An efficient one-pot synthesis of nitriles from acid chlorides

Tetrahedron Letters,Vol.23,No.l4,pp Printed in Great Britain

1505-1508,1982

0040-4039/82/14%505-04$02.00/O 01982 Pergamon Press Ltd.

AN EFFICIENT ONE-PDT SYNTHESIS DF NITRILESFROM ACIDCHLoRIoES A.Hulkenberg, and 3.3. Troost Duphar B.V. Research Laboratories P.D. Box 2, 138D AA Weesp, The Netherlands

Sumnary: Treatment of

aromatic

aliphatic,

sulfonamide in sulfolane

at 12D°C for

as

well

as

heterocyclic

acid

3 hours produces the corresponding

chlorides nitriles

with

in high

yields. In

general

requires

the conversion

two or more steps.

chloride

into

conversion

the

decomposition require

the

into a nitrile

isocyanate step’.

drastic

240°C or

acids

or

primary amide followed

of an acid

chlorosulfonyl

of

reaction

phosphorus pentachloride

makes use of

few one step

conditions, of at

chlorides

into

by dehydration’.

but the intermediate

Relatively

reaction

acid

the corresponding

One of the most popular methods consists

acids

e.g.

Another generally

the extreme air

chlorosulfonyl of

and lurnidity sensitive

aromatic acids

with para-toluenesulfonamide3

175-21O’C.

These methods give

satisfactory for the conversion of aromatic acids; poor results.

an acid

applicable

amide needs a separate basic

procedures have been described,

the conversion

nitriles

of converting

or

of

yields

and are

acids generally

The method consists

and only

give very

We wish to present a general procedure for the one-pot conversion of acid chlorides their corresponding nitriles.

them

with urea2 at

methanesulfonamide

variable

whereas aliphatic

all

into

of sirrply warming together tne acid chloride

with an equivalent of sulfonamide6 for three hours in sulfolane at 12O’C.

0 R-&Cl

+H2N-S02-NH

12oOC 2 -R-C=N

+H2N-S03H+HCl

To our knowledge this conversion of an acid chloride into a nitrile mediated by sulfonamide has not previously been described7. As can be seen from the results, sumnarized in the table, the method is successful for a large variety of acid chlorides: aliphatic-, aromatic- with electron withdrawing and electron

donating substituents,

sterically

1505

hindered as well as heterocyclic

1506

nitriles

are obtained

in high

used for upscaling.(see With the choice the possibility hindered

of sulfolane

of using

benefits

into

the

from higher

results

of

case

1.05

sulfonamide Another solvent

temperatures

took

temperatures

place

an acid

chloride

equivalent

at

of

it is also thionyl

Heating

possible

of sulfolane

feature

is necessary

to the following

the

for

the

reaction

that

the

and

sterically

quantitative

4-nitrobenzonitrile

also

a solvent

(see table entry

1) but gooo

intermediate

of

1,

e.g.

instead

into

the nitrile

with

of sulfolane

in these solvents,

however,

start of the reaction,

acid

whereas

otherwise

is

traces

pure product

amount

only

of

of hydrogen

initially

traces the

of

formed

alone

or

material. the

In

acid

chloride

and

in this

acylsulfonamide

in

of nitrile

solution

of

1

1,

Due to the poor

acid.

solubility acid

at 180°Cy

Thus

by

toluene

of hydrogen

of the added acid leads to quantitative

So

benzonitrile

or

chlorioe

has to be added

of the intermediate

120°C

drastically.

into the corresponding

of para-toluenesulfonic

at

are observed

decomposition

para-toluenesulfonic

if any conversion

poor,

and 0.012

is subsequently

poured

ether-cyclohexane

as starting

solution

at the

1 will be observed formation

of the

10

0.01 mole of an acid chloride solution

the

decomposed

can also be used.

4 and 18). Omission 7,7a acylsulfonamides .

procedure

of

accelerates

0.1 equivalent

(see table entries intermediate

the

4-methoxybenzoylsulfonamide,

a catalytic

toluene

an acid

to

+ PH IL --,wR-C=N-SO,-N&R-C=N+H2N-S03H

para-toluenesulfonic

in

added

pathway.

refluxing

remove

of all reactants

found

of

is the good solubility

is quantitatively

mixture

it was

yield

to use

is

decomposition

4-methoxybenzoylsulfonamide

the

be

+

H

no decomposition

Addition

and

can also

8 and 9).

without

chloride

important

R-t-iI-SO,-NH,

General

Thus

The

18O'C.

the reaction

3, 10 and 14).

