Romanian Society for Pharmaceutical Sciences Farmacia · În această lucrare prezentăm...

armaciaFarmaciaF

ini ţt e Ş F ae rd ma aet ceat ue i tic c eo S R a oi mnâRomanian Society for Pharmaceutical Sciences

5

Volume 62

September - October 2014

Editor-in-Chief

Associate Editor-in-Chief

Managing Editors:Prof. Adrian ANDRIEŞ, PhD

“Printech” Publishing House

Bucharest-Romania

FARMACIA, 2014, Vol. 62, 5

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SPECTRAL CHARACTERIZATION OF NEW 2-((4-ETHYLPHENOXY)METHYL)-N-(ARYLCARBAMOTHIOYL)BENZAMIDES MIRON TEODOR CĂPROIU1, CARMEN LIMBAN2, ALEXANDRU VASILE MISSIR2, DIANA CAMELIA NUŢĂ2*, LAURENȚIU MORUȘCIAG2 1Romanian Academy, Organic Chemistry Center “Costin D. Nenitzescu” 202B Splaiul Independentei, 060023, Bucharest, Romania 2“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Pharmaceutical Chemistry Department, 6 Traian Vuia Str., 020956, Bucharest, Romania * corresponding author: [email protected]

Abstract

We report here the characterization of the new synthesized thiourea derivatives by IR, 1H-NMR, 13C-NMR and elemental analysis.

In the FTIR (Fourier transform infrared) spectrum the new compounds were characterized by NH, C=N, C=S, C–H of the methyl and methylene groups, and alkyl- aryl- ether stretching vibrations.

The 1H-NMR spectrum in dmso-d6 confirmed the proposal structures showing the presence of the NH group, ethyl group, and methylene group attached to the oxygen and aromatic protons. The 13C-NMR spectrum has a singlet signal due to the C=S group, C16 being the most deshielded carbon.

The new compounds were synthesized in order to evaluate the influence of fabricated nanomaterials on the biofilm development. The results could be of a great interest for the biomedical field and open new directions for the design of film- coated surfaces with antibiofilm properties.

Rezumat

În această lucrare prezentăm caracterizarea unor noi derivați sintetizaţi ai tioureei, efectuată prin analiză spectrală IR, 1H-RMN, 13C-RMN, precum şi analiză elementală.

În spectrul FTIR (Fourier transform infrared) noii compuși au fost caracterizați prin benzile NH, C = N, C = S, C-H din grupele metil și metilen și vibrațiile de întindere alchil-aril-eter.

Spectrele 1H-RMN realizate în DMSO-d6 au confirmat structurile propuse, prezentând semnale caracteristice care arată prezența grupelor NH, etil, metilen legat de oxigen și a protonilor aromatici. Spectrul 13C-RMN prezintă un singlet datorat grupei C = S, C16 fiind atomul de carbon cel mai dezecranat.

Noii compuși au fost sintetizaţi cu scopul de a evalua influența nanomaterialelor asupra dezvoltării biofilmelor. Rezultatele ar putea fi de un mare interes pentru domeniul biomedical și ar putea deschide noi direcții pentru proiectarea de suprafeţe filmate cu proprietăți antibiofilm.

Keywords: mycophenolate mofetil, biowaiver, dissolution, sink conditions.


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Introduction

The thiourea moiety represents a prevalent scaffold in drug discovery. A substantial number of papers have been published on the synthesis and characterization of thiourea derivatives which have extensive applications in the fields of medicine [5, 7, 9, 10, 12, 13, 16, 17, 18], agriculture [3], analytical chemistry [1, 2], and as corrosion inhibitors [6].

Substituted thioureas are an important class of compounds, precursors, or intermediates towards the synthesis of a variety of heterocyclic systems such as 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivatives [21], thiohydantoins and iminothiazolidinones [8], thioxopyrimidine [19], 2-imino-1,3-thiazolines [15].

