Montmorillonite Catalyzed Synthesis of Novel Steroid Dimers

The reactions of sterols (androst-5-en-3β-ol-17-one, diosgenin, and cholesterol) and their tosylates with hydroquinone aimed at the synthesis of O,O-1,4-phenylene-linked steroid dimers were studied. The reaction course strongly depended on the conditions used. The study has shown that the major reaction products are the elimination products and unusual steroid dimers resulting from the nucleophilic attack of the hydroquinone C2 carbon atom on the steroid C3 position, followed by an intramolecular addition to the C5–C6 double bond. A different reaction course was observed when montmorillonite K10 was used as a catalyst. The reaction of androst-5-en-3β-ol-17-one under the promotion of this catalyst afforded the O,O-1,4-phenylene-linked steroid dimer in addition to the disteroidal ether. The formation of the latter compound was suppressed by using 3-tosylate as a substrate instead of the free sterol. The reactions of androst-5-en-3β-ol-17-one tosylate and cholesteryl tosylate with hydroquinone catalyzed by montmorillonite K10 carried out under optimized conditions afforded the desired dimers in 31% and 67% yield, respectively.


Introduction
During the last few decades steroid dimers have emerged as an interesting new area of steroid chemistry.The first review article on steroid dimers was published by Li and Dias in 1997 [1].Since then, numerous reports have appeared on these compounds, which have been reviewed in the book [2] and in several review articles by Nahar et al. [3,4].In the beginning, steroid dimers, which were formed as byproducts of certain reactions, were considered mere curiosities.Later, steroid dimers were found in natural sources, e.g., japindine isolated from the root bark of Chonemorpha macrophylla [5], crellastatins from marine sponge Crella sp.[6], cephalostatins from tiny marine worm Cephalodiscus gilchristi [7], and ritterazines from tunicate Ritterella tokioka (Figure 1) [8].The highly cytotoxic cephalostatins and ritterazines inspired chemists to attempt their chemical synthesis [9][10][11].The synthesis of these dimeric steroidal pyrazine alkaloids and their analogs was particularly important because the natural sources of these compounds are extremely limited.These intensive studies were covered by several review articles [12][13][14][15].Oligomeric steroids with or without spacer groups can be used as chiral building blocks to construct artificial receptors and as architectural components in biomimetic/molecular recognition chemistry.Davis has briefly reviewed his work in this area, directed toward the construction of enzyme mimics [16].The study on dimerization and oligomerization of the cholic acid skeleton as an architectural building block was particularly intensive [17][18][19].Various methods of synthesis of steroid dimers with linear [20] or cyclic [21] structures, e.g., Sonogashira coupling, Yamaguchi esterification, Wurtz reaction, ring closing metathesis, etc., were employed [22].In the last decades, the interesting chemical, biological, and physical properties of the growing number of steroid dimers synthesized or isolated from living organisms have triggered Molecules 2023, 28, 7068 2 of 14 increased activity in this field.The large number of steroid dimers described so far include compounds that have shown properties as catalysts [23], artificial receptors [24], molecular umbrellas [25], as well as activity as sulfatase inhibitors [26], antimalarials [27], and cytotoxic and antiproliferative agents [28,29], amongst others.Recent solid-state studies revealed that several crystalline steroid dimers act as molecular rotors [30].
Molecules 2023, 28, x FOR PEER REVIEW 2 of 14 physical properties of the growing number of steroid dimers synthesized or isolated from living organisms have triggered increased activity in this field.The large number of steroid dimers described so far include compounds that have shown properties as catalysts [23], artificial receptors [24], molecular umbrellas [25], as well as activity as sulfatase inhibitors [26], antimalarials [27], and cytotoxic and antiproliferative agents [28,29], amongst others.Recent solid-state studies revealed that several crystalline steroid dimers act as molecular rotors [30].Molecules 2023, 28, x FOR PEER REVIEW 2 of 14 physical properties of the growing number of steroid dimers synthesized or isolated from living organisms have triggered increased activity in this field.The large number of steroid dimers described so far include compounds that have shown properties as catalysts [23], artificial receptors [24], molecular umbrellas [25], as well as activity as sulfatase inhibitors [26], antimalarials [27], and cytotoxic and antiproliferative agents [28,29], amongst others.Recent solid-state studies revealed that several crystalline steroid dimers act as molecular rotors [30].The aim of this research was the synthesis of steroid dimers, in which steroid units are connected by an O,O-1,4-phenylene linker (Figure 2).These compounds (1−3) were selected as potential molecular rotors.Molecular motors are an important class of nanomolar-sized molecular machines that use different energy sources to generate unidirectional mechanical motion.In the crystal lattice, they contain both a static part and a fragment capable of free rotation [31].Compound 1 has a carbonyl group at C17, which allows modification of the structure by functional group manipulation.Compounds 1 and 2 have not been described before, while compound 3 was previously obtained in low yield from cholesterol hydroquinone ether as an undesired product of an electrochemical reaction [32].In the present study, a chemical procedure was elaborated for the efficient synthesis of dimers 1−3 from readily available sterols, androst-5-en-3β-ol-17-one 4a (dehydroepiandrosterone; DHEA), (25R)-spirost-5-en-3β-ol 5a (diosgenin), and cholesterol 6a, respectively.

Results and Discussion
The synthetic plan of dimers 1-3 assumed the conversion of starting sterols 4a-6a into the corresponding p-tosylates 4b-6b and their reaction with hydroquinone.It is well known that upon leaving p-TsO − the mesomerically stabilized homoallylic carbocation (Scheme 1) is generated, which can react with a nucleophilic reagent, e.g., hydroquinone, in the 3β position.For stereoelectronic reasons, only 3β-substituted steroid products can be formed.In fact, the nucleophile may also attack the 6β position, but the resulting product (so-called i-steroid) is thermodynamically less stable and is not formed as a product under acidic conditions.However, the reaction of androst-5-en-3β-ol-17-one tosylate 4b (2 equiv.)with hydroquinone (1 equiv.)did not afford the expected dimer 1.There was no reaction in boiling acetone (even in the presence of p-TsOH), while the analogous reaction carried out in dioxane (24 h at reflux) yielded mostly the nonpolar elimination products 7 and 8 (Table 1; run 1).The fast solvent−free reaction at 120 • C (run 2) gave a mixture of several products, which were carefully analyzed.
Molecules 2023, 28, x FOR PEER REVIEW 3 of 14 The aim of this research was the synthesis of steroid dimers, in which steroid units are connected by an O,O-1,4-phenylene linker (Figure 2).These compounds (1−3) were selected as potential molecular rotors.Molecular motors are an important class of nanomolar-sized molecular machines that use different energy sources to generate unidirectional mechanical motion.In the crystal lattice, they contain both a static part and a fragment capable of free rotation [31].Compound 1 has a carbonyl group at C17, which allows modification of the structure by functional group manipulation.Compounds 1 and 2 have not been described before, while compound 3 was previously obtained in low yield from cholesterol hydroquinone ether as an undesired product of an electrochemical reaction [32].In the present study, a chemical procedure was elaborated for the efficient synthesis of dimers 1−3 from readily available sterols, androst-5-en-3β-ol-17-one 4a (dehydroepiandrosterone; DHEA), (25R)-spirost-5-en-3β-ol 5a (diosgenin), and cholesterol 6a, respectively.

