kinetics of the bromination of phenols and oligonuclear phenolic compounds, 6. far reaching effects...

Makromol. Chem. 184,1793 - 1806 (1983) 1793

Kinetics of the Bromination of Phenols and Oligonuclear Phenolic Compounds, 6a)

Far Reaching Effects via Chains of Intramolecular Hydrogen Bonds

Volker Bdhmer*, Klaus Bekmann, Diethard Stotz, Wilheim Niemann b), Walter Vogt

Institut fur Organische Chemie, Universitat Mainz, Johann-Joachim-Becher-Weg 34, SB 1, D-6500 Mainz, BRD

(Date of receipt: January 20, 1983)

SUMMARY: The kinetics of the electrophilic bromination of 17 oligonuclear phenolic compounds with

molecular bromine in acetic acid were studied at 22 "C. Some of these compounds, consisting of up to 6 phenolic units, which are linked in ortho-position by methylene bridges, and having only one (or two) reactive ortho-position(s) at the end of the molecule, were synthesized for the first time. It could be shown, even for hexanuclear compounds, that the variation of substituents at one end of the molecule leads to a change in the reactivity at the other end, that means over a distance of 22 nonconjugated covalent links. So far, this can be explained only by a chain of intramolecular hydrogen bonds between the phenolic hydroxyl groups of adjacent phenolic units. If this chain is interrupted by one methoxy group, a substituent effect cannot be transferred in the same way.

Introduction

Kinetic studies on oligomers with definite structures have often been compared with the same reactions on polymeric molecules'). Mainly dimers were used to study neighboring group effects*), which always must be considered to be present in macromolecules 3). However, the reactivity of a given functional group can be influenced not only by the immediately adjacent unit, but also via cooperative effects by further functional groups. These cooperative effects are responsible for the unique properties of enzymes4), but it can be supposed, that they can also be operative in synthetic polymers 5) . Molecularly uniform oligomers with an increasing number of repeating units (degree of oligomerization) may be used to gain some insight in these problems.

Besides, the oligopeptides oligo[(hydroxy-I ,3-phenylen)methylene]s - commonly known as oligonuclear phenolic compounds - represent a group of oligomers which have been prepared probably with the largest variety of structures6). The principal variations concern the number of phenolic units, the positions of the phenolic hydroxyl groups and the nature and positions of other substituents'). Consequently, a

a) Part 5 : cf. 13). b, Present address: Fa. B. Braun, Melsungen AG, 6508 Melsungen.

0025-1 16)</83/$03.00

1794 V. BOhmer, K. Beismann, D. Stotz, W. Niemann, W. Vogt

large number of different reactions can be carried out with these oligomers which, therefore, are most suitable to study cooperative effects in different chemical reactions under various reaction conditionss).

Earlier we have shown, that the bromination of oligonuclear phenolic compounds in acetic acid may be taken as an appropriate example of an electrophilic substitution, because it can easily be followed by the change in absorbance9). The reactivity is strongly influenced in these cases by the neighboring phenolic unit via intramolecular hydrogen bonds between the phenolic hydroxyl groups’O), and first results have shown, that in this way also a third and a fourth phenolic unit may be influenceds). This far reaching influence is further established in the present paper.

Kinetic Results

Under the chosen reaction conditions (acetic acid as solvent; temp.: 22 “C; concentrations: 1,5 -6 mmol * dm-,), the bromination of the oligonuclear phenolic compound P can be described by the rate law:

The rate constants k, and k3 for the second and third order term may be determined by treating the reaction as a second order process within a small initial interval and plotting the formal second order rate constant k; versus the concentration of bromineg).

Examples are shown in Figs. 1 - 3. Tab. 1 contains the values of k, and k3 which are obtained as intercept and slope of those plots. For an easier comparison of the different compounds, values of ki for [Br,] = 3 mmol- dm-, are also reported, which means for a concentration of bromine, for which the determination of k; is most accurate under the given experimental conditions. The following discussion is mainly based on these values, since differences in k, and k3 should not be overestimated.

