22 Journal of the Japan Petroleum Institute, 54, (1), 22-29 (2011)

[Regular Paper] Synergism between Phenolic in Autoxidation

Yasukazu OHKATSU＊ and Fumie SUZUKI

Dept. of Applied Chemistry, Faculty of Engineering, Kogakuin University, 1-24-2 Nishi-shinjuku, Shinjuku-ku, Tokyo 163-6877, JAPAN

(Received March 2, 2010)

Combinations of two types of phenolic antioxidants were examined to assess synergistic or antagonistic inter- action from both scavenging rate constant (kinh) and radical scavenging number (n). The synergism of two types of phenols was observed especially with comparatively lower and similar oxidation potentials. In syn- ergism of kinh, a phenol with lower oxidation potential simply acts as a peroxy radical scavenger, whereas the other phenol with higher oxidation potential acts as a hydrogen donor in the regeneration of the former phenol from its phenoxy radical. On the other hand, synergism of n is seen for less or non-hindered phenols, especially with 4-methoxy substituent, and is controlled by the reaction conditions, such as solvent polarity. This is interpreted as a molecular association of phenols formed through hydrogen bonds and hydrophilic interactions, resulting in obstruction of coupling of the phenoxy radicals. As a result, 3,5-di-t-butyl-4-hydroxy-toluene (BHT) and 2-t-butyl-4-methoxyphenol (3 : 2 by mole ratio), and BHT and 4-methoxyphenol (3 : 2 by mole ratio) were esti- mated to show total synergism of 1.41 and 1.35 times, respectively, compared with the simple sum of the anti- oxidant activities in a hydrophobic system, such as chlorobenzene. These results are important for reduction of costs as well as environmental pollution by allowing decreased use of phenols.

Keywords Phenolic , Synergism, Antagonism, Kinetic treatment, Cost reduction

1. Introduction the number of radicals scavenged by a phenolic moirty, and kinh is the radical scavenging rate constant. Larger Polymeric materials such as plastic and rubber are n and/or kinh values will indicate better antioxidant extremely important materials in the contemporary properties. world. However, these materials gradually deteriorate  d[O]2  kp[RH] R i under the influence of external factors such as light,  −  = = Ri ()1 (1)  dt  nkinh[AH] heat, and , which mainly cause autoxidation as a inh radical chain reaction. Control of this autoxidation Most antioxidants generally show some interactions mainly depends on methods to stop the chain reaction in combined use. Phenolic antioxidants are reported or to scavenge chain carriers. to interact with many other types of antioxidants, but In general, phenols are used as antioxidants for stabi- the interactions between different types of phenols re- lizing many polymeric products and petroleum1), main unclear. The synergism of two phenols has been because of their effective scavenging of peroxy radicals reported2),3), but the details are unknown. However, if responsible for deterioration. Scheme 1 shows a general autoxidation mechanism in the pres- ence of phenolic antioxidants. The radical (R・) gener- ated in the initiation step of the deterioration promptly reacts with oxygen to form a peroxy radical, which ab- stracts a hydrogen atom from the substrates to form a and R・. This sequence forms the chain reaction. Antioxidant AH can react with peroxy radi- cals faster than substrate RH, resulting in interruption of the chain reaction. In this mechanism, the oxygen uptake rate can be represented by Eq. (1), in which n is Ri＝the rate of initiation step n＝the number of peroxy radicals scavenged by a phenol kinh＝the rate constant of peroxy radical scavenging step by a phenol ＊ To whom correspondence should be addressed. ＊ E-mail: [email protected] Scheme 1 Autoxidation in the Presence of Phenolic Antioxidant

J. Jpn. Petrol. Inst., Vol. 54, No. 1, 2011 23 the required amounts of phenols can be reduced by such as solvent, to estimate the association of phe- synergism, both costs and environmental pollution can nols in the solvent. be reduced. 2. 4. GC Measurement The present study investigated the interaction of two The consumed amount of phenols was measured by a types of phenolic antioxidants to try to identify cheap conventional gas chromatograph (GC) method using a and environmentally friendly combinations of phenolic 400-1HT column (Qudrex Corp.) to evaluate the inter- antioxidants. action of two types of phenols.

