A new method for the synthesis of n-arylphthalisoimides

T&he&cm Leaers. Vo1.32, No.23. pp 2633-2636.1991 Primted in Great Britain

A NEW

METHOD

FOR

0040-4039/91 %3.M)+ .oo Pcrgamon Press plc

THE

SYNTHESIS

OF

N-ARYLPHTHALISOIMIDES

Antonio Guirado*, Andres Zapata, and Manuel Fenor Departamento de Quimica Organica, Facultad de Ciencias, Universidad de Murcia, Campus de Espinardo, E-30071, Murcia, Spain.

Summary: by the amines.

N-arylphthalisoimides reaction,

under

have

very

mild

been

synthesized

conditions,

in almost

quantitative

of 3,3_dichlorphthalide

The majority of the procedures to synthesize N-arylphthalisoimides

with

yields aromatic

(3) are based on cyclization

processes by dehydration of N-substituted phthalamic acids I, but for many reactions the formation of the isomer phthalimides (4) is a competitive process. Either simple heating or a wide variety of reagents

have been used for dehydration

However, the reagents most frequently phthalisoimides

of phthalamic

reported for performing

are fewer in number: ethyl chloroformate,

dicyclohexylcarbodiimide

acids under different

efficient dehydrations

trifluoracetic

anhydride

giving

and N,N’-

but, judging from the literature, they would appear not to be general in

their action2-5. A comparative study of these three dehydration have been reported,

conditions2.

showing

N,N’-dicyclohexylcarbodiimide

reagents and acetic anhydride as the most general

to yield

phthalisoimides4. There is considerable phthalisoimides,

evidence

to suggest that dehydration

could proceed by intramolecular

disposed activated acyl groups W3.

to give either phthalimides

or

interaction of the amide function with suitably

Thus, phthalimide formation would take place by ring closure

with nucleophilic participation of the nitrogen of the amide group, while participation of the oxygen would lead to phthalisoimides.

On the other hand, phthalisoimides

undergo facile isomerization to

the corresponding phthalimides by thermal or catalysed rearrangement processes218-10. Thus, it is possible that after a kinetically favoured formation of isoimide, the imide however could be the isolated product, especially if the reaction temperature is relatively high as well as if nucleophilic catalysts are present in the reaction medium. In short, three main factors are involved in the formation of the final products: (i) the activation type of the acyl group, which depends on the

2633

2634

dehydration

reagent

ring, which

are implicated

conditions, effective

which

used, (ii) the electronic

in the nucleophilicity

groups attached

of the amide

in some cases could cause the isomerization

control of these variables

We herein

effects of functional

report a new, general

starting from 3,3-dichlorphthalide

group

and (iii) the experimental

of the isoimide

is dificult and erratic results can be observed’ and simple method for the synthesis (l),

Arm-NH,

which is easily available

to the N-aromatic

to the imide. An

1.

of N-arylphtalisoimides

from phthalic acid in high yield’*.

~l_t

(2) (1)

/\ R Ar

N-Ar

(6)

N0

(7)

N

0

(3)

.

2635

Reaction of (1) with aromatic amines (2) gives the phthalisoimides (3) in nearly quantitative yields. In contrast with dehydration reactions, this method shows several advantages. Thus, the reaction products can be predicted without ambiguity since the arylimino group is linked to the previously formed ring system of (l), which because is not involved along the reaction process is retained. Consequently competitive formation of phthalimides does not take place. Moreover, the reaction is fast under mild conditions and therefore the isomerization of phthalisoimides is not favoured. It is also to be noticed that this method provides a valuable entry to substituted phthalisoimides bearing functional

groups reactive toward dehydration

reagents. The reactivity of this reagent and its

synthetic usefulness remain little known. Table 1. Preparation of N-Arylphthalisoimides 3,34Iichlorphthalide

Entry

amine

by Reaction of

with Aromatic Amines.

yield (%)a

Molecular Formula

m.p. (oC)

or tit. m.p. (Oc)

I 20-l zzb

1 2

CsHeNHs 4-MeOCsH4NHs

88 85

121-122 135136

134c

3

4-BrCsH4NHs

87

165-I 67

166-l 67d 136c 123c

4

2-MeCsH4NHs

86

136-l 37

5

4-MeCsH4NHs 2-lCsH4NHs

79 87

123-125

4-CICsH4NHs

84

159-l 60

8

2,4-ClsCsHsNHs

87

118-l 20

9

4-NCsCsH4NHs

83

172-l 73

10

2-HOCHsCeH4NHs

78

178-179

C15HliNCs

11

2-CloH7NHs

91

151-152

C1sHliNCs

6 7

146-I 48

CI~H~~NCZ 16Oc ChH7Cl2N02 172c

ayields in crystallized products. All compounds gave satisfactory IR, 1H NMR, 13C NMR, mass spectra, and elemental analyses. bRef. 16; cRef. 2; dRef. 15. Tyoical Fxoerimental Procedure. A solution of 3,3-dichlorphthalide