Results and Discussion
The synthetic plan of dimers 1-3 assumed the conversion of starting sterols 4a-6a into the corresponding p-tosylates 4b-6b and their reaction with hydroquinone.It is well known that upon leaving p-TsO − the mesomerically stabilized homoallylic carbocation (Scheme 1) is generated, which can react with a nucleophilic reagent, e.g., hydroquinone, in the 3β position.For stereoelectronic reasons, only 3β-substituted steroid products can be formed.In fact, the nucleophile may also attack the 6β position, but the resulting product (so-called i-steroid) is thermodynamically less stable and is not formed as a product under acidic conditions.However, the reaction of androst-5-en-3β-ol-17-one tosylate 4b (2 equiv.)with hydroquinone (1 equiv.)did not afford the expected dimer 1.There was no reaction in boiling acetone (even in the presence of p-TsOH), while the analogous reaction carried out in dioxane (24 h at reflux) yielded mostly the nonpolar elimination products 7 and 8 (Table 1; run 1).The fast solvent−free reaction at 120 °C (run 2) gave a mixture of several products, which were carefully analyzed.In addition to a mixture of dienes 7 and 8, androst-5-en-3β-ol-17-one hydroquinone ether 9 and unexpected products 10 and 11 as stereomeric mixtures were obtained.The compound 9 could be an intermediate in the synthesis of dimer 1, but the desired compound 1 was not found among the reaction products.Instead, the different dimers were isolated, 11a-11c, and their likely precursors, 10a and 10b.The similar reaction products, but in a different ratio (more elimination products), were formed in xylenes at reflux for 3 h (run 3).The structures of the products prove that both nucleophilic sites of hydroquinone, the oxygen atom and the carbon atom C2 of the aromatic ring, take part in the reaction.Interestingly, during the reaction, the hydroquinone carbon atom binds to the steroid C3 position, while the oxygen atom binds to C5.The direction of the reaction was deduced from the analysis of 1 H NMR spectra.The chemical shifts of protons at C3 were shifted upfield (compared to δ 4.34 in tosylate 4b) and appeared at δ below 3 ppm.Therefore, the oxygen atom in this compound cannot be attached to C3.It seems that compounds 10b and 11b resulted from an attack of the carbon atom of hydroquinone on the mesomeric carbocation, which is formed upon the leaving of p-TsO − from 4b (Scheme 2).