Discussion

All compounds studied here have the same “reacting unit” at one end of the molecule, that means a 2-hydroxy-5-methylphenyl unit which is linked in ortho- position to the phenolic hydroxyl group of the adjacent phenyl ring by a methylene bridge. By thin layer chromatography of the reaction mixtures it was confirmed in several cases that the bromination occurs exclusively at 3-position of this “reacting unit”. (In compounds l a , 2a, 3a, 4a, and 5a there are of course two reachve 3-positions at both ends of the molecule. Thus, the kinetic constants must be divided by 2

Kinetics of the Bromination of Phenols and Oligonuclear Phenolic Compounds, 6 1795

Fig. 1. Plots according to Eq. 2 for tetranuclear compounds with different substituents R’ and R2: 2a (A), 2c (W), 2f ( 0 ) , 2 d (A), and 2e (0). Average values are given for experiments with the same concentration of bromine. The plot for 2 b ’ l ) is indicated for comparison as a dashed line ( - - -1

Fig. 2. Plots according to Eq. 2 for penta- and hexanuclear compounds with different substituents R’: 3a (A), 3c 0 , 4 a (A), and 4c (a). Average values are given for experiments with the same concentration, scattering of the single experiments is indicated for 3a and 4a. The plots for compounds 3b ( - - -) and 4b (- - -) are indicated for comparison without experimental values

, , 0 ,

, / ,

5

1796 V. Btihmer, K. Beismann, D. Stotz, W. Niemann, W. Vogt

Fig. 3. Plots according to Eq. 2 for trinuclear compounds with a p-methylphenol or p-methylanisole unit in the middle: l a (A), l c (m), 5a (A), and 5b (0). Average values are given for experiments with the same concentration of bromine

- [Br2]I(rnrnol ' d ~ n - ~ )

Tab. 1. acetic acid at 22 "C

Rate constants k,, k,, and ki (for [Brz] = 3 mmol. drn-,) for the bromination in

Compound k,/(dm3 . mol - l . s - l ) k, /(dm6. rnol-,. s - l ) k4/(dm3 . mo1-l. s - ' )

laa) 1,62 + 0,07 709 f 17 3,75 lbb) 0,84 f 0,04 356 f 10 1,91 l c 0,34 f 0,Ol 168 f 3 0,84 Id 1,03 f 0,03 268 + 9 1,83 l e 0,23 f 0,Ol 1 0 0 f 4 0,53 I f 0,43 f 0,02 427 f 8 1,71 1g 0,54 f 0,02 158 f 3 1,Ol 2 a 3 1,32 f 0,04 594 f 11 3,lO 2bb) 0,80 k 0,03 279 f 9 1 9 6 4 2c 0,40 k 0,Ol 133 f 4 0,80 2d 0,91 f 0,04 226 f 9 1,59 2e 0,26 f 0,Ol 7 0 + 3 0,47 2f 0,74 f 0,02 3 0 6 f 6 1,66 3aa) 1,07 f 0,12 499 f 32 2,57 3bb) 0,76 f 0,04 306 f 10 1,68 3c 0,31 f 0,02 160* 6 0,79 4aa) 0,76 f 0,07 505 f 19 2,28 4bb) 0,70 f 0,03 2 9 0 f 8 137 4c 0,68 f 0,04 8 6 * 5 0,94 5aa) 2,OO f 0,13 992 f 41 4,98 5b 1,64 f 0,09 472 f 35 3,06

a) k,/2, k3/2, and ki/2 are given, because there are two reactive 3-positions in the molecule. b) Cf.").


for statistical reasons, whereas in Id and 2d only the 2-hydroxy-5-methylphenyl unit but not the 2-hydroxy-5-nitrophenyl unit is substituted.) Furthermore, only the substituents R1 and R2 in the phenolic unit at the opposite end of the molecule are different for compounds 1 - 4 with a given number of phenolic units.

r 1

1- 4

1 : n = 3 ; 2 : n = 4 3 : i 1 = 5 ; 4 : n = 6

The following two variations were studied, particularly:

a) A change in R1 which (mainly) has some steric influence on the phenolic hydroxyl

b) A change in R2 which (only) increases the acidity of the phenolic hydroxyl group,

In both cases, in principle the same effects are observed for tri- and tetranuclear compounds (b) and even up to hexanuclear compounds (a), as we have already described for dinuclear compounds lob):

a) Increasing size of R1 causes a decrease in the reaction rate. This is found for R2 =

NO, in the compounds l d / l e and 2d/2e (Fig. l), in which the replacement of R1 = C(CH,), by R' = H is accompanied by an increase in k; by a factor of 3,4-3,5 and also for R2 = CH, where the same factor is 4,5, 3,9, 3,3, and 2,4 for the pairs l d l c (Fig. 3), 2 d 2 c (Fig. l), 3a/3c and 4 d 4 c (Fig. 2). Compounds lb , 2b, 3b, and 4b with R1 = CH,, which have already been studied earlier"), show a reactivity inbetween those with R1 = H and R1 = C(CH,), (see also Fig. 4).

group, if substituents of different size (H, CH, , C(CH,),) are taken.

if CH, is replaced by NO,.