(1) (10 mmOl) in acetonitrile (20

ml) was cooled to -lOoC. Then, a solution of the appropriate amine(2) (10 mmol) and triethylamine (20 mmol), in acetonitrile (20 mL), was added from a compensated pressure addition funnel during 10 min under vigorous stirring. The temperature was maintained between -10 oC and -5 oC. A precipitate was formed after a few drops of mixture were added. The suspension was allowed to warm up to room temperature with continued stirring for 5 min. After removal of the solvent under

2636

reduced

pressure,

dried by vacuum yields13

the solid crude product filtration.

was shaken

High purity crude reaction

which were crystallized

from acetone-water.

twice with cold water

products were isolated

to new phthalisoimides.

We have also studied

with 1,8_diaminonaphthalene.

according

to the above

and 20 mmol

experimental

of triethylamine

diphthalisoimidonaphthalene were the products.This obtained

procedure,

to 10 mmol

by the amic acid dehydration

1,8_diaminonaphthalene

leads

to

m.p. 255-256

in Table 1. Entry

In this case it was carried

4 (5) (32% yield)

oC, a previously

unknown

since the reaction

2-(2-perimidyl)benzoic

of phthalic

and 1,8-

substance,

a useful entry to (6). In contrast, this compound method

out

5 mmol of 1,8_diaminonaphthalene

of (3). Phthaloperinonel

(6) (65% yield),

reaction provides

but adding

and

in nearly quantitative

The results are summarized

numbers 6,8,10, and 11 correspond the reaction

and collected

cannot be

acid a.nhydride

acid1 4 (7) which

with

dehydrates

to

phthaloperinone(5). Acknowledgements: de Investigation

We gratefully Cientifica

REFERENCES

y Tecnica

AND

support

of the Direction

General

(project number PB89-0442).

formation

reactions

having lezs usefulness

for synthesis

Howe, R.K. J. Org. Chem.. 1973, 38, 4164.; Ganin, E.V; Makarov,

V.I. Ukr. Khim. Zh. 1987, 53, 964.;%akeuchi, 1,1988,

the financial

NOTES.

1. Further N-arylphthalisoimides in the literature:

acknowledge

are found

V.F.; Kikitin,

H.; Eguchi, H. J. Chem. Sot., Perkin Trans.

2149.

2. See for example:

W.R; Bhatia, P.L. J. Org. Chem. 1963, 28, 2018., and references

Roderick,

cited therein. 3. Kukolja,

S.; Lammer,

S.R. J. Am. Chem. Sot. 1975, 97, 5582.

4. Awad, W.I.; Wasfi, A.S.; Ewad, M.J. J. Iraqi Chem. Sot. 1977, 2, 5. 5. Pyriadi, M.; Hadi, S. Arab. Gulf. J. Sci. Res. A. 1987, 5, 341. 6. Roderick, W.R. J. Org. Chem. 1964, 29, 745. 7. Sauers, C.K.; Gould, C.L.; loannou,

ES. J. Am. Chem. Sot. 1972, 94, 8156.

8. Au, T.K.; Baydar, A.E.; Boyd, G.V. J. Chem. Sot., Perkin Trans. 1, 1981, 2884. 9. Cotter, R.J.; Sauers, C.K.; Wheland, J.M. J. Org. Chem. 1961, 26, 10. 10. Ernst, M.L.; Schmir, G.L. J. Am. Chem. Sot. 1966, 88, 5001. 11. Cur-tin, D.Y.; Miller, L.L. J. Am. Chem. Sot. 1967, 89, 637. 12. Erwin, 0.

Organic Syntheses;

Coil. Vol. II, Blatt, A.H. Ed.; John Wiley and Sons, Inc.: London,

1946; p.528. 13. I.R and high field 1H NMR spectra for crude and crystalline negligible 14. Elsevie&

products were recorded showing

differences. Encyclopaedia

Publishing

Company:

of Organic Chemistry, Radt, F. Ed.; Series Ill, Vol. 128, Elsevier

New York. 1949; p.830.

15. Bhatia, P.L.; Gupta, S.N. Indian J. Chem. 1964, 2, 295. 16. Hoogenwerff,

S.; van Drop, W.A. Rec. Trav. Chim. 1902, 21, 339.

(Received in UK 14 February 1991)