Received 3 March 2015; accepted 27 June 2015; published 30 June 2015

ABSTRACT

Results of oxidation 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid oxygen depend on temperature. At 55˚C - 60˚C, 2,4-di-tert-butylbicyclo(4,3,1)deca-4,6-dien-8-(N-ace- tylamine)-3,9-dion-1-oxa is formed. The constitution is based on dates of spectrums ¹Н and ¹³С NMR. At 95˚C - 97˚C, mixtures of 2,4-di-tert-butylbicyclo(4,3,1)deca-4,6-dien-8-(N-acetylamine)-3,9-dion-1-oxa and of 6,8-di-tert-butyl-3-(N-acetylamine)spiro(4,5)deca-1-oxa-5,8-dien-2,7-dione are produced. Structures are calculated by the method of Hartrii-Foka. Values of enthalpies and of entropies allow to assume dynamic isomerism.

Keywords:

2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic Acid, 6,8-di-tert-butyl-3-(N-acetylamine)spiro(4,5)deca-1-oxa-5,8-dien-2,7-dione Oxidation by Oxygen, 2,4-Di-tert-butylbicyclo(4,3,1)deca-4,6-dien-8-(N-acetylamine)-3,9-dion-1-oxa, NMR-Spectroscopy

1. Introduction

The oxidation by oxygen 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid (analogue tyrosine) is of interest in research of products oxidations in a presence of an antioxidant. Results of early works [1] - [3] have shown possibility to use of a synthesis of analogues tyrosine in research of biology and a investigation of specificity properties in the conditions of a reactions with acid agents. For example, in classical reaction with thionyl chloride instead of acid chloride 2-(N-acetylamine)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid, a oxidative dimerization is produced [4] . There is an eliminate of tert-butyl groups in reaction 2-(N-acety- lamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid with hydrogen chloride [5] .

The direction of oxidation by oxygen 4-replaced 2,6-di-tert-butylphenols depends on conditions and a constitution of substituent and in each specific case results, as a rule, are ambiguous [6] .

In the present work, we studied the oxidation of 2-(N-acetylamine)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-pro- pionic acid by oxygen. Results of a oxidation of 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-pro- pionic acid may by impotents in process research of products inhibitors of oxidation, especially in the conditions of a biological. We have positioned that in process interaction of 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hy- droxy-phenyl)-propionic acid with oxygen in the presence of alkali are formed 2,4-di-tert-butylbicyclo(4,3,1)- deca-4,6-dien-8-(N-acetylamine)-3,9-dion-1-oxa and 6,8-di-tert-butyl-3-(N-acetylamine)-spiro(4,5)deca-1-oxa- 5,8-dien-2,7-dione. The interrelation of results of oxidation by oxygen depends on temperature.

2. Experimental Part

NMR spectrums registered on the device “Avance-500 Bruker” rather TMS.

2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid it is synthesis on a method [7] , m.p. 204˚C - 206˚C according to [8] : m.p. 204˚C - 206˚C.

Example 1. Oxidation 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid at 55˚C - 60˚C. In solution of 3.35 g (0.01 mol) 2-(N-acetylamino)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid 1.2 g (0.04 mol) NaOH in 60 ml of ethanol at 55˚ - 60˚ passed oxygen within 6 h. In a day to solution added HCl prior to the beginning of breaking (рН ≈ 6). Organic part have separated and after crystallization in the course of solvent evaporation received 0.6 g (≈18%) 2,4-di-tert-butylbicyclo(4,3,1)deca-4,6-dien-8-(N-acetyla- mine)-3,9-dion-1-oxa (2); m.p. 101˚C - 105˚C. Found %: C 68.32 Н 8.34. С₁₉Н₂₇NO₄. Calculated %: C 68.44 Н 8.16.

Spectrum ¹Н NMR (DMSO-d₆, δ, ppm, J/Hz): 1.20 (s, 18Н, ^tBu); 1.89 (s.3Н, СН₃СО); 2.40 (dd, 2Н, СН₂СН, J = 12.9,); 4.85 (m. 1Н, СН₂СН,); 6.69 (d., 1Н, Ar , J = 2.9); 6.95 (d.,1Н,Ar, J = 2.9); 8.56 (d.,1Н, NH, J = 7.8). Spectrum ¹³С NMR (DMSO-d6, δ, ppm,): 22.18 (СН₃СО); 29.09 (C-CH₃); 36.84 (СН₂); 48.56 (СН); 76.28 (С); 138.9 (С-H) 139.6 (С-H); 145.3 (С=С) 4 146.0 (С=С) 169.3 (СОNH); 174.0 (COO); 185.4 (C=O).