1798 V. Bohmer, K. Beismann, D. Stotz, W. Niemann, W. Vogt

b) If R2 = CH, is replaced by R2 = NO,, the reaction rate decreases, too. The relation is always in the range of 1,6 -2,0 for the pairs l a / ld and 2a/2d (with R’ = H), I d l e and 2 d 2 e (with R’ = C(CH,),) and l f / l g (with R’ = NO,).

To explain these remarkable effects, we must keep in mind the distance between the substituents which are varied (R’ respectively Rz) and the position where the electrophilic substitution occurs. These are 10, 14, 18, and even 22 unconjugated links for compounds 1-4 with 3 to 6 phenolic units. This means, that inductive or mesomeric effects cannot be directly operative over this distance.

The only explanation therefore is, that the effects of the substituents R1 and R2 are transferred by a chain of intramolecular hydrogen bonds as indicated in the formula for a tetranuclear compound 2.

H

From molecules which are able to act as donor and as acceptor of hydrogen bonds it is known, that the donor activity of the molecule increases if it acts itself as an acceptor, and vice versa1,). Thus, the increase of the strength of the first hydrogen bond will propagate from one to the other phenolic hydroxyl group, from one end of the molecule to the other end. This way, the decrease of the mesomeric effect of the hydroxyl group in the reacting unit in which a free electron pair of the oxygen is engaged by a hydrogen bond is responsable for the decrease in the reaction rate. As pointed out earlier’ob*13), the strength or the probability of the first hydrogen bond can be increased by increasing the acidity of this hydroxyl group (change in R2), or if it is directed towards the adjacent phenolic unit by bulky substituents (changes in R1 ).

This explanation, though it is the only one which accounts for all the kinetic results, seems very surprising for a solvent like acetic acid which is able to form hydrogen bonds itself. Therefore, we looked for further confirmations. If the lower reaction rate of 2c in comparison with 2b is really caused by the steric effect of the bulky tert-butyl group in position 3 of the phenyl end group and if it is transferred by a chain of intramolecular hydrogen bonds, then we should find no change in the reaction rate, if in 5-position the methyl group is replaced by a tert-butyl group. (Note, that R’ and R2 have exactly the same position relative to the place, where the electrophilic substitution occurs.) Indeed, 2f shows exactly the same reaction rate as 2b (Fig. 1).

On the other hand, if one of the hydroxyl groups is replaced by a methoxy group, the chain of intramolecular hydrogen bonds would be “interrupted”, and thus, a substituent effect could not be transferred from one end of the molecule to the other end. Therefore, we studied the bromination of 5a and 5b in comparison with l a and l c . Surprisingly the introduction of a tert-butyl group into 5a decreases the reaction


rate, too. On the first sight no difference between 5a and 5b is expected, since a chain of intramolecular hydrogen bonds cannot be formed in these compounds. However, the small decrease observed (the ratio of k; being 1,6 for 5a/5b, whereas for l a / l c a much higher ratio of 4,5 is found) can be explained considering that the methoxy group can accept only one hydrogen bond. Then, the preferred conformations of the molecules are as follows:

18 58

l c 5 b

Three types of reacting 2-hydroxy-5-methylphenyl units can be distinguished.

A: a “fast” unit which forms a hydrogen bond to the neighbouring unit; B: an uninfluenced unit with a ‘‘free” hydroxyl group; C : a “slow” unit which accepts a hydrogen bond from the neighbouring unit.

The reactivity for B and C is given by the rate constants of compounds 5b and l c ,

B: k; = 3 , 0 6 d m 3 ~ m o l - ’ ~ s - ’ C: k; = 0,84dm3.mol-’.s-’

The value for A may be calculated from l a and l c

A: k; = (2.3,75 - 0334) dm3. mol-’ . s - ’ = 6,66 dm3. mol-’ . s - ’

as well as from 5a and 5b

A: k; = (2-4,98 - 3,06)dm3.mol-’.s-’ = 6,90dm3.mol-1.s-’

This calculation shows, that the values of compounds 5a and 5b are also completely in accordance with the explanation given above. The quantitative agreement for the differently calculated reactivities of A should not be overestimated, however, since it is still based on a very simplified model. The conformations indicated in the scheme are not the only ones one can think of, and surely, a “free” hydroxyl group does not exist in acetic acid solution, but a hydroxyl group which forms hydrogen bonds with and accepts hydrogen bonds from the solvent.

Altogether, however, the kinetic data represent strong evidence that the conformation of oligonuclear phenolic compounds is determined by intramolecular hydrogen


bonds even in a solvent like acetic acid, and, what is of more general interest, that the reactivity of functional groups may be influenced by substituents over a large distance via a chain of such intramolecular hydrogen bonds. Similar effects are operative obviously in enzymes, e. g. in the "charge-relay-system'' of chymotrypsin 14).

