Spectra and conformations of substituted thioureas

Journal of Molecular Structure, Elsevier

Scientific

SPECTRA

Publishing

82 (1982) 35-4 1 Company, Amsterdam

AND CONFORMATIONS

-

Printed

in The Netherlands

OF SUBSTITUTED

THIOUREAS

G. VASSILEV

Institute of Plant Physiology, Bulgarian Academy of Sciences,

V. KOLEVA,

M. ILIEVA

Sofia

1113

(Bulgaria)

and B. GALABOV*

Department of Chemistry, University of Sofia, Sofia 1126 (Bulgaria) (Received

10 November

1981)

ABSTRACT IR and ‘H NMR spectroscopic data are used to analyse the conformations of the -NH-CS-NHgroup in a series of di- and trisubstituted thioureas. In organic media (Ccl,, C,CI,, CHCI,, CH,CI,) various conformational forms are detected resulting from the possibility of cis and trans arrangements of the -CS-NHgroups. The trans +%-NHform occurs when there is no steric hindrance whereas with bulkier aliphatic or aromatic substituents a proportion of cis structures is found. The results indicate that a complex equilibrium between several rotational isomers of the type cis-cis * cis-tram = trans-cis c trans-transexists. For substituents of medium size (n-propyl, n-butyl, allyl) the spectroscopic data are consistent with a third type, the “out” conformation of the +X-NHgroup. INTRODUCTION

The conformational isomerism of the thioamide group has been the subject of numerous studies [l-3]. Results show that the --B-NHgroup can be found in both cis and trans conformations, in contrast to the amide group which is normally in the trans form [ 1,4 ] . The relative stability of these conformational forms is determined by the partial double-bond character of the C(S)-N bond due to delocalization of the electron pairs on nitrogen. The difference between the amide and thioamide conformers is attributed to the increased steric repulsion between the bulkier sulphur atom and the substituents on the nitrogen atoms. Studies on the conformations of substituted thioureas [5--S] reveal the existence of several forms, cis-cis, cis-trans, trans-cis. trans-bans, the relative proportions of which depend mainly on the type of substituents. Some ambiguity exists in the interpretation of the experimental data of cases where cis and trans -CS-NHforms are found simultaneously in that no definite conclusion can be reached as to whether the two forms appear in equilibrium or as a stabilized cis-trans structure. In a recent study of the conformational isomerism in a series of N,N’-diaryl*To whom all correspondence 0022-2860/82/0000-0000/$02.75

should be addressed. o 1982

Elsevier Scientific

Publishing

Company

36

thioureas it was shown that at room temperature C2C14, CHC13, CHZCI,, CICH,CN) the compounds equilibrium between several forms [9] .

c/s-t/am

cis-CIS

trons -c/s

in organic solvents (CC14, participate in a complex

trons - rrons

In the present study IR and ‘H NMR data are used to analyse the conformational isomerism of the -NH-CS-NHgroup in a number of N-phenylN’alkylthioureas and N-methyl-N’arylthioureas in which various polar substituents are introduced on the aromatic ring. RESULTS

AND

DISCUSSION

The existence of different conformations of the -CS-NHgroup is manifest in the IR spectra by the appearance of two distinct v(N-H) maxima near 3400 cm-’ [l-3,8,9] . The peak at higher frequency is attributed to the trans form while that at lower frequency is due to the cis form [l] . This assignment of the two bands is supported by most workers, although some ambiguity remains [I-4, 8-J. It has been proved conclusively, however, that the presence of the lower frequency band near 3400 cm-’ is not due to association effects since it is independent of concentration [l, 2, 8, 91 _ Association bands appear at much lower frequencies in the interval 30803300 cm-’ as broad absorptions whose positions and intensities change with concentration [l-3,8] . In Table 1 the characteristic N-H frequencies in CHC13 for the entire series of compounds studied are given. It can be seen that all N-alkyl-N’arylthioureas with an alkyl group bigger than methyl possess two N-H bands. This is evidently due to two different -CS-NHconformations. In the series of N-methyl-N’-arylthioureas only one band at higher frequency is observed despite variations in the polar substituents on the aromatic ring. These spectral features are illustrated in Fig. 1. The difference between methyl and other alkyl substituents must be attributed to steric effects. With bulkier alkyl substituents steric repulsion between the aulphur atom and the substituent increases, thus facilitating a conversion to the cis form. It should be noted that electronic factors do have a minor effect on the N-H frequencies. The frequency variation in the N-methyl-N’-arylthiourea series is just +3 cm-‘. Evidently the larger frequency changes observed in the alkylthioureas are therefore caused by conformational effects. It is interesting that for thioureas with medium sized alkyl substituents, e.g. n-propyl, n-butyl, allyl, the lower frequency band appears in the 33903400 cm-’ region, while for compounds with bulkier substituents it occurs at 3376-3385 cm-’ (Table 1). These frequency shifts cannot be attributed to