Structure of Products Conversion
Molecules 2023, 28, x FOR PEER REVIEW 4 of 14 compound 1 was not found among the reaction products.Instead, the different dimers were isolated, 11a-11c, and their likely precursors, 10a and 10b.The similar reaction products, but in a different ratio (more elimination products), were formed in xylenes at reflux for 3 h (run 3).The structures of the products prove that both nucleophilic sites of hydroquinone, the oxygen atom and the carbon atom C2 of the aromatic ring, take part in the reaction.Interestingly, during the reaction, the hydroquinone carbon atom binds to the steroid C3 position, while the oxygen atom binds to C5.The direction of the reaction was deduced from the analysis of 1 H NMR spectra.The chemical shifts of protons at C3 were shifted upfield (compared to δ 4.34 in tosylate 4b) and appeared at δ below 3 ppm.Therefore, the oxygen atom in this compound cannot be attached to C3.It seems that compounds 10b and 11b resulted from an attack of the carbon atom of hydroquinone on the mesomeric carbocation, which is formed upon the leaving of p-TsO − from 4b (Scheme 2).Molecules 2023, 28, x FOR PEER REVIEW 4 of 14 compound 1 was not found among the reaction products.Instead, the different dimers were isolated, 11a-11c, and their likely precursors, 10a and 10b.The similar reaction products, but in a different ratio (more elimination products), were formed in xylenes at reflux for 3 h (run 3).The structures of the products prove that both nucleophilic sites of hydroquinone, the oxygen atom and the carbon atom C2 of the aromatic ring, take part in the reaction.Interestingly, during the reaction, the hydroquinone carbon atom binds to the steroid C3 position, while the oxygen atom binds to C5.The direction of the reaction was deduced from the analysis of 1 H NMR spectra.The chemical shifts of protons at C3 were shifted upfield (compared to δ 4.34 in tosylate 4b) and appeared at δ below 3 ppm.Therefore, the oxygen atom in this compound cannot be attached to C3.It seems that compounds 10b and 11b resulted from an attack of the carbon atom of hydroquinone on the mesomeric carbocation, which is formed upon the leaving of p-TsO − from 4b (Scheme 2).Molecules 2023, 28, x FOR PEER REVIEW 4 of 14 compound 1 was not found among the reaction products.Instead, the different dimers were isolated, 11a-11c, and their likely precursors, 10a and 10b.The similar reaction products, but in a different ratio (more elimination products), were formed in xylenes at reflux for 3 h (run 3).The structures of the products prove that both nucleophilic sites of hydroquinone, the oxygen atom and the carbon atom C2 of the aromatic ring, take part in the reaction.Interestingly, during the reaction, the hydroquinone carbon atom binds to the steroid C3 position, while the oxygen atom binds to C5.The direction of the reaction was deduced from the analysis of 1 H NMR spectra.The chemical shifts of protons at C3 were shifted upfield (compared to δ 4.34 in tosylate 4b) and appeared at δ below 3 ppm.Therefore, the oxygen atom in this compound cannot be attached to C3.It seems that compounds 10b and 11b resulted from an attack of the carbon atom of hydroquinone on the mesomeric carbocation, which is formed upon the leaving of p-TsO − from 4b (Scheme 2).Molecules 2023, 28, x FOR PEER REVIEW 4 of 14 compound 1 was not found among the reaction products.Instead, the different dimers were isolated, 11a-11c, and their likely precursors, 10a and 10b.The similar reaction products, but in a different ratio (more elimination products), were formed in xylenes at reflux for 3 h (run 3).The structures of the products prove that both nucleophilic sites of hydroquinone, the oxygen atom and the carbon atom C2 of the aromatic ring, take part in the reaction.Interestingly, during the reaction, the hydroquinone carbon atom binds to the steroid C3 position, while the oxygen atom binds to C5.The direction of the reaction was deduced from the analysis of 1 H NMR spectra.The chemical shifts of protons at C3 were shifted upfield (compared to δ 4.34 in tosylate 4b) and appeared at δ below 3 ppm.Therefore, the oxygen atom in this compound cannot be attached to C3.It seems that compounds 10b and 11b resulted from an attack of the carbon atom of hydroquinone on the mesomeric carbocation, which is formed upon the leaving of p-TsO − from 4b (Scheme 2).compound 1 was not found among the reaction products.Instead, the different dimers were isolated, 11a-11c, and their likely precursors, 10a and 10b.The similar reaction products, but in a different ratio (more elimination products), were formed in xylenes at reflux for 3 h (run 3).The structures of the products prove that both nucleophilic sites of hydroquinone, the oxygen atom and the carbon atom C2 of the aromatic ring, take part in the reaction.Interestingly, during the reaction, the hydroquinone carbon atom binds to the steroid C3 position, while the oxygen atom binds to C5.The direction of the reaction was deduced from the analysis of 1 H NMR spectra.The chemical shifts of protons at C3 were shifted upfield (compared to δ 4.34 in tosylate 4b) and appeared at δ below 3 ppm.Therefore, the oxygen atom in this compound cannot be attached to C3.It seems that compounds 10b and 11b resulted from an attack of the carbon atom of hydroquinone on the mesomeric carbocation, which is formed upon the leaving of p-TsO − from 4b (Scheme 2).This attack is possible from the steroid β side only due to stereoelectronic reasons.In the next step, an intramolecular addition of phenol to the steroid C5-C6 double bond occurred, leading to a six-membered ring formation.Compound 10b obtained this way may undergo the same reaction sequence to provide the dimer 11b.The mechanism of the dimer 11a formation (via 10a) is less obvious (Scheme 3).Apparently, the attack of hydroquinone on steroid tosylate 4b occurred from the less hindered α side in this case.However, the reaction timing is not clear.It could be either a nucleophilic substitution of 3-tosylate with the carbon C2 of hydroquinone followed by an intramolecular addition to the C5-C6 double bond or a concerted attack of hydroquinone on both 3-tosylate and the double bond.
Molecules 2023, 28, x FOR PEER REVIEW 5 of 14 This attack is possible from the steroid β side only due to stereoelectronic reasons.In the next step, an intramolecular addition of phenol to the steroid C5-C6 double bond occurred, leading to a six-membered ring formation.Compound 10b obtained this way may undergo the same reaction sequence to provide the dimer 11b.The mechanism of the dimer 11a formation (via 10a) is less obvious (Scheme 3).Apparently, the attack of hydroquinone on steroid tosylate 4b occurred from the less hindered α side in this case.However, the reaction timing is not clear.It could be either a nucleophilic substitution of 3tosylate with the carbon C2 of hydroquinone followed by an intramolecular addition to the C5-C6 double bond or a concerted attack of hydroquinone on both 3-tosylate and the double bond.The dimers 11a, 11b, and 11c were separated by column chromatography since they differ in polarity.The Rf values of dimers determined by their migration on TLC plates three times developed in the solvent system hexane-ethyl acetate (74:26) were 0.77, 0.66, and 0.71, respectively.The C2 symmetrical dimers 11a and 11b were isolated in similar amounts, while the mixed unsymmetrical dimer 11c was obtained in larger quantities.Optimized structures of dimers 11a and 11b are presented in Figure 3.The 1 H NMR spectra of 11a and 11b were very similar, except for protons in the A-ring region.Particularly, the chemical shifts of protons at C3 and C3′ in these dimers proved different.The twoproton signal in dimer 11a came out at δ 2.90 ppm, while an analogous two-proton signal in 11b appeared at δ 2.85 ppm.Of course, the 1 H NMR spectrum of mixed dimer 11c, which consists of two different steroid units, showed both proton signals (δ 2.85 and 2.90 ppm) as presented in Figure 4.The difference of 0.05 ppm between the chemical shifts of protons at the C3 and C3′ positions in dimers 11a and 11b is comparable to the literature values described for analogous A/B ring systems.For example, the 3β-H signal in 3α-hydroxy-5α-androstane-17-one is located at 4.05 ppm [33], while the analogous signal (3α-H) in 3β-hydroxy-5β-androstane-17-one shows up at 4.11 ppm [34].In addition, the chemical shifts of the C4 protons in dimer 11a appear at δ 1.40 and 2.08 ppm, compared to 1.43 and 2.48 ppm for the corresponding proton signals in compound 11b.The signal of the 4α proton in 11b is significantly (0.40 ppm) shifted downfield compared to the analogous signal in 11a.A similar difference (Δδ 0.43 ppm) between the chemical shifts of protons at C4 was reported in the literature for 5α-and 5β-androstan-17-ones [35].The full assignment of signals in 1 H and 13 C NMR spectra was carried out based on different NMR techniques (DEPT, COSY, HMQC, and HMBC) and is presented in Table S1 (Supplementary Material).The dimers 11a, 11b, and 11c were separated by column chromatography since they differ in polarity.The Rf values of dimers determined by their migration on TLC plates three times developed in the solvent system hexane-ethyl acetate (74:26) were 0.77, 0.66, and 0.71, respectively.The C2 symmetrical dimers 11a and 11b were isolated in similar amounts, while the mixed unsymmetrical dimer 11c was obtained in larger quantities.Optimized structures of dimers 11a and 11b are presented in Figure 3.The 1 H NMR spectra of 11a and 11b were very similar, except for protons in the A-ring region.Particularly, the chemical shifts of protons at C3 and C3 in these dimers proved different.The two-proton signal in dimer 11a came out at δ 2.90 ppm, while an analogous two-proton signal in 11b appeared at δ 2.85 ppm.Of course, the 1 H NMR spectrum of mixed dimer 11c, which consists of two different steroid units, showed both proton signals (δ 2.85 and 2.90 ppm) as presented in Figure 4.The difference of 0.05 ppm between the chemical shifts of protons at the C3 and C3 positions in dimers 11a and 11b is comparable to the literature values described for analogous A/B ring systems.For example, the 3β-H signal in 3α-hydroxy-5α-androstane-17-one is located at 4.05 ppm [33], while the analogous signal (3α-H) in 3β-hydroxy-5β-androstane-17-one shows up at 4.11 ppm [34].In addition, the chemical shifts of the C4 protons in dimer 11a appear at δ 1.40 and 2.08 ppm, compared to 1.43 and 2.48 ppm for the corresponding proton signals in compound 11b.The signal of the 4α proton in 11b is significantly (0.40 ppm) shifted downfield compared to the analogous signal in 11a.A similar difference (∆δ 0.43 ppm) between the chemical shifts of protons at C4 was reported in the literature for 5α-and 5β-androstan-17-ones [35].The full assignment of signals in 1 H and 13 C NMR spectra was carried out based on different NMR techniques (DEPT, COSY, HMQC, and HMBC) and is presented in Table S1 (Supplementary Material).A series of experiments were performed using mechanochemistry (Table 1; run 4), microwave (run 5), or ultrasound irradiation (run 6), but none of them produced reasonable yields of tosylate 4b with hydroquinone reaction products.
In the next series of experiments, montmorillonite was used as a catalyst.Montmorillonite is a very soft phyllosilicate group of minerals that form when they precipitate from water solution as microscopic crystals, known as clay.It is named after Montmorillon in France.Montmorillonite, a member of the smectite group, is a 2:1 clay, meaning that it has two tetrahedral sheets of silica sandwiching a central octahedral sheet of alumina.The acid-treated montmorillonite clays have been extensively used in various catalytic processes [36].Other heterogeneous Brønsted and Lewis acid catalysts could be developed using the cation-exchange ability of the montmorillonite interlayer.The organic syntheses using the above acid catalysts have several advantages: ease of preparing the solid catalysts, high catalytic activities, wide applicability to large molecules, simple workup procedure, and reusability of the catalyst [37].Montmorillonite was also used for the preparation of ethers from alcohols and phenols.A comprehensive review of the catalytic Oalkylation of phenol and hydroquinone has recently appeared [38].Also, the preparation of cholesteryl ethers from cholesterol and various alcohols or phenols has been described [39].
Before we started studying reactions catalyzed with montmorillonite, the reaction of androst-5-en-3β-ol-17-one tosylate (4b) with hydroquinone in the presence of basic Al2O3 was carried out.Unfortunately, the reaction was dirty and led to i-steroid products (e.g., 3α,5α-cyclo-androst-6-en-17-one) predominately.Therefore, a conclusion has been drawn that basic conditions should be avoided, and further reactions were carried out with K10 (commercial montmorillonite) as a catalyst under different conditions (Table 2).For these A series of experiments were performed using mechanochemistry (Table 1; run 4), microwave (run 5), or ultrasound irradiation (run 6), but none of them produced reasonable yields of tosylate 4b with hydroquinone reaction products.
In the next series of experiments, montmorillonite was used as a catalyst.Montmorillonite is a very soft phyllosilicate group of minerals that form when they precipitate from water solution as microscopic crystals, known as clay.It is named after Montmorillon in France.Montmorillonite, a member of the smectite group, is a 2:1 clay, meaning that it has two tetrahedral sheets of silica sandwiching a central octahedral sheet of alumina.The acid-treated montmorillonite clays have been extensively used in various catalytic processes [36].Other heterogeneous Brønsted and Lewis acid catalysts could be developed using the cation-exchange ability of the montmorillonite interlayer.The organic syntheses using the above acid catalysts have several advantages: ease of preparing the solid catalysts, high catalytic activities, wide applicability to large molecules, simple workup procedure, and reusability of the catalyst [37].Montmorillonite was also used for the preparation of ethers from alcohols and phenols.A comprehensive review of the catalytic O-alkylation of phenol and hydroquinone has recently appeared [38].Also, the preparation of cholesteryl ethers from cholesterol and various alcohols or phenols has been described [39].
Before we started studying reactions catalyzed with montmorillonite, the reaction of androst-5-en-3β-ol-17-one tosylate (4b) with hydroquinone in the presence of basic Al 2 O 3 was carried out.Unfortunately, the reaction was dirty and led to i-steroid products (e.g., 3α,5α-cyclo-androst-6-en-17-one) predominately.Therefore, a conclusion has been drawn that basic conditions should be avoided, and further reactions were carried out with K10 (commercial montmorillonite) as a catalyst under different conditions (Table 2).For these reactions, a non-activated androst-5-en-3β-ol-17-one (4a) was used instead of tosylate 4b.In addition to the previously described products, new dimeric products, i.e., disteroidal ether 12 and the desired hydroquinone disteroidal diether 1, appeared among the reaction products.The synthesis of disteroidal ethers was previously described.They can be efficiently prepared from ∆ 5 -steroids by treating them with montmorillonite in a dichloromethane solution [40] or by an electrochemical method [41].In both cases, a mesomeric homoallylic carbocation (Scheme 1) is formed as an intermediate, which finally reacts with the starting sterol.

