Reaction of Symmetric N1,N2-Diarylamidines with a-Bromoacetophenone and Ethyl 2-Bromoethanoate$ Mohsen Abdel-Motaal Gomaa Chemistry Department, Faculty of Science, Minia University, 61519 El-Minia, Egypt 2-Bromo-1-faryl[1-(arylimino)ethyl]aminog-1-phenylethanol derivatives 3a, 3b were obtained from the reaction of N1,N2-diarylacetamidines 1a, 1b with -bromoacetophenone 2, while 1a, 1b with ethyl 2-bromoethanoate 4 afforded 2-f[1-(arylimino)]ethylgaminoethanoic acid derivatives 5a, 5b; N1,N2-diarylformamidines 6a, 6b reacted with 2 and 4 to give the arylaminoacetophenones 8a, 8b and N-arylglycine ethyl esters 11a, 11b respectively together with the corresponding formanilides 9a, 9b.N1,N2-Disubstituted formamidines condensed with active methylene compounds leading to enamines and the corre- sponding free amines.1 This condensation was utilized to synthesize quinoline derivatives by treating N1,N2-diaryl- formamidines with ethyl malonate.2 On the other hand b-cyanoesters condensed with free acetamidines to give 2-amino-4-hydroxypyridine.3 Previously it was reported that N,N,N'-triarylamidines when treated with tetrahalogeno- benzoquinones underwent cleavage into 2-(arylamino)-3,5,6- trihalogeno-1,4-benzoquinones and their 2,5-bis(arylamino) analogues together with the corresponding formanilides.4 N1,N2-Diarylformamidines reacted with dichloro-1,4- naphthoquinone (DC1NQ) and tetrachlorobenzoquinone (CHL) to give 2-(arylamino)-3-(formylarylamino)-1,4- naphthoquinones and benzimidazolinones respectively as substitution products.5 On the other hand N1,N2-diarylacet- amidines reacted with DC1NQ and CHL to a€ord the new chiral compounds 3-aryl-2-(arylimino)-9b-hydroxy-1H- benz[e]indol-5-ones and 1-aryl-2-(arylimino)-3a-hydroxy-1H- indol-6-ones respectively as substitution¡¾addition products.5 In this paper the results of the interaction of the N1,N2- diaryl-formamidines and -acetamidines with a-bromoaceto- phenone and ethyl 2-bromoethanoate are presented.N1,N2-Diarylacetamidines have two reactive sites for nucleophilic addition. When a solution of N1,N2-diarylacet- amidines 1a, 1b and a-bromoacetophenone 2 in ethanol was heated for 2 h, 2-bromo-1-{aryl[1-(arylimino)ethyl]amino}-1- phenylethanol derivatives 3a, 3b were isolated in 47¡¾50% yield. The structures of the products 3a, 3b were assigned on the basis of their elemental analysis and spectral data. In their IR spectrum the carbonyl absorption bands were not observed but the hydroxyl absorption bands were. The 1H decoupled 13C NMR spectra revealed signals between d 93.52 and 94.10 for an aliphatic quaternary carbon atom bearing a hydroxyl group.6 13C DEPT spectra exhibited negative signals between d 66.51 and 67.34 at lower ¢çeld for the methylene group attached to the bromine atom.The 1H NMR spectra showed AB patterns with dA 4.51¡¾4.61 and dB 4.71¡¾4.98 with coupling constants between 12.80 and 12.90 Hz, which indicates that a methylene group is present adjacent to a chiral carbon atom.These unexpected results indicate that the addition of the imino nitrogen atom to the carbonyl group is preferred rather than substitution on the methylene carbon atom of 2. On the other hand when the solutions of acetamidines 1a, 1b and ethyl 2-bromoethanoate 4 were heated in ethanol for 1 h, 2-{aryl[1-(arylimino)]ethyl}aminoethanoic acid deriva- tives 5a, 5b were obtained in 61¡¾64% yield.Acids 5a, 5b are formed via a replacement of