1h and 13c nmr spectral assignments of 2,4-diaryl-substituted cycloalkyl[d]pyrimidines

MAGNETIC RESONANCE IN CHEMISTRYMagn. Reson. Chem. 2002; 40: 293–299

Spectral Assignments and Reference Data

1H and 13C NMR spectral assignments of2,4-diaryl-substitutedcycloalkyl[d]pyrimidines

Antonio Herrera,1 Roberto Martınez-Alvarez,1∗

Mourad Chioua,1 Angel Sanchez,2 Dolores Molero2 andRachid Chioua3

1 Departamento de Quımica Organica, Facultad de Ciencias Quımicas,Universidad Complutense, E-28040 Madrid, Spain2 CAI de RMN, Universidad Complutense, E-28040 Madrid, Spain3 Departement de Chimie, Faculte de Sciences, Universite Abdel MalkEssadi, Tetouan, Morocco

Received 13 July 2001; revised 21 November 2001; accepted 23 November 2001

The proton and carbon spectra of new 2,4-diaryl-substituted cycloalkyl[d]pyrimidines prepared in a sim-ple one-pot reaction, are reported. Copyright 2002 JohnWiley & Sons, Ltd.

KEYWORDS: NMR; 1H NMR; 13C NMR; cycloalkyl[d]pyrimidines

INTRODUCTION

Cycloalkane fused pyrimidines are compounds with important anddifferent applications.1,2 Among these, cyclobutapyrimidines areof particular interest as the origin of ortho-quinodimethanes,3 andcyclopentapyrimidines can be used as inhibitors of opportunisticmicrobes.4 Higher derivatives exhibit pharmaceutical activity5 andare employed as intermediates in enantioselective syntheses.6 Wehave reported that the one-step reaction of a ketone with twoequivalents of the corresponding nitrile and one equivalent of triflicanhydride at room temperature leads to the formation of pyrimidinesin good yields.7

RESULTS AND DISCUSSION

We report here the 1H and 13C NMR assignments of a seriesof 2,4-diaryl-substituted cycloalkyl[d]pyrimidines (1–9) fused withdifferent alkyl rings (Scheme 1). Although the biological propertiesof the cycloalkyl[d]pyrimidines are very different, depending onthe alkyl ring size, their structural properties are closely related.Therefore, we describe a study of the 1H and 13C NMR spectra ofthese new compounds. In order to assign unequivocally the NMRsignals, 1D and 2D techniques such NOE, DEPT(135), HMQC andHMBC were performed.

The aliphatic portion of the 1H NMR spectra at 300 MHzof the cycloalkylpyrimidines are listed in Table 1. The protonscorresponding to the methyl group attached at the phenyl ring(1b–9b) and the methoxyl group for compounds 9a–c appear assinglets. For the methylene groups of the alkyl rings the resonances liein the range 3.5–1.3 ppm, forming a singlet at 4.2 ppm for compounds7. The protons of the carbon atoms bonded to the pyrimidine ringappear as first-order triplets with values of 3J in the range 5.7–8.0Hz for 2, 3, 5 and 6. In contrast, the methylene groups of 1, 8 and9 form AA’BB’ spin systems. The methylene groups of compounds4 exhibit complexity which cannot be resolved using homonucleardecoupling. The protons of the methylene group corresponding tothe C-5 and C-9 positions in compounds 4 appear as a multiplet.Homonuclear irradiation of the neighbouring nuclei at the C-6 andC-8 positions does not remove totally the multiplet structure of H-5and H-9 (see Table 1). The chemical shifts of the aromatic protons

ŁCorrespondence to: R. Martinez-Alvarez, Departamento de QuıimicaOrganica, Facultad de Ciencias Quıimicas, Universidad Complutense,E-28040 Madrid, Spain. E-mail: [email protected]/grant sponsor: DGESIC; Contract/grant number: PB 98-0803.Contract/grant sponsor: Agencia Espanola de Cooperacion International;Contract/grant number: PR 120/00-8980.

