Indian Journal of Chemistry Vol. 398, February 2000, pp. 83 - 88

The synthesis and binding characters of 1,3-bis(uracil-113-ylmethyl)benzene based acyclic and cyclic receptors

Subodh Kumar·, Dharam Paul & Harjit Singh*

Department of Chemistry, Guru Nanak Dev University, Amritsar 143 005, India.

Received 27 July 1999; accepted (revised) 26 December 1999

The phase transfer catalysed reactions of 1,3-bis(uracil-1-ylmethyl)-2-methoxy-5-methylbenzene 2 with 2-bromoethyl methyl ether, 2-bromoethyl 2-butoxyethyl ether, I ,5-dibromo-3-oxapentane, I ,8-dibromo-3,6-dioxaoctane and I, 11-dibromo-3,6,9-trioxaun-decane provide respective acyclic receptors 4a,b and cyclic receptors 6a-c. I , 14-Bis(uracil-1-yl)-3,6,9, 12-tetraoxa-2, 13-dioxotridecane 16 reacts with 1,3-bis(bromomethyl)-2-methoxy/ acetoxy-5-methylbenzene to give cyclic receptors 17a, b. The studies on the representative cases reveal that 17b, wherein 1,3-arylidene unit is placed between N-3 positions of two uracils shows much higher order of ionophore character than 4a, 4b and 6b, wherein I ,3-arylidene unit is present between N-1 positions of uracils.

The significance of uracil and its derivatives toward complexation with H+ and other biological cations is displayed remarkably in RNA strands 1 and other catalytic functions2

• Most of their functions arise from association behaviour of embedded urea unit of uracil. The urea oxygen is sterically less hindered and a stronger binding group than ether and ester oxygens3

. The incorporation of uracil, linked through urea nitrogens, in a macrocycle could orient urea C2=0 inward the cavity3

. Despite these facts the uracil based receptors have scarcely been studied4

·5

. In podand 1, which selectively extracts and transports Tl+ picrate over alkali metal pi crates, the 1 ,3-ary lidene unit seems to play an important role in the preorganisation6

. In the present work, we have synthesized both acyclic (4a-b, 10-15) and cyclic (6a-c, 17a,b) receptors having 1 ,3-arylidene spacer between N1-N 1 (design A) or N3-N3 (design B) positions of uracil units. The other nitrogens (N3 I N 1)

bear additional appendages to give acyclic receptors

or are linked through oligoethylene glycol spacers to give cyclic receptors. The extraction profiles of representative receptors 4a, 4b, 6b, 10 and 17b towards alkali (Li+, Na+, K+), alkaline earth (Mg2+, Ca2+, Sr2+, Ba2+ ), Tl+, Ag+ and Pb2+ picrates show that the presence of 1 ,3-arylidine between N3-N3 positions of uracil leads to better ionvphores.

The selective N-1 alkylation of 2,4-bis(trimethyl­silyloxy)pyrirnidine with 1 ,3-bis(bromomethyl)-2-methoxy-5-methylbenzene7 in refluxing dichloro­ethane containing 12 (catalyst) provides 28

. The phase transfer catalysed N-3 alkylation of 2 with 2-bromoethylmethyl ether 3a provides acyclic receptor 4a. Similarly, the reaction of 2 with 3b gives 4b.

The dibromides9 Sa-Sc (1.05 equivalent) react with 2 to provide the cyclic receptors 6a (3% ), mp 303 °C, MS: rnlz 440(M+); 6b (22%), mp 279 °C, MS: rnlz 484(M+) and 6c (24%), mp 48 °C, MS : rnlz 528(M+), respectively. 1H NMR spectrum of 6a exihibits one AB quartet due to Nl-CH2 groups, one multiplet and

1 n1

0 r-R-----Fl~ 0

t >=o o=< j N~N

Me

Design A Design B

84 INDIAN J. CHEM, SEC B, FEBRUARY 2000

('oR1

R1> 0 H H 0

ot'r o ~)o I;> t "Fo ~Nj ~N k .:·~:1 N~N b

Me 3b R1 = (CH2)20Bun Me

4a R1 =Me 2

(i)