Structure of Products Conversion
In addition to the previously described products, new dimeric products, i.e., disteroidal ether 12 and the desired hydroquinone disteroidal diether 1, appeared among the reaction products.The synthesis of disteroidal ethers was previously described.They can be efficiently prepared from Δ 5 -steroids by treating them with montmorillonite in a dichloromethane solution [40] or by an electrochemical method [41].In both cases, a mesomeric homoallylic carbocation (Scheme 1) is formed as an intermediate, which finally reacts with the starting sterol.The reaction was optimized against the quantity of catalyst used.With 500 mg of K10 activated at 120 °C, a 10% yield of dimer 1 was achieved (Table 2; run 1); higher amounts of catalyst deteriorated (run 2) the reaction result.The temperature of the montmorillonite activation is very important.Montmorillonite changes its properties during activation due to the desorption of water, dehydration, and alteration of crystalline structure.The activation at 120 °C causes water desorption, which exposes acid groups.This increases the number and strength of acid centers.A higher temperature of activation results in partial dehydration of Si-OH and Al-OH groups.Then the number of Brønsted acid sites decreases, while the number of Lewis acid (e.g., Al 3+ ) sites increases.The reactions of hydroquinone with 2.5 equiv. of DHEA (4a) in CHCl3 at reflux catalyzed with K10 (500 mg) activated at different temperatures were carried out (runs 3-6).The best result was obtained with K10 activated at 280 °C (run 5).The desired dimer 1 was obtained in 23% under optimized conditions.Further attempts to increase the yield of dimer 1 failed.The experiments presented in Table 2 were conducted in 5 mL of CHCl3 at reflux.The reaction carried out as in the case of run 5, but in a more diluted solution (10 mL of solvent), gave essentially the same result (23% of 1).The reaction performed in 1,2-dichloroethane at reflux (83 °C) provided only 13% of 1, while in other solvents at reflux (cyclohexane, toluene, xylenes, acetonitrile, acetone, THF, and dioxane), dimer 1 was not formed at all.Also, the attempts to carry out the reaction at room temperature were completely unsuccessful.In the next series of experiments, montmorillonite activated with hydrochloric acid was used.With this catalyst dried at 280 °C (H + -K10), up to a 57% yield of disteroidal ether 12 (Table 2; runs 7 and 8) could be achieved, but the yield of dimer 1 was negligible.It seems that increasing the number of Brønsted reactive sites deteriorates the yield of ether 12 and the desired hydroquinone disteroidal diether 1, appeared among the reaction products.The synthesis of disteroidal ethers was previously described.They can be efficiently prepared from Δ 5 -steroids by treating them with montmorillonite in a dichloromethane solution [40] or by an electrochemical method [41].In both cases, a mesomeric homoallylic carbocation (Scheme 1) is formed as an intermediate, which finally reacts with the starting sterol.The reaction was optimized against the quantity of catalyst used.With 500 mg of K10 activated at 120 °C, a 10% yield of dimer 1 was achieved (Table 2; run 1); higher amounts of catalyst deteriorated (run 2) the reaction result.The temperature of the montmorillonite activation is very important.Montmorillonite changes its properties during activation due to the desorption of water, dehydration, and alteration of crystalline structure.The activation at 120 °C causes water desorption, which exposes acid groups.This increases the number and strength of acid centers.A higher temperature of activation results in partial dehydration of Si-OH and Al-OH groups.Then the number of Brønsted acid sites decreases, while the number of Lewis acid (e.g., Al 3+ ) sites increases.The reactions of hydroquinone with 2.5 equiv. of DHEA (4a) in CHCl3 at reflux catalyzed with K10 (500 mg) activated at different temperatures were carried out (runs 3-6).The best result was obtained with K10 activated at 280 °C (run 5).The desired dimer 1 was obtained in 23% under optimized conditions.Further attempts to increase the yield of dimer 1 failed.The experiments presented in Table 2 were conducted in 5 mL of CHCl3 at reflux.The reaction carried out as in the case of run 5, but in a more diluted solution (10 mL of solvent), gave essentially the same result (23% of 1).The reaction performed in 1,2-dichloroethane at reflux (83 °C) provided only 13% of 1, while in other solvents at reflux (cyclohexane, toluene, xylenes, acetonitrile, acetone, THF, and dioxane), dimer 1 was not formed at all.Also, the attempts to carry out the reaction at room temperature were completely unsuccessful.In the next series of experiments, montmorillonite activated with hydrochloric acid was used.With this catalyst dried at 280 °C (H + -K10), up to a 57% yield of disteroidal ether 12 (Table 2; runs 7 and 8) could be achieved, but the yield of dimer 1 was negligible.It seems that increasing the number of Brønsted reactive sites deteriorates the yield of In addition to the previously described products, new dimeric products, i.e., disteroidal ether 12 and the desired hydroquinone disteroidal diether 1, appeared among the reaction products.The synthesis of disteroidal ethers was previously described.They can be efficiently prepared from Δ 5 -steroids by treating them with montmorillonite in a dichloromethane solution [40] or by an electrochemical method [41].In both cases, a mesomeric homoallylic carbocation (Scheme 1) is formed as an intermediate, which finally reacts with the starting sterol.The reaction was optimized against the quantity of catalyst used.With 500 mg of K10 activated at 120 °C, a 10% yield of dimer 1 was achieved (Table 2; run 1); higher amounts of catalyst deteriorated (run 2) the reaction result.The temperature of the montmorillonite activation is very important.Montmorillonite changes its properties during activation due to the desorption of water, dehydration, and alteration of crystalline structure.The activation at 120 °C causes water desorption, which exposes acid groups.This increases the number and strength of acid centers.A higher temperature of activation results in partial dehydration of Si-OH and Al-OH groups.Then the number of Brønsted acid sites decreases, while the number of Lewis acid (e.g., Al 3+ ) sites increases.The reactions of hydroquinone with 2.5 equiv. of DHEA (4a) in CHCl3 at reflux catalyzed with K10 (500 mg) activated at different temperatures were carried out (runs 3-6).The best result was obtained with K10 activated at 280 °C (run 5).The desired dimer 1 was obtained in 23% under optimized conditions.Further attempts to increase the yield of dimer 1 failed.The experiments presented in Table 2 were conducted in 5 mL of CHCl3 at reflux.The reaction carried out as in the case of run 5, but in a more diluted solution (10 mL of solvent), gave essentially the same result (23% of 1).The reaction performed in 1,2-dichloroethane at reflux (83 °C) provided only 13% of 1, while in other solvents at reflux (cyclohexane, toluene, xylenes, acetonitrile, acetone, THF, and dioxane), dimer 1 was not formed at all.Also, the attempts to carry out the reaction at room temperature were completely unsuccessful.In the next series of experiments, montmorillonite activated with hydrochloric acid was used.With this catalyst dried at 280 °C (H + -K10), up to a 57% yield of disteroidal ether 12 (Table 2; runs 7 and 8) could be achieved, but the yield of dimer 1 was negligible.It seems that increasing the number of Brønsted reactive sites deteriorates the yield of ether 12 and the desired hydroquinone disteroidal diether 1, appeared among the reaction products.The synthesis of disteroidal ethers was previously described.They can be efficiently prepared from Δ 5 -steroids by treating them with montmorillonite in a dichloromethane solution [40] or by an electrochemical method [41].In both cases, a mesomeric homoallylic carbocation (Scheme 1) is formed as an intermediate, which finally reacts with the starting sterol.The reaction was optimized against the quantity of catalyst used.With 500 mg of K10 activated at 120 °C, a 10% yield of dimer 1 was achieved (Table 2; run 1); higher amounts of catalyst deteriorated (run 2) the reaction result.The temperature of the montmorillonite activation is very important.Montmorillonite changes its properties during activation due to the desorption of water, dehydration, and alteration of crystalline structure.The activation at 120 °C causes water desorption, which exposes acid groups.This increases the number and strength of acid centers.A higher temperature of activation results in partial dehydration of Si-OH and Al-OH groups.Then the number of Brønsted acid sites decreases, while the number of Lewis acid (e.g., Al 3+ ) sites increases.The reactions of hydroquinone with 2.5 equiv. of DHEA (4a) in CHCl3 at reflux catalyzed with K10 (500 mg) activated at different temperatures were carried out (runs 3-6).The best result was obtained with K10 activated at 280 °C (run 5).The desired dimer 1 was obtained in 23% under optimized conditions.Further attempts to increase the yield of dimer 1 failed.The experiments presented in Table 2 were conducted in 5 mL of CHCl3 at reflux.The reaction carried out as in the case of run 5, but in a more diluted solution (10 mL of solvent), gave essentially the same result (23% of 1).The reaction performed in 1,2-dichloroethane at reflux (83 °C) provided only 13% of 1, while in other solvents at reflux (cyclohexane, toluene, xylenes, acetonitrile, acetone, THF, and dioxane), dimer 1 was not formed at all.Also, the attempts to carry out the reaction at room temperature were completely unsuccessful.In the next series of experiments, montmorillonite activated with hydrochloric acid was used.With this catalyst dried at 280 °C (H + -K10), up to a 57% yield of disteroidal ether 12 (Table 2; runs 7 and 8) could be achieved, but the yield of dimer 1 was negligible.It seems that increasing the number of Brønsted reactive sites deteriorates the yield of In addition to the previously described products, new dimeric products, i.e., disteroidal ether 12 and the desired hydroquinone disteroidal diether 1, appeared among the reaction products.The synthesis of disteroidal ethers was previously described.They can be efficiently prepared from Δ 5 -steroids by treating them with montmorillonite in a dichloromethane solution [40] or by an electrochemical method [41].In both cases, a mesomeric homoallylic carbocation (Scheme 1) is formed as an intermediate, which finally reacts with the starting sterol.The reaction was optimized against the quantity of catalyst used.With 500 mg of K10 activated at 120 °C, a 10% yield of dimer 1 was achieved (Table 2; run 1); higher amounts of catalyst deteriorated (run 2) the reaction result.The temperature of the montmorillonite activation is very important.Montmorillonite changes its properties during activation due to the desorption of water, dehydration, and alteration of crystalline structure.The activation at 120 °C causes water desorption, which exposes acid groups.This increases the number and strength of acid centers.A higher temperature of activation results in partial dehydration of Si-OH and Al-OH groups.Then the number of Brønsted acid sites decreases, while the number of Lewis acid (e.g., Al 3+ ) sites increases.The reactions of hydroquinone with 2.5 equiv. of DHEA (4a) in CHCl3 at reflux catalyzed with K10 (500 mg) activated at different temperatures were carried out (runs 3-6).The best result was obtained with K10 activated at 280 °C (run 5).The desired dimer 1 was obtained in 23% under optimized conditions.Further attempts to increase the yield of dimer 1 failed.The experiments presented in Table 2 were conducted in 5 mL of CHCl3 at reflux.The reaction carried out as in the case of run 5, but in a more diluted solution (10 mL of solvent), gave essentially the same result (23% of 1).The reaction performed in 1,2-dichloroethane at reflux (83 °C) provided only 13% of 1, while in other solvents at reflux (cyclohexane, toluene, xylenes, acetonitrile, acetone, THF, and dioxane), dimer 1 was not formed at all.Also, the attempts to carry out the reaction at room temperature were completely unsuccessful.In the next series of experiments, montmorillonite activated with hydrochloric acid was used.With this catalyst dried at 280 °C (H + -K10), up to a 57% yield of disteroidal ether 12 (Table 2; runs 7 and 8) could be achieved, but the yield of dimer 1 was negligible.It seems that increasing the number of Brønsted reactive sites deteriorates the yield of  The reaction was optimized against the quantity of catalyst used.With 500 mg of K10 activated at 120 • C, a 10% yield of dimer 1 was achieved (Table 2; run 1); higher amounts of catalyst deteriorated (run 2) the reaction result.The temperature of the montmorillonite activation is very important.Montmorillonite changes its properties during activation due to the desorption of water, dehydration, and alteration of crystalline structure.The activation at 120 • C causes water desorption, which exposes acid groups.This increases the number and strength of acid centers.A higher temperature of activation results in partial dehydration of Si-OH and Al-OH groups.Then the number of Brønsted acid sites decreases, while the number of Lewis acid (e.g., Al 3+ ) sites increases.The reactions of hydroquinone with 2.5 equiv. of DHEA (4a) in CHCl 3 at reflux catalyzed with K10 (500 mg) activated at different temperatures were carried out (runs 3-6).The best result was obtained with K10 activated at 280 • C (run 5).The desired dimer 1 was obtained in 23% under optimized conditions.Further attempts to increase the yield of dimer 1 failed.The experiments presented in Table 2 were conducted in 5 mL of CHCl 3 at reflux.The reaction carried out as in the case of run 5, but in a more diluted solution (10 mL of solvent), gave essentially the same result (23% of 1).The reaction performed in 1,2-dichloroethane at reflux (83 • C) provided only 13% of 1, while in other solvents at reflux (cyclohexane, toluene, xylenes, acetonitrile, acetone, THF, and dioxane), dimer 1 was not formed at all.Also, the attempts to carry out the reaction at room temperature were completely unsuccessful.In the next series of experiments, montmorillonite activated with hydrochloric acid was used.With this catalyst dried at 280 • C (H + -K10), up to a 57% yield of disteroidal ether 12 (Table 2; runs 7 and 8) could be achieved, but the yield of dimer 1 was negligible.It seems that increasing the number of Brønsted reactive sites deteriorates the yield of dimer 1.Some experiments were carried out with montmorillonite activated with the ions Ti 4+ or Cu 2+ .However, this modification of the catalyst promoted only the elimination processes (runs 9 and 10).
The optimal reaction conditions (as in run 5) were applied to analogous reactions of other sterols-diosgenin 5a and cholesterol 6a.In the latter case, the yield of desired dimer 3 was slightly better (28%) than that achieved for DHEA (4a).The dimer 3 was accompanied by dicholesteryl ether (22%), hydroquinone mono cholesteryl ether (10%), and the elimination products (35%).The yield of diosgenin-derived dimer 2 was lower (12%) under the same conditions.The corresponding disteroidal ether was isolated in tiny amounts [42].
In the next experiments, androst-5-en-3β-ol-17-one tosylate (4b) and cholesteryl tosylate (6b) served as substrates.The advantage of using tosylates instead of free sterols is that disteroidal ethers cannot be formed under these conditions, which is important from the point of view of reaction product separation.Also, dimers 11a-c (or analogous compounds derived from cholesterol) were formed only in negligible amounts.In addition, much milder reaction conditions were used, resulting in fewer by-products.The results of tosylate reactions are shown in Table 3.It should be noted that all reactions occurred at ambient temperature and required less catalyst.In the case of the androstane series (runs 1-3), the best yield of the desired dimer 1 (31%) was observed for the reaction catalyzed by Ti 4+ activated montmorillonite K10 (run 3).Without Ti 4+ activation, the yield of 1 was 23%, provided that K10 was calcined at 500 • C (run 2).The reactions of cholesteryl tosylate 6b with hydroquinone (runs 4-6) worked much better and provided dimer 3 in excellent yields.Especially the catalyst dried at 500 • C (run 5) was found to be very active in promoting the reaction, even in low quantities (50 mg).The likely explanation for the high activity of montmorillonite K10 against cholesterol 6a and its tosylate 6b is the lack of additional groups in these substrates capable of binding to the active catalyst sites.dimer 1.Some experiments were carried out with montmorillonite activated with the ions Ti 4+ or Cu 2+ .However, this modification of the catalyst promoted only the elimination processes (runs 9 and 10).
The optimal reaction conditions (as in run 5) were applied to analogous reactions of other sterols-diosgenin 5a and cholesterol 6a.In the latter case, the yield of desired dimer 3 was slightly better (28%) than that achieved for DHEA (4a).The dimer 3 was accompanied by dicholesteryl ether (22%), hydroquinone mono cholesteryl ether (10%), and the elimination products (35%).The yield of diosgenin-derived dimer 2 was lower (12%) under the same conditions.The corresponding disteroidal ether was isolated in tiny amounts [42].
In the next experiments, androst-5-en-3β-ol-17-one tosylate (4b) and cholesteryl tosylate (6b) served as substrates.The advantage of using tosylates instead of free sterols is that disteroidal ethers cannot be formed under these conditions, which is important from the point of view of reaction product separation.Also, dimers 11a-c (or analogous compounds derived from cholesterol) were formed only in negligible amounts.In addition, much milder reaction conditions were used, resulting in fewer by-products.The results of tosylate reactions are shown in Table 3.It should be noted that all reactions occurred at ambient temperature and required less catalyst.In the case of the androstane series (runs 1-3), the best yield of the desired dimer 1 (31%) was observed for the reaction catalyzed by Ti 4+ activated montmorillonite K10 (run 3).Without Ti 4+ activation, the yield of 1 was 23%, provided that K10 was calcined at 500 °C (run 2).The reactions of cholesteryl tosylate 6b with hydroquinone (runs 4-6) worked much better and provided dimer 3 in excellent yields.Especially the catalyst dried at 500 °C (run 5) was found to be very active in promoting the reaction, even in low quantities (50 mg).The likely explanation for the high activity of montmorillonite K10 against cholesterol 6a and its tosylate 6b is the lack of additional groups in these substrates capable of binding to the active catalyst sites.Reaction conditions: a DHEA tosylate (88.5 mg; 0.2 mmol), hydroquinone (8.4 mg; 0.076 mmol), CHCl3 (5 mL).b cholesteryl tosylate (100 mg; 0.2 mmol), hydroquinone (8.4 mg; 0.076 mmol), CHCl3 (5 mL).