2. Experimental 3. Results and Discussion

2. 1. Phenolic Antioxidants 3. 1. Effect of Substituents on Characteristics of Seven types of phenolic antioxidants were purified Phenolic Antioxidants by conventional methods, so that the melting point was Table 1 shows the oxidation potentials and anti- within 0.5℃ of that reported for authentic samples: oxidant characteristics of the seven phenols. The oxi- 3,5-di-t-butyl-4-hydroxyanisole (BHA), 2-t-butyl-4- dation potentials are based on oxidation of the phenolic methoxyphenol, 4-methoxyphenol, BHT, 2-t-butyl-4- group, and apparently depend on the types and numbers methylphenol, 4-methylphenol, and 2-t-butylphenol. of substituents. It increased with lower steric hin- 2. 2. Potential drance of the phenol group. The redox potential of each phenol was measured Electron donating substituents with higher electro- under nitrogen atmosphere using cyclic voltammetry philic substituent constant (σ＋) at the o- and p-positions (CV) using a saturated calomel reference electrode enhance the activity of phenols, and a proposed mecha- (SCE), a Pt working electrode, and a Pt counter elec- nism for the hydrogen abstraction of a peroxy radical trode. The measured solution contained 0.1 mol/dm3 from a phenol is proposed as shown in Scheme 25). of tetra-butylammonium perchlorate as electrolyte and The hydrogen abstraction starts with electron transfer 10-3 mol/dm3 of phenol in acetonitrile. from the oxygen atom of the hydroxyl group to a per- 2. 3. Antioxidant Activity oxy radical, and ends by elimination of the phenolic The antioxidant activity of phenols was measured in hydrogen as a proton. This mechanism suggests that a chlorobenzene as follows: autoxidation of phenol with low oxidation potential, which is oxidized 3 (2 mol/dm ) was carried out in the presence of phenolic easily, can be expected to have high kinh as an excellent antioxidant(s) using α,α’-azo-bis-isobutyronitrile (AIBN) antioxidant. The mechanism might be correct under (10-2 mol/dm3) as an initiator at 50℃ under oxygen. certain conditions, but Table 1 shows that phenols with The reaction was followed by measuring the uptake of low oxidation potential do not necessarily have high kinh oxygen, and analyzed in terms of n and kinh as defined on the basis of the nature and number of substituents. by Eq. (1). BHT was mainly used as the reference an- Peroxy radical can more easily approach the hydroxyl tioxidant. In addition, autoxidation was carried out group of a phenol with fewer o-substituent(s), resulting using benzonitrile or acetophenone in place of chloro- in easier formation of the intermediate shown in the

Table 1 Oxidation Potential and Antioxidant Activities of Phenolic Antioxidants

Phenolic Oxidation k Phenolic Oxidation k inh n inh n antioxidant potential [V] [×104 dm3・mol-1・s-1] antioxidant potential [V] [×104 dm3・mol-1・s-1] OH OH

0.90 1.8 1.8 1.27 1.7 1.7

OCH3 CH3 OH OH

0.99 3.6 2.2 1.29 3.3 1.6

OCH3 CH3 OH OH

1.04 3.2 1.6 1.42 5.3 1.3

OCH3 CH3 OH 1.45 3.4 1.4

J. Jpn. Petrol. Inst., Vol. 54, No. 1, 2011 24

Scheme 2 Hydrogen Abstraction from Phenol by Peroxy Radical

appears as a solid line: the interaction is called “syner- gism” for a solid line above a broken line and “antago- nism” for a solid line below the broken line. The de- gree of “synergism” is assessed semi-quantitatively by the area between the broken and solid lines: the larger area is represented by a double circle. In Fig. 2, the vertical axis shows the kinh or n value obtained experi- mentally, and the horizontal axis shows the mixed mole ratios of the two phenols. The observed intera ctions are arranged to form inter- action maps (Figs. 3(a) and 3(b)), in which the interac- tion modes of kinh and n values are plotted against the redox potentials of phenols. Comparison of the inter- action modes of kinh with n shows that kinh has prefera- ble synergism in a wider combination of phenols. In