New 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl)-benzamides were prepared in good yields according to previous research [11]. Also the new compounds were tested for their antimicrobial activity and to demonstrate how nanotechnology could improve this intrinsic activity [11].

We have demonstrated that nanomaterials based functionalized magnetite with a non-polar coating represented by different types of fatty acids such as myristic acid, associated with these thiourea derivatives could improve resistance to in vitro microbial colonization and biofilm development, in order to obtain functionalized catheter surfaces. We opted for catheter coated surfaces because catheter- related infections continue to be a significant source of morbidity and mortality in patients requiring catheterization and increase medical expenses by prolonging hospitalization.

Our results claimed the usage of hybrid nanomaterial which prevented or inhibited the microbial biofilm development on the functionalized catheter, highlighting the opportunity of using these nanosystems to obtain improved, anti-biofilm coatings for biomedical applications. Biofilms are estimated to be involved in around 80% of all chronic human infections [4], around half of them being related to the use of an indwelling medical device [14]. Also, it has been estimated that 65% of nosocomial infections are biofilm associated [20].

Materials and Methods

Follow- up of the reactions and checking the purity of the synthesized compounds were made by thin layer chromatography (TLC), which was conducted on 0.2 mm thickness silica gel plates (60 F 254, Merck) using chloroform and ethyl acetate mixture (4: 6) as eluent. Visualization was made with ultraviolet light (λ= 254 nm) and iodine vapour.


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Melting points were recorded on Electrothermal 9100 capillary melting point apparatus in open capillary tubes and the values were uncorrected.

C, H, N and S analysis were carried out using a Perkin Elmer CHNS/O Analyzer Series II 2400 elemental analyzer. Obtained results were within ±0.4% of the theoretical values.

Infrared measurements were recorded by a Fourier transform infrared (FTIR) spectrometer Bruker Vertex 70 equipped with an attenuated total reflection (ATR) accessory.

All NMR spectra were recorded on a Varian Unity Inova 400 instrument operating at 400 MHz for 1H and 100 MHz for 13C.

Results and Discussion

The general synthetic pathway and the structure of the compounds are given in Figure 1.

Figure 1.

Schematic of the proposed reaction pathway for the synthesis of target compounds


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The new compounds 1a - g were prepared by refluxing 2-(4-ethylphenoxymethyl)-benzoyl isothiocyanate (2) with primary aromatic amines in dry acetone. The isothiocyanate 2 was obtained through the reaction between 2-(4-ethylphenoxymethyl)benzoyl chloride (3) and ammonium thiocyanate in dry acetone. The isothiocyanate was not isolated and the appropriate amines were directly added to the reaction mixture to give the thioureides.

2-(4-Ethylphenoxymethyl)benzoyl chloride (3) was prepared by refluxing 2-(4-ethylphenoxymethyl)benzoic acid (4) with thionyl chloride, using anhydrous 1,2-dichlorethane as reaction medium.

The best yields in the synthesis of the 2-(4-ethylphenoxymethyl)benzoic acid (4) were obtained when used the phthalide 5, which was treated with potassium p-ethylphenoxide in xylene under reflux. This gives the potassium salt of 2-(4-ethylphenoxymethyl)-benzoic acid (6), which has good solubility in 10% aqueous potassium hydroxide solution, allowing its facile separation from xylene. The acid compound 4 is then precipitated using a mineral acid solution. The potassium p-ethylphenoxide was obtained through the reaction of p-ethylphenol with potassium hydroxide in xylene. The resulting water was removed by azeotropic distillation.

The new compounds have all been characterized by their melting point, elemental analysis, infrared and NMR spectral studies. All spectral data and elemental analyses results were in good agreement with the proposed structures.

The IR bands were given as w – weak, m – medium, s – strong, vs – very strong.

Typically, the new compounds were characterized mainly using the N–H of amide and the thioamide group, C–H of the methyl group, C–H of the methylene group, alkyl- aryl- ether, and the C=O and C=S bands.