To our knowledge, there is only one other example reported, for which the reactivity of oligonuclear phenolic compounds in electrophilic substitutions was studied as function of the chaih length. Imoto et al. found for the reaction with formaldehyde in 1,4-dioxane/water catalyzed by perchloric acid, that the reaction rate drops to about half of its former value, when the number of the phenolic units exceeds four 15). Their explanation was given on the basis of cyclic conformations, stabilized by intramolecular hydrogen bonds in which one end of the molecule is hidden and unaccessible for the reagent (Fig. 5 (a)). Our own results for three series of compounds with R1 = H, CH, , C(CH3)3 and RZ = CH, are plotted versus n, the number of phenolic units, in Fig. 4. All curves show a continuous course which should lead finally to the same value

Fig. 4. Rate constant ki for [Br,]. = 3 mmol . dm-, as a function of the number of phenolic units for three series of compounds with R' = H (A), R' = CH,(o ) , and

I R' = C(CH,), (m) 2 3 L 5 6

n

for k;. There is no indication of any kink or bend. Therefore, it may be concluded, that the predominant conformation of the molecules is a stretched one (Fig. 5 (b)). It seems possible that cyclic conformations are favoured in other (less polar) solvents. Of course, these conformations with intramolecular hydrogen bonds are not necessarily the only ones which are present. The differences in the reaction rate may also be explained by a different degree of contribution of hydrogen bonded conformations to the conformational equilibria.

If k2 or k3 is plotted versus n according to Fig. 4, some irregularities are observed which might be interpreted in terms of special conformations or other effects, favour- ing the second or third order term in Eq. (1). It is tempting to deduce some more detailed informations on the reactivity from the differences in the ratio k, /kz which are


Fig. 5 a Fig. 5 b

Fig. 5 . intramolecular hydrogen bonds

Pentanuclear compound 3b in a “cyclic” (a) and in a “linear” (b) conformation with

found for different compounds. However, the significance of these differences must not be overestimated, since the values for k, and k3 are less accurate than those for k; , as demonstrated by the scattering in Fig. 2.

Preparation of the compounds

The synthesis of tri- and tetranuclear compounds with a hydroxynitrophenyl unit at one end of the molecule (Id- lg , 2d, 2e) has already been reported7”. The homo- logeous series l c , 2c, 3c, and 4c was obtained in a similar way, as described for the compounds 1 b - 4b1@, by condensation of the suitable cr-bromo-w-hydroxyoligo[(2- hydroxyJ-methyl-1,3-phenylene)methylene] compound 17) with an excess of 2-tert- butyl-p-cresol and subsequent dehalogenation I*):

Compounds l a - 4al9) (and 2f in ref.”) were prepared in the same way, using the same hydroxymethylated compound as precursor but p-cresol (or 4-tert-butyl-o- cresol) instead of 2-tert-butyl-p-cresol in the condensation step of Eq. (3).


All samples used for the kinetic measurements were checked for purity by thin layer chromatography. Their structure which follows already from the stepwise synthesis was further confirmed by IR, 'H NMR, and mass spectra. Especially the NMR spectra proved also the absence of detectable amounts of solvents which might be included in the crystal lattice*'). Although no impurities could be detected by all these techniques, the elemental analysis of 3c and 4c showed some deviations which cannot be understood, so far. However, even if these deviations would be caused by a sub- stance not reacting with bromine a t all (e. g. silica gel from a chromatographic purification) the resulting possible error of the kinetic constants would be much smaller than the effects discussed above.

Compound 5a could be obtained, similar t o the prescription given in the litera- ture 22), by condensation of 2,6-bis(hydroxymethyI)-4-methylanisole with an excess of p-cresol. In the same way 5b was prepared using in thirtyfold excess a 2: 1 mixture of 2-tert-butyl-p-cresol and p-cresol.

R'(RZ)

2HO-&CH3 R' OH OCH3 OH

HOCH~,@ z~~ - - 2 H,O

CH3

58 R ' = R 2 = H

5 C R' = RZ = C(CH3)3 5 b R' =C(CH3)3,Rz=H

The resulting mixture was separated in this case by column chromatography. All the expected compounds 5a, 5b, and 5c were isolated and characterized by their spectra and by elemental analysis. The structure of 5b was further confirmed by demethylation with BBr, , leading nearly quantitatively to l c , as proved by thin layer chromatography, melting point and mixed melting point, and by the identity of the IR spectra.

