FARMACIA, 2014, Vol. 62, 3 494 SYNTHESIS, PHYSICO-CHEMICAL CHARACTERISATION AND MESOMORPHIC PROPERTIES OF SOME NOVEL AZODERIVATIVES GABRIELA RĂU 1 , GEORGE DAN MOGOŞANU 2 *, CĂTĂLINA GABRIELA PISOSCHI 3 , CAMELIA ELENA STĂNCIULESCU 3 1 Department of Organic Chemistry, Medicinal Chemistry 2 Department of Pharmacognosy & Phytotherapy 3 Department of Biochemistry University of Medicine and Pharmacy of Craiova, Faculty of Pharmacy, 2 Petru Rareş Street, 200349 Craiova, Romania * corresponding author: [email protected]Abstract The synthesis of some novel compounds, four 4-(N-phenylacetamidoxy)azo- benzenes and one 4-(N-phenylacetamidoxy)-4’-(phenylazo)biphenyl, was completed through the condensation of the 4-(phenylazo)phenols or 4-hydroxy-4’-(phenylazo) biphenyl, in alkaline medium, with 4-methoxy-N-chloroacetylaniline. The purification of the compounds was achieved by recrystallisation from toluene and checked by gas chromatography. The compounds are solid, with different colours and high melting points. Their structures were established through elemental and spectral analysis (UV–Vis, FTIR, 1 H–NMR, GC–MS). For the novel synthesized azoderivatives, the mesomorphic behaviour was studied by polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). It was found that the size, position and polarity of the terminal group strongly influence the type of mesophase and the transition temperatures of a given compound. Rezumat Sinteza unor noi compuşi, patru 4-(N-fenilacetamidoxi)azobenzeni şi unu 4-(N- fenil-acetamidoxi)-4’-(fenilazo)bifenil, s-a realizat prin condensarea unor 4-(fenilazo)fenoli sau 4-hidroxi-4’-(fenilazo)bifenil, în mediu alcalin, cu 4-metoxi-N-cloroacetilanilina. Purificarea compuşilor s-a realizat prin recristalizare din toluen. Gradul de puritate a fost verificat prin gaz-cromatografie. Compuşii sunt solizi, diferit coloraţi, cu temperaturi de topire ridicate. Structura lor a fost confirmată atât prin analiză elementală, cât şi prin metode spectrale (UV–Vis, FTIR, 1 H–RMN, GC–MS). Comportamentul mezotrop a fost studiat prin microscopie în lumină polarizată şi calorimetrie diferenţială. Mărimea, poziţia şi polaritatea grupei terminale influenţează semnificativ tipul mezofazei şi temperaturile de tranziţie. Keywords: azoderivatives; synthesis; physico-chemical characterisation; meso- morphic properties. Introduction In the specialty papers [4–9] it is described a method for the obtaining of azoderivatives, which supposes the condensation of some 4-
Transcript
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SYNTHESIS, PHYSICO-CHEMICAL CHARACTERISATION AND MESOMORPHIC PROPERTIES OF SOME NOVEL AZODERIVATIVES GABRIELA RĂU1, GEORGE DAN MOGOŞANU2*, CĂTĂLINA GABRIELA PISOSCHI3, CAMELIA ELENA STĂNCIULESCU3 1Department of Organic Chemistry, Medicinal Chemistry 2Department of Pharmacognosy & Phytotherapy 3Department of Biochemistry University of Medicine and Pharmacy of Craiova, Faculty of Pharmacy, 2 Petru Rareş Street, 200349 Craiova, Romania * corresponding author: [email protected]
Abstract
The synthesis of some novel compounds, four 4-(N-phenylacetamidoxy)azo-benzenes and one 4-(N-phenylacetamidoxy)-4’-(phenylazo)biphenyl, was completed through the condensation of the 4-(phenylazo)phenols or 4-hydroxy-4’-(phenylazo) biphenyl, in alkaline medium, with 4-methoxy-N-chloroacetylaniline. The purification of the compounds was achieved by recrystallisation from toluene and checked by gas chromatography. The compounds are solid, with different colours and high melting points. Their structures were established through elemental and spectral analysis (UV–Vis, FTIR, 1H–NMR, GC–MS). For the novel synthesized azoderivatives, the mesomorphic behaviour was studied by polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). It was found that the size, position and polarity of the terminal group strongly influence the type of mesophase and the transition temperatures of a given compound.