General Experimental Data
All solvents were freshly distilled prior to use.Anhydrous solvents were prepared by distillation over appropriate drying agents under an argon atmosphere.The stabilizer (ethanol) contained in commercially available chloroform was removed before use.The olecules 2023, 28, x FOR PEER REVIEW 8 of 14 dimer 1.Some experiments were carried out with montmorillonite activated with the ions Ti 4+ or Cu 2+ .However, this modification of the catalyst promoted only the elimination processes (runs 9 and 10).
The optimal reaction conditions (as in run 5) were applied to analogous reactions of other sterols-diosgenin 5a and cholesterol 6a.In the latter case, the yield of desired dimer 3 was slightly better (28%) than that achieved for DHEA (4a).The dimer 3 was accompanied by dicholesteryl ether (22%), hydroquinone mono cholesteryl ether (10%), and the elimination products (35%).The yield of diosgenin-derived dimer 2 was lower (12%) under the same conditions.The corresponding disteroidal ether was isolated in tiny amounts [42].
In the next experiments, androst-5-en-3β-ol-17-one tosylate (4b) and cholesteryl tosylate (6b) served as substrates.The advantage of using tosylates instead of free sterols is that disteroidal ethers cannot be formed under these conditions, which is important from the point of view of reaction product separation.Also, dimers 11a-c (or analogous compounds derived from cholesterol) were formed only in negligible amounts.In addition, much milder reaction conditions were used, resulting in fewer by-products.The results of tosylate reactions are shown in Table 3.It should be noted that all reactions occurred at ambient temperature and required less catalyst.In the case of the androstane series (runs 1-3), the best yield of the desired dimer 1 (31%) was observed for the reaction catalyzed by Ti 4+ activated montmorillonite K10 (run 3).Without Ti 4+ activation, the yield of 1 was 23%, provided that K10 was calcined at 500 °C (run 2).The reactions of cholesteryl tosylate 6b with hydroquinone (runs 4-6) worked much better and provided dimer 3 in excellent yields.Especially the catalyst dried at 500 °C (run 5) was found to be very active in promoting the reaction, even in low quantities (50 mg).The likely explanation for the high activity of montmorillonite K10 against cholesterol 6a and its tosylate 6b is the lack of additional groups in these substrates capable of binding to the active catalyst sites.Reaction conditions: a DHEA tosylate (88.5 mg; 0.2 mmol), hydroquinone (8.4 mg; 0.076 mmol), CHCl3 (5 mL).b cholesteryl tosylate (100 mg; 0.2 mmol), hydroquinone (8.4 mg; 0.076 mmol), CHCl3 (5 mL).