Experimental Part

Kinetic Measurements9-"): The bromination was followed at 22°C in glacial acetic acid (p.a., from Fa. Merck) by measuring the absorbance of the bromine at 450 nm ( E = 124,8 dm3. mol-' . cm-', spectral photometer PMQ 11, Fa. Zeiss, recorder "Servogor", Fa. Metrawatt AG). 6 cm3 of the appropriate solution of the phenolic compound were placed in 2 cm-cuvettes and 2 cm3 of the bromine solution were added rapidly from a glass syringe with magnetical stirring. Mixing time was about 2 - 6 s. The recorder plot was extrapolated to t = 0 (the absorbance of bromine thus obtained was within k 2% of the expected value) and a second order rate constant ki was evaluated for the beginning (-15% conversion of bromine). This formal constant ki was independent of the concentration of the phenolic compound but linearily increasing with the bromine concentration. It was normally reproducible within +. 5% for different experiments with constant concentration of bromine and varied concentration of phenol.


For each compound ki was determined at least in 24 single experiments for at least 6 different concentrations of bromine between 1 ,O and 5,5 mmol * drn-,. Plots of k; versus concentration of bromine after 7,5% conversion are shown in Figs. 1 - 3. The rate constants k2 and k, (Tab. 1) were evaluated as slope and intercept using the least squares method. The statistical limits of error thus obtained are also indicated in Tab. 1. By eventual systematic errors in ki, which are most probable for high and low concentrations of bromine the real errors in k2 and k, , may be somewhat higher und thus, different values for k,/k2 should not be overinterpreted.

The concentration of the phenolic compound was generally varied between 1,5 and 4 3 mmol . drn-,. For the penta- and hexanuclear compounds complete dissolution could be achieved only by longer heating. In the case of 4c reproducible values of ki could be obtained only for concentrations not higher than [PI = 2 mmol . dm-, which may be due to precipita- tion during the measurements. For 3c three different fractions (recrystallized from acetone, purified by column chromatography, recrystallized again from ethanol) were used, and inde- pendently synthesized samples were taken in the case of 2c. In all these cases reproducible values for ki were obtained. Only for 4c one fraction was observed which gave ki-values being 20% higher than those reported in Fig. 2. But even these values would be lower than those for 4b and distinctly lower than those for 4a.

Synthesis of the compounds

The purity of all samples used for the kinetic measurements was checked by thin layer chromatography on silicagel (GF,,,, from Fa. Woelm), using mainly CHCl, , CH2C12, and CHCI, /acetic acid (vo1.-ratio 30: 1) as solvents. Purifications by column chromatography (length: 30 -40 cm, diameter: 3 cm) were done on silicagel (0,M -0,2 mm; from Fa. Woelm) with CH2C12 or CHCl, as eluent. Melting points were determined, if possible, by the automatic apparatus FP1 (Fa. Mettler). 'H NMR spectra were measured in [2H],-acetone, [,H],-DMSO, or CDCl, on a HX-60 or WH-90 spectrograph (Fa. Bruker) with TMS as internal standard. Mass spectra were obtained on a Varian 7a mass spectrometer with an ionisation energy of 70 eV.

Preparation of compounds l c , Zc, 3c, and 4c (Eq. (3))

Generalized procedure for the condensation: 0,Ol mol of the a-bromo-w-hydroxyoligo[(2- hydroxy-5-methyl-l,3-phenylene)methylene] and 16 - 82 g (0,l -0,5 mol) of 2-tert-butyl-p- cresol were heated with stirring under argon to 90°C. Then, 5 ml of conc. HC1 were added. (With the higher molecular weight compounds a clear solution was obtained only after the addition of HCl, and the reaction product precipitated during the condensation.) After 8 h, during which the temperature was finally raised to 100°C, the excess of tert-butylcresol was eliminated either by steam distillation (tri- and tetranuclear compounds) or by addition of 50 ml of petroleum ether (b.p. 70-100°C) per 0,2 mol of tert-butylcresol to the warm reaction mixture (tetra-, penta- and hexanuclear compounds). In the latter case, directly a purer product was obtained as precipitate, which was collected after the mixture was kept in the refrigerator over night. The further purification is given for the single compounds.

a-Bromo-w-(2-hydroxy=I-tert-butyl-5-methy~heny~b~[(2- hydroxy-5-methyl-1,3-phenylene)- methylenel: Recrystallization from methanol yielded 85% of white crystals; m. p. 179,9 "C,

C2,H3,Br0, (483,5) Calc. C 67,08 H 6,46 Found C 66,62 H 6,39

Rf = 0,6 (CH2Cl2).

a-Bromo-w-(2-hydroxy-3-tert-butyl-5-methy~heny~tr~[(2-hydroxy-S-methyl-l,3-phenylene)- methylenel: Recrystallization from ethanol gave 65% of white crystals; m. p. 172,6 'C; Rf = 0,8

C3,H3,BrO, (603,6) Calc. C 69,65 H 6,51 Found C 69,60 H 6,46

(CHZCl,).


a-Bromo-w-(2-hydroxy-3-tert- butyl-5-methylpheny~tetrakis((2-hydroxy-5-methyl-l,3-phenylene)methylene]: The precipitate in petroleum ether (74%) was chromatographically pure (R, = 0,75 (CHCI,)) and directly taken for the preparation of 3c. A sample was recrystallized twice from ethanol and than from acetic acid/water. The white, cristalline product melted around 165 - 170°C, resolidified on further heating completely (180'C) to show finally m.p.

