MAGNETIC RESONANCE IN CHEMISTRY, VOL. 30, 11 11-1 116 (1992)

'H and 13C NMR Study of Novel Fused 1,2,4=Triazole Heterocycles

Zoltan SzabÓ* and Ferenc Kóródi

Gyula Batta

Alkaloida Chemical Company Ltd, H-4440 Tiszavasvári, Hungary

Research Group for Antibiotics of the Hungarian Academy of Sciences, Lajos Kossuth University PO Box 70, H-4010 Debrecen, Hungary

The 'H and I3C NMR spectra of some novel 1,2,4triazolo( 1,31thiazinoquinoline isomeric pairs are interpreted in terms of structural assignments. The structure of most compounds has been confirmed by NOE difference spectro- scopy. Characteristic differences have been observed in both 'H and I3C NMR spectra of these isomeric pairs: some of the 'H and I3C chemical shifts, and also the one bond 13C-'H couplings of triazole protons, differ consistently in the NMR spectra of the isomers. The coupling constants have been determined using a combination of INEPT and chemical shift selective filtering.

KEY woms 1,2,4-Triazolothiazinoquinolines NOE I3C shifts Chemical shift selective filtering

INTRODUCTION EXPERIMENTAL

Variously condensed 1,2,4-triazole heterocyclic com- pounds have become important because of their signifi- cant biological propertie~.'-~ Given this importance, a number of studies have been reported on the cyclization reaction of 1,2,4-triazole-3(5)-thiols with a-haloketones or 1,2-dihaio compounds leading to fused triazole het- e ro~yc le s .~ -~ These reactions may lead to two structural isomers depending on the orientation of the cyclization, due to the tautomerism of triazole t h i ~ l s . ~ , ~ The distinc- tion between the isomers has been achieved by compari- son of the NMR data of these compounds with those of related known compound~,~- ' ' or the structures have been proved by their unequivocal syntheses.'2*'3

An unambiguous differentiation between mono- or disubstituted triazole regioisomers based on NOE results has been p~b1ished. l~ These results confirm earlier knowledge about the structure of substituted azole deri~atives."-'~ In the preceding paper we described the synthesis of some 5H-1,2,4-triazolo[5', 1' : 2,3][ 1,3]thiazino[6,5-c]quinoline-5-ones, representa- tives of a novel ring ~ y s t e m . ~ We have extended our studies to other types of the triazolo[1,3]thi- azinoquinoline ring system, and now report the com- plete 'H and I3C assignments and structural differentiation of some new 1,2,4-triazolo[ 1,3]thi- azinoquinoline structural isomeric pairs. Our results are consistent with previously published work and provide general rules valid for these ring systems. The synthesis of the compounds investigated are published else- where."

Author to whom correspondence should be addressed.

'H (200 MHz) and 13C (50 MHz) NMR spectra were recorded on a Varian GEMINI-200 spectrometer at a probe temperature of 20°C. A 5 mm dual'probe head was used. The solvent was DMSO-d,, which also served as the interna1 reference for the 13C spectra (6 = 39.7). The 'H spectra are referenced to tri- methylsilane (TMS). Concentrations were ca. 0.5 mol 1-'. The pulse widths for the routine spectra were 10 ps (90' pulse width = 23.5 ps) for 'H and 8 ps (90° pulse width = 16.5 ps) for 13C.

Protonated carbons were assigned by running the standard Varian HETCOR sequence. The digital resolution was chosen to be good enough to allow the separation of close chemical shifts in each dimension. Non-protonated carbons were assigned by long-range INEPT spectra using DANTE type excitation of suit- able protons." A presaturation time of 6 s was applied for the standard Varian NOEDIF experiments. The samples were not degassed.

The one-bond ' 3C-'H couplings were determined easily by a chemical shift filtered INEPT experi- ment.20-22 The pulse sequence is shown in Fig. 1. The 7 delay was incremented from 1 to 32 ms in 32 steps and the signals were coadded.