General Experimental Data
All solvents were freshly distilled prior to use.Anhydrous solvents were prepared by distillation over appropriate drying agents under an argon atmosphere.The stabilizer (ethanol) contained in commercially available chloroform was removed before use.The Molecules 2023, 28, x FOR PEER REVIEW 8 of 14 dimer 1.Some experiments were carried out with montmorillonite activated with the ions Ti 4+ or Cu 2+ .However, this modification of the catalyst promoted only the elimination processes (runs 9 and 10).
The optimal reaction conditions (as in run 5) were applied to analogous reactions of other sterols-diosgenin 5a and cholesterol 6a.In the latter case, the yield of desired dimer 3 was slightly better (28%) than that achieved for DHEA (4a).The dimer 3 was accompanied by dicholesteryl ether (22%), hydroquinone mono cholesteryl ether (10%), and the elimination products (35%).The yield of diosgenin-derived dimer 2 was lower (12%) under the same conditions.The corresponding disteroidal ether was isolated in tiny amounts [42].
In the next experiments, androst-5-en-3β-ol-17-one tosylate (4b) and cholesteryl tosylate (6b) served as substrates.The advantage of using tosylates instead of free sterols is that disteroidal ethers cannot be formed under these conditions, which is important from the point of view of reaction product separation.Also, dimers 11a-c (or analogous compounds derived from cholesterol) were formed only in negligible amounts.In addition, much milder reaction conditions were used, resulting in fewer by-products.The results of tosylate reactions are shown in Table 3.It should be noted that all reactions occurred at ambient temperature and required less catalyst.In the case of the androstane series (runs 1-3), the best yield of the desired dimer 1 (31%) was observed for the reaction catalyzed by Ti 4+ activated montmorillonite K10 (run 3).Without Ti 4+ activation, the yield of 1 was 23%, provided that K10 was calcined at 500 °C (run 2).The reactions of cholesteryl tosylate 6b with hydroquinone (runs 4-6) worked much better and provided dimer 3 in excellent yields.Especially the catalyst dried at 500 °C (run 5) was found to be very active in promoting the reaction, even in low quantities (50 mg).The likely explanation for the high activity of montmorillonite K10 against cholesterol 6a and its tosylate 6b is the lack of additional groups in these substrates capable of binding to the active catalyst sites.

