Iodine-catalyzed Transformation of Aryl-substituted Alcohols Under Solvent-free and Highly Concentrated Reaction Conditions

Iodine-catalyzed transformations of alcohols under solvent-free reaction conditions (SFRC) and under highly concentrated reaction conditions (HCRC) in the presence of various solvents were studied in order to gain insight into the behavior of the reaction intermediates under these conditions. Dimerization, dehydration and substitution were the three types of transformations observed with benzylic alcohols. Dimerization and substitution reactions were predominant in the case of primaryand secondary alcohols, whereas dehydration prevailed in the case of tertiary alcohols. The relative reactivity of substituted 1-phenylethanols in I2-catalyzed dimerization under SFRC provided a good Hammett plot ρ + = −2.8 (r2 = 0.98), suggesting the presence of electron-deficient intermediates with a certain degree of developed charge in the rate-determining step.


Introduction
Green chemistry is currently a popular topic in chemistry.5][6][7] In the solid/solid system, a remarkable reaction rate enhancement was observed just by introducing small amounts of solvent vapor into the reaction mixture. 8Moreover, the course of the reaction can be dramatically influenced under highly concentrated reaction conditions (HCRC). 94][25] In recent years, iodine 26,27 has emerged as remarkable catalyst exhibiting high water tolerance in diverse types of reactions.One of beneficial properties of iodine is its high affinity towards molecular oxygen as well as functional groups bearing at least one oxygen atom. 28,292][33] This protocol has been already applied under various conditions [34][35][36] all indicating participation of the reaction intermediates having a partial positive charge.Recently, important mechanistic studies on the iodine-catalyzed reactions in solution have been published, 37,38 but the knowledge of the behavior of iodine under SFRC and HCRC remains largely undiscovered. 39ereb and Vražič: Iodine-catalyzed Transformation of Aryl-substituted ... The above reasons prompted us to investigate the reactivity of several model substrates in iodine-catalyzed transformations of alcohols under SFRC and HCRC.The alcohol substrates were selected to study different electronic effects and geometry.The role of the potentially present heteroatom and antiaromaticity of intermediates on transformations will be validated on sterically hindered dibenzo-substituted alcohols.Stereochemistry and regioselectivity of dehydration reactions and the role of the reaction medium polarity (protic vs. aprotic), nucleophilicity and pK a under HCRC will be examined as well.

General Procedure for Iodine-catalyzed Transformation of Alcohols Under SFRC
The procedure is the same for solid and liquid substrates.Alcohol (1 mmol) and iodine (3 mol%) were mixed together in a 5 mL conical reactor and the reaction mixture stirred at 25 °C or 55 °C for various times (5 min to 192 h), progress was monitored by TLC or by 1 H NMR spectroscopy.The crude reaction mixture was diluted with tert-butyl methyl ether, washed with an aqueous solution of Na 2 S 2 O 3 , water, dried over Na 2 SO 4 and the solvent evaporated under reduced pressure.The crude reaction mixture was subjected to column chromatography or preparative TLC using hexane or petroleum ether/tert-butyl methyl ether mixtures and pure product(s) were obtained.Conversions were determined by 1 H NMR spectroscopy.The effects of reaction variables on the type of transformation and conversions are stated in Tables and Figures.In order to obtain the information (role) of the reaction variables and structure of substrate, the data (reaction times with lower conversion) are presented in some Tables.In the experimental section, the best reaction conditions are named; 3 mol% of I 2 were used, giving the highest yield.

