The structure of 2,5 - dimercapto-1,3,4-thiadiazole and some
derivatives was studied from the dependence of UV spectra on
pH and H 0 and a monomercapto monodipolar structure is proposed.
Evidence was presented tha t addition reactions of 2,5-dimercapto-
1 ,3,4-thiadiazoles on unsaturated systems proceed with the formation
of S-akyla ted derivatives involving thus the mercapto
group 

B. Stanovnik

M. Tišler

English

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CCA-355 CR 0 AT IC A CHEM I CA ACT A 37 (1965) 17 547.569.1.02 :547.781 Original Scientific Paper Contribution to the Structm·e of 2,5-Dimercapto-1,3,4-thiadiazole and Related Compounds"',** B. Stanovnik and M. Tisler Department of Chemistry, Univer sity of Ljubljana, Ljubljana, Slovenia, Yugoslavia Received November 23, 1964 The structure of 2,5 -dimercapto-1,3,4-thiadiazole and some derivatives was studied from the dependence of UV spectra on pH and H 0 and a monomercapto monodipolar structure is proposed. Evidence was presented tha t addition reactions of 2,5-dimercapto--1 ,3,4-thiadiazoles on unsaturated systems proceed with the for-mation of S-akyla ted derivatives involving thus the mercapto group. Among the features of sulfur compounds is undoubtedly the complexi-ty of the electronic structure of the chemical bond, especially where bonds can be formed either by non-charged structures or where participation of an adjacent group or atom to form charged structures due to a shift of electrons is posstble. This is also true fo r thioamides where the dipolar character is predom~nant (see ref. 1•2 and references quoted therein). · In the preceeding papers of this series2- 6 the structure of dtl.fferent cyclic thioamides was investigated. The main feature of these investigations was that such compounds exist predominantly in the dipolar form. As an extension of this work we have recently investigated different pyridazines1 having the system -CS-NH-NH-CS- or its iminothiol forms incorporated in the molecule. The obtained results were interpreted in terms of a striucture w iith a monomercapto group present and while the other is non-enolized with an important contribution of the dipolar character. A similar, but non-cyclic system was investigated recently by Sandstri:im7 when examining the structure of acetyl thiohydrazides. He found no indication for the existence of the possible tautomeric forms I or II. R-C= N-NH-CO- CH3 I SH I R-CS- NH-N = C-CHa I OH II Considerable controversy ha.s ·surrounded the assi.gnme.nt of the struc-ture to 2,5-dimercapto-1,3,4-thiadiazole and related compounds. Theoretically, * Presented in part at the XIth Colloquium Spectroscopicum Internationale, Beograd, 1963. · ** Here and alsewhere terms »mercapto« and »dimercapto« are used for the sake of simplicity. 18 B STANOVNIK AND M. TISLER this compound could exist in three alternative tautomeric forms as III, IV or V. sys'js sy51fsH HSJi5rsH HN-NH HN-N N-N Ill IV v There exist different approaches to the determination of this structure · and consequently some authors prefer either the bis-thioamide form III8 or the monomercapto thioamide form IV9• Recently Thorn tried to resolve this problem on the basis of spectroscopic evidence. The correlation of UV spectra of the parent compound with those of d ifferent on ring nitrogen or exo-cycliic sulfur substituted derivatives led Thorn to postulate that the parent com-pound as well as VI and VII exist in the dithione form as present in III and that the p ossibility of enethiolization does not exist. sy5'js HJC-N-NH sy5'js HJC-N-N-CH3 sy5rS-CH3 sy51rs-CH3 HN--N H3C-N--N VI VII VIII IX In compounds where one thioamide group is fixed in the iminothiol form the second thioamide group was considered as non-enolized (c.f. VIII and IX). However, further examination of IR spectra led Thorn to conclude that the structure assignments are n ot a5 conclusive as .given above. He supplemented his statement so far that the parent compound