RESULTS AND DISCUSSION

Homonuclear NOE difference spectroscopy has proved to be a powerful tool for the structural differentiation between N-4-cyclized (type A) and N-1-cyclized (type B) isomers of 1,2,4-triazolo[1,3 Jthiazinoquinolines with the

0749-1581/92/111111-O6 $08.00 0 1992 by John Wiley & Sons, Ltd.

Received 8 May 1992 Accepted (revised) 3 July 1992

1112 Z. SZAB6, F. KÓR6DI AND G. BATTA

1 2

a) R1 = H , RZ=H, R,=H; t)) K l= l l , R2=H. R3=OCHzCHzOH; c ) R 1 = H , R Z = C H ~ . R ~ = C I I z C I I , O I I ; d ) K , = I I . Rz=CI,R3=OCH2CHZO€1

3 4

5 6

R , = I l ; i ) R I = H ; b) Rl=CIí ,

“’ ” ,,= KI ’ z

7 8

a)RI=H.R~=II;h)Rl=CH~,R,=H;c~II,=Ctl,CH,. R,=H;d)Rl=H,Rz=CI

Nomendature of Compounds l ad: 1 lH-[l,2,4]triazolo[3’,4 : 2,3][1,3]thiazino[6,5-b]quinolines 2ad: 1 SH-[l,2,4]triazolo[5’, 1’ : 2,3][ 1,3]thiazino[6,S-b]quinolines 3a, b: 6-CH3-5H-1,2,4-triazolo[3’,4‘ : 2,3][1,3]thiazin0[5,6-~]quinolines 4a, b: 6-CH3-5H-[ 1,2,4]triazolo[5’,1’ : 2,3][ 1,3]thiazino[5,6-~]quinolines 5: 6-CH 3-5H-[ 1,2,4]tnazolo[3’,4 : 2,3][ 1,3]thiazino[5,4-c]quinoline 6a, b: 6-CH,-5H-[l,2,4]triazolo[S,l’ : 2,3][ 1,3]thiazin0[5,4-~]quinolines 7ad: 5H-[ 1,2,4]tnazolo[3’,4 : 2,3][ 1,3]thiazino[4,5-b]quinolines 8a-b: 5H-[ 1,2,4]triazolo[5’,1’ : 2,3][ 1,3]thiazino[4,5-b]quinolines

Scherne 1

l 1 I M P I 1 CSSF 1

Figure 1. Pulse sequence for the chemical shift filtered INEPT experirnent D1 is the relaxation delay, D3 = 1/4 J(CH) and T is an incrernented delay for the CSSF effect

exception of compounds 7 and 8. The results of the NOE experiments are given in Table 1. The irradiation of H-11 caused a strong enhancement of the triazole-H signal in compounds la-d, but this signal remaiiied nearly unaffected in compounds 2 a 4 , reflecting t he larger distance between H-11 and the triazole proton. A negative three spin effect was also observed in both instances due to a quasi-linear H-11, H-10, 11-9 arrangement, making possible the assignment of tbe homoaromatic H-9 protons. For compounds 3a, b and 4a, b the methylene protons of the thiazine ring were also irradiated. In the spectra of 3a, b, in addition to the effects on the 6-CH3 protons, marked enhancements were observed on the triazole proton or the triazole- methyl proton (3-CH3}, whereas in 4a, b only the 6-CH3 protons showed an NOE. For compound 5, a signifi- cant through-space dipolar interaction between H-1 1 and the triazole proton was observed on irradiation of homoaromatic H-11 protons, resulting in a 36% NOE; however, in compounds 6a, b the triazole proton or tri- azole methyl (2-CH3) protons showed negligible en hancement .