3. General Procedure for Iodine-catalyzed Transformation of Alcohols Under HCRC
The procedure is the same for solid and liquid substrates.To the mixture of alcohol (1 mmol) and various amounts of solvent (CH 2 Cl 2 , MeOH, EtOH, i-PrOH, TFE, HFIP, HCOOH, AcOH and H 2 O 3-300 mmol) iodine (3 mol%) was added in 5 mL conical reactor and the reaction mixture stirred at 25 °C from five minutes to 360 hours.Isolation and purification procedure was the same as described above.Conversions were determined by 1

4. Determination of Hammett Reaction
Constant ρ + for the I 2 -catalyzed Dimerization of 1-phenylethanols 1-phenylethanols (0.5 mmol) (1a, 1o, 1p, 1q, 1r, 1s) were separately placed in the conical reactors, transformation was induced by iodine (0.015 mmol, 3.8 mg, 3 mol %) at 55 °C.Alcohols 1o and 1p were stirred for two hours, and alcohols 1q, 1r and 1s were stirred for three hours.The transformation was stopped by cooling, the reaction mixture was analyzed by 1 H NMR spectroscopy and relative rate constants calculated from the equation 59 ), derived from the Ingold-Shaw relation 60 where A and B are the amounts of starting material and X and Y the amounts of products derived from them.The relative rate factors thus obtained, collected in Figure 1, are the averages of at least two measurements, giving a good reproducibility, deviation of k rel ranged (± 3%).The reaction of reference substrate 1-phenylethanol 1a was quenched separately after 2 h and 3 h and relative rate constants were obtained by means of 1 H NMR spectroscopy utilising internal standard 1,1-diphenylethene.

Results and Discussion
Most of the published I 2 -catalyzed transformations of alcohols were conducted in relatively diluted solution, in a concentration range of 23 mol to 157 mol of solvent per mol of alcohol. 61,62In contrast, we examined the behavior of substituted benzylic alcohols in highly-concentrated Jereb and Vražič: Iodine-catalyzed Transformation of Aryl-substituted ... reaction medium, that contained only 3 mol of solvent per mol of the reactant.Variously substituted secondary and tertiary benzylic alcohols 1a-l, possessing different structural features were selected as substrates (Scheme 1).Groups Ar, R 1 , and R 2 having electron-releasing substituents should enhance the stability of electron-deficient intermediates, whereas β-halogen atom R 2 in 1f and 1g should increase the acidity of the methylene protons.The results of the iodine catalyzed transformation under SFRC and HCRC with alcohols 1a-l are summarized in Table 1 indicating that tertiary alcohols underwent dehydration, while secondary alcohols predominantly dimerized into ether derivatives 2. The aggregate state of alcohols played an important role; reaction mixtures in the case of solid alcohols 1 became pasty, which proved to be essential for the reaction progress.On the other hand, liquid alcohols were less challenging in terms of their aggregate state.1-Phenylethanol 1a yielded exclusively ether 2a under both types of the reaction conditions (entries 1 and 2, A=SFRC, B=HCRC-CH 2 Cl 2 ).Introduction of an additional phenyl group at C-2 (1b) increased the reactivity affording dimer 2b as the major product (81%), and trans-stilbene (19%) as the sole dehydration product (entry 3).Enhanced reactivity of 1b could be ascribed to the stabilizing effect of the additional phenyl group.A remarkable decrease in reactivity was observed for fluoro-substituted analogues of 1a: 1-(2,3,4,5,6-pentafluorophenyl)ethanol and 1-phenyl-2,2,2-trifluoroethanol remained intact after three days at 85 °C under SFRC.Tertiary alcohols 1c, 1d and 1e only underwent dehydration into alkene 3 (Table 1, entries 5-10).A mixture of (Z)-and (E)-1,2-diphenylpropene was formed from 1c, with the latter being the major product.The transformation of 1c was accompanied by the formation of 2,3-diphenyl-1-propene (entries 5 and 6).1c remained intact without iodine under conditions A and B, signifying the role of iodine.The role of acidity of the hydroxyl group and the C-2 hydrogen atom of C-2 halogenated tertiary alcohols 1f and 1g in I 2 -catalyzed transformation was examined (Table 1, entries 11-14).
