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Molbank 2015, 2015(4), M877;

Short Note
Department of Organic Chemistry, Kaunas University of Technology, LT-50254 Kaunas, Lithuania
Department of Physical and Inorganic Chemistry, Kaunas University of Technology, LT-50254 Kaunas, Lithuania
Author to whom correspondence should be addressed.
Academic Editor: Norbert Haider
Received: 24 September 2015 / Accepted: 16 November 2015 / Published: 23 November 2015


A synthesis of N′-(1,3-dithiolan-2-ylidene)-3-(phenylamino)propanehydrazide from 3-(phenylamino)propanehydrazide, carbon disulfide and 1,2-dibromoethane is reported. The title compound was characterized by 1H NMR, 13C NMR, ESI/MS, and elemental analysis.
1,3-dithiolane; propanehydrazide; amino acid

1. Introduction

N-Substituted β-amino acids and their derivatives are structural units of various natural compounds, such as alkaloids, antibiotics, and co-enzymes. Carboxylic acid hydrazides and hydrazones exhibit a broad spectrum of biological activity [1].
1,3-Dithiolane is an attractive scaffold for the synthesis of heterocyclic compounds possessing valuable properties. It is embodied by many widely used compounds. Among them, an important place is taken by the compounds containing the 1,3-dithiolan-2-ylidene moiety. Such compounds can be used for selective sorption [2]. 2-Alkylidene-1,3-dithiolanes containing the sulfoxide group form dinuclear iron(0) complexes [3], whereas 2-salicylichydrazono-1,3-dithiolane derivatives form complexes with cobalt [4] and manganese [5] ions. A facile method for functionalization of thioamides involves ring fragmentation of 2-acetylmethylene-1,3-dithiolane in the presence of amine [6].
An interesting method for the synthesis of 2-imino-1,3-dithiolane derivatives by the treatment of allyl dithiocarbamates with iodine in methylene chloride has been reported in [7]. A simple synthesis method of N′-(1,3-dithiolan-2-ylidene)isonicotinehydrazide involves reaction of isonicotinehydrazide with carbon disulfide in alkali solution followed by the treatment with dibromoethane [8]. A similar procedure was employed for preparation of 1,3-dithiolane-2-ylidenhydrazidebenzoic acid [9].
In the search for new potentially biologically active compounds and in light of the data listed above, we report the synthesis of a compound containing both β-amino acid and 1,3-dithiolane moieties.

2. Results and Discussion

N′-(1,3-Dithiolan-2-ylidene)-3-(phenylamino)propanehydrazide 2 was synthesized according to the synthesis protocol described in [8] by stirring 3-(phenylamino)propanehydrazide 1 [10] with carbon disulfide in ethanolic KOH solution and subsequent heating at reflux after addition of 1,2-dibromoethane (Scheme 1). The obtained residue was recrystallised from methanol.
The formation of the dithiolane moiety has been confirmed by the 1H NMR resonances in the range of 3.49–3.54 ppm and 3.59–3.72 ppm attributable to the methylene group protons of s-E/s-Z isomers. These isomers are formed in the DMSO solution owing to the restricted rotation around the amide bond. Signals attributable to the COCH2 and NH groups protons are also observed in two line sets in the 1H NMR spectrum. Usually, the most information about the existing isomers can be obtained from the NH group resonances [11]. The NH group singlets are present down-field at 10.13 ppm (s-Z) and 10.30 ppm (s-E) and the intensity ratio is 0.3:0.7.
The presence of the carbon resonance at 162.52 ppm attributable to the C=N group and the spectral line at 35.12 ppm attributable to the CH2 group in the 13C NMR spectrum indicate the formation of the target product as well.

3. Experimental Section

3.1. General

All the reagents and chemicals were obtained from commercial sources and used without further purification. Melting points were measured on a B-540 Melting Point Analyzer and are uncorrected (Büchi Corporation, New Castle, DE, USA). 1H and 13C NMR spectra were recorded at ambient temperature on a Varian Unity Inova (300 MHz) spectrometer (Palo Alto, CA, USA). Chemical shifts (δ) are reported in parts per million (ppm) calibrated from TMS (0 ppm) as an internal standard for 1H NMR, and DMSO-d6 (39.5 ppm) for 13C NMR. The J constants are given in Hz. Mass spectrum was recorded on a Waters Micromass ZQ 2000 instrument (Milford, MA, USA). Elemental analysis was performed on a CE-440 elemental analyzer (Exeter Analytical Inc., North Chelmsford, MA, USA). TLC was performed using Silica gel 60 F254 (Kieselgel 60 F254) (Merck, Darmstadt, Germany) plates.