Unfortunately, there were no possibilities for dis- tinguishing between the isomeric pairs by homonuclear NOE difference spectroscopy in compounds 7a-d and 8a-d. Heteronuclear NOE experiments did not result in useful effects, and also the long-range 3C-’H couplings were not sensitive for differentiation between the 7 and

Table 1. NOE data of 1,2,4-triazolothiazinoquinolines investigated

Compound

l a I b l c I d 2a 2b 2c 2d 3a 3b 4a 4b 5 6a 6b

lrradiated proton

H-11 H-11 H-11 H-11 H-11 H-t 1 H-11 H-11 H-5 H-5 H -5 H-5 H-11 H-11 H-11

H-1 (8.7) H-1 (17.1) H-1 (13.4) H-1 (15.3) H-2 (3.2) H-2 (1.5) H-2 (1.4) H-2 (0.8) H-3 (19.1) 3-CH, (12.5) 6-CH3 (18.5) 6-CH3 (17.1) H-1 (36.0) H-2 (1.2) 2-CH3 (1 .O)

Observed NOE (%)

H-10 (14.0) H-1 O (1 9.0) H-10 (14.5) H-10 (15.7) H-10 (11.3) H-10 (18.1) H-10 (17.4) H-10 (16.9) 6-CH3 (21.1) 6-CH3 (18.0)

H-10 (16.0) H - l O (1 2.8) H-10 (15.7)

H-9 (-2.7) H-9 (-0.8) OCH, (13.3) H-9 (-2.2) OCH, (9.5) H-9 (-2.4) OCH, (10.8) H-9 (-3.2)

H-9 (-1.4) OCH, (1 1.7) H-9 (-1.8) OCH, (7.8)

H-9 (-2.6) OCH, (9.0)

'H AND 13C NMR STUDY OF NOVEL FUSED l,Z,CTRIAZOLE HETEROCYCLES 1113

Table 2. 'H and I3C NMR sbifts of cornpounds la-d and Za-dl'

H-1

H -2

H-6 H-7 H -8 H-9 H-10 H-11 7-CH3 OCH,CH ,OH

OCH ,CH,O H c-1 c -2 C-3a C-4a C-5a C-6 c-7 C-8 c -9 C-9a c-1 o C-loa c-11 7-CH3 OCH,CH ,OH OCH,CH,OH

l a

8.85 (21 4.6) -

7.95 7.83 7.65 8.03 8.49 5.60 -

-

- 144.1 7

144.89 151.80 146.77 127.66 131.19 127.46 128.26 126.1 4 135.90 123.50 45.45

-

- - -

l b

9.1 9 (21 4.5) -

8.02 7.90 7.70 8.1 3 8.73 7.09

3.48 3.67 3.48

144.26

144.73 150.58 147.30 127.60 132.07 127.52 128.76 125.90 138.60 123.40 82.1 9

70.04 59.86

-

-

-

lc

9.1 9 (21 5.9) -

7 .O8

7.54 8.01 8.70 7.06 2.55 3.47 3.68 3.47

144.30

144.93 150.39 147.57 126.51 142.47 129.66 128.34 123.99 138.26 122.51 82.26 21.69 70.07 59.92

-

-

Id

9.21 (21 5.7) -

8.1 O

7.74 8.1 8 8.82 7.09

3.48 3.68 3.48

144.36

144.46 152.25 147.50 126.43 136.74 130.72 128.1 9 124.59 138.63 123.85 82.1 O

70.1 8 59.98

-

-

-

-

a Nurnbers in parentheses are one-bond 'H-13C couplings in Hz

2a

-

8.22 (209.3)

7.95 7.83 7.63 8.00 8.46 5.77 -

-

-

- 152.1 5 145.52 150.70 146.69 127.56 131.17 127.40 128.1 5 126.05 135.97 122.69 48.99 -

-

-

2b

-

8.36 (21 0.7)

8.02 7.90 7.70 8.1 2 8.81 7.1 9

3.65 3.82 3.50

152.37 146.87 150.06 147.26 127.63 132.1 6 127.55 128.76 125.97 139.27 123.38 84.55

70.97 59.96

-

-

-

2c

-

8.34 (21 1.4)

7.79

7.53 8.00 8.73 7.1 5 2.55 3.65 3.80 3.48

152.32 146.99 149.79 147.50 126.44 142.48 129.62 128.25 124.02 138.80 122.39 84.60 21.70 70.96 60.02