Fig. 1 Relationship between kinh and n of Phenols particular, strong synergism of kinh was observed for combinations of phenols with lower oxidation poten- tials, such as phenols with a methoxy group on the parenthesis of Scheme 2. Therefore, such a chemical 4-position. In contrast, the combination of phenols structure should govern the reaction of Scheme 2 and with 4-methyl group and/or with a high difference of result in high kinh for the phenol. In fact, phenols show their redox potentials showed no interaction or antago- a higher kinh in the order of no o-＞one o-＞two o- nism. substituent(s). Therefore, the activity of a phenol is Figure 4 shows the representative synergism and likely controlled by the o-substituent rather than the antagonism profiles for kinh and n, respectively, to rec- oxidation potential. ognize how such phenomena are observed in the pres- Figure 1 shows the relationship between kinh and n ence of two types of phenolic antioxidants. The left of of the seven phenols. 4-Methyl-phenols showed some the Fig. 4 shows strong synergism for kinh of a combi- relationship between higher kinh and lower n. A simi- nation of 4-methoxyphenol and BHT, and the right of lar relationship is also observed for commercialized Fig. 4 shows strong antagonism of BHA and 2-t-butyl- phenols6). This phenomenon can be explained by the phenol for n. The synergism was heavily biased idea that a phenol with no or few o-substituent(s) easily toward the higher concentration of 4-methoxyphenol reacts with the peroxy radical due to the ease of access with higher kinh. In contrast, the antagonism of n was to the phenolic hydroxyl group, but the resulting phe- apparently controlled by 2-t-butylphenol, as observed noxy radical also couples easily with another phenoxy over a wider concentration of 2-t-butylphenol with radical in place of scavenging another peroxy radical to higher oxidation potential or lower n (Table 1). decrease the n value (see, Fig. 7). On the other hand, These findings indicate that synergism of kinh occurs 4-methoxy-phenols did not show such characteristics. through combination of two phenols with comparatively Therefore, the n value of a phenol seems to be affected lower oxidation potentials, and the synergism mode can by the nature of the 4-substituent as well as the number be controlled by the preferential capture of peroxy radi- of 2- (or 2,6)-substituent(s). cals by a phenol with higher kinh, whereas the antago- 3. 2. Interaction of Phenols nism of n is caused by a phenol with higher oxidation The combination of two types of phenols showed potential and lower n. several modes of interactions. Figure 2 shows some 3. 2. 1. Synergism for kinh interactions displaying synergism to antagonism, as in- Figure 4 indicates that 4-methoxyphenol dominates dicated by the corresponding symbol marks. Figure 2 the synergism of kinh in combination with BHT, imply- shows independence of the phenols as a broken line ing that the methoxyphenol is the leading agent in the (‘arithmetical mean’), whereas an observed interaction scavenging of peroxy radicals. To further clarify such

J. Jpn. Petrol. Inst., Vol. 54, No. 1, 2011 25

Fig. 2 Action Modes of Two Types of Phenols

Fig. 3(a)● Interaction Mode of kinh against Oxidation Potential of Fig. 3(b)● Interaction Mode of n against Oxidation Potential of Phenol Phenol

synergism, the combination of 2-t-butyl-4-methoxy- ally decreased and BHT was completely consumed phenol and BHT was chosen and the consumed amounts after about 15 h. During this period, the concentration of both phenols during autoxidation were followed of 2-t-butyl-4-methoxyphenol remained constant due to quantitatively by a GC method (Fig. 5). BHT and the regeneration. After the consumption of BHT, the 2-t-butyl-4-methoxyphenol were first added in the mole concentration of 2-t-butyl-4-methoxyphenol started to ratio of 3 : 2, but the GC area ratios of both phenols did decrease and it completely disappeared after 21 h. not correspond to the original mole ratio, probably due The synergism of kinh is illustrated in Fig. 6. In the to the hydrogen-flame ionization detector (FID) of the combination of 2-t-butyl-4-methoxyphenol and BHT, GC or other factors. However, this variation does not the former phenol first scavenges a peroxy radical to affect observation of the consumption of the two phe- form the phenoxy radical, which is reduced to 2-t-butyl- nols, because the GC detection sensitivity is indepen- 4-methoxyphenol by hydrogen donation from BHT. dent of the compound concentration. As mentioned in As a result, the kinh value of the combined phenols shifts Table 1, 2-t-butyl-4-methoxyphenol with lower oxida- towards 2-t-butyl-p-methoxyphenol with higher kinh tion potential is likely to first scavenge peroxy radicals, (see, Fig. 4). Therefore, the mechanism of synergism but the concentration remained constant, as if BHT is based on 2-t-butyl-4-methoxyphenol scavenging per- scavenged peroxy radicals faster (Fig. 5). Considering oxy radicals, whereas BHT acts as a hydrogen donor to this phenomenon similarly to the previous proposal3), regenerate 2-t-butyl-4-methoxyphenol. The mecha- BHT is presumably consumed to regenerate 2-t-butyl- nism seems similar to that proposed3), but this study is 4-methoxyphenol. The concentration of BHT gradu- concerned only with the kinh factor in relation with the