are collected in Table 2. In most cases these protons form AA’XX’systems. To differentiate the H-1 chemical shifts of ring 1 from thoseof ring 2, NOE experiments were carried out. Irradiation at thefrequency of the protons at C-5 reveals the chemical shifts of theprotons located at the ortho position of ring 1. A further (H,H)COSYexperiment allows one to determine the position of all the otheraromatic protons of ring 1 and hence the position of the aromaticprotons of ring 2. For compounds 7 irradiation at the frequency of C-5also reveals the position of H-6, while irradiation of C-5 and C-6 in 8and 9 is used to assign the protons of ring 3. 13C NMR signals wereassigned in a straightforward manner by the analysis of the HMQCspectrum for the protonated carbons on the basis of the chemicalshift theory, substituent effects and DEPT data. The assignmentswere supported by the HMBC cross peaks. The 13C NMR spectra ofthe compounds exhibit signals in the aromatic and aliphatic regions(see Table 3). For the heterocyclic systems, the spectra showed fourquaternary carbon signals.8,9 In order to assign all of these signalswe used the 1D and 2D techniques. The signal corresponding to thehighest frequency is assigned to the bridge carbon atom attachedto the N-1 position and the signal at lowest frequency is due to thebridge carbon atom C-4a. These signals are relatively insensitive tothe size of the alkyl fused ring. The calculated values10 of chemicalshifts of the methylene groups of the alkyl rings indicate that thesignal at highest frequency could be assigned to C-6 for 2, 3, 4, 5and 6 (the theoretical chemical shift values were calculated usingUpsol NMRPrediction 1.110). These values are in disagreement withthe observed υ values, which indicate that the deshielded methylenesignal corresponds to the carbon atom in the ˇ-position to N-1. Incontrast, cyclopentapyrimidines 2 exhibit a higher υ value for C-5.These assignment were confirmed by the cross peaks in the HMQCand HMBC spectra.

EXPERIMENTAL

MaterialCompounds were prepared according the reported synthetic methodby reaction of cyclic ketones with the appropriate aromatic nitrile.7The corresponding pyrimidines were purified by recrystallization.Compatible IR and mass spectra and combustion analyses weretaken for each compound.

SpectraAll NMR experiments were performed at 293 K for a solution of30 mg of compound dissolved in 0.7 ml of CDCl3 on a BrukerAvance-300 instrument with a 5 mm QNP probe head equippedwith shielded Z-gradient coil. 1H NMR spectra were recorded at a1H frequency of 300.13 MHz with a spectral width of 4.5 kHz and a2.4 µ s (30°) pulse. The acquisition time was 1.8 s and the relaxationdelay 1 s; 16 scans with 16K data points each were used. The 13 C NMRspectra were recorded using a spectral width of 20 kHz and a 1.9 µ s(30°) pulse. The acquisition time was 1.7 s and 512 scans with 64 Kdata points each were used. Exponential multiplication was appliedbefore Fourier transformation in both cases. The chemical shiftswere referenced to tetramethylsilane. The one-bond heteronuclearcorrelation (HMQC) spectra were obtained using the inv4gs programin the Bruker software. The spectra resulted from a 128 ð 2048 datamatrix with eight scans per t1 increment. Spectral widths of 16.7 kHzin F1 and 3.5 kHz in F2 were recorded. The acquisition time was0.22 s, the delay was set to 3.45 ms for an averaged 1J(C,H) of 145 Hzand the recycle time was 1.55 s. Fourier transformation was done ona 2K ð 1K data matrix. The long range 1H–13C correlation (HMBC)spectra were obtained using the inv4gslplrnd program in the Brukersoftware. The spectra resulted from a 128 ð 2048 data matrix sizewith 16 scans per t1 increment. Spectral widths of 3.5 kHz in F1 and16.7 kHz in F2 were recorded. The acquisition time was 0.28 s, thedelay was set to 3.45 ms [1/2 J(C,H)] and 65 ms [1/nJ(C,H)] andthe recycle time was 1.55 s. Fourier transformation was done on a2K ð 1K data matrix.