-

-

2d

-

8.35 (21 0.8)

8.1 1

7.73 8.1 8 8.85 7.1 9

3.65 3.80 3.48

152.42 146.55 151.63 147.39 126.38 136.78 130.64 128.1 5 124.57 139.25 123.74 84.42

71 .O8 59.95

-

-

-

-

8 type structures. It was therefore necessary to find chemical evidence to prove their structures. Desulphur- ization of compounds 7a and 8a with Raney nickel led to different products which could be distinguished easily. Desulphurization of 7a resulted in an N-4-substi- tuted triazole derivative, whereas that of 8a led to an N-1-substituted product according to the structure of the starting heterocycles. The 'H NMR spectrum of the latter compound showed two separated triazole singlets, whereas the triazole protons of the N-4-substituted product were equivalent and appeared as one two- proton signal.

After the structural identification of the isomeric pairs we focused our attention on their 'H and 13C chemical shifts, which are presented in Tables 2-5. The analysis of these data gave a number of correlations between the structures and chemical shifts of isomers.

In the 'H NMR spectra of the isomeric pairs the largest differences were found between the chemical shifts of the triazole protons. Triazole singlets of type A (N-4-cyclized) isomers appeared at markedly lower fields than the corresponding protons of type B (N-l- cyclized) isomers, in accordance with the results published for non-cyclized regioisomers. l4 However, it was found that the differences between the chemical shifts of the triazole protons are larger for %a, 7a-8a and 7d-8d (ca. 1.1 ppm) than in the other instances (ca. 0.6-0.8 ppm), due to the more downfield-shifted triazole protons in 5, 7a and 7d. This downfield shift in 5 can be explained by the effects of the homoaromatic ring cur-

Table 3. 'H and I3C NMR shifts of compounds 3a, b and 4a, b"

H-2

H-3

H-5 H-8 H-9 H-10 H-11 6-CH3 3-CH, c -2 c -3 c -5 C-5a C-6 C-7a C-8 c -9 c - l o c-11 C - l l a C-11 b C-12a 6-Me 3- Me

3a 3b

- -

- 8.86 (214.9)

5.63 5.44 8.00 8.01 7.83 7.83 7.69 7.68 8.04 8.01 2.71 2.72 - 2.56

144.39 152.04 43.91 43.32

120.72 120.00 155.96 156.1 9 145.56 145.53 129.1 1 129.1 2 130.48 130.49 127.1 7 127.1 7 122.42 122.47 122.88 122.70 134.22 133.40 142.1 1 141.24

23.39 23.39 - 10.43

- -

4a

8.30 (21 0.0) -

5.77 8.02 7.85 7.73 8.02 2.72

152.28

48.25 1 18.48 155.05 146.07 129.42 130.45 126.98 122.37 123.09 134.95 143.85 23.55

-

-

-

4b

5.65 7.96 7.82 7.67 8.00 2.68

160.73

47.59 11 9.84 156.29 145.40 129.1 5 130.46 127.22 122.45 122.50 132.81 142.1 1 23.31 13.72 (2-CH3)

2.33 (2-CH3)

-

a Nurnbers in parentheses are one-bond 'H-13C couplings in Hz.

1114 Z. SZABÓ, F. KÓRÓDI AND G . BATTA

pounds 5 and 6a, b" Table 4. 'H and I3C NMR shifts of com-

6b

H-1

H-2

H-5

H-9 H-10 H-11 6-CH3 2-CH3 c - l c-2 C-3a c-5 C-5a C-6 C-7a C-8 c -9 c - l o c-11 C-1 l a C-11 b

2-CH3

a Numbers

H-8

6-CH,

5

9.62 (21 9.5) -

4.40 8.06 7.84 7.70 8.21 2.81

143.43

148.76 26.69

120.02 156.56 147.46 129.23 130.26 127.75 122.35 11 7.68 135.87 24.1 2

-

-

-

6a

-

8.49 (21 1.9)

4.52 8.01 7.80 7.65 9.20 2.81 - -

152.1 1 153.08 25.63

11 6.23 156.25 147.87 128.97 130.01 127.06 124.93 11 7.28 136.43 24.1 9 -

in parentheses are 'H-13C couplings in Hz.

