme

TABLE

1

H+ (k2)

cF<

_ /CF3

Transfer --

Nu
(4)

(5)

1

Base catalysed

NucH

additions

Solvent

of alcohols

to hexafluoro-Z-butyne

Temperature,

CH30H

'C

% trans (3)

20

96

n-C3H70H

-

20

92

n-C4HgOH

-

20

89

n-C4HgOH

-

117

86

117

92

n-C4HgOH

sulpholan

2-C4HgOH

-

20

91

t-C4HgOH

-

20

86

The effect alcohols higher

is, however,

required

additions

demanding

case (Table 2)

In contrast,

gave more _cis-addition

of and even

t-B&H and ca. 90% i.e. closely resembling

however,

use of diethyl

ether or

(5) than trans-addition

(6).

Additions very readily contrast

in each

processes.

as diluent

products

Uncatalysed

e.g. 95O for methanol

for the more sterically

was obtained

the base-catalysed sulpholan

small.

very high temperatures,

temperatures

trans-addition

relatively

of diethylamine

and ether and sulpholan

between

(5) predominating sulpholan.

are shown in Table

results with

3.

Reactions

were used as separate

these solvents

with ether and mainly

is quitesignificant,

trans-addition

occurred

solvents.

The

cis-addition

(3) occurring

with

49

TABLE 2 Uncatalysed additions of alcohols to hexafluoro-2-butyne

NucH

Solvent

Temperature, 'C

% trans (3)

CH30H

95

92

n-CqH90H

95

90

n-CqHgOli

ether

95

t

n-CqH90H

ether

150

27

n-CqH90H

sulpholan

100

*

n-CqH9011

sulpholan

150

30

t-CqH9011

95

t-CqH90H

150

.I. 90

t No detectable reaction. TABLE 3 Additions of diethylamine to hexafluoro-2-butyne

Solvent

Temperature, 'C

% trans (3)

ether

2

40

sulpholan

2

61

Base-catalysed additions of alcohols to (1) occur readily and lead to preferential formation of trans-additionproducts (3) either when carried out using the corresponding alcohol or sulpholan as solvent. There is a slight increase in the proportion of -cis-addition (5) with increasing steric requirements of the alcohol and this may be attributed to interactionswith adjacent trifluoromethyl,which makes (2a) less stable relative to (&a) (Scheme 2). It is not easy to envisage a realistic mechanism for direct equilibration of vinyl anions and, indeed, calculations carried out for the vinyl anion itself indicate that the barrier to inversion is large [31.

50

-Ro/

'CF

(3)

3

(2a) CF3C-CCF3

+ RO-

(1) CF3 \CJCF3 RO'

--d

(5)

Q

(4a) Scheme

2

Therefore

it seems reasonable

to discount

direct

(2a) and (4a) or (2) and (4), as processes this conclusion

is valid,

the products kT/kC.

addition

(2) is preferred

We can attribute

In sulpholan whereas

this change

to differences

intermediates

trans-isomer

(2) and its formation constant.

amine is a sterically

The mechanism differs

the product

catalysed involves whereas

concerted addition

additions

of diethylamine.

In contrast,

transfer

products

in the

is greater

in the

by a solvent of higher

the fact that diethylsteric demand will

of a proton

led to preferential uncatalysed

concerted in Scheme

process 3.

(7) over

transfer (6).

of alcohols, formation addition

(3).

of

These

for the un-

Addition

from another molecule

intramolecular

then favour

to (1) apparently

In the addition

however,

as outlined

via (7) involves

of alcohols

of trans-addition

an essentially

of alcohols,

dilution would

separation

and increased

or ether as solvent

therefore,

addition

Obviously,

nucleophile

gives principally,

indicate,

trans-

(4) is preferred.

to (4).

of -cis-addition.

neat alcohols

are markedly

constant)

should be assisted

of the uncatalysed

sulpholan

If

1 where,

in charge separation

Charge

we must not overlook

demanding

from that of addition

use of either

results

(2) and (4).

However,

(2) relative

the products

(high dielectric

in ether -cis-addition

Zwitterionic

destabilise

(3) and (5).

(3)/(5) represents

the ratio of the rate constant

In this case, however,

by solvent.

of either

k'

(3) and (5) represents

affected

dielectric

to both

for the addition process. Tlk'C of diethylamine may be represented by Scheme

The addition

for addition

leading

then the ratios of products,

the ratio of rate constants

again,

interconversion

via -

(6)

of alcohol,

of a proton.

of

51 A.OR

CF,

H'

(1)

Scheme 3

(7)

The results described above form evidence that -cis-addition to (1) may be increased, in some cases, by one or more of the following factors: (a) increasing the steric requirement of the nucleophile, (b) using a neutral nucleophile and therefore generating Zwitterionic intermediates,or (c) use of a solvent of low dielectric constant. Consistent with these conclusions,we have discovered at least one all-cis nucleophilic addition to hexafluoro-2-butyne(1) i.e. the reaction of sulphur, suspended in sulpholan. Krespan [4] has synthesised perfluorotetramethylthiophene(8) by reaction of sulphur with (1) at 200°C and concluded that the process involves reaction of an intermediate dithietene with (I), probably in a free-radical process. Ue find that reaction with sulphur will occur at llO°C in sulpholan giving (8), surprisingly readily. No other sulphur heterocycles were detected and we conclude that a different process operates under our conditions, from that operating under the conditions used by Krespan. Indeed, it seems reasonable to conclude that a nucleophilic cyclisation process operates, as shown in Scheme 4, the -cisaddition occurring because sulphur is both a bulky and a neutral nucleophile.