Reactivity was diminished in both cases, but fluoro derivative 1g (entry 13) reacted considerably more sluggishly than the bromo analogue 1f (entry 11), suggesting the ease of the proton removal from C-2 not being the most crucial in the process of dehydration, but the electron-accepting properties of the halomethyl group on the stability of the electron-deficient reaction intermediates.The introduction of methoxy group to the aromatic ring did not alter the reaction pathway in the case of 1-(4-methoxyphenyl)ethanol 1h, but dimerization was remarkably faster than with 1-phenylethanol 1a (entries 15 and 16).A similar enhancement of reactivity, induced by methoxy group, was observed also in the case of 1-(4-methoxyphenyl)-2-phenylethanol 1i; dimerization was the major process, the proportion of the dehydration grew to 27% (Table 1, entry 17) when compared with 1b (entry 3) under SFRC.Interestingly, 1i gave dimeric ether 2i as the sole product under HCRC (entry 18).Tertiary alcohols 1j and 1k underwent dehydration, while position of the methoxy group (p-MeO vs. o-MeO) did not play a substantial role on the type of transformation and reaction rate (entries 19-22).The substantially lower reactivity of triaryl-substituted alcohol 1l could be ascribed to the fact that substrate has the highest melting point and the lowest solubility among alcohols 1, and the reaction mixture required a longer time to become pasty under SFRC (31% conversion, entry 23).In spite of the poor solubility of 1l in CH 2 Cl 2 , enhanced molecular migration was achieved, reflecting in a considerably higher degree of conversion under HCRC (entry 24).In general, the reactivity of the secondary and the tertiary alcohols differs drastically regardless on the conditions SFRC or HCRC.The secondary alcohols have a strong tendency of dimerization into ethers, while the tertiary alcohols underwent dehydration into alkenes.Such a clear-cut might be surprising; however, it could be somehow anticipated. 31One of the reasons for smooth dehydration of the tertiary-, in comparison with the secondary alcohols, might be the formation of the thermodynamically more stable alkenes.In addition, dimerization of the sterically hindered tertiary alcohols is disfavored.It could be concluded that substantially higher reactivity of methoxy-substituted alcohols (Table 1, entries 15-24) is likely a consequence of stabilization of the intermediates involved -the electron deficient species.Furthermore, we examined the role of geometry, ring size and heteroatom on I 2 -catalyzed transformation of the dibenzo-substituted tertiary alcohols 4 under HCRC-CH 2 Cl 2 ; the results are collected in Table 2.
Fluorene derivative 4a yielded 9-ethylidenefluorene 5a (Table 2, entries 1 and 2) but phenyl-substituted derivative 4b was not reactive under these conditions (entries 3 and 4).The low reactivity of 4a and 4b might be associated with the geometry and formation of the potential anti-aromatic fluorenyl carbocation. 31,63,64Dibenzosuberan deriva-tives 4c and 4d are not planar and were considerably more reactive than 4a an additional phenyl group did not enhance the reactivity of 4d.The substitution of a CH 2 CH 2 group in the dibenzosuberan derivative with an O-atom decreased the reactivity of 9-ethyl-xanthen-9-ol 4e, while phenyl derivative 4f was more reactive than 4e.The results showed the importance of the geometry of the structure of the electron-deficient intermediates in dehydration reactions under HCRC.
Further, we examined the role of nucleophilic, protic solvents (possessing different acidity, ionizing power, hydrophobicity, and solubility of 1 and I 2 ) on iodine-catalyzed transformations of secondary benzylic alcohols under HCRC (Table 3).
Three reaction pathways were operative: dimerization, dehydration and substitution.The important role of solvent added on the type of transformation was demonstrated on 1,2-diphenylethanol 1b (entries 1-4).No reaction took place in MeOH, in the presence of HCOOH, only substitution occurred yielding 7ba (entry 3); in contrast, in the presence of H 2 O, dimerization was the dominant process (entry 4).Substrate 1b is considerably hydrophobic and does not possess a strong electron-donating group, which is reflected in its relatively low reactivity.Introduction of methoxy group to the para position of the phenyl ring remarkably enhanced the reactivity and selectivity of reaction of 1-(4-methoxyphenyl)-2-phenylethanol 1i under HCRC (entries 5-8); contrary to 1b, in the case of MeOH, the methyl ether 6ia was obtained.Another surprising difference was established in the presence of Jereb and Vražič: Iodine-catalyzed Transformation of Aryl-substituted ... HCOOH, where dimerization was the main process (entry 7), while transformation without I 2 furnished a mixture of 2i and 7ia in reversed ratio (23/77).The contrasting result suggests that iodine activated 1i.Results of reactivity of 1i (entries 5-8) suggest that iodine activated 1i which dimerized predominantly in the absence of good nucleophiles (entries 5, 7 and 8).In the presence of MeOH, a methoxy ether 6ia was the major product (entry 6), while a small extent of dehydration was observed in the cases of 1,2-diaryl-substituted alcohols only.1-(4-methoxyphenyl) ethanol 1h, the least hydrophobic and sterically-hindered in this series, was the most reactive (entries 9-12), but with altered selectivity.In the presence of CH 2 Cl 2 and H 2 O, dimerization took place (entries 9 and 12), while substitution was the main process in the presence of MeOH and HCOOH, giving 6ha and 7ha, respectively (entries 10 and 11).1h was esterified with HCOOH under SFRC without iodine, 32 thus signifying the role of pK a , and iodine has little influence on reaction of 1h with HCOOH (entry 11).The reactivity pattern of 1h is similar to 1i, where substitution predominantly took place in the presence of relatively good nucleophiles, whereas dimerization is prevalent in their absence.