AcknowledgmentsWe thank the DGESIC (Spain) (PB 98-0803) and Agencia Espanolade Cooperacion Internacional (PR 120/00-8980) for financial sup-port. We thank the reviewer who suggested carrying out the NOEexperiments.

DOI: 10.1002/mrc.1002 Copyright 2002 John Wiley & Sons, Ltd.

294


Tab

le1.

1H

NM

Rd

ata

ofal

ipha

ticp

roto

nsfo

rco

mp

ound

s1a

–9c

(υ,p

pm

;J,H

z)

Com

pou

ndH

-5H

-6H

-7H

-8H

-9H

-10

Oth

ers

CH

3

1a3.

533.

61A

A‘B

B’s

yste

m1b

3.43

3.53

2.45

AA

‘BB

’sys

tem

1c3.

513.

62A

A‘B

B’s

yste

m2a

3.12

(t)

2.17

(q)

3.22

(t)

�JD

8.0�

�JD

8.0�

�JD

8.0�

2.43

2b3.

10(t

)2.

15(q

)3.

21(t

)2.

44�J

D7.

5��J

D7.

5��J

D7.

5�2c

3.10

(t)

2.20

(q)

3.20

(t)

�JD

6.5�

�JD

6.5�

�JD

6.5�

3a2.

80(t

)1.

80(m

)1.

95(m

)3.

05(t

)2.

42�J

D6.

5��J

D6.

5�2.

443b

2.80

(t)

1.75

(q)

1.95

(q)

3.05

(t)

�JD

6.5�

�JD

6.5�

3c2.

75(t

)1.

77(q

)1.

96(q

)3.

02(t

)�J

D6.

5��J

D6.

5�4a

2.90

(m)

1.81

(m)

1.72

(m)

1.90

(m)

3.15

(m)

4b2.

87(m

)1.

81(m

)1.

72(m

)1.

93(m

)3.

15(m

)2.

402.

454c

2.85

(m)

1.82

(m)

1.70

(m)

1.93

(m)

3.15

(m)

5a2.

85(t

)1.

62(m

)1.

46(m

)1.

95(m

)3.

10(t

)�J

D5.

7��J

D5.

7�5b

2.85

(t)

1.60

(m)

1.50

(m)

1.90

(m)

3.05

(t)

2.40

�JD

6.0�

�JD

6.0�

2.45

Copyright 2002 John Wiley & Sons, Ltd. Magn. Reson. Chem. 2002; 40: 293–299

295

Spectral Assignments and Reference Data5c

2.80

(t)

1.65

(m)

1.45

(m)

1.90

(m)

3.00

(t)

�JD

6.0�

�JD

6.0�

6a2.

65(t

)1.

65(m

)1.

35(m

)2.

90(t

,JD

7.0,

H-1

7)�J

D7.

0�to

geth

erw

ith

H-1

1,H

-12,

H-1

3,H

-14

and

H-1

51.

95(m

,H-1

6)6b

2.63

(t)

1.63

(m)

1.30

(m)

2.85

(t,J

D7.

0,H

-17)

2.40

�JD

7.0�

toge

ther

wit

hH

-11,

H-1

2,H

-13,

H-1

4an

dH

-15

1.92

(m,H

-16)

2.43

6c2.

60(t

)1.

65(m

)1.

35(m

)2.

85(t

,JD

7.0,

H-1

7)�J

D7.

0�to

geth

erw

ith

H-1

1,H

-12,

H-1

3,H

-14

and

H-1

51.

90(m

,H-1

6)7a

4.20

(s)

2.46

7b4.

25(s

)2.

477c

4.25

(s)

8a2.

923.

10A

A‘B

B’s

yste

m8b

2.91

3.10

2.44

AA

‘BB

’sys

tem

2.46

8c2.

923.