J. Jpn. Petrol. Inst., Vol. 54, No. 1, 2011 26

Fig. 4 Actual Interaction of Two Phenols

Fig. 5● Autoxidation of AIBN in the Presence of BHT and 2-t- Butyl-p-methoxyphenol Fig. 6 Synergism of BHT and 2-t-Butyl-p-methoxyphenol oxidation potential of a phenol and explains well the experimental results shown in Fig. 5. more combinations of two phenols than synergism of n. 3. 2. 2. Synergism for n Furthermore, synergism of kinh is mainly developed in In general, the n value is 1 if a phenoxy radical cou- combinations of BHA, 2-t-butyl-4-methoxyphenol, ples with another phenoxy radical, and 2 if a phenoxy 4-methoxyphenol, and BHT, or combinations of BHT radical scavenges another peroxy radical because two and other 4-methyl-substituted or unsubstituted phe- phenoxy radicals cannot couple due to steric hindrance nols, whereas synergism of n value is observed only for (see, Fig. 7). Therefore, the total n value of a combi- a combination of two types of phenols with 4-methoxy nation of two types of phenols should be the simple substituents. Therefore, the synergism of n seems re- sum of the n values of the combined phenols. Thus, lated to the presence of the 4-methoxy group. synergism of n will not be expected. However, as Chlorobenzene used as solvent in this study has low shown in Fig. 3(b), a higher n value than that estimated polarity or is rather hydrophobic. On the other hand, was observed in some combinations of phenols. This phenols showing synergism of n value are rather hydro- is the first finding recognized in this study. This philic, due to the hydroxyl and methoxy substituents. strange obsevation is difficult to explain, but must be Therefore, the same inhibited-oxidation reaction was ascribed to the behavior of a less hindered phenol re- repeated in solvents with different polarity to investi- sembling a hindered phenol. gate the effect of the hydrophilic nature of phenols. Figure 3 shows that areas of synergism of kinh and n Measurement of the antioxidant activity in aceto- are different, and synergism for kinh is observed over phenone (polarity: 17.3) and benzonitrile (polarity:

J. Jpn. Petrol. Inst., Vol. 54, No. 1, 2011 27

Fig. 7 Relationship between Chemical Structure and n of Phenol

Fig. 8 Antioxidant Activity (n) Promoted by Types of Solvents

25.2), instead of chlorobenzene (polarity: 5.7), observed formed by interaction of hydrophilic groups including different interactions of phenols (Fig. 8). The syner- the 4-methoxy group. gistic interaction observed in chlorobenzene with the The probable mechanism of synergism of n of a com- lowest polarity or dielectric constant disappeared grad- bination of phenols containing 4-methoxyphenol is ually with higher polarity or dielectric constant of a sol- shown in Fig. 9 as an example. The 4-methoxy- vent. Acetophenone showed medium synergism, phenoxy radical exists as a monomer in hydrophilic whereas benzonitrile showed no synergism. This find- benzonitrile, and easily approaches another phenoxy ing implies that 2-t-butyl-4-methoxyphenol is dissolved radical. As a result, the two phenoxy radicals can cou- in a monomolecular form in a polar solvent such as ple and the n value becomes the simple sum of the n benzonitrile, and forms a molecular association in a less- values of the two phenols. On the other hand, hydro- polarized solvent such as chlorobenzene. Consequently, philic phenols in a hydrophobic solvent will behave just the associated 2-t-butyl-4-methoxyphenol will behave as if they had bulky o-substituent(s) due to the molecu- like a hindered phenol and have some unusual syner- lar association, resulting in disturbance of the coupling gism of n in chlorobenzene. This molecular associa- of phenoxy radicals and a synergistic n value. This tion form remains unknown, but probably involves two idea seems to explain the observation of synergism of n phenoxy radicals which cannot couple with each other, for a phenol with a 4-methoxy group, especially phe- for example, due to a stack of two or more phenols nols with no o-substituent(s), such as 4-methoxyphenol

J. Jpn. Petrol. Inst., Vol. 54, No. 1, 2011 28

Fig. 9 Proposed Action Mechanism of Molecular Associated Phenols (＊)