The FTIR spectra showed the expected frequencies of the νN-H of the amide group (3380–3337 cm–1) and the νN-H of the thioamide group (3226–3119 cm–1).

The absorption bands for the antisymmetric stretching vibrations, the νC–H of the methyl and methylene groups, appeared at 2964–2956 cm–1 and 2930–2923 cm–1, respectively. These bands are typical for aromatic compounds containing some saturated carbon.

The medium-strong νC=O band appeared at 1677–1663 cm–1, which was lower than that of ordinary carbonyl absorption (1730 cm–1); this can be attributed to the formation of hydrogen bonds. The formation of H-bond leads to an increase of their polarity, so the strength of their double bond


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decreased, and absorption moved to lower wave number. The IR spectra of the target compounds showed very strong characteristic absorption of the νN–H amide group in the range of 1511–1505 cm–1.

These compounds also showed typical alkyl-aryl ether at 1242–1221 cm–1 for the antisymmetric vibration and 1033–1.18 cm–1 for the symmetric one. The spectra showed absorption bands at 1178–1147 cm–1, which can be attributed to the νC=S stretching frequency.

The structures of the new compounds were also determined from their NMR spectra.

The new thioureides were dissolved in dmso-d6 (hexadeuteriodimethyl sulphoxide) and the chemical shifts values, expressed in parts per million (ppm), were referenced downfield to tetra-methylsilane, for 1H-NMR and 13C-NMR and the constants (J) values in Hertz.

The chemical shifts for hydrogen and carbon atoms were established also by GCOSY, GHMBC, GHSQC experiments.

The 1H-NMR data are reported in the following order: chemical shifts, multiplicity, the coupling constants, number of protons, signal/ atom attribution. The apparent resonance multiplicity is described as s (singlet), d (doublet), t (triplet), q (quartet), qv (quintet ), sxt (sextet), spt (septet), m (multiplet), dd (double doublet), td (triple doublet), and br (broad) signal.

In the 1HNMR spectra, the ethyl group exhibited a characteristic quartet at δ 2.51–2.54 ppm and triplet at δ 1.12–1.15 ppm with an expected vicinal coupling constant of 3J≈7.5 Hz. The methylene group attached to the oxygen atom showed a singlet at δ 5.25–5.27 ppm.

The signals of aromatic protons were observed in a range of δ 6.89–7.63 ppm with the intensities and multiplicity according to each aromatic spin system.

The NH protons exhibited two characteristic broad singlets at δ 11.77–11.96 ppm and δ 12.12–12.39 ppm, the most acidic being the NH near C=S group which is involved in six member ring structure by a hydrogen bond with neighbour C=O group, respectively.

For the 13C-NMR data the following order were: chemical shifts and

signal/ atom attribution (Cq- quaternary carbon). In the 13CNMR spectra, the thiocarbonyl carbon showed a

characteristic signal at δ 176.73–180.78 ppm, the carbonyl carbon at δ


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170.04–170.62 ppm, the methylene carbon of CH2O group at δ 67.45–67.64 ppm, and the carbons of ethyl group at δ 27.21–27.30 ppm (CH2) and δ 15.71–15.92 ppm (CH3).

2-((4-Ethylphenoxy)methyl)-N-(2-n-propylphenylcarbamothioyl)benzamide (1a)

yield 53%; mp 106- 107.2°C; 1H-NMR (dmso-d6, δ ppm): 12.24 (br s, 1H, NH); 11.89 (br s, 1H,

NH); 7.63 (br d, J = 7.4 Hz, 1H, H-7); 7.61- 7.59 (m, 2H, H-4, H-22); 7.57 (td, J = 1.4 Hz, J = 7.4 Hz, 1H, H-5); 7.47 (td, J = 1.4 Hz, J = 7.5 Hz, 1H, H-6); 7.29- 7.20 (m, 3H, H-19, H-20, H-21); 7.09 (d, J = 8.6 Hz, 2H, H-11, H-13); 6.90 (d, J = 8.6 Hz, 2H, H-10, H-14); 5.26 (s, 2H, H-8); 2.52 (q, J = 7.5 Hz, 2H, H-15); 2.46 (t, J = 7.3 Hz, 2H, H-23); 1.46 (sxt, J = 7.3 Hz, 2H, H-24); 1.13 (t, J = 7.5 Hz, 3H, H-15’); 0.79 (t, J = 7.3 Hz, 3H, H-25).