06A

A‘B

B’s

yste

m9a

2.90

3.08

3.90

�OC

H3�

AA

‘BB

’sys

tem

9b2.

883.

103.

90�O

CH

3�2.

45A

A‘B

B’s

yste

m2.

509c

2.87

3.04

3.90

�OC

H3�

AA

‘BB

’sys

tem


296


Table 2. 1H NMR data of aromatic protons for compounds 1a–9c (υ, ppm; J, Hz)

Compound Ring 1 Ring 2 Ring 3

1a 8.20 (H-8, H-80), 8.60 (H-12, H-120)7.55 (H-9, H-90, H-10) 7.55 (H-13, H-130, H-14)

1b 8.10 (H-8, H-80) 8.50 (H-12, H-120)7.35 (H-9, H-90) 7.55 (H-13, H-130)

1c 8.10 (H-8, H-80) 8.50 (H-12, H-120)7.50 (H-9, H-90) 7.63 (H-13, H-130)

2a 8.05 (H-9, H-90) 8.55 (H-13, H-130)7.55 (H-10, H-100, H-11) 7.55 (H-14, H-140, H-15)

2b 8.00 (H-9, H-90) 8.45 (H-13, H-130)7.35 (H-10, H-100) 7.35 (H-14, H-140)

2c 8.00 (H-9, H-90) 8.50 (H-13, H-130)7.45 (H-10, H-100) 7.45 (H-14, H-140)

3a 7.70 (H-10, H-100) 8.45 (H-14, H-140)7.45 (H-11, H-110, H-12) 7.45 (H-15, H-150, H-16)

3b 7.70 (H-10, H-100) 8.40 (H-14, H-140)7.60 (H-11, H-110) 7.60 (H-15, H-150)

3c 7.60 (H-10, H-100) 8.41 (H-14, H-140)7.45 (H-11, H-110) 7.45 (H-15, H-150)

4a 7.65 (H-11, H-110) 8.50 (H-15, H-150)7.45 (H-12, H-120, H-13) 7.45 (H-16, H-160, H-17)

4b 7.55 (H-11, H-110) 8.35 (H-15, H-150)7.30 (H-12, H-120) 7.30 (H-16, H-160)

4c 7.50 (H-11, H-110) 8.45 (H-15, H-150)7.45 (H-12, H-120) 7.45 (H-16, H-160)

5a 7.54 (H-12, H-120) 8.47 (H-16, H-160)7.47 (H-13, H-130, H-14) 7.47 (H-17, H-170, H-18)

5b 7.45 (H-12, H-120) 8.35 (H-16, H-160)7.26 (H-13, H-130) 7.26 (H-17, H-170)

5c 7.47 (H-12, H-120) 8.42 (H-16, H-160)7.42 (H-13, H-130) 7.42 (H-17, H-170)

6a 7.52 (H-19, H-190) 8.47 (H-23, H-230)7.46 (H-20, H-20, H-21) 7.46 (H-24, H-24, H-25)

6b 7.45 (H-19, H-190) 8.37 (H-23, H-230)7.25 (H-20, H-200) 7.25 (H-24, H-240)

6c 7.45 (H-19, H-190) 8.43 (H-23, H-230)7.40 (H-20, H-200) 7.40 (H-20, H-200)

7a 7.55 (H-11, H-110) 8.75 (H-15, H-150) 8.40 (H-6, H-9), 7.67 (H-7, H-8)7.52 (H-12, H-120, H-13) 8.35 (H-16, H-160, H-17)

7b 7.30 (H-11, H-110) 8.62 (H-15, H-150) 8.35 (H-6), 7.53 (H-9), 7.40 (H-7, H-8)7.25 (H-12, H-120) 8.18 (H-16, H-160)

7c 7.55 (H-11, H-110) 8.65 (H-15, H-150) 8.20 (H-6), 7.57 (H-9), 7.67 (H-7, H-8)7.53 (H-12, H-120) 8.25 (H-16, H-160)