A ;tn=\ • Br 0 Br

5a n = 1 5b n = 2 5c n = 3

OTN;(-\f"\~0 \_ )=o 0=( _j N~N b

Me 6a n = 1 6b n =2

4b R1 = (CH2)20sun (i) CH3CN, K2C03, TBAHS04, reflux 6c n = 3

one distorted triplet due to two N3-CH2 CH2 groups, rnlz 472(M+). Alternatively, 13 (50%) has been also three singlets due to OCH3, ArCH3 and 2 x ArH obtained by refluxing 10 with hydroiodic acid. The protons along with two doublets due to U5-H and U6- esterification of the diacid 13 with anhydrous ethanol H. 1H NMR spectrum of 6b exihibits N1-CH2 as a in refluxing benzene containing p-tolu~nesulphonic singlet and N3-CHz and OCH2 protons as two triplets acid (with azeotropic distillation of water) affords the and one singlet and 6c shows N1-CH2 as a singlet and diester 14 (50%), mp 72 °C, MS : m/z 528(M+)_ The N3-CHz. and OCH2 as well defined four triplets along acidic hydrolysis (EtOH + HCl) of the receptor 10 with other expected signals. Therefore, 6a is a rigid provides diacid 15 (80%), mp 65 °C, MS : rn/z molecule where Nl-CH2 appear as AB quartet and 6b 486(M+). and 6c are flexible molecules. The transe:sterification of 10 with one equivalent of

The reaction of 1-(ethylcarboxymethyl)-1, 2, 3, 4- triethylene glycol under acidic (H2S04 or p-tetrahydropyrimidine-2,4-dione10 7 with 1,3-bis(bromo- toluenesulphonic acid) as well as basic (triethylamine methyl)-2-methoxy-5-methylbenzene 8 in refluxing or DBU) conditions leads to multitude of products, acetonitrile containing K2C03 and TBAHS04 gives from which pure cyclic receptor of type B could not 10 (85%), mp 58 °C, MS : ri1/z 542(M+). Similarly, the be isolated. So, to synthesize the cyclic receptors of reaction of 7 with 1,3-bis(bromomethyl)-2-acetoxy-5- type B, selective N-1 alkylation of 2,4-bis(trimethyl-methylbenzene11 9 gives the acyclic receptor 12 silyloxy)pyrimidine with appropriate dihalides and (80%), mp 92 °C, MS : rn/z 570(M+). Alternatively, subsequent cyclization with 8/9 has been used. 1,14-the acy'clic receptor 10 has been synthesized by the Bis(uracil-1-yl)-3,6,9, 12-tetraoxa-2, 13-dioxotridecane alkylation of 7 with 8 in DMF containing NaH. The has been obtained by reported procedure12. The triethylamine catalysed transesterification of 10 in n- cyclocondensation of 16 with I ,3-bis(bromomethyl)-butanol gi-ves ~he diester 11 (60%) as a thick liquid. 2-methoxy-5-methylbenzene 8 ·in retluxing aceta-

The hydrolysis of 12 in ethanol - hydrochloric acid nitrile containing K2C03 and TBA HS04 provides the (1:1) provides the diacid 13 (85%), mp 124 °C, MS: white solid (15%), m.p.118 °C. Its 1H NMR spectrum

i. acetonitrile, K2C03, TBAHS04, reflux ii. Et3N, n-BuOH, reflux iii Aqueous EtOH, HCI, reflux iv EtOH, benzene, H2S04 (catalyst),

azeotropic removal of water v HI, reflux; 36 h

(

10 R1 = Et, v 11 H1 :=sun

12 R1 = Et 13 R1 = H

14 R1 = Et

15 R1 = H

KUMAR et al.: SYNTHESIS OF ACYCLIC AND CYCLIC RECEPTORS 85

exihibits six singlets at 8 2.20(3H), 3.38(3H), 3.86(3H), 4.50(4H), 5.14(4H) and 6.66(2H); two triplets at 8 3.45(4H) and 4.25(4H); and two doublets at 8 5.81(2H) and 5.46(2H). From these data, its mass spectrum and elemental analysis, this compound has been assigned the structure 17a. Similarly, 16 reacts with 9 to provide 17b (16%), mp 125-27 °C, MS: mfz 628(M+).