2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionate sodium (3)

Mixture of 3.35 g (0.01 mol) 1, 0.5 g (0.01 mol) NaOH in 20 ml of ethanol maintain ≈15 min time, solvent evaporate, the residue crystallization from EtOH-H₂O (1:1). A yield ≈3 g, m.p. > 250˚. Spectrum ¹Н NMR (DMSO-d₆, δ, ppm, J/Hz): 1.35 (s., 18 Н, ^tBu); 1.77 (s., 3Н, СОСН₃); 2.73 (dd., 1Н, CH-CHH, J = 6.8); 2.95 (dd., 1Н, CH-CHH, J = 4.6); 3,97 (m. 1Н, СН-СН₂); 6.6 (s., 1Н, OH); 6.89 (s. 2Н, Ar); 7.23 (d., 1 Н, J = 7.4). Spectrum ¹³С NMR (DMSO-d6, δ, ppm): 22.93 (СН₃СО); 30.48 (С-СН₃); 34.27 (С); 37.45 (СН₂); 55.73 (СН); 125.5 (С=С-Н); 130.46 (С-С=С); 138.09 (С-С=С); 151.58 (С-С=О); 167.63 (СОNHCH₃); 173.93 (COO).

Example 2. Oxidation 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid at 95˚C - 97˚C. In solution of 3.35 g (0.01 mol) 2-(N-acetylamino)-2-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid, 1.2 g (0.04 mol) NaOH in 60 ml of ethanol at 55˚C - 60˚C passed oxygen within 6 h. Processing and allocation of resultants of reaction made similarly to an example 1. 6,8-Di-tert-butyl-3-(N-acetylamine)spiro(4,5) deca-1- oxa-5,8-dien-2,7-dione from a reaction mixture divide on Al₂O₃; m.p.102˚C - 105˚C.

Spectrum ¹Н NMR (1) (DMSO-d₆, δ, ppm, J/Hz): 1.36 (s., 18 Н, ^tBu); 1.82 (s.3Н, СН₃СО); 2.74 (dd. 1Н, CH-CHH, J = 9.2; J = 9.2; J = 13.9); 2.91 (dd.1Н, CH-CHH, J =4.85; J =6.94; J =13.9); 4.32 (m. 1Н, СН-СН₂); 6.94 (s, 2Н, Ar); 8.16 (d., 1Н, NH, J = 7.8); Spectrum ¹Н ЯМР (2) (DMSO-d₆, δ, ppm, J/Hz): 1.36 (s., 18 Н, ^tBu); 1.80 (s.3Н, СН₃СО); 2.74 (d. 2Н, СН₂, J =3.2); 4.01 (m. 1Н, СН-СН₂); 6.90 (s.2Н, Ar); 8.30 (d., 1Н, NH, J = 7.3);

Spectrum ¹³С NMR (DMSO-d6, δ, ppm): 22.4 (СН₃СО); 26.9 (С); 30.32 (С-СН₃); 36.57 (СН₂); 53.58 (С¹Н); 53.84 (С²Н); 60.18 (C-spiro); 125.07 (С=С¹-Н); 125.15 (С=С¹-Н); 127.8 (С=С²-Н); 128.4 (С=С²-Н); 145.90 (С¹=С); 145.95 (С¹=С); 152.24 (С²=C); 152.37 (С²=C); 168.97 (С¹ОNH); 169.09 (C²ONH; 171.83 (C¹OO); 173.22 (C²OO); 185.37 (C=O).

3. Results and Discussions

In conditions of interaction 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid (1) with NaOH in air atmosphere at ambient temperature 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-pro- pionate sodium is formed, solvable in aqueous-alcoholic solutions. However at temperature of 55˚C - 60˚C oxidation process proceeds, which speed above in oxygen atmosphere. For 6 h reactions »18 % 2,4-di-tert-butyl- bicyclo(4,3,1)deca-4,6-dien-8-(N-acetylamine)-3,9-dion-1-oxa (2) is formed (Scheme 1) At ambient temperature on air salt 3 does not react with oxygen. The composition analysis of reactionary masses and a yield of compound 2 are resulted from the data of the spectrum ¹Н NMR (Figure 1).