8a 8.66 (H-12, H-120) 7.55 (H-16, H-160) 8.60 (H-10), 7.40 (H-8, H-9), 7.29 (H-7)7.45 (H-13, H-130, H-14) 7.45 (H-17, H-170, H-18)

8b 8.57 (H-12, H-120) 7.65 (H-16, H-160) 8.60 (H-10), 7.40 (H-8, H-9), 7.29 (H-7)7.35 (H-13, H-130) 7.35 (H-17, H-170)

8c 8.66 (H-12, H-120) 7.70 (H-16, H-160) 8.50 (H-10), 7.50 (H-8, H-9), 7.30 (H-7)7.40 (H-13, H-130) 7.40 (H-17, H-170)


297


Table 2. (Continued)

Compound Ring 1 Ring 2 Ring 3

9a 8.83 (H-12, H-120) 7.72 (H-16, H-160) 8.55 (H-10, J D 8.4), 6.98 (H-9, J D 8.4, 2.5), 6.78 (H-7, J D 8.4, 2.5)7.50 (H-13, H-130, H-14) 7.50 (H-17, H-170, H-18)

9b 8.53 (H-12, H-120) 7.63 (H-16, H-160) 8.33 (H-10, J D 8.5), 6.97 (H-9, J D 8.5, 2.5), 6.78 (H-7, J D 8.5, 2.5)7.29 (H-13, H-130) 7.29 (H-17, H-170)

9c 8.53 (H-12, H-120) 7.67 (H-16, H-160) 8.50 (H-10, J D 8.4), 6.97 (H-9, J D 8.4, 2.4), 6.78 (H-7, J D 8.4, 2.4)7.45 (H-13, H-130) 7.45 (H-17, H-170)

Table 3. Significant 13C NMR chemical shifts for compounds 1a–9c (υ ppm)

Compound Cycloalkyl ring Pyrimidine ring Phenyl rings

1a 28.1 (C-5), 36.2 (C-6) 132.1 (C-4a), 155.0 (C-2),164.4 (C-4), 174.3 (C-6a)

127.8 (C-9), 128.1 (C-13), 129.2 (C-14), 129.6 (C-12),131.4 (C-8), 136.1 (C-10), 140.4 (C-11), 141.4 (C-7)

1b 29.1 (C-5), 36.2 (C-6) 131.4 (C-4a), 154.6 (C-2),164.3 (C-4), 174.0 (C-6a)

21.5 �CH3�, 21.7 �CH3�, 127.9 (C-9), 128.1 (C-13), 128.5(C-14), 128.9 (C-12), 130.3 (C-8), 135.1 (C-10), 135.8(C-11), 138.7 (C-7)

1c 29.0 (C-5), 36.0 (C-6) 132.0 (C-4a), 153.5 (C-2),163.4 (C-4), 174.5 (C-6a)

128.6 (C-9), 129.0 (C-13), 129.2 (C-14), 134.0 (C-12),136.5 (C-8), 136.9 (C-10), 137.2 (C-7, C-11)

2a 22.7 (C-6), 30.8 (C-7),34.3 (C-5)

128.0 (C-4a), 159.1 (C-2),163.0 (C-4a), 176.4 (C-7a)

128.3 (C-10), 128.4 (C-14), 128.6 (C-15), 128.9 (C-13),129.7 (C-9), 130.0 (C-11), 137.9 (C-12), 138.1 (C-8)

2b 22.8 (C-6), 30.9 (C-7),34.4 (C-5)

128.0 (C-2), 159.1 (C-2),163.0 (C-4), 176.2 (C-7a)

21.4 �CH3�, 21.5 �CH3�, 128.3 (C-10), 128.6 (C-14), 129.1(C-15), 129.2 (C-13), 135.3 (C-11), 135.6 (C-12), 140.0(C-8)

2c 22.8 (C-6), 30.9 (C-7),34.3 (C-5)

128.0 (C-2), 158.1 (C-2),162.1 (C-4), 176.9 (C-7a)