General Experimental Data
All solvents were freshly distilled prior to use.Anhydrous solvents were prepared by distillation over appropriate drying agents under an argon atmosphere.The stabilizer (ethanol) contained in commercially available chloroform was removed before use.The Molecules 2023, 28, x FOR PEER REVIEW 8 of 14 dimer 1.Some experiments were carried out with montmorillonite activated with the ions Ti 4+ or Cu 2+ .However, this modification of the catalyst promoted only the elimination processes (runs 9 and 10).
The optimal reaction conditions (as in run 5) were applied to analogous reactions of other sterols-diosgenin 5a and cholesterol 6a.In the latter case, the yield of desired dimer 3 was slightly better (28%) than that achieved for DHEA (4a).The dimer 3 was accompanied by dicholesteryl ether (22%), hydroquinone mono cholesteryl ether (10%), and the elimination products (35%).The yield of diosgenin-derived dimer 2 was lower (12%) under the same conditions.The corresponding disteroidal ether was isolated in tiny amounts [42].
In the next experiments, androst-5-en-3β-ol-17-one tosylate (4b) and cholesteryl tosylate (6b) served as substrates.The advantage of using tosylates instead of free sterols is that disteroidal ethers cannot be formed under these conditions, which is important from the point of view of reaction product separation.Also, dimers 11a-c (or analogous compounds derived from cholesterol) were formed only in negligible amounts.In addition, much milder reaction conditions were used, resulting in fewer by-products.The results of tosylate reactions are shown in Table 3.It should be noted that all reactions occurred at ambient temperature and required less catalyst.In the case of the androstane series (runs 1-3), the best yield of the desired dimer 1 (31%) was observed for the reaction catalyzed by Ti 4+ activated montmorillonite K10 (run 3).Without Ti 4+ activation, the yield of 1 was 23%, provided that K10 was calcined at 500 °C (run 2).The reactions of cholesteryl tosylate 6b with hydroquinone (runs 4-6) worked much better and provided dimer 3 in excellent yields.Especially the catalyst dried at 500 °C (run 5) was found to be very active in promoting the reaction, even in low quantities (50 mg).The likely explanation for the high activity of montmorillonite K10 against cholesterol 6a and its tosylate 6b is the lack of additional groups in these substrates capable of binding to the active catalyst sites.