13C-NMR (dmso-d6, δ ppm): 180.10 (C-16); 170.42 (C-1); 156.23 (C-9); 137.05 (Cq); 136.16 (Cq); 136.13 (Cq); 135.59 (Cq); 133.41 (Cq); 130.87 (C-5); 129.55 (C-19, C-20, C-21); 128.56 (C-7); 128.52 (C-11, C-13); 128.39 (C-4); 127.73 (C-19, C-20, C-21); 126.90 (C-6); 125.90 (C-19, C-20, C-21); 114.44 (C-10, C-14); 67.48 (C-8); 32.82 (C-23); 27.21 (C-15); 22.89 (C-24); 15.73 (C-15’); 13.51 (C-25).

FT-IR (solid in ATR, ν cm-1): 3167m; 3034w; 2961m; 2930m; 2870m; 1677m; 1610w; 1585w; 1540vs; 1511vs; 1456m; 1383w; 1346m; 1302w; 1256m; 1238s; 1192w; 1178w; 1160s; 1117w; 1093w; 1076w; 1056w; 1033m; 953w; 888w; 867w; 746m; 667w; 572w. Anal. calcd for C26H28N2O2S (432.58): C, 72.19; H, 6.52; N, 6.48; S, 7.41%; Found: C, 72.37; H, 6.61; N, 6.51; S 7.45%.

2-((4-Ethylphenoxy)methyl)-N-(2-isopropylphenylcarbamothioyl)benzamide (1b)

yield 86%; mp 119.4- 120°C; 1H-NMR (dmso-d6, δ ppm): 12.12 (br s, 1H, NH); 11.89 (br s, 1H,

NH); 7.63 (d, J = 1.3 Hz, J = 7.4 Hz, 1H, H-7); 7.59 (dd, J = 1.8 Hz, J = 7.4 Hz, 1H, H-4); 7.56 (td, J = 1.3 Hz, J = 7.4 Hz, 1H, H-5); 7.47 (td, J = 7.4 Hz, J = 1.8 Hz, 1H, H-6); 7.37 (dd, J = 1.4 Hz, J = 7.4 Hz, 1H, H-22); 7.35 (dd, J = 1.8 Hz, J = 7.4 Hz, 1H, H-19); 7.29 (td, J = 7.4 Hz, J = 1.4 Hz, 1H, H-20); 7.22 (td, J = 7.4 Hz, J = 1.8 Hz, 1H, H-21); 7.11 (d, J = 8.6 Hz, 2H, H-11, H-13); 6.90 (d, J = 8.6 Hz, 2H, H-10, H-14); 5.26 (s, 2H, H-8); 2.9 5(spt, J = 7.1 Hz, 1H, H-23); 2.52 (q, J = 7.5 Hz, 2H, H-15); 1.14 (t, J = 7.5 Hz, 3H, H-15’); 1.09 (d, J = 7.1 Hz, 6H, H-24).

13C-NMR (dmso-d6, δ ppm): 176.73 (C-16); 170.31 (C-1); 156.32 (C-9); 143.71 (Cq); 136.16 (Cq); 135.59 (Cq); 135.30 (Cq); 133.56 (Cq); 130.92 (C-5); 128.72 (C-7); 128.61 (C-11, C-13); 128.47 (C-4); 127.86 (C-


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6); 127.71 (C-19 or C-22); 127.65 (C-22 or C-19); 125.82 (C-21); 125.74 (C-20); 114.45 (C-10, C-14); 67.64 (C-8); 27.79 (C-23); 27.28 (C-15); 22.89 (C-24); 15.80 (C-15’).