and VI exist in concentrated solutions in chloroform primarily in their monomercapto form, but in alcoholic solution the bis-thioamide structure should be predominant. Accordingly we undertook the study of this system, particularly to investigate the dependence of the UV spectra o.n pH and H0 • The ac!idity function H0 11 has found wide a.pplication in the determination of basicity of very weak acids. In the present investigation we have used a similar technique as in previous communications. The spectrophotometrically determined pK values are collected in Table I and changes ~n UV spectra in dependence on pH and H" are presented in Table II and Figs. 1-3. TABLE I Compound 2,5-Dimer ca pto-1,3,4-thiadiazole 2-Mer ca pto-4-ph eny 1-1 ,i), 4-thia diazoline--5-thione 2-Mercapto-4-methyl-1 ,3,4-thiadiazoline--5-thione pKn+ -5.40 -1.36 7.53 -6.50 -1.59 -5.30 -1.40 A comparison of the pK values of the parent compound with those of both on the ring nitrogen substituted derivatives clearly demonstrates that 2,5-DIMERCAPT0-1,3,4-THIADIAZOLE 19 TABLE II Changes in UV spectra in dependence on pH and H 0 ------~ ----H o -8.98 -8.27 -6.97 -5.65 -4.89 -3.87 -2.76 -1.85 -0.84 2, 5-Dimercapto-1,3,4-thia-pH diazole 296 310 314 315 255 ,..,250 Am :-lx 0 0 0 0 0 0 0 1 ,..,250 0 2 "'250 0 3 ,..,250 0 4-5 ,..,250 0 6 ,..,250 0 7 ,..,250 0 3160 3270 3270 3270 3270 3270 3230 3230 8 3150 9-12 3120 I £ } 9100 8.400 10.900 13.000 13.300 4.200 12.500 4.400 12.100 4.500 11.950 4.550 11.550 4.800 11.100 5.100 11.000 5.100 11.200 4.960 11.120 11.280 11.350 2-Mercapto-4-phenyl-1,3,4--thiadiazoline-5-thione Amax I £ } 2250, 2970 } 7.700 7.750 "'2750 7.400 2350 3000 8.900 7.300 "'2670 6.100 "'2350 3120 10.000 7.800 "'2350 3180 11.500 8.300 3200 8.800 3220 9.400 3230 9.100 3310 8.800 ,..,2550 3330 11.300 la.700 ,..,2550 3330 l r2.200 10.200 "' = inflexion - 3 8? - 4.89 11. - 565 - 6.9? -8.98 -12 10 6 2 240 260 280 ;·,.\ :: I \ :. £ \ \ I : I : 1 ·. I I : , .. I : , ... I ". , .. , .. , ... , .. 300 \ .. \ .. , . ''.:.· 360 ;l.[mµJ F ig. 1: UV spectrum of 2,5-dimercapto-1 ,3,4- thiadiazole at H o -8.98 to - 3.87. the pK1 value corresponds to the dissociation of the mercapto group whereas the pK2 value of the parent compond is in the range characteristic for the 20 e ·10-3 14 12 10 ' ' ' 240 B. STANOVNIK AND M. TISLEB - 0.94 - lBS - 275 I I I I I I I 260 280 300 I /\ I l I I I 320 340 >.[mµJ Fig. 2: UV spectrum of 2,5-dimercapto- 1,3,4-t h iad'nzole at H 0 -2.76 to -0 .84. e .10-3 12 10 220 \ \ 1 J-6 e 9-11 -21. 0 260 280 300 320 31.0 360 380 >. [ m µ J F ig. 3: UV spectrum of 2,5-d imerca.pto-1 ,3,4-thiad ·azole at pH 1 to 12. dissociation of s1mple thioamides. There can 1be little doubt about the site of proton loss or gain in these compounds and the assignment of the pKu• values which corresponds to the protonation of the second sulfur of the dipolar thioamide group. This evidence arises from the comparison of pK1/ values of derivatives where half of the molecule is fixed in the iminothiol form (cf. 2,5-DIMERCAPT0-1,3,4-THIADIAZOLE 21 2-mercapto-5-methylmercapto-1,3,4-thiadiazole, pK1/ = 4.85; 2-methylmercap-to-4-phenyl-1,3,4-thiad:iazoline-5-thicme, pK1t = -5.44). The presence o.f one true mercapto group in compounds such as the parent compound and all derivatives monosubstituted only on the ring nitrogen cannot be disputed as all these compounds exhibit in the infrared spectrum bands characteristic for the presence of SH groups. Furthermore, the parent compound is susceptible to changes of the solvent polarity whereas other simple thioamides are not. Accordingly, the various protonated and deprotonated species are shown in following equations. HS.../s"'-.,...SH es.../s......,,_SH es..,.,.....