J. CHEM. RESEARCH (S), 1998 655
s, CO2H); MS m/z (%) 296 (M , 70), 189 (60), 136 (20), 107 (49)
(Found: C, 72.59; H, 7.24; N, 9.35. Calc. for C18H20N2O2: C, 72.96;
H, 7.04; N, 9.45%).
N-(4-Methoxyphenyl)-N-[1-(4-methoxyphenylimino)ethyl]glycine 5b.
ÐColourless crystals (200 mg, 61%), mp 144±145 8C (from ethyl
1
acetate±cyclohexane); IR (KBr) 3297 (OH), 1660 cm (CO); 1H
NMR (CDCl3) ꢁ 1.94 (3 H, s, CH3), 3.77 (3 H, s, OCH3), 3.81 (3 H,
s, OCH3), 4.86 (2 H, s, CH2), 6.80±4.73 (8 H, all m, aryl H), 8.62
(1 H, s, CO2H); 13C NMR (CDCl3) ꢁ 22.32 (CH3), 55.34 (CH2),
55.50 (OCH3), 55.53 (OCH3), 114.13, 115.06, 121.64 and 128.68 (all
aryl H), 131.11 and 136.06 (aryl CN), 156.39 and 159.41 (aryl
COCH3), 172.50 (CO2H); MS m/z (%) 328 (M , 28), 206 (55), 178
(21), 136 (100), 123 (50), 108 (13) (Found: C, 65.65; H, 6.10; N,
8.58. Calc. for C18H20N2O4; C, 65.84; H, 6.14; N, 8.53%).
Scheme 4
The structures of compounds 11a, 11b were identi®ed by
comparison of their melting points with those previously
reported.11 Thus it is obvious that the reaction of the form-
amidines with 2 and 4 replaces the bromine atom to give the
intermediates 7a, 7b and 10a, 10b followed by spontaneous
hydrolysis (by absorption of water from the ethanol used),
probably due to the presence of the liberated HBr to 8a, 8b,
11a, 11b and 9a, 9b respectively.
Reaction of N1,N2-Diarylformamidines 6a, 6b with ꢀ-Bromoaceto-
phenone 2.ÐSolutions of compounds 6a, 6b (1.0 mmol) in ethanol
(10 cm3) were added to a solution of 2 (199 mg, 1.0 mmol) in etha-
nol (5 cm3) and heated to re¯ux temperature for 1 h. After this
period yellow crystals of 8a, 8b were precipitated which were ®ltered
o and recrystallized from ethanol. The ®ltrates were concentrated
and the residues subjected to PLC using toluene±ethyl acetate (10:1)
as the developing solvent to give two zones. The faster moving one
contained 8a, 8b while the more slowly moving one contained 9a,
9b. The zones were extracted, crystallized and identi®ed as follows:
ꢀ-(4-methylphenylamino)acetophenone 8a, 90 mg (40%), yellow
crystals (from ethanol), mp 126±127 8C (lit.,7 128±129 8C); ꢀ-(4-
methoxyphenylamino)acetophenone 8b, 88 mg (37%), yellow crys-
tals (from ethanol), mp 90±92 8C (lit.,8 93 8C); 4'-methylformanilide
9a, 61 mg (45%), colourless crystals (from light petroleum, bp
40±60 8C), mp 53 8C (lit.,9 52 8C); 4'-methoxyformanilide 9b, 70 mg
(46%), colourless crystals (from light petroleum), mp 83 8C (lit.,10
84±85 8C).
Conclusion
N1,N2-Diaryl-formamidines and -acetamidines react with
the bromo-active methylene derivatives by nucleophilic sub-
stitution rather than by condensation,1±3 while acetamidines
1a, 1b with bromoacetophenone 2 they undergo nucleophilic
addition. This is probably due to electronic eects, where in
the case of 2 the carbonyl group is attached to a benzene
ring, which leads to faster addition than in the saturated
analogues.
Reaction of N1,N2-Diarylformamidines 6a, 6b with Ethyl 2-Bromo-
ethanoate 4.ÐA solution of compound 4 (167 mg, 1.0 mmol) in
ethanol (5 cm3) was added dropwise to a solution of formamidines
6a, 6b (1.0 mmol) in ethanol (10 cm3) at room temperature, giving a
yellow colour. The reaction mixture was left standing for 1 h, con-
centrated and subjected to PLC using toluene±ethyl acetate (10:1)
as developing solvent to give two zones. The faster moving one con-
tained 11a, 11b while the second zone contained the corresponding
formanilides 9a, 9b. The zones were extracted, crystallized and
identi®ed as follows: N-(4-methylphenyl)glycine ethyl ester 11a,
100 mg (52%), colourless crystals (from cyclohexane), mp 50 8C
(lit.,11 51 8C); N-(4-methoxyphenyl)glycine ethyl ester 11b, 120 mg
(57%), colourless crystals (from cyclohexane), mp 58±59 8C (lit.,11
59 8C).
Experimental
General experimental details have been described previously.12
Reaction of N1,N2-Diarylacetamidines 1a, 1b with ꢀ-Bromoaceto-
phenone 2 and Ethyl 2-bromoethanoate 4.ÐSolutions of compounds
1a, 1b (1.0 mmol) in ethanol (10 cm3) were added to a solution of 2
or 4 (1.0 mmol) in ethanol (5 cm3) and heated to re¯ux temperature
for 1 h. The reaction mixtures were then concentrated and the resi-
dues subjected to PLC using toluene±ethyl acetate (1:2) as the devel-
oping solvent to give one main zone which contained 3a, 3b or 5a,
5b. The zones were extracted, crystallized and identi®ed as follows:
2-Bromo-1-{(4-methylphenyl)[1-(4-methylphenylimino)ethyl]amino}-
1-phenylethanol 3a.ÐColourless crystals (204 mg, 47%), MP 218 8C
The author is indebted to Professor Dr. D. Dopp,
Division of Organic Chemistry Grhard-Mercator Universitat
GH Duisburg, for the elemental analyses, NMR and mass
spectra.