Rezumat
Sinteza unor noi compuşi, patru 4-(N-fenilacetamidoxi)azobenzeni şi unu 4-(N-fenil-acetamidoxi)-4’-(fenilazo)bifenil, s-a realizat prin condensarea unor 4-(fenilazo)fenoli sau 4-hidroxi-4’-(fenilazo)bifenil, în mediu alcalin, cu 4-metoxi-N-cloroacetilanilina. Purificarea compuşilor s-a realizat prin recristalizare din toluen. Gradul de puritate a fost verificat prin gaz-cromatografie. Compuşii sunt solizi, diferit coloraţi, cu temperaturi de topire ridicate. Structura lor a fost confirmată atât prin analiză elementală, cât şi prin metode spectrale (UV–Vis, FTIR, 1H–RMN, GC–MS). Comportamentul mezotrop a fost studiat prin microscopie în lumină polarizată şi calorimetrie diferenţială. Mărimea, poziţia şi polaritatea grupei terminale influenţează semnificativ tipul mezofazei şi temperaturile de tranziţie.
In the specialty papers [4–9] it is described a method for the obtaining of azoderivatives, which supposes the condensation of some 4-
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(phenylazo) phenols, in alkaline medium, with different N-chloroacetyl-anilines [1–3].
The five novel synthesized azoderivatives are: four 4”-methoxy- 4-(N-phenylacetamidoxy)azobenzenes and one 4-(p-methoxy-N-phenyl-acetamidoxy)-4’-(phenylazo)biphenyl. The synthesis of these compounds supposes the condensation, in alkaline medium, of 4-(phenylazo)phenols and respectively 4-hydroxy-4’-(phenylazo)biphenyl with 4-methoxy-N-chloro-acetylaniline [2-chloro-N-(4-methoxyphenyl)acetamide].
The following intermediates, 4-(phenylazo)phenols and 4-hydroxy-4’-(phenylazo)biphenyl, were used for the synthesis: 4-(4’-nitro-phenylazo) phenol, 4-(4’-cyano-phenylazo)phenol, 4-(4’-trifluorometil-phenylazo)phenol, 4-(4’-chloro-phenylazo)phenol and 4-hydroxy-4’-(p-chloro-phenylazo)biphenyl.
The chemical reactions for the synthesis of the novel azoderivatives were as follows (Figure 1):
+ NaClN NR CH 2 C NHO
O
R '
N NR O-‐Na+ + ClCH 2 C NH
O
R '
R = NO2, CN, CF3, Cl. R’ = OCH3.
R 'N N O-‐Na+R
O
+ ClCH 2 C NH
R ' + NaClR
O
CH 2N N C NHO
R = Cl, CH3. R’ = OCH3.
Figure 1 The synthesis of the novel azoderivates, after bimolecular substitution reaction
mechanism (SN2)
Materials and Methods
The synthesis of these compounds supposes an anhydrous medium, because of the presence of azophenoxide extremely sensitive to water traces. For this purpose, an azeotropic distillation was achieved with the separation of azeotropic mixture water–ethanol–benzene, because the synthesis of azophenoxide was performed in a mixture of benzene–ethanol (1:1, v:v). The synthesis was performed in five or six hours. Solid products with different colours, from yellow to dark red were obtained. The
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recrystallisation was made from toluene. 4”-Methoxy-4-(N-phenyl-acetamidoxy)azobenzenes have higher melting points compared with 4-(p-methoxy-N-phenylacetamidoxy)-4’-(phenylazo)biphenyl, taking into account the presence of different substitutes in para position. The yields depend on the solubility of reaction products in toluene. The presence of a single chromatographic (GC) peak certifies that these compounds are pure.