-s"-vse e s e II II pKH®•-51.0 II II oK,=- 136 u II pK,·753 51( )'S HN-N HN-. -N -- HN-N = N-N <±:> <±:> 0 The monomercapto monodipolar form of 2,5-dimerca:pto-1,3,4-thiadiazole seems to be most .adequate also in view of the fact that the planar ring system permits a greater resonance stabilization. If one accepts the above evidence for the structure, the addition reactions which are characteristic for mercaptans should proceed similarly in the case of compounds under investigation. We have performed addition reactions with acrylonitrile and ethyl acrylate. As already pointed out, such additions to compounds containing thioamide groups are liable to proceed on nitrogen, but with 3-mercapto-6(1H)-pyridazinethione it was shown to proceed on the sulfur1• Thus, acryloni:trile reacted with 2,5-dimercapto-1 ,3,4-thiadiazole to form a monocyanoethyl derivative X and a similar reaction course was observed with ethyl acrylate XI. Both products were hy drolyzed to the corresponding acids which were found to be identical XII. The IR spectra of all these compounds exhibited no absorption bands characteristic for the presence of an SiH group and the site of addition was ascertained through the reaction with ethyl p-bromopropionate. In this case there is no doubt that the reaction proceeds on the exo-cyclic sulfur12 a:nd the product was ideil1tical with that from the reaction with ethyl .acrylate. x IV s ~ sy 1rsCH2CH2COOC2Hs HN-N XI sy5)'SCH2CH2COOH HN-N XII An analogous reaction takes place with 2-mercapto-4-phenyl-1,3,4-thiadiazo-line-5-thione. Contrarily to the observations with similar compounds in the 22 B . STANOVNIK AND M. TISLER p yridazine series the cyan oeth yl or carbethoxy- ethyl groups are here n ot eliminated during hydrolysis which may b e attributed to the influence of the endo-cyclic su lfur. EXPERIMENTAL Melting points were determined on a Kofler heating microscope. UV spectra in eth anol were measured with a Beckman model DU spectrophotometer and were recorded as described precious1y1.2. The spectrophotometrically determined pK values were calculated in the usual m annert3,l4. For the determination of pKH• values the following, concentrations of sulfuric acid were used: 1,2,4,6,8 and 10 moles/liter and 70, 80, and 96°/o sulfuric acid corresponding to the H 0 valuest5 presented in Table II. 2,5-Dimercapto- 1,3,4- thiadiazole was prepared according to the procedure of Lo-sanitchtG, a modification of the Busch synthesisl7. UV spectrum: '' ""''· 3360 A, E 13,500; inf!. at 2600 A, E 5,400; in CHCl3: /,m"' · 3230 A, E 12.70Q. From the IR spectrum the presence of a SH group (2490 cm- t) and NH group (3075 cm- t) is evident. 2-Mer capto-4-methyl -1 ,3,4- thiadiazoline-5-thione and 2-mercapto-4- phenyl-1,3,4--thiadiazo line-5-thione were prepared by an analogous procedure as the parent com-pound starting with the corresponding substituted hydrazinesl6,11. Both compounds exhibit in their IR spectra the presence of SH groups (2247 and 2300 cm-1 respectively) and no NH groups. , 2-Mercapto-5-methylmercapto - 1,3,4 - thiadiazole was prepared following the pro-cedure of Thorn and Ludwigts and 2-methylmercapto-4-phenyl-1,3,4 -thiadiazoline--5-thione was synthesized according to Bush17. UV spectrum: /, max. 3250 A, e 12.400. 2-(2' -Cyanoethy lmercapto )-5-mercapto-1,3,4-thi.adiazole (X) To a solution of 2,5-dimercapto- 1,3,4-thiadiazole (1.52 g.) in 10 ml. of dioxane acrylonitrile (0.53 g.) and few drops of triethylamine were added. The mixture wa~ heated on water ba th a t 700 for 15 min., cooled to room temperature and poured in cold water. The separated yellow crystals were crystallized from ethanol. Yield: 52°/o m.p. 1400 .. The iodine-azide reactionio was positive. UV spectrum: ),max. 2430 and 2860 A, E 3.240 and 12.150. Anal. C5H 5N3S3 (203.11) calc'd : C 29.57; H 2.48; N 20.69; S 47.270/o found: C 29.23; H 2.65 ; N 20.78; S 47.430/o 2-(2' -Carbethoxyethylmercapto )-5-mercapto-1,.3 ,4-thiadiazole (XI) a) A mixture of 2,5-dimercapto-1 ,3,4-thiadiazole (1.52 g.), 10 ml. of dioxane, 1.0 g. of ethyl acrylate and few drops of triethylamine was heated on a water bath at 700 for 15 min. The cooled reaction mix ture w as poured in water and the separ a ted crystals were recrystallized from chloroform and petroleum ether . Yield: 34°/o. M.p . of colorless crystals 630. UV spectrum : ),10:ix. 3200 A, E 12,300. Anal. C7H10N202S3 (250.37) calc'd: C 33.60; H 4.02 ; N 11.200/o found: C 33.63; H 4.39; N 11.340/o b) 2,5-Dimercapto-1 ,3,4-thiadiazole (1.52 g.) was dissolved in an ethanolic so-lution of sodium ethoxide (prepared from 0.23 g. sodium in 15 ml. of absolute ethanol), ethyl ~-bromopropionate added and the mixture heated to reflux on a water bath for 10 min. The r eaction mixture was treated as above and the purified product was identical with the compound dbtained by procedure (a) . 2-(2' -Carboxyethylmercapto )-5-mercapto-1,3 ,4-thiadiazole (XU) The compound XI (0.41 g.) was hydrolized w ith 100/o aqueous hydrochloric (or sulfuric) acid with heating on a water bath for 3 hrs. Upon cooling the deposited crystals were crystallized from ethanol. Yield: 440/o, m .p. 1180. AnaL C5H 6N202S3 (222.11) calc'd : C 27.04; H 2.72; N 12.61 ; S 43.220/o found: C 26.82 ; H 2.95; N 12.31; S 43.410/o 2,5-DIMERCAPT0-1,3,4-THIADIAZOLE 23 2-(2' -Cyanoethy l mercapto )-4-pheny l-1,3 ,4-thi.:zdiazoline-5-thione 2-Mercapto-4-phenyl-1 ,3,4-thiadiazoline-5-thione (2.26 g. ) was suspended in l 0 ml. of acrylonitrile and the mixture was gently refluxed on a water bath for 45 min. Thereafter it was filtered hot and upon cooltng the separated crystals were crystal-lized from acrylonitrile. M.p. 1000, yi eld: 2.1 g. UV spectrum: Arn:ix . 3320A, £ 11,920; (in dioxane): ''"""· 3330 A, £ 11 ,280. Anal. C11 H 9N3S3 (279 .41) calc'd : C 47 .32; H 3.25; N 15.05°/o found : C 47.21; H 3.52; N 14.900/o Acknowledgment. The a uthors wish to thank the Boris Kidric Fund for financial support of this r esearch. REFERENCES 1. B. St. ;i no v n i k a nd M. Ti s 1 er, Croat. Chem. Acta 36 (1964) 81. 2. B. St an o v n i k and M. ·Tis 1 er, Arzneimittel-Forsch . 14 (1964) 1004. 3. B . St an o v n i k and M. Ti s 1 er, Bull. sci., Conseil Acad. RSF Yougoslavie 9 (1964) 2. 4. B. St an o v n i k and M. Tis 1 er, Vest. Slov . k em . Drustva JO (1963) 1. 5. B. St an o v n i k and M. Ti s 1 er, Anal. Biochem . 9 (1964) 68. 6. B. St an o v n i k and M. Tis 1 er, Anal. Biochem. 9 (1964) 411. 7. J . Sands tr 6 m, Acta Chem. Scand. 17 (1963) 1380,, 8. R. Zahradnik, Collection Czechoslov. Chem. Commun. 24 (1959) 3193. 9. J . N. Shein k er, I. J. Po sto vs k i j, and N. M. Vo r on in a , Zhur. Fiz. Khim. 33 (1959) 302. 10. G. D. Thorn, Canad. J. Chem. 38 (1960) 1439. 11 . L. P. Hammett and A. J . D ey r up, J. Am. Chem . Soc. 54 (1932) 2721. 12. N. Korn b 1 um, R. A. Sm i 1 e y, R. K. B 1 a c kw o o d , and D. C. I ff 1 a n d, J. Am. Chem. Soc. 77 (1955) 6269. 13. E . E. Sager, M. R. Schoo 1 e y , A. S . Carr, and S. F . Acree, J . Res. Natl. Bur. Std. 35 (1945) 521. 14. L. A. F 1 ex er, L. P . H a mm e tt, and A. Din g w a 11, J . Am. Chem. Soc. 57 (1935) 2103. 15. M. A. Pa u 1 and F . A. Lon g, Chem. Rev. 57 (1957) 1. 16. M. S. Los an itch, J . Chem. Soc. 121 (1922) 2542. 17. M. Busch, Ber. 27 (1894) 2507. 18. G. D. Thorn and F . A. L u d w i g, Canad. J. Botany 36 (1958) 389. 19. F. Feig 1, Spot T ests, Vol. 2, Organic Applications, Elsevier, Amsterdam 1954, p . 164 . . IZVLECEK Prispevek k strukturi 2,5-dimcrkapto-1,3,4-tiadiazola in sorodnih spojin B. Stanovnik in M . Tisler Obravnavana je struktura 2,5-dimerkapto-1,3,4-tia diazola in nekaterih derivatov na podlagi studija odvisnosti ultravijolienih spektrov od pH in Ho, ter je predlagan a struktura kot monomerkapto monodipolarna. Ugotovlj eno je, da potekajo reakcij e adicije pri 2,5-dimerkapto-1 ,3,4-tia diazolih na neka tere nenasicene spojine s tvorb':l S-alkiliranih spojin pri cemer reagira merkapto skupina. ODDELEK ZA KEMIJO FAKULTETA ZA NARAVOSLOVLJE IN TEHNOLOGIJO LJUBLJANA Sprejeto 23. novembra 1961 . 

Contribution to the Structm·e of 2,5-Dimercapto-1,3,4-thiadiazole and Related Compounds

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