0

xylene

The method

at all at 120°C but a nearly

(see table entries

to perform

procedure.

of good solubility

if needed.

did not react

(see table entries

which

according

gives

work-up

are not always obtained8.

Instead this

a simple

19 and 20)

chloride

nitrile

It is also possible

after

there is the advantage

higher

2.6-dichlorobenzoyl

conversion

yield

table entries

into

75

(1:l).

The

of sulfolane, resultsl'.

ml

warmed of

organic dried

1

mole of sulfonamide for three N

layer

over

sodium is then

sodium

hours

hydroxide washed

sulfate

are dissolved

at 12O'C.

and

and three

After

in 10 ml of sulfolane cooling,

extracted times

subsequently

with

the reaction

three

times

water

in order

evaporated;

an

with to

almost

1507

:sionof acid chloridesinto nitriles 'dconver 4. Sulfonamide-mediate Table:RCEF nr.

T°C

R121

yield (%)13

Remarks no solventused

1

120

89

2

120

97

3

120

95

from RCOOH

4

120

78

tolueneas solvent para-toluenesulfonic acid as catalyst

5

120

91

6

120

93

7

180

93

120

62

150

78

120

82

120

87

120

81

120

95

120

88

c-c-

120

80

GC-

120

90

o-c-

120

78

120

85

120

8515

120

8115

8

no reactionat 1200C

Lw 9 10

im CH3Cv

11

I,, from RCOOHL4

0 12

0 0

13 # 14

from RCOOH

u

15 0 16 017 18 19

-c-c-c-c-

F

C-f-

C

20

Cl-C-C-

tolueneas solvent para-toluenesulfonic acid as catalyst

.1508

References

and Notes

1.

Ruehler

and Pearson,

2.

J. Lilcke, R.E. Winkler,

3.

C.S. Miller,

4.

E.N.

5.

H. VorbrSggen,

6.

Sulfonamide

7.

Acylsulfonamides,

Organic

Grivsky,

are

well

anhydrides

Synthesis,

Tetrahedron

e.g.

to

nitrile

presence

acylsulfonamide c.s.,

into

Zhurnal

11. Purity

established

12. All the structures

gives

a nitrile

a good melt

(Received

acid

reaction

chlorides

or

it

.seems

of the isolated

nitriles

were confirmed

not corrected

for

available

the

decompose

an

by N.P. Aktaev

purity

in tne table.

1H MR spectra

of the

prepared.

acid

chlorides.

The yields

given

The

are

‘H NMRdata.

acid gives

on a 0.25 mole scale

1982)

to

as indicated

by their

or freshly

from quantitative

2-carbomethoxybenzoic

UK 28 January

possible

Only one example is described

PO to >98%

commercially

remains

again of the

462 (19731

‘H NR analysis:

as evaluated

120°C but hardens unchanged.

by quantitative

and are

12172d

amount of the acid chloride substituents 2

at

-48

Only traces

at temperatures

was synthesized

in

with sulfonamide

on a 10 mmole scale

are performed

yield

in this

and

of the 4-chlorobenzoylsulfonamide.

by thermolysis. Khimii,

14. Under the same conditions 15. The nitrile mixture.

intermediates

sulfonamide

876, 846 (19531, Chemical Abstracts

electronegative

13. Yields are not optimized acid chlorides used are based on isolated

which are from

solvents.

Organicheskoi

10. All experiments

646 (1955)

245 (1971)

synthesized

due to the formation

of

Vol. 3

as aromatic,

be

are formed and a considerable

the

N.Y. 951 (1970)

from Fluka A.G. Switzerland

Bayer A.G. Germ.Pat.

some time,

Wiley Interscience

1631 (1968)

as well

4-chlorobenzoylchoride

after

g

available

in hydrocarbon

8.

Collective

Letters,

aliphatic

synthesis,

94 (1971)

Bull.Soc.Chim.Belges,

known compounds

Farbenfabriken

In

Chimia, 25

is commercially

7a

9.

Survey of organic

phthalimide

and distilled

directly

from the

reaction