In order to evaluate the binding characters of these receptors, the extraction profiles of receptors 4a, 4b, 6b, 10 and 17b towards alkali ( Li+, Na+, K+ ), alkaline earth (Mg2+, Ca2+, S~+, Ba2+ ), Tl+, Ag+ and Pb2+ cation picrates have been determined. The receptors 4a, 4b and 6b possessing 1 ,3-ary lidene unit between N !-positions of two uracils, poorly extract all metal pi crates (Table 1). The receptor 17b with 1,3-arylidene unit placed between N3 positions of uracils and possessing four effective ligating sites (2 x C2=0, and two ether units ) shows reasonable extraction of alkali, alkaline earth, Tl+, Ag+ and Pb2+ picrates but lacks selectivity towards any of the cations. Probably, in consonance with earlier results, the presence of 1,3-arylidene unit between N-3 positions of uracils provides better organisation of ligating sites and thus better extraction of metal picrates.

Therefore, selective N-1 alkylation of uracil with appropri~te dihalides to achieve bis uracil derivatives and subsequent N-3 alkylation I cyclization provides an efficient method for synthesis of acyclic and cyclic receptors. The presence of 1 ,3-arylidene units between N-3 positions of uracil leads to better organisation of ligating sites than when present between N -1

positions. However, appropriate choice of ligating sites needs to be rationalised for attaining selective binding.

Experimental Section

For general experimental see ref. 13.

Synthesis of 4a,b: General procedures: A suspension of 2 (3.70 g, 0.01 mole) in acetonitrile (100 mL) containing 2-bromoethylmethyl ether (3a; 3.48 g, 0.025 mole), K2C03 (5 g) and TBA HS04 (100 mg) was heated to reflux and the progress of reaction was monitored by TLC. After completion of reaction, K2C03 was filtered off and washed with acetonitrile. The filtrate and washings were combined and, the solvent was distilled off and the residual mixture was column chromatographed on silica gel (60-120 mesh) using ethyl acetate - chloroform (20:80) as eluent to get pure product 4a. Similarly, the reaction of 2 with 3b provided the acyclic receptor Sb.

4a: Yield 70%; (30 hr) , thick liquid; MS: rnlz 486(M+); 1H NMR (CDCh): 8 2.29(3H, s, CH3) , 3.36(6H, s, 2 x OCH3), 3.63( 4H, t, J = 5.6Hz, 2xCH2), 3.81(3H, s, OCH3), 4.20( 4H, t, J = 5.6Hz, 2 x CH2), 4.94( 4H, s, 2 x NCH2), 5.71 (2 H, d, J = 7.8Hz, U5-H ), 7.01(s, 2H, ArH), 7.14(2H, d, J = 7.8 Hz, U6-H); 13C NMR (normal I DEPT-135) (CDCh): 8 20.9l(+ve, CH3), 40.14(-ve, NCH2), 46.87(-ve, NCH2), 58.59(+ve, OCH3), 62.03(+ve, OCH3), 69.07(­ve, OCH2), 102.03(+ve, C5-H), 128.97(absent, C), 130.67(+ve, ArCH), 135.29(absent, C), 142.00(+ve, C6-H) 151.79(absent, C), 154.22(absent, C), 162.70

' I (absent, C) ; IR(KBr): 1709 (C=O), 1662 em- (C=O) (Found: C, 58.37; H, 7.32; N, 10.82. C24H3o0 1N4 requires C, 59.23; H, 6.22; N, 11.52%).

4b: Yield 80%; (30 hr), thick liquid; MS: rnlz 658(M+); 1H NMR (CDC13): 8 0.90( 6H, t, J = 7.2Hz, 3 x CH3), l.34(4H, quintet, J = 7.8Hz, 2 x CH2), 1.54 (4H, pentet, J = 7.0Hz, 2 x CH2), 2.29(3H, s, CH3), 3.41( 4H, t, J = 6.6Hz, CH2), 3.51( 4H, t, J = 4.0Hz, CH2), 3.64( 4H, t, J = 4.0Hz, CH2), 3.72(4H, t, J =

Table I- Extraction(%) profile of the receptors Sa, Sb, 7b and 18b

Metal picartes u• Na• K• Tt• Mg2• Ca2• Sr2• Ba2• Pb2• Ag•

~

Receptors.l.