From the data of the spectrum ¹Н NMR follows that signals of 6.69 and 6.95 ppm (J = 2.9 Hz) to belong to two various protons in a hexatomic cycle of structure 2. In the spectrum ¹³С NMR signals of 138.92 and 139.59 ppm from atoms of carboneum correspond to the data, which analysis in a format debt (Figure 2) specifies in communication of these atoms with hydrogen.

Signal of 185.4 ppm in spectrum ¹³C NMR (Figure 3) confirms presence of a carbonyl group at a hexatomic cycle of structure 2.

At last, a signal of 76.28 ppm belongs to tetrahedral atom of carboneum, forming communications with cycle carboneums atom, tert-butyl group and atom of oxygen (Figure 4).

According to [9] , a position of a signal from tetrahedral atom of carboneum in spiran to system with atom of nitrogen is in area of 75 ppm.

Data of spectrums NMR is sufficient for conclusions about structure of compound, producing by a interaction of 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid wih O₂ at temperature of 50˚C - 60˚C in solution of ethanol. This fact confirms bonding between atom of oxygen of a carboxyl group and of carboneum atom from hexatomic cycle.

In reaction 1 at temperature 95˚C - 97˚C (thermostatic control) 6,8-di-tert-butyl-3-(N-acetylamine)spi-ro(4,5) deca-1-oxa-5,8-dien-2,7-dione (4)\is formed, along with compound 2 (Scheme 2).

The interrelation of resultants of reaction (2 and 4) are found from comparison there of integrals signals in spectrum ¹H NMR reactionary mass (Figure 5 and Figure 6).

The analysis of dates of a spectrum specifies in presence at reactionary mass of three compounds are identified: one of them is with structure 2 and two compounds are with structure 4 which, apparently, are structure of isomers (Figure 6).

Signals “doublet of doublets” belong to one of structure 4а, the signal “triplet” belongs to 4b (Scheme 3).

4a 4b

Scheme 3. Isomers of compound 4.

One of the possible factors influencing allocation of frequencies in spectrums ¹Н and ¹³С NMR can be asymmetry because of influence tert-butyl groups on geometrical parameters.

Path comparison of structures 2 and 4 by method of Hartrii-Foka (UHF) on energy formations the result is received: (H_f˚) for 2 H_f˚ = −179.3-for 4 = −144.4 kcal∙mol⁻¹, values of charges on atoms of oxygen [2, O (15) q = −0.58; 4, O (15) q = −0.59].

Distinctions in charges on atoms of carboneum in a hexatomic cycle [2, C (1) q = −0.02, 4, C (1) q = +0.3].

Angle between a plane of hexatomic cycle and communication С=О (15), for 2 [C (2)-C (1)-(O)-(16)] w/ hailstones = 27.6˚, for 4 [C (2) - C (1)-O (15)] w/ hailstones = 26˚.

2 4

A calculates of enthalpies (H˚_f) and of entropies (S˚_f) for structures 2 and 4 have appeared comparable (2, H_f˚ = 17.5 kcal∙mol⁻¹, S_f˚ = 182.3 unite∙cаl∙К⁻¹∙мол⁻¹; 4, ^Hfo = 17.1 kcal∙mol⁻¹, S_f˚ = 174.9 unite, cаl∙К⁻¹∙mol⁻¹). These results in of set with calculation of geometry of structures 2 and 4 specifies in dynamic isomerism possibility.

4. Conclusion

At oxidative ring, the formation is produced in process interaction of 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hy- droxyphenyl)-propionic acid with oxygen in the presence of alkali and 2,4-di-tert-butylbicyclo(4,3,1)deca-4,6- dien-8-(N-acetylamine)-3,9-dion-1-oxa and 6,8-di-tert-butyl-3-(N-acetylamine)-spiro(4,5)deca-1-oxa-5,8-di-en- 2,7-dione are formed. The interrelation of results by oxygen depends on temperature. These results may by impotent for investigation of components during reactions 2-(N-acetylamine)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)- propionic acid in the conditions of biological researches.

References