'H NMR: 6 = 1,36 (-C(CH,),), 2,09-2,13 (-CH,), 3,86 (-CH,-) 6,6-7,15 (Ar-H). MS: m/e 724/722 (M+; 16%), 404 (17%), 342 (20%), 2% (82%), 239 (42%).

208-210OC.

C&47Bfl, (72398) Calc. C 71,36 H 6,54 Br 11,04 Found C 69,59 H 6,65 Br 11,45

a-Bromo-w-(2- hydroxy-3-tert-butyl-5-methylpheny~pentakis~(2-hydroxy-5-methyl-l,3-phenylene)methylene]: The precipitate in petroleum ether (92%) was directly taken for the synthesis of 4c. A sample was recrystallized from ethanol to form a white, microcrystalline product; m. p. 180,5 "C; R, = 0,4 (CHCI,).

'H NMR: 6 = 1,36 (-C(CH,)3), 2,08 -2,12 (-CH,), 3,86 (-CH2-) 6,65 -7,15 (Ar-H). MS: m/e 843/841 (M+ - 1; 9%), 480 (13%), 342 (30%), 296 (54%), 239 (39%).

C,,H,,Br06 (84359 Calc. C 72,58 H 6,57 Found C 72,35 H 6,57

Generalized procedure for the debromination: 5 mmol of the a-bromo-w-(2-hydroxy-3-tert- butyl-5-methylphenyl)oligo[(2-hydroxy-5-methyl-1,3-phenylene)methylene] were dissolved in about 50 ml of methanolic potassium hydroxide (1,l mol of KOH for each hydroxyl group and for the bromo atom), Raney-Ni was added in methanolic suspension and the hydrogenation was carried out with vigorous stirring at normal pressure. When the hydrogen uptake was complete (to ensure this, the mixture was warmed to 60°C at the end of the reaction) the catalyst was removed by suction and the alkaline filtrate was dripped into aqueous HCl. The white precipitate was further purified as indicated for each compound. 2-(2-Hydroxy-5-methyIbenzyl)-6-(2-hydroxy-3-tert- butyl-5-methylbenzyl)-4-methylphenol

(lc): Recrystallization from methanol yielded 89% of white crystals; m. p. 178,3"C; R, = 0,35 (CH2C1,).

'H NMR: 6 = 1,33 (-C(CH,),), 2,14 (-CH,), 3,80 and 3,83 (-CH2-), 6,8-7,05 (Ar-H).

MS: m/e 404 (M+; 96%), 296 (730/0), 284 (41%), 240 (96%), 228 (92%).

C27H3203 (404,6) Calc. C 80,16 H 7,97 Found C 79,97 H 8,09

a-(2-Hydroxy-5-methylpheny[)-w-(2- hydroxy-3-tert-butyl-5-methyl)bis[(2- hydroxy-5-methyl- 1,3-phenylene)methyLne] (2c): Recrystallization from ethanol or ethanol/water gave 70% of white crystals or needles, showing a very unsharp melting point of 108 - 118 "C; R, = 0,5 (CH,Cl,).

'H NMR: 6 = 1,38 (-C(CH,),), 2,2 (-CH,), =3,75 (-CH2-), 6,65 -7,O (Ar-H). MS: m/e 524 (M+; 55%), 342 (44%), 296 (loo%), 284 (35%), 240 (72%).

C35H&4 (52497) Calc. C 80,12 H 7,68 Found C 79,81 H 7,39

a-(2-Hydroxy-5-methyIphenyl)-w-(2- hydroxy-3-tert-butyl-5-rnethyl)tris[(2-hydroxy-5- methyl-1,3-phenylene)methylene] (3c): After column chromatography (CHCl!) the pure fractions were recrystallized from ethanol or ethanol/acetone to give 45% of a white microcrystalline product; m.p. 166OC; R, = 0,6 (CHCI,).