-

-

4.48 7.98 7.78 7.63 9.25 2.78 2.48

160.92 153.1 7

25.53 11 5.50 156.1 7 147.88 128.92 129.92 126.83 125.1 7 11 7.29 136.40

24.1 5 14.1 2

one- bond

-

rents of the quinoline ring. For 7a and 7d it is probably due to an anisotropy caused by the non-bonding elec- tron pair of the quinoline n i t r~gen . '~ . '~

The methylene protons of the thiazino ring in isomers of type A gave a signal at higher field (ca. 0.1 ppm) than that in their isomeric pairs of type B. Shift differences isf the methylene protons can even be observed within the same type of isomers due to their different chernical environment. The methylene signals of compounds la, 2a, 3a,b and 4a,b are between 5.40 and 5.80 pprn, whereas the same protons gave a signal between 4.40 and 4.60 ppm for the other compounds. The intro- duction of a OCH,CH,OH group into the thiazine ring caused an approximate 1.5 ppm downfield shift of the thiazine methine proton of lb-d and 2b-d.

As can be seen from the data presented, the effect »f substituents introduced into the quinoline ring is negli- gible on the chemical shifts of the triazole proton, and it also seems to be true that the substitution of the triazole proton by a methyl or ethyl group has no effect on the homoaromatic protons. The chemical shifts of the homoaromatic protons in the isomeric pairs showe:d slight differences, except for compounds 5 and 6a,b. In compound 5 the H-11 proton is shifted downfield (0.2 ppm) compared with H-9 in la-d, H-11 in 3a,b and H-7 in 7a-d. In compounds 6a,b this downfield shift is sig- nificantly larger, (1.2 ppm) which is probably caused by the non-bonding electron pair of t he triazole 2-nitrogen, whereas in the former instance the smaller downfield shift is caused by the effects of the aromatic ring cur-

H-1

H-2

H-5 H-6 H-7 H -8 H-9 H-10 CH 3

CH,-CH, CH3-CH, c - l c - 2 C-3a c -5 C-5a C-6 C-6a c -7 C-8 c - 9 c-10 C- l Oa C - l l a CH, CH3- CH CH,-CH,

7a 7b

9.50 -

(21 9.7)

4.56 4.49 8.58 8.55 8.05 8.05 7.66 7.67 7.84 7.83 8.00 8.01 - 2.93

- -

140.68 1 51.25

147.71 148.1 9 28.07 29.32

11 8.90 120.70 137.38 136.73 127.1 7 126.78 128.25 128.21 127.37 127.48 131.1 7 130.93 127.91 128.04 145.34 145.1 4 143.81 145.55 - 14.55

Table 5. 'H and 13C NMR shifts of compounds 7a-d and 8a-d"

a Numbers in parentheses are one-bond 'H-l3C couplings in Hz.

7c

-

__

4.50 8.56 8.05 7.67 7.83 8.00

1.39 3.42

155.70

148.33 29.1 7

120.75 136.72, 126.73 128.02 127.47 130.92 128.1 4 145.1 5 145.39

11.61 21.54

-

-

-

7d

9.45 (21 9.0) -

4.55 8.67 8.1 O 7.70

8.22 -

-

-

-

140.66

147.76 28.00

11 9.36 137.51 125.81 130.20 127.96 135.68 126.62 145.75 144.73

-

- -

-

8a ' 8b

8.33 -

4.64 4.60 8.56 8.51 8.05 8.02 7.65 7.63 7.84 7.82 8.05 8.02

2.40

(208.2)

-

- - 152.76 161.72 153.02 153.25

28.11 28.08 11 8.75 11 8.47 136.97 136.86 127.09 126.96 128.35 128.29 127.22 127.06 130.99 130.97 128.06 128.09

