Хімія та хімічні технології/ 6. Органічна хімія

T. V. Panasenko, V. P. Buryak, M. V. Parchenko, T. O. Samura, A. S. Gotsulya

Zaporozhye State Medical University, Ukraine

UV-spectrophotometry of O- and O,N-hetero-cyclic derivatives (LITERATURE REVIEW)

Key words: UV-spectra, oxazolidine, morpholine, dioxane

Analysis of scientific professional literature information allows us to make conclusions, that nowadays exist different views on the thin chemical structure and on the nature of the compounds electronic spectra emergence, which are O- and O, N-heterocyclic derivatives (sexazolidine, morpholine, dioxane). Specified heterocyclic compounds show spectral characteristics in dependence from the substituents nature, their position in research cycles and polarity of used solvents.

Established that the steric position of substituents significantly affect the nature of the considered ultraviolet spectra. There are different points of view on the question of simultaneous introduction in heterocyclic molecule of electro donor and electro acceptor nuclear groups and it certainly requires more in-depth study of their UV-spectra. There is no any information in several articles about the research of spectra basic optical characteristics, which allow defining the basic chromophore and pharmacologically active part of the compound - pharmacophore.

Heterocyclic compounds, containing in their structure O- and O, N-heterocyclic structures are the part of drugs molecules (tritetine, mepholine, morphocycline trioxazine, piroxane), which has been successfully used in clinical practice at various diseases treatment. This all is the basis for a detail study of their physical and chemical properties and especially of the absorption electronic spectra. Their detail studying allows determining the chromophore.

The purpose of work was studying of the primary literature sources, concerning of the electronic structure of oxazolidine, morpholine and dioxane derivatives, the nature of their UV-spectra in dependence from the substituents proliferation in molecules of the research compounds.

Materials and methods. Informational sources allowed us to consider and analyze information of a scientific professional literature about UV-spectra studying of the oxazolidine, morpholine and dioxane derivatives. This allows scientists to determine the further direction in drugs creation that contain in their molecules O- and O, N- heterocyclic fragments.

Results and their discussion. Rekker and other [15] researched the UV-spectra of the alkylated oxazolidone-2,4 derivatives. Authors noticed that the absorption spectra of 5,5-dimethyloxazolidone 2,4; 3,5,5-trimethyloxazolidone-2,4 (trimethine) and 3-ethyl-5,5-dimethyloxazolidone-2,4 have one absorption band within the ranges from 220 to 230 nm. Replacement of the methyl and ethyl groups in accordance with methoxy- and ethoxygroups leads to the specified absorption band disappearance. In an acidic environment (pH 4,5) 5,5-dimethyloxazolidone-2,4 UV-spectrum have one absorption band within the ranges from 230 to 240 nm, which disappears in an alkaline environment (pH 12,5).

Absorption spectra of 3-aryloxzolidyndone-2,4 were studied by Shapiro and other [14]. It was established that different steric location of a substituent in position 3 significantly affects the nature of UV-spectra of the compounds. If the aryl group is located in area, which is typical for the A structure, and for a compound, which shows the uncharacteristic aniline spectrum, and changing of the character of an absorption band depends on the position of a substituent U. If the electron pairs of nitrogen and aryl groups connected coplanary, as it defined for B structure, spectral characteristics similar to those, which characterizing α-hydroxylamides. In turn, if the electron pairs of nitrogen, aryl groups connected caplanary, as specified for C structure, the spectral characteristics of our compound is similar with spectral characteristics of substituted phenyl urea derivatives.

UV-spectra of studied compounds demonstrate quite strong absorption within the ranges from 217 to 231 nm. Hypo- and hypsochromic displacements of the absorption bands that occur for B and C structures authors associated with steric ban of the amide resonance. In 0,1M solution of sodium hydroxide, 3-aryl-oxazolidyndione-2,4 hydrolyzed to carbomoiloxyacids, that confirmed by the similarity of spectra, absorbing hydrolysis products and corresponding carbomoiloxyacids.

Morphocycline is a synthetic derivative of the tetracycline, in which one hydrogen atom in carboxamide group (-CONH₂) is substituted on methylmorpholine group.