4a 0.()()1 0.005 0.007 0.008 0.022 0.016 0.022 0.026 0.061 0.01 1

4b 0.011 O.ot5 0.016 0.032 0.016 0.012 0.017 0.009 0.050 0.042

6b 0.004 0.013 O.ot5 0.086 0.004 0.006 0.011 0.010 0.059

10 0.013 0.025 0.028 0.048 0.014 0.016 0.024 0.039 0.075 17b 8.849 8.712 8.803 9.165 5.411 4.834 5.269 4.875 5.578 8.384

86 INDIAN J. CHEM, SEC B. FEBRUARY 2000

6.4Hz, 2 x CH2), 3.80(3H, s, OCH3), 4.18( 4H, t, J = 6.0Hz, 2 x NCH2), 4.92( 4H, s, 2 x NCH2), 5.69(2 H, d, J = 7.9Hz, U5-H ), 7.01(2H, s, ArH), 7.14( 2H, d, J = 7.9 Hz, U6-H); 13C NMR (normal/DEPT-135) (CDCh): 8 13.80(+ve, CH3), 19.11(-ve, CH2), 20.77 (+ve, CH3), 31.57(-ve, CH2), 39.84(-ve, NCH2), 46.66(-ve, NCH2), 61.90(+ve, OCH3), 67.26(-ve, OCH2), 69.76(-ve, OCH2), 69.89(-ve, OCH2), 70.91(­ve, OCH2), 101.79(+ve, US-H), 128.84(absent, C), 130.58(+ve, ArCH), 135.08(absent, C), 141.90(+ve, U6-H), 151.54(absent, C), 154.10(absent, C), 162.49(absent. C); IR(KBr): 1709 (C=O), 1662 em- ' (C=O) (Found: C, 63.21; H, 6.76; N, 10.05. C34Hso09N4 requires C, 61.97; H, 7.65; N, 8.51%).

Synthesis of 6a-c : General procedure. A suspension of 2 (3 .70 g, 0.01 mole) in acetonitrile (800 mL) containing bis(2-bromoethyl)ether Sa ( 2.32 g, 0.01mole), K2C03 (5 g) and TBA HS04 (100 mg) was heated to reflux and the progress of reaction was monitored by TLC. After completion of reaction; K2C03 was filtered off and washed with acetonitrile. The filtrate and washings were combined and, the solvent was distilled off and the residual mixture was column chromatographed on silica gel (60-120 mesh) using ehtyl acetate - chloroform (20:80) as eluent to get pure product 6a. Similarly, the reaction of 2 with Sb and Sc provided the cyclic receptor 6b and 6c, respectively.

6a: Yield 3%; (30hr), mp 303 °C (CHCh); MS: mlz 440(M+); 1H NMR (CDC13): 8 2.41(3H, s, CH3), 3.74(3H, s, OCH3), 3.83-3.90, 4.72(4H, AB broad quartet, CH2), 4.16( 2H, d, J = 15.0Hz, 2 x NCH2) ,

5.70-5.94(4 H, m, 2 x NCH2 and U5-H ), 6.80( 2H, d, J = 7.8Hz, U6-H), 7.22(s, 2H, ArH); 13C NMR (normal I DEPT-135) (CDCh): 8 20.57(+ve, CH3), 41.30(-ve, CH2), 48.75(-ve, CH2), 62.38(+ve, OCH3), 67.70(-ve, CH2), 101.62(+ve, US-H), 130.86(absent, ArC), 133.16(+ve,ArCH), 13:'i.97(absent,ArC), 142.87 ( +ve, U6-H), 152.08(absent, ArC), 155.70(absent, C=O), 165.86(absent, C=O); IR(KBr): 1714(C=0), 1660 em- ' (C=O) (Found: C, 59.83; H, 5.63; N, 12.32. C22H24N40 6 requires C, 60.00; H, 5.45; N, 12.73%).