'H NMR: 6 = 1,36 (-C(CH&), 2,07 -2,13 (-CH,), 3,78 (-CHy-), 6,65 -6,8 (Ar-H). MS: m/e 644 (Mf; 56%), 480 (15%), 404 (21%), 342 (46%), 296 (71%), 239 (47%).

C~,H@S (64499) Calc. C 80,09 H 7,SO Found C 77,86 H 7,44

a-(2-Hydroxy-5-methylphenyl)-w-(2- hydroxy-3-tert- butyl-5-methyl)-tetrakis[(2-hydroxy-5- methyl-1,3-phenylene)methylene] (4c): Recrystallization from ethanol gave 25% of a white microcrystalline product; m.p. 196,5 "C; R, = 0,45 (CHCI,). Further pure material could be obtained from the mother liquors by column chromatography.

'H NMR: 6: 1,36 (-C(CH,),), 2,08 (-CH,), 3,84 (-CHZ--), 6,65 -6,8 (Ar-H). MS: m/e 764 (M'; 25%), 480 (40%), 360 (24%), 342 (62Vo), 296 (51%), 239 (47%).

C51H&,5 (76590) Calc. C 80,07 H 7,38 Found C 77,43 H 7,20

Preparation of compounds 5 a - c (Eq. 4)

2,6-Bis(2-hydroxy-5-methylbenzyl)-4-methylanisole (5 a): 9,l g (0,05 mol) of 2,6-bis(hydroxy- methyl)-4-ani~ole~~) and 130 g (1,2 mol) of p-cresol were mixed at 80°C under argon. 7 ml of conc. HCI were added and the reaction was carried out for 11 h with stirring, while the temperature was finally raised to 110 "C. Excess of p-cresol was removed by steam distillation, and the residue was purified by recrystallization from CHCI,/petroleum ether (b. p. 70- 100°C), to yield 11,l g(61Vo) ofwhitecrystalsof5a; m.p. 155,6"C (Lit.21): m.p. 150-151 "C); R, = 0,2 (CHCI,).

'H NMR: 6 = 2,12 and 2,17 (Ar-CH,), 3,78 (OCH,), 3,82 (-CH2-), 6,77 (Ar-H). MS: m/e 362 (MC; 83%), 254 (27070), 242 (970/0), 223 (39%), 209 (33%).

C&z603 (3623 Calc. C 7933 H 7,23 Found C 79,lO H 7,06

2-(2-Hydroxy-3-tert-butyl-5-methylbenzyl)-6-(2- hydroxy-5-methylbenzyl)-4-methylanisole (5 b) and 2,6-B~(2-hydroxy-3-tert-butyl-5-methylbe~~~-methylan~ole (Sc): 10,8 g (0,l mol) of p-cresol and 32,8 g (0,2 mol) of 2-tert-butyl-p-cresol were molten at 90°C under argon, then 1,82 g (0,Ol mol) of 2,6-bis(hydroxymethyI)-4-methylanisole were added, and after complete dissolution 3 ml of conc. HCI. After 3 h, again 3 ml of conc. HCI were added, and the temperature was maintained now for 5 h at 100 "C. Excess of cresols was removed by steam distillation, and the crude residue was dried, dissolved in CHzC12, and separated by column chromatography on silica gel. The first fractions (0,56 g) contained compound 512, which after recrystallization from petroleum ether (b. p. 70 - 100 "C) formed white needles (0,36 g); m. p.

'H NMR: 6 = 1,37 (-C(CH,),), 2,16 (Ar-CH,), 3,93 (OCH,/-CH,), 6,82, 6,93

MS: m/e 474 (M'; 1OO%), 310 (20%), 298 (83%), 279 (24V0), 242 (50/0), 222 (25%).

195,5 "C; R, = 0,9 (CHCI,).

(Ar-H).

C32H4203 (474,7) Calc. C 80,97 H 8,92 Found C 80,89 H 8,88

The main fractions (1,l g) contained 5b which formed white needles (0,74 g) after recrystal-

'H NMR: 6 = 1,37 (-C(CH3)3), 2,16 and 2,19 (Ar-CH,), 3,90 (OCH,/-CH,-), 3,96

MS: m/e 418 (M'; 88%), 310 (lo%), 298 (180/0), 279 (~VO), 242 (100%), 223 (13%).

lization from methanol; m.p. 144,4'C; R, = 0,75 (CHCI,).

(-CH2-), 6,78, 6,80, and 6,91 (Ar-H).

C,,H,,O, (41896) Calc. C 80,34 H 8,19 Found C 80,35 H 8,17

1806 V. Bohmer, K. Beismann, D. Stotz, W. Niemann, W. Vogt

Finally, fractions of 5a (0,58 g) could be isolated; m.p. 152-153°C without further purification.