144.66 144.62 - 14.07

145.68 145.77

8c

-

4.62 8.50 8.00 7.63 7.81 8.05

1.31 2.77

166.24 153.1 6 28.1 O

11 8.51 136.81 126.92 128.04 127.00 130.91 128.27 145.74 144.66

12.32 21.61

-

-

-

8d

8 34 (210.6)

4.63 8.60 8.09 7.64 -

8.08 -

__ -

- 152.94 153.1 O 28.04

119.17 137.1 O 125.74 130.00 127.80 135.01 1 27.07 146.14 145.53 -

- -

' H AND I3C NMR STUDY OF NOVEL FUSED 1,2,4-TRIAZOLE HETEROCYCLES 111s

1 ~ " ~ I " " I ' ' ' ' I ~ ~ " / ' ' ~ ' ~ " ' / ~ ~ ~ ' 1 ' " ' 1 ~ ~ ~ ~ 1 ~ ~ " / ~ ~ ~ ' I ' 160 155 150 145 140 13kj 130 125 120 115 110 PPM 105

Figure 2. (a) Partial 13C NMR spectrum of compound 6a. (b) One-bond 13C-'H coupling measured by the chernical shift filtered INEPT rnethod. Al1 carbon pulses were hard pulses.

rents. Similar large downfield shifts of aromatic protons caused by the proximity of a pyrazole or quinoline nitrogen have also been r e p ~ r t e d . ' ~

The 13C chemical shifts also show characteristic dif- ferences which allow us to distinguish between the isomers. In compounds of type A one of the triazole carbons, C-1 (C-3 in compound 3a), gave a signal at about 143-144 ppm, whereas in compounds of type B the corresponding carbon appeared at about 152-1 53 ppm unless there is a substituent at this position. A methyl group resulted in a ea. 10 and an ethyl group in a ea. 15 ppm downfield shift of this carbon signal in both types of isomers. A similar phenomenon can be observed for the other triazole carbon, i.e. these carbons in compounds of type A resonate at higher field than those in the B type compounds. These carbon signals differ only slightly in compounds la-d7 2 a 4 , 3a,b and 4a-d but show noteworthy differences in the case of 5 and 6a as well as in the 7a-d and 8a-d isomers. The substituents introduced into the triazole ring have no effect on these carbon shifts. The opposite trend can be observed for the thiazine methylene carbons. These differ only slightly in the 5, 6a,b, 7a-d and 8a-d isomers, whereas a 3-5 ppm difference was found between the corresponding signals of the A and B type of isomers in the other compounds. In a similar manner to the homo- aromatic proton shifts, the signals of the corresponding homoaromatic carbons of the isomers do not differ sig- nificantly, with the exception of 5 and 6a. In compound 5 the C-11 signal appeared at a higher field compared with the corresponding carbon signal in compound 6a, due to the steric interactions of the closely spaced H-1 and H-11 protons. A similar high field shift caused by the touching of the van der Waals radii of hydrogens in close proximity are known for saturated open-chain and cyclic systems.26

It has been observed that one-bond proton-carbon coupling constants of N-1 substituted 1,2,4-triazoles differ, and usually 'J(C-5,H-5) > 'J(C-3,H-3). On the basis of published dataI4 a similar relationship seems to be valid for 1,5- and 3,4-substituted triazoles. To confirm the validity of this finding in our cyclized systems, we determined the one-bond coupling con- stants of triazole protons for the corresponding isomers. These were determined easily by the pulse sequence given under Experimental. The spectra are shown in Fig. 2 for compound 6a, and couplings are given in the tables in parentheses. The coupling constants in the A type of compounds are larger than those in the corre- sponding B type of isomers, and are in line with the observed proton shifts. Consequently, the above- mentioned relationship proved to be true and can give a further possibility for the discrimination of the isomeric pairs.