(Fig. 3(b)). Table 2 Synergistic Combinations of Phenols Concentration ratio Phenolic antioxidants Synergistic ratio 4. Conclusion [×10-5] OH OH In a combination of 2-t-butyl-4-methoxyphenol and BHT, the phenol with higher kinh, 2-t-butyl-p-methoxy- (2 : 3) 1.25 phenol, first scavenges a peroxy radical to form the OCH3 OCH3 phenoxy radical (Fig. 6). The phenoxy radical will OH OH then accept a hydrogen atom from BHT with lower k . inh (1 : 4) 1.04 As a result, 2-t-butyl-4-methoxyphenol is regenerated, OCH OCH and again acts as a stronger antioxidant. Therefore, 3 3 OH OH synergism of kinh can be observed in such a system, be- cause 2-t-butyl-p-methoxyphenol is the leading peroxy (2 : 3) 1.28 radical scavenger as long as this phenol is regenerated. OCH3 OCH3 In contrast, the synergism of n is controlled by the OH OH solvent polarity. Phenolic antioxidants, especially less or non-hindered and more polar phenols, easily form (2 : 3) 1.41 molecular associations in a hydrophobic solvent. As a OCH3 CH3 result, the phenol can scavenge more peroxy radicals OH OH than expected, acting as a hindered phenol preventing (2 : 3) 1.35 the coupling of the phenoxy radicals. Thus, the syner- OCH CH gism is observed in the terms of n value. Such phenolic 3 3 antioxidants, however, behaves as the monomolecular form in a hydrophilic solvent such as benzonitrile. Consequently, no synergism is observed. form intermolecular associations in a hydrophobic The conclusions obtained by this study are as fol- solvent. lows: ・Total synergism of phenolic antioxidants seems re- ・Strong synergism of phenols is shown by a combina- markable in hydrophobic materials, for example, pe- tion of two types of phenolic antioxidants, with com- troleum and polymer materials such as polyethylene paratively low and similar oxidation potentials. and polypropylene. ・Synergism of kinh is observed over a wider combina- Combination of phenols with great synergism of both tion than that of n. n and kinh was examined in sets of two types of phenols. ・Interaction of phenols changes depending on the Table 2 shows the optimum combinations of phenols polarity or dielectric constant of a solvent. together with the concentration ratios giving better syn- ・Synergism of n can be observed for less or non- ergism and the achieved synergistic ratios (observed an- hindered phenols with 4-methoxy substituent, which tioxidant value to sum of antioxidant values shown by

J. Jpn. Petrol. Inst., Vol. 54, No. 1, 2011 29 individual phenols). Okabe, H., Ohkatsu, Y., CMC Publishers, (1998). Better stabilization of polymer materials and petro- 2) Ingold, K. U., Chem. Rev., 61, 563 (1961). 3) Mahoney, L. A., DaLooge, M. A., J. Am. Chem. Soc., 89, 5619 leum will be achieved in the future by studying not only (1967). the synergism of the phenolic antioxidants, but also the 4) Howard, J. A., Ingold, K. U., Can. J. Chem., 41, 1744 (1963). effect of the reaction conditions. 5) Howard, J. A., Ingold, K. U., Can. J. Chem., 41, 2800 (1963). 6) Ohkatsu, Y., Haruna, T., Osa, T., J. Macromol. Sci. Chem., References A11, 1975 (1977).

1) “Development of Additives for Petroleum Products,” eds. by

要 旨

自動酸化におけるフェノール系酸化防止剤同士の相乗作用

大勝 靖一，鈴木 史恵

工学院大学工学部応用化学科，163-6877 東京都新宿区西新宿1-24-2

2 種類のフェノール系酸化防止剤を組み合わせた場合，それ これは水素結合や疎水性相互作用によりフェノールの分子会合 が相乗作用を示すか，拮抗作用を示すかについてフェノールの 体が形成し，その結果，ラジカル捕捉によって生成するフェノ

ラジカル捕捉定数（kinh）およびラジカル捕捉数（n）の両面か キシラジカル同士のカップリングが妨害されるためである。以 ら詳細に検討した。二つのフェノールの相乗作用は，特にそれ 上より，疎水性の系，たとえばポリアルキレンや石油類の環境 らの酸化電位が比較的低く，かつ近寄っている場合に見られた。 中では，BHT と2-t-ブチル-4-メトキシフェノールのモル比3 : 2 kinh の解析から酸化電位の低いフェノールはもっぱらペルオキ での酸化防止剤の組合せがそれぞれのフェノールの活性の単純 シラジカルの捕捉に関わり，一方，酸化電位の高いフェノール な和と比べて 1.41 倍の，また BHT と p-メトキシフェノールの は生成したフェノキシラジカルへの水素供与体，すなわち還元 モル比 3 : 2 での酸化防止剤の組合せが 1.35 倍の相乗作用を示 剤として働き，低酸化電位フェノールの再生に寄与することが すことが推定できた。これらの結果の活用は，フェノールの使 分かった。一方，n の相乗作用は特に p-メトキシ置換基を有す 用量の低減に伴うフェノールの使用経費の削減や環境汚染の減 るレスまたはノンヒンダードフェノールで見られ，もっぱら 少に役立つものと思われる。 フェノールの周囲に存在する環境，たとえば溶媒に左右された。

J. Jpn. Petrol. Inst., Vol. 54, No. 1, 2011