3.2. Experimental Procedure for the Preparation of N′-(1,3-Dithiolan-2-ylidene)-3-(phenylamino)propanehydrazide (2)

To a mixture of KOH (1.2 g, 20 mmol) and ethanol (10 mL), hydrazide 1 (1.79 g, 10 mmol) was added with stirring. Afterwards, CS2 (0.6 mL, 10 mmol) was added dropwise followed by 1,2-dibromoethane (0.86 mL, 10 mmol). The reaction mixture was refluxed for 0.5 h. After cooling it to room temperature, water (50 mL) was added. Precipitate formed was filtered off, washed with water, and recrystallized from methanol.
Yield: 0.65 g (80%), white, m.p. 133–134 °C.
1H NMR (300 MHz, DMSO-d6), δ: 2.50 (t, 1.4H, J = 7.2 Hz, s-Z COCH2); 2.69 (t, 0.6H, J = 7.2 Hz, s-E COCH2); 3.22–3.33 (m, 2H, NHCH2); 3.49–3.54 (m, 2H, s-Z SCH2CH2); 3.59–3.72 (m, 2H, s-E SCH2CH2); 5.57 (s, 1H, NHCH2); 6.56 (t, 1H, J = 7.5 Hz, Har4); 6.60 (d, 2H, J = 7.5 Hz, Har2,6); 7.09 (t, 2H, J = 1.2 Hz; J = 7.5 Hz, Har3,5); 10.13 (s, 0.3H, s-Z NH); 10.30 (s, 0.7H, s-E NH).
13C NMR (75 MHz, DMSO-d6), δ: 33.41 (C-8); 35.12 (C-11,12); 38.60 (C-7); 112.03 (C-2,6); 115.72 (C-4); 128.82 (C-3,5); 148.44 (C-1); 162.52 (C-10); 166.71 (C-9).
MS (ESI, 20 V) m/z (%): 282 ([M + H]+, 80).
Anal. Calcd. (%) for C12H15N3OS2: C, 51.22; H, 5.37; N, 14.93., found: C, 51.09; H, 5.37; N, 14.67.
1H NMR (Figure S1) and 13C NMR (Figure S2) spectra for the title compound 2 are available in the Supplementary Information.

Supplementary Materials

Supplementary File 1Supplementary File 2Supplementary File 3Supplementary File 4

Author Contributions

Ingrida Tumosienė performed the synthesis and spectral analysis; Kristina Kantminienė contributed to the data analysis and prepared the manuscript; Zigmuntas J. Beresnevičius designed the synthesis and supervised the work. All authors read and approve the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Rollas, S.; Kucukguzel, S.G. Biological Activities of Hydrazone Derivatives. Molecules 2007, 12, 1910–1939. [Google Scholar] [CrossRef] [PubMed]
  2. Sato, S.; Hirano, A.; Takenaka, S. Selective immobilization of double stranded DNA on a gold surface through threading intercalation of a naphthalene diimide having dithiolane moieties. Anal. Chim. Acta 2010, 665, 91–97. [Google Scholar] [CrossRef] [PubMed]
  3. Ortega-Alfaro, M.C.; Hernandez, N.; Cerna, I.; Lopez-Cortes, J.G.; Gomez, E.; Toscano, R.A.; Alvarez-Toledano, C. Novel dinuclear iron(0) complexes from α,β-unsaturated ketones β-positioned with sulfide and sulfoxide groups. J. Organomet. Chem. 2004, 689, 885–893. [Google Scholar] [CrossRef]
  4. Toussaint, C.; Beghidja, C.; Welter, R. Cobalt complexes supported by salicylichydrazono derivative ligands and various coordination solvents. C. R. Chim. 2010, 13, 343–352. [Google Scholar] [CrossRef]
  5. Bouchameni, C.; Beghidja, C.; Beghidja, A.; Rabu, P.; Welter, R. Synthesis, structural characterizations, spectroscopic and magnetic properties of MnII and MnIII complexes with an unprecedented bridging coordination mode of 2-salicylichydrazono-1,3-dithiolane ligand. Polyhedron 2011, 30, 1774–1778. [Google Scholar] [CrossRef]
  6. Liang, F.; Li, Y.; Li, D.; Cheng, X.; Liu, Q. A tandem reaction of 2-acetylmethylene-1,3-dithiolanes via fragmentation of the dithiolane ring in the presence of amines: a facile route to functionalized thioamides. Tetrahedron Lett. 2007, 48, 7938–7941. [Google Scholar] [CrossRef]
  7. Halimehjani, A.Z.; Maleki, H.; Saidi, M.R. Regiospecific iodocyclization of S-allyl dithiocarbamates: synthesis of 2-imino-1,3-dithiolane and 2-iminium-1,3-dithiolane derivatives. Tetrahedron Lett. 2009, 50, 2747–2749. [Google Scholar] [CrossRef]
  8. Foks, H.; Mieczkowska, J.; Janowiec, M.; Zwolska, Z.; Andrzejczyk, Z. Synthesis and tuberculostatic activity of methyl 3-isonicotinoyldithiocarbazate and S,S'-dimethyl dithiocarbonate isonicotinoylhydrazone, and their reactions with amines and hydrazines. Chem. Heterocycl. Compd. 2002, 38, 810–816. [Google Scholar] [CrossRef]
  9. Bouslimani, N.; Clement, N.; Rogez, G.; Turek, P.; Choua, S.; Dagorne, S.; Welter, R. Stability, molecular structures and magnetic properties of dinuclear iron complexes supported by benzoic hydrazide derivative ligands. Inorg. Chim. Acta 2009, 363, 213–220. [Google Scholar] [CrossRef]
  10. Aelony, D. Storage stable epoxy B-stage resins. J. Appl. Polym. Sci. 1969, 13, 227–232. [Google Scholar] [CrossRef]
  11. Hesse, M.; Meier, H.; Zeeh, B. Spectroscopic Methods in Organic Chemistry, 2nd ed.; Thieme: Stuttgart, Germany, 1997; p. 468. [Google Scholar]
Scheme 1. Synthesis of N′-(1,3-dithiolan-2-ylidene)-3-(phenylamino)propanehydrazide 2.
Scheme 1. Synthesis of N′-(1,3-dithiolan-2-ylidene)-3-(phenylamino)propanehydrazide 2.
Molbank 2015 m877 sch001
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