37 TABLE N-H

1

stretching

frequencies

R,R,N-CS-NHAr,

of alkylarylthioureas,

R,

R,

Ar

UNH(ciS) (Cm-‘)

CH,CH,CH, CH,CH,CH,CH3 CH,CH=CH,

H H H H H CH, H H H H H H H H H H H H H H H

Ph Ph Ph Ph Ph Ph Ph

3398 3391 3394 3381 3385 3393 3376 -

CH(CH,), C&H, ,(cyclohexyl) CH, Ph CH, CH, CH, CH,

CH, CH, CH, C% CH, CH, CH, CH, CH, CH,

;?CH )Ph (m&,)Ph (p-CH,)Ph (o-OCH,)Ph (m-OCH,)Ph (o-OC,H,)Ph (m-OC,H,)Ph WOC,H,)Ph (m-OH)Ph (m-NO,)Ph (mCOOCH,)Ph (p-COOCH,)Ph (p-COCH,)Ph

2800

Fig. 1. Infrared spectra of N-methyl-N’-phenylthiourea thiourea (II) in CHCl,.

-3,cm

UNH.(ttWZs)

3411 3413 3411 3413 3413 3423 3412 3407 3403 3405 3406 3404 3404 34@6 3402 3404 3402 3408 3407 3407 3407

-

3200

in CHCl,

-1

(I) and N-iso-propyI-N’-phenyl-

(cm-‘)

38

electronic effects, for the reason discussed above, and therefore presumably

arise from conformational

differences.

With this in mind, the N-H

frequen-

cies observed in the interval 3405-3413 cm-’ are assigned to the trans -CSNH- group and the bands appearing below 3390 cm-’ to the cis conformation_ The most plausible explanation for the bands observed in the 3390-

3400 cm-’ region is that they are due to an intermediate form, described by Mido and Hisamoto [lo] as the “out” conformation. For most of the compounds studied, broad association bands are observed below 3200 cm-’ (Fig.

1).

As mentioned be due either to librium between possibilities the

earlier, the appearance of two N-H bands in thioureas may a stabilized trans-cis (or “out”) conformation or to an equiseveral rotational isomers. In order to decide between these influence of the solvent polarity on the spectral character-

istics was studied. Changes in solvent polarity would only be expected to affect the relative intensities of the two N-H bands in the case of an equi-

librium- The results for two compounds of the present series are given in Table 2 along with the data obtained previously for NJV’diphenylthiourea [9] . The percentage ratios, cis (or “out”)/trans, are estimated from the intensities of the two bands assuming the absorption

coefficients

to be equal.

As can be seen, a marked change in the ratio is found for R = CH(CH,),; Fig. 2 illustrates this. It is apparent therefore that in the media studied an equilibrium between various rotational isomers with trans and cis (or “out”) -CS-NHstructures exists. This conclusion is confirmed by the appearance of two Y(N-H) maxima in the spectrum of NJV-dimethyl-IV’-phenylthiourea which possesses only one N-H bond. No clear correlation between solvent polarity and conformational

TABLE Influence R

2 of solvent polarity on the conformational ccl,

CH(CH,), C,H, =

isomerism

3389 3385

NH(f’~S)

3415 3418 3418

cis/fruns

o/100 54146 50150

ratiob

NH(cis’OUc)

NH(trm2s)

cis/trans

3388 3385

3415 3416 3417

o/100 57143 50150

CH,Cl,

CHCI, CH, CH(CH,), C,H,

in RNH-CS-NHC,H,a

C*Cl‘l

NH(CiS/OU’)

CH,

equilibrium is found.

3381 3376

3407 3413 3412

aFrequencies are in cm-‘. bPercentage ratio between ‘From ref. 9.

cis

o/100 51149 53147

3381 3373

(out) and trans forms. See text.

3404 3404 3405

o/100 53147 55145

ratiob

39

-I

7, cm Fig. 2. Variations of the relative thiourea with solvents.