Gottstein et al [11] studied the UV-spectra of methyl solutions of tetracycline and mophocycline. Notes that tetracycline and its chlorderivative absorption band is characterized by two absorption bands with maximums at 268-, 365-, 270 and 366 nm. Hydrogen substitution in the amide group on N-methyl-morpholine leads to the bathochromic shift of the maximum of long-wave absorption band on 15nm. Maximum of the medium-wave absorption band is shifted slightly and situated at 380 nm. Bands of the morphocycline electronic spectra in aqueous, ethanol and alkaline solutions characterized by two absorption bands (O. N. Ryvuak). So, absorption maximum in aqueous solution of a drug is observed at 275 and 366 nm, and in the acidic medium at 270 and 359 nm, namely, they are hypochromically removed on 5-7 nm towards the morphocycline maximum. Ultraviolet spectrum of morphocycline in ethanol has two absorption maximums at 268 and 368nm. Slightly different is morphocycline absorption spectrum in an alkaline medium, the first maximum is at 240 nm. And it is less intense as compared with a maximum of other morphocycline solutions, which is located in the same part of the spectrum. Spectrum of the second absorption band of such drug solution has a maximum at 385 nm and removed bathmochromically, nearly on 20 nm as compared with the same morphocycline maximum in other solvents.

Simoni and other [16] had studied the electronic absorption spectra of the trioxazine and some table substances (3,4,5-trimethyltoxybenzolic acid and morpholine) in methanol. Absorption band, respectively, at 214 and 248 nm, 3,4,5- trimethoxybenzolic acid at 218 - 260 nm, morpholine at 206 nm. The authors have developed a method of the spectrophotometric determination of the trioxazine in tablets. Determination of methanol solutions absorption of the drug is performed at 248 nm. The determining error ± 2%.

Drug against anorexic people - mepholine also contains in its molecule morpholine. Sarsanova and other [10] developed a spectrophotometric method of quantitative determination of the mepholine in drug forms after its previous separation by means of thin layer chromatography on the aluminum oxide and determine the solution intensity at 254 nm. The determining error is in the ranges from – 4,3 to + 2,5%.

In 1,4-dioxane spectrum there are bands with maximums at 55500, 63000, 59500 and 72000 cm^-1 [12]. Lower 72000 cm^-1 absorption coefficient decreases rapidly and reaches a minimum at 76750 cm^-1, and then quickly increases, but there is no any maximums. Perhaps, the intense absorption in this interval connected with the first ionization potential (9,52). Electrons transitions at 63000, 69000 and 72000 cm^-1 can be connected with the Rydberg series.

For the comparison of cis- and trans-dyaril-1,4-dioxanes and structurally similar compounds, had studied UV-spectrum of 19 different substances [15]. Measurements were performed in the wavelength ranges from 220 to 300 nm in ethanol as compared with benzene. Similarity of the monophenyldioxane spectrum and trans-2,5-diphenyl-1,4-dioxane spectrum confirms a representation about the final compound as a trans-isomers, confirms the cis- structure of cis-2,5-diphenyl-1,4-dioxane. 2,3-di-(o-tolyl)-1,4-dioxane and 2,3-di-(m-tolyl)-1,4-dioxane spectra are similar and removed towards longer wavelengths as compared with obtained quantities. Authors made a conclusion that if phenol groups in dioxane cycle become closer - increases the number of maximums, for example, trans-2,5-diaryl-1,4-dioxane has only one clearly expressed maximum, cis-2,5-diphenyl-1,4-dioxane - two, and 2,3-diphenyl-1,4-dioxane - three.

Stump [17] had studied the absorption UV-spectra of cis- and trans-2,3-pharm diphenyldioxane and 2,5-diphenyldioxane in dioxane. For all compounds, absorption bands of the benzene ring save their position and intensity. Number of bands, as in the case of toluene and ethylbenzene, reduced as compared with benzene absorption spectrum. Absorption bands of cis-2,5-diphenyldioxane and trans-2,5-diphenyldioxane have weakly marked inflection at 285 nm, which is not presented in 2,5-dibenzyldioxane spectrum. Trans-2,3-diphenyldioxane characterized by intense absorption without an explicit maximum in long-wave part of the spectrum. Absorption curve of cis-2,3-diphenyldioxane has a broad maximum at 315 nm. Position of this maximum is largely dependents on the solvent and in methanol removed on 8 nm in a short - wave part of the spectrum, but absorption bands of the benzene ring are not changed. This band is absent in the diphenylethane spectrum and is not a result of the phenol cycles interaction. Author explains an appearance of the additional maximum at 315 nm in the spectrum of cis-2,3-diphenyldioxane as the result of phenol ring interaction with an oxygen nucleus of dioxane radical (type of the hydrogen connection formation).

Optical properties of the benzodioxane-1,4 which molecule can be regarded as a molecule, consisting of benzene and dioxane parts and its derivatives have been studied insufficiently. Until nowadays, it was managed to find some works, which are containing some spectral characteristics by means of the electronic spectra.

Baddelay, Smith [19] had researched the cyclic effect in complex esters of benzodioxane-1,4 derivatives on the electronic absorption spectra and established intensity and frequency of the vibration bands of long-wave transition. Changes in complex esters spectra were explained due by inductive effects that were caused by oxygen atoms interaction through the chain of methyl groups and partially by spatial effects that occur during heterocyclic quantity changing. N-electron density distribution by means of alkoxygroups caplanarity had calculated, using the method of molecular orbital for the benzodioxane-1,4 molecules. Calculation performed with explanation of the reactionary ability, in dependence from different positions of the benzene ring [1].