FT-IR (solid in ATR, ν cm-1): 3157m; 3030w; 2964m; 2929m; 2868w; 1665m; 1608w; 1581w; 1506vs; 1385w; 1331m; 1306w; 1242m; 1218m; 1158m; 1026m; 950w; 826w; 737m; 664m; 609w.

Anal. calcd for C26H28N2O2S (432.58): C, 72.19; H, 6.52; N, 6.48; S, 7.41%; Found: C, 71.97; H, 6.64; N, 6.42; S 7.35%.

2-((4-Ethylphenoxy)methyl)-N-(4-isopropylphenylcarbamothioyl)benzamide (1c)

yield 81%; mp 139.1- 140.4°C; 1H-NMR (dmso-d6, δ ppm): 12.39 (s, 1H, NH); 11.78 (s, 1H, NH);

7.62 (br d, J = 7.4 Hz, 1H, H-7); 7.59 (m, 1H, H-4); 7.56 (td, J = 1.4 Hz, J = 7.4 Hz, 1H, H-5); 7.51 (d, J = 8.4 Hz, 2H, H-18, H-22); 7.46 (td, J = 1.4 Hz, J = 7.5 Hz, 1H, H-6); 7.26 (d, J = 8.4 Hz, 2H, H-19, H-21); 7.09 (d, J = 8.6 Hz, 2H, H-11, H-13); 6.90 (d, J = 8.6 Hz, 2H, H-10, H-14); 5.27 (s, 2H, H-8); 2.90 (spt, J = 7.1 Hz, 1H, H-23); 2.51 (q, J = 7.5 Hz, 2H, H-15); 1.21 (d, J = 7.1 Hz, 6H, H-24,); 1.12 (t, J = 7.5 Hz, 3H, H-15’).

13C-NMR (dmso-d6, δ ppm): 178.79 (C-16); 170.14 (C-1); 156.27 (C-9); 146.42 (Cq); 136.49 (Cq); 135.78 (Cq); 135.53 (Cq); 133.32 (Cq); 130.92 (C-5); 128.56 (C-19, C-21); 128.43 (C-7); 128.30 (C-11, C-13); 127.65 (C-4); 126.33 (C-6); 124.11 (C-18, C-22); 114.56 (C-10, C-14); 67.50 (C-8); 32.97 (C-23); 27.22 (C-15); 23.75 (C-24); 15.72 (C-15’).

FT-IR (solid in ATR, ν cm-1): 3352w; 3159w; 3040m; 2961m; 2924m; 2868w; 1670m; 1596m; 1552m; 1505vs; 1344m; 1288m; 1257m; 1226m; 1177w; 1141vs; 1029m; 831m; 764w; 734m; 704w; 665m; 601w.


2-((4-Ethylphenoxy)methyl)-N-(2-sec-butylphenylcarbamothioyl)benzamide (1d)

yield 80%; mp 98.5- 99.2°C; 1H-NMR (dmso-d6, δ ppm): 12.12 (br s, 1H, NH); 11.88 (br s, 1H,

NH); 7.63 (d, J = 1.3 Hz, J = 7.4 Hz, 1H, H-7); 7.59 (dd, J = 1.8 Hz, J = 7.4 Hz, 1H, H-4); 7.56 (td, J = 1.3 Hz, J = 7.4 Hz, 1H, H-5); 7.47 (td, J = 7.4 Hz, J = 1.8 Hz, 1H, H-6); 7.37 (dd, J = 1.4 Hz, J = 7.4 Hz, 1H, H-22); 7.30- 7.23 (m, 2H, H-19, H-20); 7.22 (td, J = 7.4 Hz, J = 1.8 Hz, 1H, H-21); 7.10 (d, J = 8.6 Hz, 2H, H-11, H-13); 6.89 (d, J = 8.6 Hz, 2H, H-10, H-14); 5.26 (s, 2H, H-8); 2.71 (sxt, J = 7.1 Hz, 1H, H-23); 2.54 (q, J = 7.5 Hz, 2H, H-15); 1.45 (m, J = 7.1 Hz, 2H, H-25); 1.14 (t, J = 7.5 Hz, 3H, H-15’); 1.10 (d, J = 7.1 Hz, 3H, H-24); 0.68 (t, J = 7.1 Hz, 3H, H-26).