6b: Yield 22%;. nohr), mp 279 °C (CHCl3); MS: mlz 484(M+); 1H NMR_ (CDC13): 8 2.35(3H, s, CH3), 3.34( 4H, s, 2 x OCH2), 3.62( 4H, t, J = 5.0Hz, 2 x CH2), 3.76(3H, s, OCH3), 4.13(4H, t, J = 5.0Hz, 2 x OCH2), 4.89( 4H, s, 2 x NCH2), 5.58(2 H, d, J = 8.0Hz , US-H), 6.99( 2H, d, J = 8.0Hz, C6-H), 7.17(2H, s, ArCH) ; 13C NMR (normal I DEPT-135)

(CDCh): 8 20.59(+ve, CH3), 40.77(-ve, NCH2),

48.26(-ve, NCH2), 61.58(+ve, OCH3), 67.63(-ve, OCH3), 70.32(-ve, OCH2), 101.37(+ve, C5-H), 129.22(absent, C), l33.15(+ve, ArCH), 134.29(absent, C), 141.01(-tve, C6-H), 151.54(absent, C), 155.78 (absent, C), li 62.68(absent, C) ; IR(KBr): 1707(C=O), 1660 cm-1 (C=O) (Found: C, 59.31 ; H, 4.78; N, 11.57. Cz4H2307N4 requires C, 59.50; H, 5.78; N, 11.5%).

6c: Yield 24%; (24hr), mp 48 °C (hygroscopic); MS: mlz 528(M+); 1H NMR (CDC13): 8 2.30(3H, s, CH3), 3.01(4H, t, J = 5.0Hz, CH2), 3.36( 4H, t, J = 5.0Hz, CH2), 3.64( 4H, t, J = 5.0Hz, CH2), 3.81(3H, s, OCH3), 4.14( 4H, t, J = 5.0Hz, CH2) , 4.85( 4H, t, J = 5.0Hz, NCH2), 5.70(2 H, d, J = 7.9Hz , U5-H ), 7.12(s, 2H, ArH), 7.28( 2H, d, J = 7.8 Hz, U6-H); 13C NMR (normal/DEPT-135) (CDCh): 8 20.92(+ve, CH3), 39.70(-ve, NCH2), 46.23(-ve, NCH2), 62.05(+ve, OCH3), 67.00(-ve, OCH2), 69.71(-ve, OCH2), 70.06(-ve, OCH2), 101.52(+ve, US-H), 129.08(absent, C), 131.38( +ve, ArCH}, 134.69(absent, C), 142.54( +ve, U6-H), 151.49(absent, C), 154.65 (absent, C), 162.64(absent, C) ; IR(KBr): 1709 (C=O), 1662 cm-1 (C=O).

1,3-Bis[1-(ethylcarhoxymethyl)-2,4-dioxo-1, 2, 3, 4-tetrahydropyrimidin-3-yl )methyl]- 2-methoxy-5-methylhenzene 10. A suspension of 7 (1.98 g, 0.02 mole) in acetonitrile (30 mL) containing 8 (3.08 g, 0.01 mole), K2C03 (4 g) and TBAHS04 (50 mg) was heated to reflux and the progress of reaction was monitored by TLC. After the completion of reaction, the reaction mixture was filtered and the solid was washed with acetonitrile. The filtrate and washings were collected, the solvent was removed under vaccum and residue was column chromatographed on silica gel (60-120 mesh) using ethyl acetate- hexane (3 :7) as eluent to isolate pure 10 (85%) (24hr), mp 58°C; MS: mlz 542(M+); 1H NMR (CDCh): 8 1.29(6H, t, J = 7.2Hz, 2 x CH2), 2.18 (3H, s, CH3), 4.24 (3H, S, OCHJ), 4.45 ( 4H, S, 2 X NCH2). 5.19 ( 4H, s, 2 x NCH2}, 5.84(2 H, d, J = 8.0Hz , U5-H ), 6.68 (2H, s, ArCH),) .1 0 (2H, d, J = 8.0 Hz, U6-H ); 13C NMR (normal I DEPT-135) (CDCl3): 8 13.93(+ve, CH3), 20.99( +ve, CH3), 39.39 (-ve, CH2), 49.84(-ve, CH2), 61.05 (+ve, OCH3), 62.02(-ve, CH2), 101.97 (+ve, US-H), 126.57(+ve, Ar-CH), 129.02(absent, C), 133.56(absent, C), 142.47(+ve, U6-H), 151.37(absent, C), 153.44(absent, C), 162.36(absent, C), 167.40 (absent, C) ; IR(KBr): 1710 cm- 1 (C=O) (Found: C, 58.94; H, 6.26; N, 9.21. Cz6H300 9N4 requires C, 57.56;H, 5.57; N, 10.33%).