128.8 (C-10), 129.1 (C-14), 129.4 (C-15), 130.0 (C-13),136.1 (C-9), 136.3 (C-11), 136.4 (C-12), 136.5 (C-8)

3a 22.4 (C-7), 22.9 (C-6),26.9 (C-5), 32.7 (C-8)

125.0 (C-4a), 161.4 (C-4),165.1 (C-2), 166.5 (C-8a)

128.0 (C-11), 128.2 (C-15), 128.3 (C-16), 128.9 (C-14),129.0 (C-10), 129.9 (C-12), 138.1 (C-13), 138.6 (C-9)

3b 21.4 (C-7), 21.5 (C-6),27.8 (C-5), 32.7 (C-8)

125.6 (C-4a), 160.4 (C-4),165.0 (C-2), 166.5 (C-8a)

128.0 (C-11), 128.9 (C-15), 129.0 (C-16), 129.1 (C-14),135.5 (C-10), 135.9 (C-12), 138.9 (C-13), 140.0 (C-9)

3c 22.3 (C-7), 22.8 (C-6),27.0 (C-5), 32.7 (C-8)

125.6 (C-4a), 160.4 (C-4),164.0 (C-2), 167.8 (C-8a)

128.4 (C-11), 128.5 (C-15), 129.3 (C-16), 130.4 (C-14),135.2 (C-10), 136.2 (C-12), 136.4 (C-13), 136.8 (C-9)

4a 26.1 (C-6), 27.7 (C-7),29.1 (C-5), 32.2 (C-8),39.3 (C-9)

130.3 (C-4a), 161.0 (C-4),164.3 (C-2), 172.7 (C-9a)

128.0 (C-16), 128.1 (C-12), 128.3 (C-11), 128.6 (C-13),129.2 (C-15), 129.9 (C-10), 138.1 (C-17), 139.2 (C-14)

4b 26.1 (C-6), 27.7 (C-7),29.1 (C-5), 32.3 (C-8),39.5 (C-9)

130.0 (C-4a), 161.0 (C-4),164.2 (C-2), 172.5 (C-9a)

21.3 �CH3�, 21.4 �CH3�, 127.9 (C-16), 128.0 (C-12), 128.9(C-11), 129.0 (C-13), 129.2 (C-15), 135.4 (C-10), 136.4(C-17), 139.9 (C-14)

4c 26.0 (C-6), 27.6 (C-7),29.1 (C-5), 32.1 (C-8),39.3 (C-9)

130.2 (C-4a), 160.0 (C-4),164.4 (C-2), 173.1 (C-9a)

128.5 (C-16), 128.6 (C-12), 129.3 (C-11), 135.0 (C-13),136.3 (C-15), 137.0 (C-10), 137.2 (C-17), 144.2 (C-14)

5a 25.8 (C-7), 26.2 (C-8),26.5 (C-5), 30.3 (C-9),31.3 (C-6), 35.0 (C-10)

129.9 (C-4a), 161.5 (C-4),165.5 (C-2), 170.8 (C-10a)

128.1 (C-16, C-17), 128.3 (C-12, C-13), 128.5 (C-18),128.6 (C-11), 138.1 (C-14), 139.5 (C-15)

5b 25.8 (C-7), 26.3 (C-8),26.5 (C-5), 30.0 (C-9),31.4 (C-6), 35.0 (C-10)

129.0 (C-4a), 161.6 (C-4),165.4 (C-2), 170.5 (C-10a)

21.3 �CH3�, 21.4 �CH3�, 128.0 (C-16), 128.6 (C-17,C-12), 128.8, (C-13) 135.5 (C-18), 136.8 (C-11), 138.3(C-14), 140.6 (C-15)

5c 25.7 (C-7), 26.2 (C-8),26.5 (C-5), 30.3 (C-9),31.2 (C-6), 35.0 (C-10)

129.4 (C-4a), 160.6 (C-4),164.3 (C-2), 171.2 (C-10a)