A sample of 5b (100 mg; 0,24 mmol) was dissolved in 1 ml of CH’Cl,. At -40°C 2,9 mmol of BBr3 in 1 3 ml of CH,CI, were added, and the mixture was kept over night, slowly reaching room temperature during this time. Ice was added to hydrolize borone complexes, and the organic compound was extracted with ether. The crude product was already chromatographically pure. Recrystallization from CHC13/petroleum ether (b.p. 70- 100°C) gave 60 mg of white crystals; m.p. 177,7OC. The mixed melting point with l c showed no depression.

This research was supported by the Deutsche Forschungsgemeinschaft. We are also indepted to Prof. Dr. H. Kammerer for his continuous and encouraging interest.

H. Morawetz, “Macromolecules in Solution”, Wiley-Interscience, New York 1975

Worsdorfer, Z. Naturforsch., Teil B 33, 439 (1978) ’) a) E. Gaetjens, H. Morawetz, J. Am. Chem. SOC. 82, 5328 (1960); b) V. Bohmer, K.

3, V. Bbhmer, Chem.-Ztg. 98, 169 (1974) and references cited therein 4, W. P. Jencks, “Catalysis in Chemistry and Enzymology”, McGraw-Hill, New York 1969;

C. J. Gray, “Enzym-katalysierte Reaktionen”, G. Fischer, Stuttgart 1976 5, a) E. W. Westhead Jr., H. Morawetz, J. Am. Chem. SOC. 80, 237 (1958), b) G. Smets, W.

van Humbeeck, J. Polym. Sci., Part A 1, 1227 (1963) ‘) a) H. Kammerer, Kunststoffe 51,26 (1961), H. Ktimmerer, ibid. 56,154 (1966); b) A. Knop,

W. Scheib, “Chemistry and Application of Phenolic Resins”, Springer, Berlin 1979 7, a) C. D. Gutsche, B. Dhawan, K. H. No, R. Muthukrishnan, J. Am. Chem. SOC. 103,3782

(1981); b) G. Casiraghi, M. Cornia, G. Sartori, G. Casnati, V. Bocchi, G. D. Andreetti, Makromol. Chem. 183, 2611 (1982); c) V. Bbhmer, W. Lou, J. Pachta, S. Tiitiincu, Makromol. Chem. 182, 2671 (1981)

8, V. Bohmer, G. Stein, C. Antes, D. Stotz, H. Kammerer, 26th International Symposium on Macromolecules, Maim 1979, Preprints Vol. 1, p. 554

9, V. Bohmer, W. Niemann, Makromol. Chem. 176,2883 (1975) lo) a) V. Bohmer, W. Niemann, Makromol. Chem. 177,787 (1976); b) V. Bohmer, D. Stotz, K.

Beismann, W. Niemann, Monatsh. Chem. 114, 411 (1983) 11) W. Niemann, V. Bohmer, Makromol. Chem. 177, 803 (1976) 12) P. L. Huyskens, J. Am. Chem. SOC. 99, 2578 (1977)

V. Bohmer, D. Stotz, K. Beismann, W. Vogt, Monatsh. Chem., in press 14) D. M. Blow, J. J. Birktoft, B. S. Hartley, Nature (London) 221, 337 (1969) Is) M. Imoto, J. Ijichi, C. Tanaka, M. Kinoshita, Makromol. Chem. 113, 117 (1965) 16) H. Kammerer, W. Niemann, Makromol. Chem. 169, 1 (1973) 17) a) H. KBmmerer, G . Happel, Makromol. Chem., Rapid Commun. 1, 461 (1980); b) H.

Kammerer, W. Niemann, Makromol. Chem. 174, 39 (1973) H. K-erer, G. Happel, V. Bohmer, Org. Prep. Proced. Int. 8,245 (1976) and references cited therein

19) H. KBmmerer, W. Rausch, H. Schweikert, Makromol. Chem. 56, 123 (1962) ’O) H. Kammerer, G . Happel, Makromol. Chem. 179, 1199 (1978)

G. D. Andreetti, R. Ungaro, A. Pochini, J . Chem. SOC., Chem. Commun. 1979, 1005; b) M. Coruzzi, G . D. Andreetti, V. Bocchi, A. Pochini, R. Ungaro, J. Chem. SOC., Perkin Trans. 2: 1982, 1133

*,) H. Ktimmerer, H. Schweikert, H.-G. Haub, Makromol. Chem. 67, 173 (1963) 23) F. Ullmann, K. Brittner, Ber. Dtsch. Chem. Ges. 42, 2539 (1909)

kinetics of the bromination of phenols and oligonuclear phenolic compounds, 6. far reaching effects...

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