Synthesis of 4’-trifluoromethyl-4-(p-methoxy-N-phenylacetamidoxy) azobenzene
To a one-necked round-bottomed flask equipped with a mechanical stirrer, thermometer and condenser, 1.33 g (5 × 10-3 M) of 4-(4’-trifluoro-methyl-phenylazo)phenol, 0.2 g (5 × 10-3 M) sodium hydroxide and 40 mL of ethanol–benzene mixture (1:1, v:v) were added. The reaction mixture was stirred two hours at 700C, until azophenol reacted with sodium hydroxide. The reaction water was removed by the distillation of 20 mL of ethanol–benzene–water azeotropic mixture. 0.9975 g (5 × 10-3 M) of 4-methoxy-N-chloroacetylaniline were added to anhydrous azophenoxide and the reaction mixture was stirred 5–6 hours at 50–550C. After cooling at room temperature, the solid product was filtered, then washed with water for the removal of sodium chloride and dried in a heating chamber, at 1050C. The reaction product was then recrystallized from 80 mL of toluene to obtain (yield 78.32%) 4’-trifluoromethyl-4-(p-methoxy-N-phenylacetamidoxy)azobenzene (m.p. 190–1910C).
The synthesis was similar for all five novel compounds. By coupling of adequate diazonium salts with phenol, 4-(4’-nitro-phenylazo)phenol, 4-(4’-cyano-phenylazo)phenol, 4-(4’-trifluoromethyl-phenylazo)phenol, and 4-(4’-chloro-phenylazo)phenol were obtained. Similarly, 4-hydroxy-4’-(p-chloro-phenylazo)biphenyl was synthesized by coupling of appropriate diazonium salts with 4-hydroxybiphenyl. 4-Methoxy-N-chloroacetylaniline was obtained by chloroacetylation of p-anisidine (p-methoxyaniline or 4-methoxybenzene-amine).
nitrile), p-nitroaniline and p-trifluoromethylaniline used for the preparation of diazonium salts were Fluka or Merck products. Phenol and 4-hydroxy-biphenyl used in the coupling reaction were also Fluka products. Chloro-acetyl chloride and p-anisidine used for the synthesis of 4-methoxy-N-chloroacetylaniline were Fluka or Merck products.
Equipments The melting points were established in capillaries (sulphuric acid
bath) and with a Boetius apparatus.
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Elemental analysis was performed on CHNOS Vario El analyzer. Electronic spectra were recorded with a UV–Vis Jasco V–530
spectrophotometer, within 200–700 nm range. Dioxane solutions (4 × 10-5 M) were prepared one day before spectra recording and kept in a dark place.
FTIR spectra were recorded in potassium bromide pellets (KBr, Merck), with a Bio-Rad FTS 135 spectrophotometer, within the range 3500–400 cm-1.
Mass spectra were obtained using a HPGC–MS 5890 MD 5971 spectrometer, at 70 eV, with carrier gas He at 2 mL/min.
1H–NMR spectra were recorded with a Varian NMR-System 300 spectrometer, at 300 MHz, in CDCl3 or DMSO–d6. Tetramethylsilane (TMS) was used as internal standard.
Phase sequences and phase transition temperatures were determined by polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). The first method was applied using an IOR MC–5A polarized light microscope with a heating table at 100C/min. rate for both heating and cooling. The second method analysed the compounds with a Perkin Elmer DSC–2 device with the same heating–cooling rate (100C/min.). Sometimes, to separate the transition peaks, the study was carried out at lower speeds (50C/min., 20C/min.). The device was set at a sensitivity of 5 mcal/s in an inert atmosphere of argon.
Results and Discussion
Table I shows structural formulas, molecular masses, melting points and yields for the five novel synthesized compounds.
UV–Vis spectra Absorption bands of moderate intensity at 249–291 nm were due to
benzenoid-type E- or B-bands. Intense absorption bands correspond to K-bands at 347–372 nm. Some low intensity R-type bands from Vis were also observed at 436–442 nm, due to –N=N– chromophore group. The conjugated system Ar–N=N–Ar leads to the formation of intense K-type bands. Conjugation of π electrons of benzene rings leads to moderate intensity E- or B-type bands. Names of the compounds, elemental analysis (C, H, N), maximum UV–Vis absorptions and molar extinction coefficients are presented in Table II.
FTIR spectra FTIR spectra show absorption specific bands for –N=N–, –NH–, Ar–
O–CH2–, –CO–NH– groups and also for the aromatic rings. Table III presents the absorption bands of the five novel synthesized azoderivatives.