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13C-NMR (dmso-d6, δ ppm): 180.78 (C-16); 170.53 (C-1); 156.29 (C-9); 142.49 (Cq); 136.11 (Cq); 135.88 (Cq); 135.57 (Cq); 133.54 (Cq); 130.90 (C-5); 128.71 (C-7); 128.58 (C-11, C-13); 128.46 (C-4); 127.82 (C-6); 127.62 (C-19 or C-22); 127.54 (C-22 or C-19); 126.20 (C-21); 125.74 (C-20); 114.41 (C-10, C-14); 67.59 (C-8); 38.91 (C-23); 29.92 (C-25); 27.27 (C-15); 20.77 (C-24); 15.76 (C-15’); 11.86 (C-26).

FT-IR (solid in ATR, ν cm-1): 3164m; 3029w; 2964m; 2926m; 2869w; 1663m; 1607w; 1580w; 1506vs; 1455m; 1381w; 1331m; 1307m; 1245m; 1221s; 1155s; 1026m; 949w; 892w; 828m; 734m; 664m; 610w.


2-((4-Ethylphenoxy)methyl)-N-(4-sec-butylphenylcarbamothioyl)benzamide (1e)


NH); 7.61 (br d, J = 7.4 Hz, 1H, H-7); 7.59 (m, 1H, H-4); 7.56 (td, J = 1.4 Hz, J = 7.4Hz, 1H, H-5); 7.52 (d, J = 8.4 Hz, 2H, H-18, H-22); 7.47 (td, J = 1.4 Hz, J = 7.5 Hz, 1H, H-6); 7.22 (d, J = 8.4 Hz, 2H, H-19, H-21); 7.08 (d, J = 8.6 Hz, 2H, H-11, H-13); 6.89 (d, J = 8.6 Hz, 2H, H-10, H-14); 5.27 (s, 2H, H-8); 2.59 (sxt, J = 7.2 Hz, 1H, H-23); 2.51 (q, J = 7.5 Hz, 2H, H-15); 1.56 (qv, J = 7.2 Hz, 2H, H-25); 1.19 (d, J = 7.2 Hz, 3H, H-24); 1.12 (t, J = 7.5 Hz, 3H, H-15’); 0.78 (t, J = 7.2 Hz, 3H, H-26).

13C-NMR (dmso-d6, δ ppm): 178.40 (C-16); 170.04 (C-1); 156.29 (C-9); 145.20 (C-20); 136.17 (Cq); 135.79 (Cq); 135.46 (Cq); 133.34 (Cq); 130.94 (C-5); 128.57 (C-11, C-13); 128.44 (C-7); 128.34 (C-4); 127.69 (C-6); 126.94 (C-19, C-21); 123.88 (C-18, C-22); 114.58 (C-10, C-14); 67.53 (C-8); 40.41 (C-23); 30.45 (C-24); 27.23 (C-15); 21.58 (C-26); 15.73 (C-15’); 11.99 (C-25).

FT-IR (solid in ATR, ν cm-1): 3337w; 3119w; 3032m; 2963m; 2923m; 2867w; 1672m; 1596m; 1551m; 1506vs; 1451m; 1340m; 1260m; 1224s; 1176w; 1141s; 1027m; 956w; 832m; 733m; 669m; 601w.