the bromine atom by the amidine molecule, followed by hydrolysis by taking up a molecule of water from the ethanol used, with liberation of an ethanol molecule. This is probably due to the presence of the liberated HBr which catalyses this hydrolysis. The structures of compounds 5a, 5b were assigned on the basis of the following data. Their IR spectra showed sharp bands at 3297¡¾3295 and 1662¡¾1660 cm¢§1 for the OH and C.O of the carboxylic group respectively.In their 13C NMR spectra the characteristic signal of the carboxylic ester group at d 166.60 was replaced by signals at d 172.5 which are characteristic for the carboxylic acid carbon atom.6 The replacement of the bromine atom was also con¢çrmed from the mass spectra (m/z a 296 and 328 for 5a and 5b respect- ively) and the correct elemental analysis. N1,N2-Diarylformamidines 6a, 6b were investigated with both a-bromoacetophenone 2 and ethyl 2-bromoethanoate 4.Heating solutions of 6a, 6b and 2 in ethanol for 1 h gave the arylaminoacetophenones 8a, 8b together with the corresponding formanilides 9a, 9b. The structures of 8a, 8b7,8 and 9a, 9b9,10 were identi¢çed by comparison of their melting points with those previously reported. Also compound, 6a, 6b reacted with the ethyl 2-bromo- ethanoate in ethanol to a€ord N-arylglycine ethyl esters 11a, 11b together with the corresponding formanilides 9a, 9b. J.Chem. Research (S), 1998, 654¡¾655$ Scheme 1 Scheme 2 Scheme 3 $This is a Short Paper as de¢çned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). 654 J. CHEM. RESEARCH (S), 1998The structures of compounds 11a, 11b were identied bycomparison of their melting points with those previouslyreported.11 Thus it is obvious that the reaction of the form-amidines with 2 and 4 replaces the bromine atom to give theintermediates 7a, 7b and 10a, 10b followed by spontaneoushydrolysis (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.ConclusionN1,N2-Diaryl-formamidines and -acetamidines react withthe bromo-active methylene derivatives by nucleophilic sub-stitution rather than by condensation,1¡Ó3 while acetamidines1a, 1b with bromoacetophenone 2 they undergo nucleophilicaddition.This is probably due to electronic eects, where inthe case of 2 the carbonyl group is attached to a benzenering, which leads to faster addition than in the saturatedanalogues.ExperimentalGeneral experimental details have been described previously.12Reaction of N1,N2-Diarylacetamidines 1a, 1b with -Bromoaceto-phenone 2 and Ethyl 2-bromoethanoate 4.Solutions of compounds1a, 1b (1.0 mmol) in ethanol (10 cm3) were added to a solution of 2or 4 (1.0 mmol) in ethanol (5 cm3) and heated to reux temperaturefor 1 h.The reaction mixtures were then concentrated and the resi-dues subjected to PLC using toluene¡Óethyl 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 identied as follows:2-Bromo-1-{(4-methylphenyl )[1-(4-methylphenylimino)ethyl ]amino}-1-phenylethanol 3a.Colourless crystals (204 mg, 47%), MP 218 8C(from ethyl acetate¡Ócyclohexane); IR (KBr) 3413 cm£¾1 (OH); 1HNMR (CDCl3) 2.15 (3 H, s, CH3), 2.27 (3 H, s, CH3 aryl), 2.41(3 H, s, CH3 aryl), 4.61 (1 H, d, 1a'-H), 4.98 (1 H, d, 1b'-H, j2Jj 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),129.38 and 132.0 (aryl CCH3), 138.98 (aryl CCOH), 140.16 and140.47 (aryl NC), 164.62 (C.N); MS m/z (%) 438 (M2, 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. forC24H25BrN2O: C, 65.91; H, 5.76; N, 