KUMAR et al.: SYNTHESIS OF ACYCLIC AND CYCLIC RECEPTORS 87

1,3-Bis[l-(n-butylcarboxymethyl)-2,4-dioxo-1, 2, 3, 4-tetrahydropyrimidin -3-yl)methyl]-2-methoxy-5-methylbenzene 11. The solution of diester 10 (lg, 0.0018 mole) in n-BuOH (10 mL) containing triethyl­amine (two drops) was refluxed in an oil-bath. The progress of reaction was monitored by TLC. After the completion of reaction, the solvent was removed under vaccum. The product was isolated by column chromatography on silica gel (60-120 mesh) using hexane - ethyl acetate (30:70) as eluent (60%); thick liquid; 1H NMR (CDCh): 8 0.93 (6H, t, J = 7.2Hz, CH3), 1.38 (4H, sextet, J = 7.2Hz, CH2), 1.63(4H, pentet, J = 7 .2Hz, CH2), 2.17 (3H, s, CH3), 3.93 (3H, s, OCH3), 4.17(4H, t, J = 6.6Hz, OCH2), 4.42 (4H, s, 2 x NCH2), 5.17 (4 H, s, 2 x N CH2), 5.81(2 H, d, J = 8.0Hz, U5-H), 6.66 (2H, s, ArCH), 7.11(2H, d , J = 8.0 Hz, U6-H ); 13C NMR (normal/DEPT-135) (CDC13) : 8 13.66(+ve, CH3), 19.0(-ve, CH2), 21.15 (+ve, Ar-CH3), 30.51 (-ve, CH2), 39.52(-ve, CH2), 49.84(-ve, CH2), 61.12 ( +ve, OCH3), 65.86(-ve, CH2), 102.ll(+ve, C5), 126.84 (+ve, ArC), 129.15(absent, C), 133.53(absent, C), 142.32(+ve, C6), 151.39 (absent, C), 153.66(absent, C), 162.74(absent, C), 167.40(absent, C); IR(KBr): 1710 cm-1 (C=O).

1,3-Bis[1-(ethylcarboxymethyl)-2,4-dioxo-1, 2, 3, 4-tetrahydropyrimidin- 3 -yl)methyl]- 2-acetoxy-5-methylbenzene 12. The alkylation of 7 with 9, as described for the synthesis of 10, gives the diest~r 12 (90%), mp 92 °C; MS: rnlz 570(M+); 1H NMR (CDCh): 8 1.28(6H, t, J = 7.2Hz, 2 x CH2), 2.26(3H, s, OAc), 2.37 (3H, s, CH3), 4.23 (3H, s, OCH3), 4.39(4H, S, 2 X NCH2). 4.97 (4 H, S, 2 X NCH2). 5.76(2H, d, J = 8.0Hz, U5-H ), 7.03 (2H, d, J = 8.0 Hz, U6-H), 7.08(2H, s, Ar-H),); 13C NMR (normal I DEPT-135) (CDCh): 8 13.94(+ve, CH3), 20.84(+ve, CH3), 39.50 (-ve, NCH2), 49.73(-ve, CH2), 61.72 (-ve, OCH3), 101.51(+ve, U5-H), 128.59(absent, ArC), 129.54(+ve, Ar-CH), 135.22(absent, C), 142.68(+ve, U6-H), 144.81(absent, C), 151.21(absent, C), 162.36 (absent, C), 167.28(absent, C), 169.22(absent, C); IR(KBr): 1666(C=O), 1707(C=O), 1751 cm-1 (C=O);