The alcohols and alkenes substituted with electron rich-aromatic groups might be sensitive to polymerization and are known to undergo different types of transformation.Indeed, 4-methoxybenzyl alcohol 1m proved to be the right target in this regard (Table 4); under SFRC, dimerization giving 2m was the main process (entry 1), ipso-substitution also took place, however polymerization completely prevailed after 200 minutes producing tar material only.Similar product distribution was obtained under HCRC-CH 2 Cl 2 (entry 2).No other alkylation of the aromatic ring was noted.
The third reaction channel was substitution; it occurred in the presence of MeOH giving 6ma, and a small proportion of dimer 2m was also formed, but no polymerization was noted, even after 190 hours (entry 3).Dimerization was the main process in the absence of a nucleophile, and ipso-substitution appeared as minor, but additional reaction channel.Considering that ipso-substitution is often related with cationic intermediates, 65 it could be assumed that formation of 8 is another suggestion of involvement of electron-deficient intermediates.
Next, we studied the transformation of sterically hindered and hydrophobic tertiary alcohol with the electron-rich aromatic ring, 1-phenyl-2-(4-methoxyphenyl)-2-propanol 1n in the presence of a catalytic amount of iodine (Table 5).
1n is a substrate of choice because it possesses an activated aromatic ring for good reactivity and it could form a well stable potential intermediate to study its fate under SFRC and HCRC.Reaction mixture after 30 minutes at room temperature under SFRC contained at least three products.The major product was easily identified as the Zaitsev-type product, (E)-2-(4-methoxyphenyl)-1-phenyl-1-propene 3na (entry 1).However, the two other products had very similar physicochemical properties, reflecting in almost identical retention factors; the molecular mass of 448 indicated that dimerization occurred.The structures of these two alkenes were elucidated on the basis of 1D and 2D NMR spectra and identified as (E)-1,5diphenyl-4-methyl-2,4-bis(4-methoxyphenyl)pent-1-ene 9a and its (Z)-isomer 9b.The explanation of the formation of these two alkenes is presented in Table 5.The results suggest that iodine likely induced the formation of tertiary electron-deficient intermediate or related species, probably similar to the intermediate A; its subsequent dehydra-  tion predominantly led to the mixture of (Z)-and (E)-2-(4-methoxyphenyl)-1-phenyl-1-propene 3na and 3na' , the Hofmann type dehydration furnished 2-(4-methoxyphenyl)-3-phenyl-1-propene 3nb.However, the latter 3nb was not stable under the studied conditions and further attacked primarily formed species A, resulting in a cationic-like intermediate B or a related species, and removal of the benzylic proton furnished the isomeric alkenes 9a and 9b.Continuing, we examined the effect of 3 mmol of CH 2 Cl 2 on the transformation of 1 mmol of 1n.The added solvent had no significant impact on the type of transformation (entry 2).Alkene 3nb was isolated and treated in an independent experiment with 3 mol% of I 2 in dichloromethane until the full consumption of 3nb.Alkenes 3na, 3na', 9a and 9b were formed in this process potentially via A'.A could furnish 3na and 3na' or it could add to the rest of 3nb producing 9a and 9b.In contrast, an independent transformation of a mixture of the isolated alkenes 3na and 3na' with 3 mol% of I 2 failed, since 3na and 3na' remained intact.Alkenes 3na and 3na' are thermodynamically more stable than 3nb and were not be activated by iodine.In contrast, a larger amount (30 mmol) of CH 2 Cl 2 suppressed addition of the species A to alkene 3nb and favored the formation of the Zaitsev type product 3na (entry 3).Interestingly, 1n remained unreacted in a highly diluted solution of 300 mmol of dichloromethane (entry 4).It is obvious that the vicinity of the reacting species is of the prime importance, demonstrating a crucial role of the concentration.In the presence of 3 mmol of MeOH, dehydration