2-((4-Ethylphenoxy)methyl)-N-(2-tert-butylphenylcarbamothioyl)benzamide (1f)


NH); 7.63 (d, J = 1.3 Hz, J = 7.4 Hz, 1H, H-7); 7.59 (dd, J = 1.8 Hz, J = 7.4 Hz, 1H, H-4); 7.56 (td, J = 1.3 Hz, J = 7.4 Hz, 1H, H-5); 7.47 (td, J = 7.4 Hz, J = 1.8 Hz, 1H, H-6); 7.42 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H, H-22);


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7.29- 7.21 (m, 3H, H-19, H-20, H-21); 7.12 (d, J = 8.6 Hz, 2H, H-11, H-13); 6.89 (d, J = 8.6 Hz, 2H, H-10, H-14); 5.25 (s, 2H, H-8); 2.54 (q, J = 7.5 Hz, 2H, H-15); 1.25 (s, 9H, H-24); 1.15 (t, J = 7.5 Hz, 3H, H-15’).

13C-NMR (dmso-d6, δ ppm): 180.73 (C-16); 170.62 (C-1); 156.30 (C-9); 145.11 (C-18); 136.19 (Cq); 135.96 (Cq); 135.57 (Cq); 133.45 (Cq); 131.04 (C-20); 130.94 (C-5); 128.94 (C-7); 128.61 (C-11, C-13); 128.53 (C-4); 127.91 (C-6); 127.53 (C-22); 126.61 (C-21); 126.20 (C-19); 114.49 (C-10, C-14); 67.45 (C-8); 34.37 (C-23); 30.36 (C-24); 27.30 (C-15); 15.92 (C-15’).

FT-IR (solid in ATR, ν cm-1): 3154m; 2994m; 2956m; 2927m; 2869s; 2873m; 1671m; 1607w; 1578w; 1506vs; 1387w; 1328w; 1300w; 1230s; 1148s; 1057w; 1018m; 864w; 826w; 729m; 657m; 615w.


2-((4-Ethylphenoxy)methyl)-N-(4-tert-butylphenylcarbamothioyl)benzamide (1g)


NH); 7.61 (br d, J = 7.4 Hz, 1H, H-7); 7.59 (m, 1H, H-4); 7.56 (td, J = 1.4 Hz, J = 7.4 Hz, 1H, H-5); 7.52 (d, J = 8.4 Hz, 2H, H-18, H-22); 7.47 (td, J = 1.4 Hz, J = 7.5 Hz, 1H, H-6); 7.41 (d; J = 8.4 Hz, 2H, H-19, H-21); 7.08 (d, J = 8.6 Hz, 2H, H-11, H-13); 6.89 (d, J = 8.6 Hz, 2H, H-10, H-14); 5.27 (s, 2H, H-8); 2.51 (q, J = 7.5 Hz, 2H, H-15); 1.29 (s, 9H, H-24); 1.12 (t, J = 7.5 Hz, 3H, H-15’).

13C-NMR (dmso-d6, δ ppm): 178.76 (C-16); 170.14 (C-1); 156.27 (C-9); 148.66 (C-20); 136.15 (Cq); 135.78 (Cq); 135.24 (Cq); 133.33 (Cq); 130.93 (C-5); 128.56 (C-11, C-13); 128.43 (C-7); 128.31 (C-4); 127.67 (C-6); 125.25 (C-19, C-21); 123.75 (C-18, C-22); 114.56 (C-10, C-14); 67.50 (C-8); 34.23 (C-23); 31.05 (C-24); 27.21 (C-15); 15.71 (C-15’).

FT-IR (solid in ATR, ν cm-1): 3380w; 3226w; 3108w; 3039w; 2960s; 2930m; 2869w; 1673m; 1584m; 1533s; 1506vs; 1374m; 1333m; 1290m; 1231s; 1147s; 1054w; 1023m; 834m; 773w; 763m; 733w; 690w; 657w; 599w.


Conclusions

The structure of the new 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl)-benzamides were confirmed by physical and


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spectroscopic techniques. Previous work [11] has shown that it is possible to improve their antimicrobial activity by nanotechnological solutions.

References

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__________________________________ Manuscript received: October 2013

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