General Experimental Data
All solvents were freshly distilled prior to use.Anhydrous solvents were prepared by distillation over appropriate drying agents under an argon atmosphere.The stabilizer (ethanol) contained in commercially available chloroform was removed before use.The

General Experimental Data
All solvents were freshly distilled prior to use.Anhydrous solvents were prepared by distillation over appropriate drying agents under an argon atmosphere.The stabilizer (ethanol) contained in commercially available chloroform was removed before use.The reactions were monitored by TLC on silica gel plates 60 F254, and spots were visualized either by a UV hand lamp or by charring with molybdophosphoric acid/cerium(IV) sulfate in H 2 SO 4 .The reaction products were isolated by chromatographic methods using silica gel pore size 40 Å (70-230 mesh). 1 H and 13 C NMR (400 and 100 MHz, respectively) spectra of all compounds were recorded using a Bruker Avance II spectrometer in a CDCl 3 or CDCl 3 /MeOD mixture and referenced to TMS (0.0 ppm) and CDCl 3 (77.0ppm), respectively.Infrared spectra were recorded using Attenuated Total Reflectance (ATR) as solid samples with a Nicolet 6700 FT-IR spectrometer.Mass spectra were obtained with an Accurate-Mass Q-TOFLC/MS 6530 spectrometer with electrospray ionization (ESI).Melting points were determined on a Kofler bench melting point apparatus.

Molecules 2023 ,Figure 3 .Figure 3 .Figure 3 .
Figure 3. Ball and stick presentation of optimized structures of dimers 11a and 11b.Figure 3. Ball and stick presentation of optimized structures of dimers 11a and 11b.

Run No./ Reaction Conditions Structure of Products Conversion
Scheme 2. A presumable mechanism of 11b formation.

Run No./ Reaction Conditions Structure of Products Conversion
Scheme 2. A presumable mechanism of 11b formation.

Run No./ Reaction Conditions Structure of Products Conversion
Scheme 2. A presumable mechanism of 11b formation.

Run No./ Reaction Conditions Structure of Products Conversion
Scheme 2. A presumable mechanism of 11b formation.Scheme 2. A presumable mechanism of 11b formation.

Table 3 .
Reactions of tosylates 4b and 6b with hydroquinone catalyzed with montmorillonite K10 under different conditions.

Table 3 .
Reactions of tosylates 4b and 6b with hydroquinone catalyzed with montmorillonite K10 under different conditions.

Table 3 .
Reactions of tosylates 4b and 6b with hydroquinone catalyzed with montmorillonite K10 under different conditions.

Table 3 .
Reactions of tosylates 4b and 6b with hydroquinone catalyzed with montmorillonite K10 under different conditions.

Table 3 .
Reactions of tosylates 4b and 6b with hydroquinone catalyzed with montmorillonite K10 under different conditions.