Tetrahedron

Letters,Vol.30,No.21,pp
Printed in Great Britain

A CONVENIENT

SYNTHESIS

CARBOXYLIC
J.

U.F.R.

There

is considerable

methods

formation

employed

may

AND PRIMARY

FROM
AMINES

PALE-GROSDEMANGE

Photochimie,
Associe au CNRS,
Reims, B.P. 347, 51062 Reims,
France

2
used , utilizing
coupling

subsequently

method

reagents
first

to

formation

of N-acylureas
carboxamides

affords

the

To

act as activating
benzoxazole
have

commercially

Similar

these

problems,

to be prepared
available

11

further

and phosphorus
before

but

they

between

yield

reagent

containing
13

amines.
2771

Most of the
which undergo

dicyclohexylcarbodiimide
usually
the

reagents

any selectivity

leads

long

have

are efficient

disulfide
between

method4

reaction

been

14

of the

times.

are very sensitive

and oxalate

12

to the

isolation

reported

as

8, which

tetrazolel,

coupling

, pyridinium
primary

to

such

derivatives

such as DCC. Benzotriazole,

, 2,2-dipyridyl

do not present

intermediates

after

agents

diphenylphosphate7,

coupling

and amines.

but the intermediates

condensing

has been

with the acyl carbamate

even

the

involves

procedure

rendering

encountered

as

of the carboxyl.

carboxamides

the DCC method

as by-products,

agent

many

into

in particular

However,

moderate

use. Triazine

acids

and amines,
In general,

the activation

acids

were

acylating

synthesis.

reaction

Carbodiimides,

N-succinimidyl

without

implies

acids to give activated

problems

IS a reactive

acids

lactam

a one-pot

agents.

in

and

acids

but in most cases

anhydrides

only

carbonate6,

derivatives

the coupling

by amines.

from carboxylic

of carboxylic

acyl chloridel,

and carboxylic

carboxamides

agents

in peptide

conversion

used as condensing

difficult.

overcome

N,N-disuccinimidyl

into

of amides

and carboxylic

for the

attack

N,N-Carbonyldiimidazole5
moisture.

utilized

with the carboxylic

a nucleophilic
are frequently

be

promote

react

(DCC)Y3,

desired

also

of the acid

reagents

in the formation

from amines

used

the transformation

they

de
de

interest

of carboxamides

A frequently

which

Laboratoire
Sciences

C.

OF AMIDES

+ .OO

method for the formation

of carboxamides
from
carboxylic
acids and
: A convenient
primary amines in the presence of molecular
sieves is described.
This process is very
chemoselective.

Abstract

the

ACIDS

COSSY*,

0040-4039/89
$3.00
Pergamon Press plc

2771-2774,1989

and

agents
salts

15

but
are

secondary

2772

Sultone~~~,

used

chlorosulfonyl

boranes17,

as coupling

reagents

18

isocyanate

but either

low yields

19

, sulfinylamines

were

obtained

, dr-n-butyltin

or no general

20

oxide

application

are also
has been

found.
We report
carboxylic

here

acids

and

mild,

facile,

primary

amines

general

and

selective

by a one-pot

formation

reaction

using

of

carboxamides

from

sieves.

molecular

moleculag
R
R-CO,H

sieves

4 A

R
+

N-H

R-C-N

R2

A summary
or alkynic
the

acids

of the results
(entries

corresponding

temperature
acids
9-11).

to the formation

between

21

pyrrolidine

and

of the ammonium

other

ester
The

selectivity

is not

of

the

reaction

of

amides
reaction

salt rather

is

with saturated,

two hours,
aromatic

of secondary

(entry

due

to

amines

of

requires

with

carboxylic

even at 180C (entries

12). This difference

the

ethylenic

the formation

amines

than carboxamides

with pyrrolidine
amines

after

from

may

with acids in the presence

only

handling

higher

of reactivity

nucleophilicity

of

of
make

the

amide

molecular
this

of molecular

is obtained
sieves,

process

the

in good

their

low

method

sieves,

yield

price

the formation

(entries

and

of choice

for

the

15-16).
high

the

chemo-

large

scale

carboxamides.

of carboxylic

sieves
mixture

cristallisation

of

react

part

A mixture
molecular

secondary

but

reaction

of primary

Experimental

observed

are reacted

detected,

convenience

preparation

amines

R2

When aminoalcohols
of the

obtention

7-S). On the contrary,

is, however,

pyrrolidine

Primary

17-21) at 140C to give,

The

carboxamides.

One exception

in the table.

l-6 and entries

of 170C (entries

leads

is given

::

acid (5.3 x IO- moles),

(0.2 g) is heated
is filtered

under

on Celite

or on a silica

gel

argon.

After

and washed

column

with

amine

(5.3 x 10e3 moles)

2 h, methylene

with methylene
a mixture

chloride

chloride.

and activated

(10 ml) is added.

The amide

of methanol-chloroform

is purified
as eluent.

4 i
The
by

2773

Table

TC

Yield
%

benzylamine

140

95

118-119
(I 19123
59-6 1
(6&6l)24

Amine

Acid 1

Entry

phenylacetic
acid

I,

allylamine

140

98

II

N,N-dimethyl
ethylamine

140

98

oil

I!

methoxyethyl
amine

140

99

oil

1,

isopropylamine

140

95

79-80

II

H2N-(CH2)3NHTS

140

95

110

II

toluidine

180

70

116-117

aniline

180

morpholine

180

10

N-methyl
cyclohexylamine

180

11

I,

diallylamine

180

12

11

pyrrollidine

150

98

oil

15

11

H2N-(CH2j3-OH

150

90

oil

16

1,
I

prolinol

150

17

propionic
acid

18

hydrocinnamic
acid

19

H2N-(CH2J3-NHTS

95

oil

140

90

95

II

140

90

115-116

trans-cinnamic
acid

,I

140

95

93-94

20

4-pentenoic
acid

II

140

60

110-112

21

4-pentynoic
acid

11

140

97

74-73

a Isblated

yield.

Satisfactory

microanalyses

were

obtained

Ck0.25,

Hk0.12,

Nk0.13.

2774

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(Received

in

France

2 February

1989)