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The presence of benzene rings is highlighted by bands due to the ring vibrations, around 1600 cm-1.
Table I
Formulas, melting points and synthesis yields of the novel azoderivatives
No. Structural formulas Molecular formulas M M.p.
[oC] η [%]
1. N NO2N CH 2 C NHO
O
N NO2N CH 2 C NHO
O
OCH 3
C21H18N4O5 406 188–189 70.44
2. OCH 3N NN N CH 2 C NHO
O
CH 2 C NHO
O
NC
C22H18N4O3 386 199 85.49
3. NCF3 N O CH2 C
O
NH OCH3
C22H18N3O3F3 429 190–191 78.32
4. OCH 3N NN N CH 2 C NHO
O
CH 2 C NHO
O
Cl
C21H18N3O3Cl 395.5 205–
206 92.54
5. OCH 3CH 2N NCl C NHO
O C27H22N3O3Cl 471.5 159–
160 77.20
M – Molecular mass; M.p. – Melting point; η – Yield.
Table II UV–Vis absorption bands and elemental analysis of the novel azoderivatives
FTIR absorption bands: i – Intense; vi – Very intense; w – Weak; m – Moderate; antisym. – Anti-symmetric; sym. – Symmetric.
The groups CH2 and CH3 show absorption bands in the aliphatic
radicals’ zone. Thus, for νCH3 anti-symmetric valency vibrations there is one band at 2971–2960 cm-1 and other bands at 2933–2918 cm-1. Symmetric valency vibrations for the groups CH2 and CH3 lead to a single weak band at 2863–2840 cm-1.
Valency vibration νNH of amide group appears at high values of the wave number, because the N–H bond is strong. This band is usually sharpened but wide for some spectra. The values of the wave number are different (3434–3380 cm-1) depending on the intensity of amide group association.
Very weak bands between 3076 and 3029 cm-1 highlight the C–H bonds from the aromatic rings.
An important band is due to νCO valency vibration of the amide group, the so-called amide I band, which appears at 1686–1654 cm-1. Usually, the most intense band in the spectra (1545–1537 cm-1) was considered as amide II band.
Very intense bands at 1246–1233 cm-1 were assigned to the anti-symmetric valency vibrations and weaker bands at 1066–1032 cm-1 to the etheric symmetric valency vibrations.
The valency vibration νN=N band should be characteristic for these compounds but because of the very weak bond polarity, the absorptions occur at small values of the wave numbers and the bands have low intensities (1441–1436 cm-1).
Compound 2 is characterized by a CN group band at 2231 cm-1.
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1H-NMR spectra 1H–NMR spectra of the five novel compounds are characterized by
chemical shifts δ (ppm) of protons of the main components such as NH, CH2 of the group (–O–CH2–), CH3 of the group (–O–CH3) and of course of the aromatic protons. For these compounds, 1H-RMN spectra highlight four signals from which a multiplet specific to the aromatic protons at δ (ppm) 7.4–7.6 and three non-splitted signals: singlet given by protons of groups NH [δ (ppm) 8.3–8.8], CH2 [–O–CH2–, δ (ppm) 4.6–4.8], and CH3 of methoxy group [–O–CH3, δ (ppm) 2.6–3.7].
Validity of the structural formulas has been confirmed by 1H–NMR spectra and the chemical shifts of the novel azoderivatives are shown in Table IV.
Table IV 1H–NMR data of the novel azoderivatives (CDCl3 or DMSO–d6)
No. δ [ppm]
Aromatic protons NH CH2 (–O–CH2–) CH3 (–O–CH3) 1. 7.6 m; J=0.49 8.4 s 4.8 s 3.7 s 2. 7.5 m; J=0.11 8.4 s 4.8 s 3.7 s 3. 7.6 m; J=0.49 8.8 s 4.8 s 2.6 s 4. 7.4 m; J=0.07 8.3 s 4.8 s 3.7 s 5. 7.4 m; J=0.07 8.3 s 4.7 s 3.6 s
m – Multiplet; s – Singlet.
