Preparation of 1-Phenyl-3-phenylaminopyrrolidine-2,5-dione

An Organic Laboratory Experiment on the Michael Addition

Ram N. Ram1 and Kiran Varsha Indian Institute of Technology, Delhl Hauz Khas, New Delhl-110016, India

The Michael Addition is one of the important synthetic methods for the preparation of 1,3- and 1,5-difunctionalized compounds ( I ) . Virtually all undergraduate organic chemis- try textbooks use a consideration of the Michael addition, hut few suitable laboratory experiments have been puh- lished on this subject to supplement the lectures. Most of the reported procedures (2) suffer from one or more of the fol- lowing disadvantages-long reaction time ranging from sev- eral hours to days, lengthy product isolation and purification procedures, and the highly toxic Michael-acceptor. Presnm- ably because of these reasons, most of the modern lahoratory manuals are found short of an experiment on the Michael addition. (3).

We describe, herein, a two-step laboratory experiment involving the Michael addition of aniline as one of the steps. The first step involves the acylation of aniline with maleic anhydride to give maleanilic acid 1. In the second step ma- leanilic acid undergoes the Michael addition of aniline and cyclization to yield I-phenyl-3-pl~enylaminopyrrolidine-2,5- dione 2 (Method A). Compound 2 can also he obtained in one step by using commercially available maleanilic acid

' Authw to whom conespondence should be addressed.

ref lux reflux 90 min. 30 min.

(Merck) or, albeit in slightly lower overall yield, by refluxing maleic anhydride and aniline in 12 molar ratio in acetic acid (Method B) (Fig. 1). The experiment is operationally simple, requiring simply manual stirring, filtration, and recrystalli- zation, readily available inexpensive reagents, and short re- action time. Thus, it is ideally suited to the students. The NMR and IR spectra of the compound 2 may he used to illustrate the geminal and vicinal couplings along with the effect of the dihedral angle on the latter (Fig. 2) and the coupled vibrations of the imide carhonyls, respectively.

Figure 1. Reanion of anlline wlm malelc anhydride. Figure 2. 'H NMRspecburn 01 l-phenyl-3phenylarnlnopyn0Iidine-2~5dlone 2.

Volume 67 Number 11 November 1990 985

Experimental The IR and NMR spectra were recorded on Nicolet 5DX IR and

100 MHz JEOL JNM-FX100 NMR FT spectrometers, respectively.

Method A 1. Moleanilie acid 1. Finely powdered maleic anhydride (3 g, 30

mmol) and aniline (3 g, 32 mmol) are stirred in glacial acetic acid (15 mL) for 30 min a t room temperature. The solid thus obtained is filtered under suction, washed with a little ethanol, and dried. Stu- dents' average yield of the product, m.p.192-197 'C, is 5.2 g (90%). The crude product is sufficiently pure for the next step but may be recrystallized from ethanol to get light yellow prisms, m.p.195-197 "C (lit. (4) m.p.197-198'C). IR (KBr): 3450 (hr,OH), 3270 (hr, NH), 1700 (str., COZH), 1630 (str., CONHPh) em-'.

2. I-Phenyl-3-phenylamin0pyrr01idine-2,5-dioe 2. A mixture of aniline (1 g, 11 mmol), maleanilic acid (2 g, 10 mmol), and glacial acetic acid (10 mL) is refluxed for 30 min, and the solid thus oh- tained is filtered under suction, washed with a little ethanol, and dried. The students' average yield of the product is 1.5 g (55%). Recrystallization of the product from benzene affords colorless nee- dles, m.p.201-203 *C (lit (5) m.p.215 "C). IR (KBr): 3430 (br, NH), 1785 (w. asvm.imide). 1710 (str.. svm. imide) cm-'. 'H NMR (6) (cDc~,. T ~ I S internal srandard):bi.46 (IH, hr, SHL 2.79 (IH, dd, H d , J A n = I h H r . J . ~ u = 6 H z , . 3 . 3 8 r l H , d d . H n , J . ~ n = 1RHz.Jnx = R HrJ.4.46 IlH, dd, Hx, J,x = 6 H z I , ~ , , ~ = R Hz),6.61-7.4: rlOH, m, aromatic) ppm

Method B A mixture of maleie anhydride (3 g, 30 mmol), aniline (6 g, 64

mmol). and elacial acetic acid (10 mL) is refluxed for 90 min. The solid obtain& after cooling is filtered,washed with a little ethanol, and dried to get compound 2 (3.8 g, 41%).

Acknowledgment

Financial support t o K. V. by the CSIR, New Delhi, is gratefully acknowledged.

Literature Cited 1. Warren. S. Orpnie gvnfhesk: The Disronnecrion Approach; Wiloy: New York, 1982:

pp 48,170. 2. Furniss. 8. S.: Hannaford, A. J.; Rogers, V: Smith, P. W. G.; Tafehell. A. R. Vogrl's

Textbook o f P r a r f i ~ o l O ~ g n n i r Chemistry, 4th ed.; Longman: London, 1978; pp494- 497,525-527,555,656;Cason. J.;Rspporf, H. L o b o r a l o ~ Text in01ganie Chem~stry, 2nd ed.: Prentice-Hall: Englewood Cliffs, NJ, 1962: p 390: Gare ia -ko , A,: Garcia- Rsso. J.:Sinisfprra.J. V.: Mestre.. R . J . ChemEduc. 1986.63.443.

1 In la - , , e wnl) thr. .rch a r s h r e \ tms.<c collertlon . I r ~ ~ n l ursanh lelrrnl r ) ulan~sl; Y e!dcd I n r ru . , ronq~.e. I. 11, w n a r :, i.r*r rwp oc in* n n t n c w oi chm. lhnr Tur\ccs?c?src .A. l t ,A I? ,<" jb. , a ? 2 K x r . e r . n . . n ~ ~ l r c ~ r . m . f 1 , 3 . z .

, . , r ) 51hd ..\l.vn*nd na. 11 Rn.tm. 1s.- p p W i 4 c Lcnnan.J 14 ,,pdro'., no. (.,SO. corm ..,) 4 I.,+ mr r) - Lrll. . L ~ , nnl. n, R .t 1 w pp 44)-

986 Journal of Chemical Education