G. P. Ionaytis and other [3], using electron spectroscopy, studied the effect of substituent’s structure on the absorption spectra of the derivatives of benzodioxane-1,4,6-substituted (alkyl-, alkoxy-, aminoalkyl-, oxyamin-, alkyl, alkoxyaminoalkil-, acyl- and bromine derivatives) in ethanol, n-heptane, 1,2-dichloroethane, carbon tetrachloride. Benzodioxane-1,4 spectrum in ethanol has two bands: 220 nm (ɛ = 6500) and 278,5 nm (ɛ = 2800). Substitutes with an unshared pair of electrons remove K and B bands bathmochromic, and intensity of B band at the same time increases.

Spectrum of 6-acylderivatives is characterized by three absorption bands with maximums at 230, 275 and 310 nm. Shift of the absorption band, which is caused by lateral substituent change, was slight. Vibrational structure of B band depends on the substituent structure and nature of the solvent. Bathmochromic shift, which was caused by methyl-, phenyl-, bromine-substituents was proportional to their negative inductive effect. In the UV-spectra of 6-alkyl and 6-acylsubstituents derivatives of benzodioxane-1,4 changes only the vibrational structure of the electron. Phenol radical, which introduced in the side chain of 6-alkyl, 6-aminoalkyl, 6-alkoxy- and 6-oxyaminoalkylsubstitutes causes an appearance of weak absorption band at 315 nm.

Devoted the labor of G. P. Ionaytis, V. A. Urta to the question of studying of the influence of solvents on the absorption spectrum of benzodioxane-1,4. Established that position and intensity of absorption band does not depend on the concentration of substance, but depends on the nature of the solvent (n-hexane, n-heptane, n-octane, 1,4-dioxane, acetonitrile, acetone, chloroform, carbon tetrachloride, benzene, chlorobenzene).

There was considered the impact of foundation parameter, dielectric insight (ɛ) and the dipole moment of the solvent on the absorption band shift (Δν). One of the most important factors, which determines the effect of solvents on the position of absorption band - is the polarization of molecules of dissolved substance. Dependence of Δν from ɛ is primarily associated with dipole-dipole interaction between molecules of dissolved substance and solvent. The specific effect of solvents, containing oxygen and chlorine atoms in conjugate aromatic system is not connected with quantity of their dipole moment. G. I. Ionaytis [4], V. A. Churba and other [7] had studied the absorption UV-spectra of benzodioxan-1,4 derivatives (ethanol and n-hexane solvent), which have in position 6 and auxochromic and chromophore groups. In the case when C=O group of the substituent conjugated with the cycle, in UV-spectra observed R- band (300 - 340 nm) B-band (230 - 265 nm) and K-band (220 - 240 nm). And if the buffer substituent has two conjugate with each other and with the cycle chromophores (C=C or C=O) or auxochromic group (NO₂, NH₂), in spectra also is noticeable the B band (255 - 275 nm). R-band points at the presence of chromophores in the aromatic cycle and does not depend on the structure of lateral substituent and the nature of its conjugation with cycle.

B-band depends on all substituents which are situated in aromatic cycle, K-band characterizes the presence of auxochromes and conjugative chromatophores in lateral substituent. C=O conjugation with benzodioxane ring is stronger than with phenyl.

In electronic absorption spectrum of 1,4-benzodioxane in its short-wave part is observed two bands. The short-wave band with a maximum at 221 nm (ɛ = 6400) is characterized with intensity, which is almost twice as much than intensity of the long-wave band that has clearly expressed vibrational structure with maximums at 275, 278 and 284 nm [8].

CONCLUSIONS

Our literature information about UV-spectrophotometry of O- and O,N-heterocyclic derivatives allows to make the following conclusions:

1. There are different views on the fine chemical structure and the reason of the absorption bands emergence in the electronic spectra of O- and O,N-heterocyclic derivatives.

2. Do not uniquely identified types of the electrons transitions that cause the occurrence of maximums in the UV-spectra of O- and O,N-heterocyclic derivatives.

3. There aren’t any information about a determination of the basic septic characteristics of UV-spectra of drugs, derivatives of the oxazolidine (trimethine) morpholine (mepholine, trioxazine, morphocycline and dioxane (piroxane) that can uniquely identify chromophores, which are the reason of our research absorption bands appearance.

4. Till nowadays it doesn’t exist a method , which allows to perform quantitative determination of trimethine, mepholine, trioxazine, morphocycline and pyroxene, mixed with other drugs without their pre-separation.

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