1, 3-Bis[1-(carboxymethyl)-2,4-dioxo-1, 2, 3, 4-tetrahydropyrimidin- 3- yl)methyl)- 2-hydroxy- 5-methyl benzene 13. The diester 12 (5 g, 0.009 mole) was refluxed in ethanol (25 mL) containing 50% HCl (25 mL) for 36 hrs. The solvent was removed under vaccum and residue was dissolved in ethyl acetate. The organic layer was filtered, concentrated and the residue was column chromatographed using ethyl acetate- hexane (5:5) to isolate 13 (85%); mp 124 °C;

MS: rnlz 472(M+); 1H NMR (CDCh+DMSO-d6): 8 2.15 (3H, S, CH3). 4.50(4H, S, 2 X NCH2). 5.00 (4H, s, 2 x NCH2), 5.78(2 H, d, J = 7 .8Hz , U5-H ), 6.83(2H, s, Ar-H), 7.55(2H, d, J = 8.0 Hz, U6-H ); 13C NMR (normal/DEPT-135) (CDCh+DMSO-d6): 8 19.21(+ve, CH3), 38.54(-ve, NCH2), 48.75(-ve, NCH2), 51.12 (+ve, OCH3), 99.40(+ve, U5-H), 121.66(absent, ArC), 126.87 (absent, ArC), 127.31(+ve, ArCH), 143.49 (+ve, U6-H), 149.33(absent, C), 150.38(absent, C), 162.16(absent, C), 167.91(absent, C); IR(KBr): 1650(C=0), 1702(C=0), 1742 cm-1 (C=O) (Found: C, 53.05; H, 4.72; N, 11.28. C21H2o09N4 requires C, 53.39; H, 4.27; N, 11.86%). Alternatively, 13 was obtained by refluxing the diester 12 in HI for 36 hrs (75%).

1,3-Bis[1-( ethylcarboxymethyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)methyl]-2-hydroxy-5-methyl benzene 14. The solution of diacid 13 (2g, 0.0042mole) in ethanol (60 mL) and benzene (180 mL) containing p-toulenesulphonic acid (catalytic amount) was refluxed and water was removed by azeotropic distillation (using Dean and Stark apparatus) and the progress of reaction was monitored by TLC. After the completion of reaction, the solvent was removed under vaccum and residue was taken in chloroform and washed with aqueous NaHC03. The organic layer was dried with anhydrous Na2S04 and chloroform was distilled off. The residue was column chromatographed on silica gel (60-120 mesh) column using hexane - ethyl acetate (30:70) as eluent to isolate 14 (60%) ; mp 72 °C ; MS: rn/z 528(M+); 1H NMR (CDCh): 8 1.27 (3H, t, J = 7.4Hz, CH3), 2.17(3H, s, CH3), 4.22 ( 4H, q, J = 7 .4Hz, OCH2), 4.39(4H, s, 2 x NCH2), 5.06(4H, s,2 x NCH2), 5.72(2 H, d, J = 8.0Hz, U5-H ), 6.92(2H, s, Ar-H), 6.99( 2H, d , J = 8.0 Hz, U6-H ), 8.86(1H, s, OH); 13C NMR (normal/DEPT-135) (CDCh): 8 14.02 (+ve, CH3), 20.47(+ve, CH3), 38.54(-ve, CH2), 49.98(-ve, CH2), 61.89 ( -ve, CH2), 101.60(+ve, U5-H), 122.74 (absent, C), 128.64(absent, ArC), 129.79(+ve, ArCH), 143.06(+ve, U6-H), 151.05(absent, C), 151.61 (absent, C), 163.36(absent, C), 167.16(absent, C); IR(KBr): 1660(C=0), 1705(C=O), 1758 cm-1 (C=O).

1, 3-Bis[l-(carboxymethyl)-2,4-dioxo-1, 2, 3, 4-tetrahydropyrimidin- 3 -yl)methyl]- 2- methoxy- 5-methyl benzene 15. The diester 10 (5 g, 0.009 mole) was refluxed in ethanol (50 mL) containing 50% HCl (50 mL) for 24 hrs. The solvent was removed under vaccum and residue was dissolved in methanol and insoluble material was filtered off and solvent was

88 INDIAN J. CHEM, SEC B, FEBRUARY 2000

removed under reduced pressure to get pure 15 (80%); mp 65 °C ; MS: rn/z 486(M+); 1H NMR (CDCh): 8 2.17 (3H, s, CH3), 3.92 (3H, S, OCHJ), 4.46(4H, S, 2 X