6.41%).2-Bromo-1-{(4-methoxyphenyl )[1-(4-methoxyphenylimino)ethyl ]-amino}-1-phenylethanol 3b.Colourless crystals (234 mg, 50%), mp205¡Ó207 8C (from ethyl acetate¡Ócyclohexane); IR (KBr) 3414 cm£¾1(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'-H, j2Jj 12.80 Hz, CH2), 6.93, 7.16, 7.27, 7.35, 7.40, 7.40, 7.73 and7.75 (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 (allaryl CH), 128.26 (aryl CCOH), 138.0 (aryl NC), 159.57 and 159.65(aryl COCH3), 164.63 (C.N); MS m/z (%) 471 (M2, 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.Colourless crystals (190 mg, 64%), mp 154 8C (from ethyl acetate¡Ócyclohexane); IR 3295 (OH), 1662 cm£¾1 (CO); 1H NMR (CDCl3) 2.12 (3 H, s, CH3), 2.30 (3 H, s, aryl CH3), 2.33 (3 H, s, arylCH3), 4.40 (2 H, s, CH2), 7.01¡Ó7.40 (8 H, all m, aryl H), 8.70 (1 H,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.Colourless crystals (200 mg, 61%), mp 144¡Ó145 8C (from ethylacetate¡Ócyclohexane); IR (KBr) 3297 (OH), 1660 cm£¾1 (CO); 1HNMR (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¡Ó4.73 (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 (allaryl H), 131.11 and 136.06 (aryl CN), 156.39 and 159.41 (arylCOCH3), 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%).Reaction of N1,N2-Diarylformamidines 6a, 6b with -Bromoaceto-phenone 2.Solutions 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 reux temperature for 1 h.After thisperiod yellow crystals of 8a, 8b were precipitated which were lteredo and recrystallized from ethanol. The ltrates were concentratedand the residues subjected to PLC using toluene¡Óethyl acetate (10:1)as the developing solvent to give two zones. The faster moving onecontained 8a, 8b while the more slowly moving one contained 9a,9b. The zones were extracted, crystallized and identied as follows:-(4-methylphenylamino)acetophenone 8a, 90 mg (40%), yellowcrystals (from ethanol), mp 126¡Ó127 8C (lit.,7 128¡Ó129 8C); -(4-methoxyphenylamino)acetophenone 8b, 88 mg (37%), yellow crys-tals (from ethanol), mp 90¡Ó92 8C (lit.,8 93 8C); 4'-methylformanilide9a, 61 mg (45%), colourless crystals (from light petroleum, bp40¡Ó60 8C), mp 53 8C (lit.,9 52 8C); 4'-methoxyformanilide 9b, 70mg(46%), colourless crystals (from light petroleum), mp 83 8C (lit.,1084¡Ó85 8C).Reaction of N1,N2-Diarylformamidines 6a, 6b with Ethyl 2-Bromo-ethanoate 4.A solution of compound 4 (167 mg, 1.0 mmol) inethanol (5 cm3) was added dropwise to a solution of formamidines6a, 6b (1.0 mmol) in ethanol (10 cm3) at room temperature, giving ayellow colour.The reaction mixture was left standing for 1 h, con-centrated and subjected to PLC using toluene¡Óethyl acetate (10:1)as developing solvent to give two zones. The faster moving one con-tained 11a, 11b while the second zone contained the correspondingformanilides 9a, 9b.The zones were extracted, crystallized andidentied 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¡Ó59 8C (lit.,1159 8C).The author is indebted to Professor Dr. D. Do pp,Division of Organic Chemistry Grhard-Mercator Universita tGH Duisburg, for the elemental analyses, NMR and massspectra.Received, 16th April 1998; Accepted, 25th June 1998Paper E/8/02858CReferences1 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,J. Chem. Soc., 1943, 388.4 A. M. Nour El-Din, A. E. Mourad, A. A. Hassan and M. A.Gomaa, Bull. Chem. Soc. Jpn., 1991, 64, 1966.5 D. Do pp, M. A.-M. 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