(8) (61%)

I

+

1

s-s (i) llO", sulpholan. Scheme 4

1

I

52 Since we were (1) we attempted Dawson giving

able to effect

a corresponding

[5] have previously the ketone

catalysed

described

of water

work is progressing

to (1) occurs

with this interesting

+

H20

QL

catalysed

between

alcohols

Cullen

addition

and

and

of water

We now find that as solvent

using sulpholan

to (1) unat

Further

(9) in very high yield. ketone. (91%)

CF3CH2COCF3

(1) (i)

base

tube giving the ketone

llO°C in a nickel

3

reaction

hydrolysis.

(9) but only as a minor product.

addition

CF3C-CCF

uncatalysed uncatalysed

(9)

llO", sulpholan

EXPERIMENTAL 19

F n.m.r.

spectrometer, shifts

spectra were measured

with

are quoted

columns packed

30% silicone

or 20% diisodecyl-phthalate on a V.G. Micromass

Addition

of nucleophiles (a)

tubes were

or allowed

catalysed

conditions

reactions

used for reactions

were performed above 100°C.

were

in Carius

alkoxide.

Catalysed

reaction

vessel

reactions

pressure,

from a variable

but were studied by lgF n.m.r. reaction mixture. resonances JCF3_CF3

Isomer

at elevated

reservoir.

!cis)*

were

The

amount

4-5% of the

carried out

being introduced

into the

were not isolated

spectroscopy

ratios were determined

due to the CF3 groups and noting

containing

The products

and m.s.-g.1.c.

20h.

the appropriate

temperatures

the hexafluorobut-2-yne

(1)

and the tube was either

for approximately

carried out by dissolving

of sodium in the alcohol in order to give a solution

at atmospheric

tubes but

Hexafluorobut-2-yne

an excess of the alcohol

to stand at room temperature

reactions

Mass spectra were

g.1.c.

to hexafluorobut-2-yne

was sealed in the tube with heated

P (Column A).

12 B linked with

Reaction

Most of the addition

u?field

reference;

was carried out using

SE-30 on chrorrpsorb P (Column 0)

gum rubber

on chromosorb

retarded

nickel

as external

Gas chromatography

as positive.

with

Alcohols

using a Varian EM 360~ or A56/F-

trichlorofluoromathane

on the crude

by identification

of the

that JCF _cF (trans) << 3 3-

53 (b)

Base

Alcohol

catalysed

Solvent

(g, mnol)

reactions

Tern0 OC

(1) (9. mm11

(g)

Remvered (1)

% tram _

(g)

s&?i! 5.1,

160

6.0,

37

20

0.0

96

135

4.0,

25

20

0.0

92

n-c~7~

8.1, rlC,H,OH

9.0,

120

5.3,

33

20

0.0

89

15.8,

214

6.8,

42

117

0.0

86

3.8,

23

117

0.0

92

62

2.4,

15

20

0.0

91

130

4.0,

25

20

2.2

86

5.2,

70

Sulpholan (25.0)

2-C&m 4.6,

t-c9.9,

Uncatalysed

Cc)

reactions

Solvent

Alcohol (9, mm011

(g)

(1) (g, mml)

Tenp

Oc

Recovered (1) (g)

% trans -

‘$E 4.5,

140

4.5,

28

95

0.0

92

70

n-C,H,OH

8.0,

11.0

1.8,

24

Ether,

3.5,

47

Ether,

-

6.1

38

95

3.7

5.5,

,

34

95

5.5

10.0,

62

150

7.5

5.8,

36

100

5.8

4.8,

28

150

3.4

(6.5) 27

(14.2) 1.8

24

Sulpholan (12.7)

1.2,

16

Sulpholan

30

(9.0) t-C
251

4.2,

26

95

4.2

9.8,

130

3.0,

19

150

2.5

90

54 The following

were identified:

hexafluorobut-Z-ene known sample (Found:

(by covarison

[l]); (Z)-2-n-propoxy-1,1,1,4,4,4-hexafluorobut-2-ene

M+-CH3,

207.