128.4 (C-16), 128.5 (C-17), 128.8 (C-12), 130.0 (C-13),134.8 (C-18), 136.2 (C-11), 136.4 (C-14), 137.7 (C-15)

(continued overleaf )


298


Table 3. (Continued)

Compound Cycloalkyl ring Pyrimidine ring Phenyl rings

6a 25.2, 25.4, 25.8, 26.1,26.4, 26.5, 26.7, 27.3,27.4, 27.5 (C-6), 28.0(C-16), 28.9 (C-5), 34.5(C-17),

129.4 (C-4a), 160.1 (C-4),164.8 (C-2), 170.2 (C-17a)

128.5 (C-24), 128.8 (C-20), 130.0 (C-19), 134.7 (C-21),136.2 (C-23), 136.5 (C-18), 137.9 (C-25, C-22)

6b 25.2, 25.4, 25.8, 26.1,26.4, 26.5, 26.7, 27.3,27.4 (C-6), 28.0 (C-16),28.9 (C-5), 34.5 (C-17)

129.0 (C-4a), 161.1 (C-4),165.9 (C-2) 169.6 (C-17a),

21.3 �CH3� 21.4 �CH3�, 128.0 (C-24), 128.2 (C-20), 128.5(C-19), 128.8 (C-21), 135.5 (C-23), 136.9 (C-18), 138.3(C-25), 139.9 (C-22)

6c 25.2, 25.4, 25.8, 26.1,26.5, 26.7, 27.2, 27.3,27.4 (C-6), 28.0 (C-16),28.8 (C-5), 34.5 (C-17)

129.4 (C-4a), 160.1 (C-4),164.8 (C-2), 170.2 (C-17a)

128.5 (C-24), 128.8 (C-20), 129.4 (C-19), 130.0 (C-21),134.7 (C-23), 136.2 (C-18), 136.5 (C-25), 137.9 (C-22)

7a 35.3 (C-5) 159.4 (C-2), 161.0 (C-4a)163.8 (C-4), 169.4 (C-4b)

122.4 (C-8), 125.1, 127.5, 127.6 (C-5a), 128.4, 128.7,130.1, 130.3, 130.8 (C-9a), 136.7 (C-7), 138.0, 138.4 (C-6),139.3 (C-9), 145.0

7b 35.4 (C-5) 159.1 (C-2), 160.2 (C-4a),163.6 (C-4), 169.0 (C-4b)

21.4 �CH3�, 21.5 �CH3�, 122.3 (C-9), 125.0 (C-6), 127.0(C-7), 127.4 (C-10), 128.3 (C-11), 128.6 (C-16), 129.1(C-13), 129.3 (C-12), 130.5 (C-8), 135.3 (C-15), 135.8(C-17), 136.5 (C-5a), 139.4 (C-14), 140.4 (C-9a)

7c 35.5 (C-5) 159.4 (C-2), 162.1 (C-4a)163.8 (C-4), 169.4 (C-4b)

122.4 (C-9, C-6), 125.1 (C-7, C-10), 127.7 (C-11), 128.6(C-16), 129.0 (C-13), 129.7 (C-12), 129.9 (C-8), 131.0(C-15, C-14), 136.6 (C-17, C-15), 144.8 (C-5a), 145.0(C-9a)

8a 24.8 (C-5), 27.8 (C-6) 123.4 (C-4a), 160.1 (C-2),162.1 (C-4b), 164.3 (C-4)

126.0 (C-9), 127.2 (C-8), 127.7 (C-7), 128.1 (C-10a), 128.2(C-17, C-16), 128.3 (C-12), 129.2 (C-15, C-11), 130.2(C-10), 130.8 (C-13), 133.3 (C-14), 138.2 (C-18), 139.0(C-6a)

8b 24.7 (C-5), 27.8 (C-6) 123.4 (C-4a), 160.1 (C-2),162.1 (C-4b), 164.3 (C-4)