NCH2), 5.16 (4H, s, 2 x NCH2), 5.81(2 H, d, J = 7.8Hz, U5-H ), 6.62(2H, s, ArCH), 7.4(2H, d, J = 8.0 Hz, U6-H ); 13C NMR (normal/ DEPT-135) (CDCh): 8 21.15(+ve, CH3), 39.52(-ve, CH2), 49.84(-ve, CH2), 61.12 ( +ve, OCH3), 102.11(+ve, U5-H), 126.84 (+ve, ArCH), 129.15(absent, C), 133.53(absent, C), 142.32 ( +ve, U6-H), 151.39(absent, C), 153.66(absent, C), 162.74(absent, C), 167.40(absent, C); IR(KBr): 1662 (C=O), 1724 cm-1 (C=O) (Found: C, 52.98; H, 5.35; N, 10.86. C22H22N40 9 requires C, 54.32; H, 4.52; N, 11.52%).

Synthesis of 17a,b. The receptors 17a, b have been synthesized by using the procedure as given for receptors 6.

17a-:-Yi~ld 12% (36 hr), mp 118 °C (chloroform+ methanol); MS: rnfz 600(M+); 1H NMR (CDCI3 + DMSO-d6): 8 2.20(3H, s, CH3), 3.38(4H, s, 2 x OCH2), 3.45(4H, t, J = 4.6Hz, 2 x OCH2), 3.88(3H, s, OCH3), 4.25(4H, t, J = 4.6Hz, 2 x OCH2), 4.50(4H, s, 2 X NCH2), 5.14(4H, s, 2 X NCH2), 5.81(2H, d, J = 8.0 Hz, U5-H), 6.66(2H, s, ArH), 7.46(2H, d, J = 8.0Hz, U6-H); 13C NMR (normal/DEPT-135) (CDCh + DMSO-d6): 8 20.89( +ve, CH3), 38.65( -ve, CH2), 50.53 (-ve, CH2), 60.70(+ve, CH3), 63.81(-ve, CH2), 67.83(-ve, CH2), 69.87(-ve, CH2), 100.69(+ve, US­H), 125.98(absent, ArC), 129.09(+ve, ArCH), 133.13(absent, ArC), 144.32(+ve, U6-H), 150.99 (absent, C), 153.19(absent, C), 162.99(absent, C), 167.49 (absent, C); IR(KBr): 1680(C=0), 1702 cm-1

(C=O) (Found C, 55.70; H, 4.61; N, 9.45. C2sH32011N4 requires C, 56.00; H, 5.37; N, 9.33%).

17b. Yield 16% (36 hr), mp 125-27 °C (chloroform +methanol); MS: rnfz 628(M+); 1H NMR (CDC13): 8 2.27(3H, S, CHJ), 2.36(3H, S, CHJ), 3.48(4H, s, 2 X

OCH2), 4.31(4H, t, J = 4.6Hz, 2 x OCH2), 4.41(4H, s, 2 X NCH2). 4.97( 4H, S, 2 X NCH2), 5.80(2H, d, J = 8.0 Hz, U5-H),7.07(2H, s, ArH), 7.09(2H, d, 1=8.0Hz,

U6-H); 13C NMR (normal/DEPT-135) (CDCh): 8 20.94(+ve, CH3), 39.72(-ve, CH2), 50.44(-ve, CH2), 64.61(-ve, CH2), 68.38(-ve, CH2), 70.39(-ve, CH2), 100.76(+ve, U5-H), 128.50(absent, ArC), 129.96(+ve, ArCH), 135.26(absent, ArC), 142.49(+ve, U6-H), 145.09(absen[, C), 150.86(absent, C), 162.72 (absent, C), 167.12(absent, C), 169.53; IR(KB ): 1655 (C=O), 1718 cm-1 (C=O) (Found C, 55.82; H, 4.93; N, 7.70. C29H32012N4 requires C, 55.41; H, 5.1 3; N, 8.91%).

Acknowledgement

We thank UGC and DST, New Delhi for financial assistance.

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