In summary, the presented NOE approach allows an unambiguous structural determination. The observed 'H and I3C chemical shifts of N-1- and N-4-cyclized ring systems are in accordance with the results described for disubstituted 1,2,4-triazole regioisomers. The following rules can be established on the basis of the data presented. (1) Triazole protons in N-4-cyclized isomers give signals at a lower field than the corre- sponding protons in N-1-cyclized isomers. (2) The methylene protons of the thiazino ring in N-4-cyclized isomers absorb at higher field than in the N-1-cyclized products. (3) Both triazole carbons in N-4-cyclized isomers resonate at a higher field than those in the cor- responding N-1-cyclized isomers. (4) one-bond triazole proton-carbon couplings in N-4-cyclized isomers are larger than those in N-1-cyclized isomers. These find- ings could be useful in establishing the anellation pat- terns of other fused 1,2,4-triazoles.

REFERENCES

1. C. J. Paget, US Par. 3,974286 (1968); Chem. Abstr. 86, 4. 2. Szabó and F. Kóródi. synth. Commun. 20, 2473 (1 990). 5. K. Jain and R. N. Handa, lndian J. Chem. 21 B. 732 (1 982).

2. L. D. S. Yadav, A. R. Micra and H. Singh, J. Agric. íood. 6 . K. S. Dhaka, J. Mohan, V. K. Chadha and H. K. Pujar¡, lndian J. Chem. 12, 966 (1974).

3. N. F. Eweiss and A. A. Bahajaj, J. Heterocyctic Chem. 24, 7. A. J. Backman and J. B. Polya, J. Chem. Soc.[C] 1016

5468n (1 977).

Chem. 36,633 (1 988).

1173 (1987). (1 971 ).

1116 Z. SZABÓ, F. KÓRÓDI A N D G. BATTA

8. S. Kubota and M. Uda, Chem. Pharm. Bull. 20,2096 (1 972). 9. G. Giamona, M. Neri, B. Carlici, A. Palazo and C. La Roca, J.

Heterocyclic Chem. 28, 325 (1991). 10. J. S . Bajwa and P. J. Sykec, J . Chem. Soc. Perkin Trans. 1

2146 (1980). 11. J. P. Clayton, P. J. O’Hanlon and T. J. King, J. Chem. Soc.

Perkin Trans. 1 1352 (1 979). 12. K. S. Dhaka, J. Mohan, V. K. Chadha and H. K. Pujari, lndian

J. Chem. 12,485 (1 974). 13. R. P. Gupta, M. L. Sachdeva and K. Pujari, lndian J. Chem.

16B. 1143 (1978). 14. W. Holzer, Tetrahedron 47, 5471 (1 991 ). 15. T. J. Batterham, NMR Specfra of Simple Heferocycles

(General Heterocycles Chemisfry Series), p. 21 9, New York (1973).

16. J. Elguero, C. Marzin and J. D. Roberts, J. Org. Chem. 39, 357 (1974).

17. M. Begtrup. R . M. Clararnunt and J. Elguero, J . Chem. Soc. Perkin Trans. 2 99 (1 978).

18. F. Kóródi, 2. Cziáky and Z. Szabó, Heferocyctes, in precs. 19. G. Morric and R . Freeman, J. Magn. Reson. 29,433 (1978). 20. L. Hall and T. Norwood, J. Magn. Reson. 78, 582 (1988) 21. Gy. Batta and K. E. Kovér, Tefrahedron 47, 3535 (1991). 22. D. Uhrin, Gy. Battq and K. E. Kovér, J. Magn. Reson. 97, 54

23. T. M. Spottswood and C. l. Tanzer, Tefrahedron Lett. 10, 91 1

24. G. Dolecchall and K. Lempert, Tefrahedron 29, 639 (1973). 25. S. P. Singh, L. S. Tarar, R . K. Vaid, J. Elguero and A. Martirier,

26. E. Breitmayer and W. Voelter, Carbon 13C NMR Spectroscopy,

(1992).

(1 967).

J. Heterocyclic Chem. 26, 733 (1989).

p. 1 1 5, VCH, New York (1 990).