In

the ‘H NMR spectra

intensities

of N-H

of chloroform

bands in N-iso-propyl-N’-phenyl-

solutions

of the N-alkyl-N’-phenyl-

thioureas no separate resonances due to different conformational forms are observed at ambient temperature. The chemical shifts of the alkyl protons neighbouring the N-H group are given in Table 3. These alkyl resonances

appear as various multiplets depending on the rest of the molecule with some of the lines further split by distant spin-spin couplings_ Two typical examples are shown in Fig. 3. It appears that due to short lifetimes, the different conformational forms found in the IR spectra cannot be traced by NMR at ambient temperature_ Lowering the temperature to 223 K results only in broadening of the NMR peaks of the chloroform solutions of the compounds. It was therefore necessary to use a solvent which allows spectra to be obtained at lower temperatures. Thus acetone-d, solutions of N-propyl-N’-phenylthiourea were examined at temperatures ranging from 188.2 to 313.2 K. The temperature dependence of the signals due to the methylene protons adjacent to the NH group is shown in Fig. 4. At 188.2 K, although the fine structure is almost lost due to peak broadening, two distinctly different resonances are observed. The separation between the two lines, 15 Hz (at 80 MHz), is similar to that between the resonances due to the rotational isomers found by Sullivan and Price [ 51 in their NMR study of the conformations of some di- and tri-alkylthioureas. According to their assignment, the high-field resonance is due to the trans conformation, while the low-field resonance is due to the cis form. In our case, of N-propyl-N’-phenylthiourea, the low-field resonance can be attributed, in accord with the IR spectral data, to an “out” conformation of the -CS-NHgroup. The kinetics of the conformational transformations in Nalkyl-N’-phenylthioureas will be examined in a future study.

40 TABLE

3

Chemical-shift 80 MHz

data for

N-alkyl-IV’-phenylthioureas, R,R;N--CS-NHPh,

Rla

R,

6 (ppm)b

CH:

H

3.10

CH:CH,CH, CH:CH,CH,CH,

H H

CH*CH=CH:

3.62 3.61

H H

4.61

H

4.30

CHp

3.27

CH*(CJU

CH* CH:

,CH,-CHz\ CH,

‘CH,-CH/

=Data refer to the protons bRelative to TMS.

in CDCl, at

4.01

marked by an asterisk.

-

I

330

260

J,Hz)

c

Fig. 3. NMR spectra of N-propyl-N’-phenylthiourea (I) and N-allyl-N’-phenylthiourea in CDCl,, at 80 MHz and a sweep width of 250 Hz, in the N-CH,region.

(II)

EXPERIMENTAL

IR spectra were recorded on a UR-10 Zeiss spectrometer, with a LiF prism, with inthe 2000-3700 cm-’ region. The N-H frequencies were determined an accuracy of 4 2 cm-’ using ammonia vapours for calibration. The NMR spectra were obtained on a Tesla BS 487C (80~MHz) spectrometer using TMS as internal standard. The compounds were synthesized as described in refs. 11 and 12.

41

Fig, 4. NMR spectra of N-CH, protons 80 MHz and a sweep width of 250 Hz.

in N-propyl-N’-phenylthiourea

in acetoned*

at

REFERENCES 1 H. E. Hallam and C. M. Jones, J. Mol. Struct., 5 (1970) 1. 2 I. Suzuki, M. Tsuboi, T. Shimanouchi and S. Mizushoma, Spectrochim. Acta, 16 (1960) 471. 3 I. D. Rae, Can. J. Chem., 45 (1967) 1. 4 Y. Mido, Bull. Chem. Sot. Jpn., 47 (1974) 1833. 5 R. H. Sullivan and E. Price, Org. Magn. Reson., 7 (1975) 143. 6 G. Isaksson and J. Sandstrijm, Acta Chem. Stand., 24 (1970) 2565. 7 W. Waiter and K. P. Ruess, Chem. Ber., 102 (1969) 2640. 8 R. K. Gosavi, U. Agarwala and C. N. R. Rao, J. Am. Chem. Sot., S9 (1967) 235. 9 B. Galabov, G. Vassilev, N. Neykova and A. Galabov, J. Mol. Struct., 44 (1978) 15. 10 Y. Mido and Y. Hisamoto, J. Mol. Struct., 65 (1980) 27. 11 G. Vassilev and E. Karanov, C. R. Acad. Agric. G. Dimitrov, 4 (1971) 45. 12 G. N. Vassilev and P. A. Jonova, Pharmazie, 33 (1978) 270.