(from ethyl acetate±cyclohexane); IR (KBr) 3413 cm (OH); 1H
NMR (CDCl3) ꢁ 2.15 (3 H, s, CH3), 2.27 (3 H, s, CH3 aryl), 2.41
1
2
(3 H, s, CH3 aryl), 4.61 (1 H, d, 1a'-H), 4.98 (1 H, d, 1b'-H, j Jj
12.90 Hz, CH2Br), 7.06, 7.32, 7.38, 7.57, 7.58 and 7.82 (13 H, all m,
aryl H), 8.48 (1 H, br, OH); 13C NMR (CDCl3) ꢁ 13.72 (CH3),
21.19 (CH3 aryl), 21.29 (CH3 aryl), 67.34 (CH2Br), 94.10 (COH),
126.09, 126.86, 128.57, 129.39, 129.92 and 132.85 (all aryl CH),
Received, 16th April 1998; Accepted, 25th June 1998
Paper E/8/02858C
129.38 and 132.0 (aryl CCH3), 138.98 (aryl CCOH), 140.16 and
.
140.47 (aryl NC), 164.62 (C N); MS m/z (%) 438 (M 2, 1), 436
(M , 1), 393 (3), 356 (M -HBr, 4), 250 (25), 132 (83), 106 (100),
81 (14), 79 (10) (Found: C, 65.81; H, 5.70; N, 6.30. Calc. for
C24H25BrN2O: C, 65.91; H, 5.76; N, 6.41%).
References
1 F. B. Dains, O. O. Malleis and J. T. Meyers, J. Am. Chem. Soc.,
1946, 68, 1251.
2 R. M. Roberts, J. Org. Chem., 1949, 14, 297.
3 G. W. Kenner, B. Lythgoe, A. R. Todd and A. Toppham,
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4 A. M. Nour El-Din, A. E. Mourad, A. A. Hassan and M. A.
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5 D. Dopp, M. A.-M. Gomaa, G. Henkel and A. M. Nour
El-Din, J. Heterocycl. Chem., 1995, 32, 603.
2-Bromo-1-{(4-methoxyphenyl)[1-(4-methoxyphenylimino)ethyl]-
amino}-1-phenylethanol 3b.ÐColourless crystals (234 mg, 50%), mp
1
205±207 8C (from ethyl acetate±cyclohexane); IR (KBr) 3414 cm
(OH); 1H NMR [(CD3)2SO] ꢁ 2.07 (3 H, s, CH3), 3.71 (3 H, s,
OCH3), 3.83 (3 H, s, OCH3), 4.51 (1 H, d, 1a'-H), 4.71 (1 H, d, 1b'-
2
H, j Jj 12.80 Hz, CH2), 6.93, 7.16, 7.27, 7.35, 7.40, 7.40, 7.73 and
7.75 (13 H, all m, aryl H), 8.48 (1 H, s, OH); 13C NMR [(CD3)2SO]
ꢁ 13.61 (CH3), 55.27 and 55.55 (OCH3), 66.51 (CH2Br), 93.52
(COH), 114.25, 114.88, 126.8, 127.64, 128.0, 128.92 and 129.87 (all
6 H. O. Kalinowski, S. Berger and S. Braun, in 13C NMR
Spectroscopy, Georg Thieme, Stuttgart, 1984, pp. 155 and 207.
7 K. Heyns and W. Stumme, Chem. Ber., 1956, 89, 2833.
8 M. Bush and G. Hefele, J. Prakt. Chem., 1911, 83, 524.
9 M. D. Farnow and C. K. Ingold, J. Chem. Soc., 1924, 125,
2534.
10 F. Benington, R. D. Morin and L. C. Clark Jr, J. Org. Chem.,
1958, 23, 19.
11 A. Bryson, N. R. Davies and E. P. Serjeant, J. Am. Chem. Soc.,
1963, 85, 1933.
aryl CH), 128.26 (aryl CCOH), 138.0 (aryl NC), 159.57 and 159.65
.
(aryl COCH3), 164.63 (C N); MS m/z (%) 471 (M 2, 1), 469
(M , 1), 425 (8), 407 (34), 389 (M -HBr, 9), 370 (19), 283 (8), 148
(6), 136 (29), 108 (100), 81 (15), 80 (24), 79 (15) (Found: C, 61.50;
H, 5.37; N, 6.35. Calc. for C24H25BrN2O3: C, 61.41, H, 5.37;
N, 5.97%).
N-(4-Methylphenyl)-N-[1-(4-methylphenylimino)ethyl]glycine 5a.Ð
Colourless crystals (190 mg, 64%), mp 154 8C (from ethyl acetate±
cyclohexane); IR 3295 (OH), 1662 cm (CO); 1H NMR (CDCl3)
1
ꢁ 2.12 (3 H, s, CH3), 2.30 (3 H, s, aryl CH3), 2.33 (3 H, s, aryl
CH3), 4.40 (2 H, s, CH2), 7.01±7.40 (8 H, all m, aryl H), 8.70 (1 H,
12 M. A.-M. Gomaa, S. K. Mohamed and A. M. Nour El-Din,
J. Chem. Res. (S ), 1997, 284.