7.5 Hz., Fa) and 71.5 but-2-ene

(2) and (E)-2-methoxy-1,1,1,4,4,419 F n.m.r. spectra with those of a of

(nc)

~~~9~60

requires

207; hF 59.0

(3 F, m, Fa) and 69.8

(3 F, q, J 10 Hz, Fb);

(Z)-2-n-butoxy-l,l,1,4,4,4-hexafluorobut-2-ene C8HloF60

requires

207;

6F 58.9

and

(3 F, m, Fa)

69.7

1,1,1,4,4,4-hexafluorobut-2-ene requires F,,’

;

M-C2H5,

(3 F, q, J 10 Hz, Fb); (nc)

6F 59.5

207;

and 69.9

4,4,4-hexafluorobut-2-ene

(Found:

M+-C2H5,

(3 F, d, J 7.5 Hz, Fa)

6F 59.5

(3 F, q, J 10.5 Hz, Fb); (Found: M+-H,

(nc)

and 68.2

M+-CR3

(nc)

207.

and 71.5 (nc),

(Z)-2-secbutoxy207.

C8H1~F60 and 70.0 (3 F,

S,

6F 54.6

(nc),

(Z)-2-tert-butoxy-l,l,l,-

235.

and 70.1

(3 F, d, J 7.5 Hz, Fa)

tert-butoxy-1,1,1,4,4,4-hexafluorobut-2-ene

C9H10F60

requires

(3 F, s, Fb); AF 61.5

M-H,

(E)-2-

(3 F, m, Fa)

(3 F, m, Fb'.

(Z) R = n-C3R7-,

(E)

n-C4Hg-,

C2H5(CH3)CX-

(d)

Attempted

equilibrium

(i)

A portion

of the mixture

of n-butanol

with

equal volume

of a 5% solution to

and

obtained

of sodium

was

n-butoxide

reaction

at 20°C with an

in n-butanol.

over a period

repeated

On cooling to 20°C and opening

to have occurred.

from the uncatalysed

at 150°C was stirred

remain unaltered

(ii) The above experiment

(cR~)~c-

reactions

(1) in sulpholan

of isomers was found

48h.

(Found:

(E)-2-sec-butoxy-l,l,1,4,4,4-hexafluorobut-2-ene

(3 F, m, Fa)

235;

(nc)

(3 F, d, J 7.5 Hz, Fa)

(E)-2-n-butoxy-l,l,1,4,4,4-hexaflwrobut-2-ene

(3 F, S, Fb); AF 55.0

M-CH3,

(3 F, d, J

(El-2-n-propoxy-1,1,1,4,4,4-hexafluoro-

(3 F, s, Fb);

6F 55.1

M+-DI3,

(nc)

The ratio

of 48t1.

using a Carius

tube at 150°C for

the tube, no isomerisation

was found

55 Diethylamine

[21

The reactions

were

carried out at 22OC and at atmospheric

the hexafluoro-2-butyne variable

reservoir.

products

were isolated

being

Reaction

Solvent

Dielectric

(10 ml)

Constant

was allowed to proceed

Et2NH

2

Diethyl Ether

into the reaction

pressure,

vessel

for 14h.

from a

The

only in the case of sulpholan (85% yield). from the 19F n.m.r. spectra, as before.

ratios were determined

Cyclohexane

introduced

4.3

Isomer

% trans

(1)

(g, mrrol)

(g, mmol)

2.1,

28.8

4.8,

29.6

34

1.85,

25.3

4.1,

25.3

40

Sulpholan

44

1.94,

26.6

4.3,

26.5

61

Acetonitrile

38

2.1,

28.8

4.8,

29.6

89

Sulphur A suspension stirred

of sulphur

(3 g, 93.8 mnol) in sulpholan

at llO°C under an atmosphere

37 rmnol).

After 5 days,

was transferred

liquid was shown by g.1.c. identified

of hexafluorobut-2-yne

(1) (2.5 g) was recovered

at 9o°C under vacuum (Column 0;

(lit. value

64.26;

S, 9.29%,

M+,

64.04;

S, 8:99%;

M, 356 (for32S).

134-5OC 356

141). (for

(1)

and volatile

to a oold trap.

(6.0 g, material

The resultant

170°C) to consist of one component,

as tetrakistrifluoromethylthiophene

134Oc,

(40 ml) was

(8) (2.4 g, 61%) b.p.

Analysis:

%) .

Found:

C8F12S

C, 26.89;

requires

F,

C, 26.97;

F,

Water Water

(2.2 g, 120 nmrol), hexafluorobut-2-yne

and sulpholan 114h.

(10.9 g, 67 mrrol)

(10 g) were sealed in a Carius tube and shaken

On opening

was transferred dried

(1)

the tube,

(1) (5.0 g) was recovered

under vacuum to a cold trap.

(P205) and transferred

was shown to be a single

54.2OC

at 747 ma Hg [5]). 161.

C4H2F6

by g.1.c.

Analysis:

requires

The resulting

(Column A;

liquid which

70°C) and identified

(9) (5.9 g, 91%) b.p. 56OC Found:

C, 26.55;

C, 26.67; H, 1.11;

for

material

liquid was

under vacuum to give a colourless

component

as 1,1,1,4,4,4-hexaflu3robutan-2-one

M+-19,

at llO°C

and volatile

(lit. value

H, 1.08;

F, 63.33%;

M-19,

F, 63.49%; 161.

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R.N. Haszeldine,

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(1952)

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