Mass spectra All the compounds have similar fragmentation, as can be seen from
the molecular ion fragmentations of the compound 4’-trifluoromethyl-4-(p-methoxy-N-phenylacetamidoxy)azobenzene (Figure 2), obtained by cleavage of O–CH2 bond:
m/e 265 m/e 164
m/e 429
N NCF 3
. -‐ C 9H10NO2
CH 2 C NHO
O
N N O+CF 3 COCH 2 NH+
. -‐ C 13H8N2OF 3
OCH 3
OCH 3
+.
Figure 2
Cleavage of O–CH2 bond leads to formation of radicals and cations characterized by m/e
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In the mass spectrum of the compound 3, the occurance of a rearrangement peak m/e 235 formed by electrocyclic processes was observed (Figure 3).
+Om/e 265
N N
CF 3
+
N N
OH H
CF 3 conrotatoryprocess
+
N NH H
O
- N2- H2
+
m/e 235O
CF 3
CF 3
Figure 3
Electrocyclic processes for the compound 3 After a skeletal transposition (Figure 4), tropylium ion m/e 91
specific for monoalkyl aromatic compounds was formed. After successive losses of acetylene, cyclopentadienylium m/e 65 and respectively cyclopropenylium m/e 39 ions were formed.
++
m/e 91
CH2+
m/e 65
- C2H2 - C2H2+
m/e 39 Figure 4
Monoalkyl aromatic compounds transposition Table V presents the characteristic fragmentations of the five novel
compounds. Table V
Mass spectra data of the novel azoderivatives Compound 1 2 3 4 5
Investigation of liquid crystal properties The compound 1 is an enantiotropic liquid crystal exhibiting nematic
and smectic A phase. As shown in Figure 5, the phase sequence is: ▪ at heating: K 167.45 SA 192.85 N 210.65 I (K – crystalline phase,
SA – smectic A phase, N – nematic phase, I – isotropic liquid); ▪ at cooling: I 203.85 N 134.05 SA 117.85 K.
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A strongly exothermal behaviour specific for most compounds with –NO2 as terminal group was observed at heating. At cooling, the nematic phase appears from the isotropic sub-cooled liquid.
The compound 3 shows a monotropic smectic A phase and a polymorphism of the solid phase. From the DSC diagram (Figure 6), a slightly pre-transitional effect was observed. At cooling, the phase sequence is I 176.35 SA 165.65 K1 151.25 K (K, K1 – crystalline phases).
Figure 7 shows the smectic A–K1 transition for the compound 3. The compound 4 exhibits a polymorphism of the solid phase, at
heating, and a nematic phase followed by a smetic A phase, at cooling. From the DSC diagram (Figure 8), at cooling was observed the following phases’ sequence: I 195 N 193 SA 189.15 K1 166.85 K.
Figure 9 presents the occurance of the nematic phase from the sub-cooled isotropic liquid, for the compound 4.
The compound 5 gives at heating a nematic phase and at cooling a nematic–smectic A polymorphic solid phase sequence. Resulting from polarized light microscopy method and confirmed by differential calorimetry method the phases’ sequence (Figure 10) is:
▪ K 157.25 K1 163.6 N 171.65 I, at heating; ▪ I 144 N 130.25 SA 128.05 K1 126.15 K, at cooling.
Figure 5
DSC thermodiagram of the compound 1
Figure 6
DSC thermodiagram of the compound 3
Figure 7
Smectic A–K1 transition for the compound 3
Figure 8
DSC thermodiagram of the compound 4
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Figure 9
Apparition of the nematic phase from the sub-cooled isotropic liquid, for the compound 4
Figure 10
DSC thermodiagram of the compound 5
Conclusions
The synthesis of some novel compounds, four 4-(N-phenyl-acetamid-oxy) azobenzenes and one 4-(N-phenylacetamidoxy)-4’-(phenylazo)biphenyl, was achieved through the condensation of sodium azophenoxydes with 4-methoxy-N-chloroacetyl-aniline, and their structures were established through elemental and spectral analysis. The mesomorphic behaviour was studied by polarizing optical microscopy and differential scanning calorimetry. The obtained DSC diagrams and textures confirmed the liquid crystals properties of the novel azoderivatives.
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