21.4 �CH3�, 21.5 �CH3�, 126.0 (C-9), 127.2 (C-8), 127.7(C-7), 128.1 (C-10a), 128.2 (C-17, C-16), 128.3 (C-12),129.2 (C-11, C-15), 130.2 (C-10), 130.8 (C-13), 133.3(C-14), 138.2 (C-18), 139.0 (C-6a)

8c 24.7 (C-5), 27.7 (C-6) 123.6 (C-4a), 160.4 (C-2),161.2 (C-4b), 163.1 (C-4)

126.0 (C-9), 127.3 (C-8), 127.8 (C-7), 128.6 (C-10a), 129.4(C-17, C-16), 130.5 (C-12), 131.0 (C-15, C-11), 133.0(C-10), 135.5 (C-13), 136.4 (C-14), 136.6 (C-18), 139.0(C-6a)

9a 24.8 (C-5), 28.2 (C-6) 138.3 (C-4a), 161.8 (C-4b)162.0 (C-2), 163.7 (C-4)

55.4 (OCH3), 112.8 (C-9), 126.3 (C-7), 128.1 (C-6a),128.2 (C-10), 128.3 (C-16, C-17), 128.5 (C-12, C-13),129.0 (C-14), 129.1 (C-11), 129.5 (C-18), 129.7 (C-15),130.1 (C-10a), 160.5 (C-8)

9b 24.8 (C-5), 28.2 (C-6) 139.0 (C-4a), 159.8 (C-4b)161.0 (C-2), 163.3 (C-4)

21.4 �CH3�, 21.5 �CH3�, 55.4 �OCH3�, 112.7 (C-9), 112.8(C-7), 121.9 (C-6a), 126.4 (C-10), 127.8 (C-16), 128.0(C-14), 128.9 (C-11), 129.1 (C-17), 129.7 (C-10a), 135.0(C-12), 136.8 (C-13), 139.0 (C-15), 139.5 (C-18), 140.4(C-15), 162.0 (C-8)

9c 24.7 (C-5), 28.0 (C-6) 122.5 (C-4a), 161.0 (C-4b)162.0 (C-2), 162.6 (C-4)

55.4 �OCH3�, 112.8 (C-9), 113.0 (C-7), 125.9 (C-6a),127.9 (C-10), 128.5 (C-16), 129.4 (C-14), 129.7 (C-11),130.5 (C-17), 132.0 (C-15), 133.3 (C-10a), 136.3 (C-12),136.6 (C-13), 139.7 (C-18), 160.3 (C-8)


299


Scheme 1. Compounds studied.

REFERENCES

1. Brown DJ. In The Pyrimidines, Taylor EC, Weissberger A (eds).Wiley: Sons: New York, 1994; 241.

2. Katrizky AR, Rees CW. Comprehensive Heterocyclic Chemistry, vol.3. Pergamon Press: Oxford, 1984; 111.

3. Martin N, Segura JL. Chem. Rev. 1999; 99: 3199.4. Rosowsky A, Papoulis AT, Queener SF. J. Med. Chem. 1998; 41:

913.5. Bernath G, Lazar J, Gera L, Gondos G, Ecsery Z. Acta Chim. Hung.

1984; 115: 231.

6. Szakonyi Z, Fulop F, Bernath G, Torok G, Peter P. Tetrahedron:Asymmetry 1998; 9: 993.

7. Martınez AG, Fernandez AH, Jimenez FM, Fraile AG, Subrama-nian LR, Hanack M. J. Org. Chem. 1992; 57: 1627.

8. Tsujimoto T, Kobayashi C, Sasaki Y. Chem. Pharm. Bull. 1979; 27:691.

9. Proba Z, Wierzchowski KL. J. Chem. Soc. Perkin Trans. 2 1978;1119.

10. Pretsch E, Buhlmann P, Affolter C, Herrera A, Martınez R.Determinacion Estructural de Compuestos Organicos. Springer:Barcelona, 2001.


1h and 13c nmr spectral assignments of 2,4-diaryl-substituted cycloalkyl[d]pyrimidines

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