and substitution processes were observed, giving alkenes 3na, 3na' and 3nb and methoxy ether 6na (entry 5).Methanol blocked the addition of A to alkene 3nb, the Jereb and Vražič: Iodine-catalyzed Transformation of Aryl-substituted ... selectivity Zaitsev vs. Hofmann decreased (entry 5) in comparison with the entries 1-3.Turnover in transformation occurred in the presence of a 10-fold higher amount of MeOH, and only ether 6na was obtained (entry 6); no reaction took place in the presence of 300 mmol of methanol (entry 7).In the presence of 3 mmol of ethanol (entry 8), the same reaction pathways were observed as in the presence of methanol (entry 5).In the presence of i-PrOH and (CF 3 ) 2 CHOH (HFIP), no substitution occurred (entries 9 and 10); the Zaitsev alkene was more favored than in EtOH (entry 8), and finally reached 72% in the presence of HFIP, where alkene 3nb was further transformed to 9a and 9b (entry 10).It could be concluded that dehydration and further reaction of the formed intermediates took place under SFRC and HCRC in the presence of a non-nucleophilic solvent (CH 2 Cl 2 ) and HFIP.The latter solvent is known to stabilize the carbocationic intermediates, 66,67 and this could be an indication that our intermediates may be similar.The competition between dehydration and substitution took place under HCRC (3 mmol of alcohol, entries 5 and 8) in a nucleophilic solvent (MeOH and EtOH), while in the presence of 30 mmol of methanol, substitution took place exclusively.It is noteworthy to say that certain processes take place under SFRC and HCRC, but not under classical diluted conditions in a solution -the formation of 9a and 9b is such an example.4-methoxybenzyl alcohol 1m proved to be very reactive substrate under the studied conditions, and it tended to yield insoluble, probably polymerized products after prolonged reaction time.Consequently, we decided to explore the reactivity of exceedingly acid sensitive 9H-xanthene-9-ol 10 in the presence of catalytic amount of I 2 (Table 6).
Alcohol 10 was found to be very reactive; the reaction under SFRC was accomplished in 15 minutes at room temperature in spite of a solid reactant and catalyst.To our surprise, disproportionation took place giving the product 11a and 11b as the only products (entry 1).Similar observation could be made in detritylation of ethers using I 2 in methanol. 68We published a detailed iodine-catalyzed disproportionation of ethers under SFRC. 39Disproportionation took place also in the presence of dichloromethane under HCRC, and it was even faster probably due to the higher migration of the reactants (entry 2).Transformation of 10 under HCRC in the presence of MeOH yielded the related methoxy ether 11c, a very acid sensitive compound, too (entry 3).
In order to obtain information about the role of geometry (cyclic 9-xanthhydrol vs. acyclic diphenyl methanol) and substituents, the transformation of diphenyl methanol and bis(4-methoxyphenyl)methanol was studied under HCRC-CH 2 Cl 2 .Only dimerization took place, and no disproportionation was noted.Dimerization of bis(4-methoxyphenyl)methanol to bis[bis(4-methoxyphenyl)methyl] ether occured in five minutes, while bis(diphenylmethyl) ether was obtained in 71% yield after two days at room temperature.In MeOH, substitution took place, and bis(4-methoxyphenyl)methyl methyl ether was formed in 77% yield.Diphenyl methanol yielded the corresponding methyl ether as the main product, and a small amount of bis(diphenylmethyl)ether.Bis(pentafluorophenyl)methanol was found inert in the I 2 -catalyzed reaction; no conversion was noted after two days at 85 °C under SFRC.It can be concluded that reactivity is essentially dependent on the structure and geometry of the alcohol; the electron-accepting groups tend to disfavor the transformation.
4-Methoxyphenyl-substituted alcohols 1m and 1h were proved very sensitive to the reaction conditions; for that reason, we investigated the role of pK a of alcohols added under HCRC, Table 7.
Dimerization of 4-methoxybenzyl alcohol 1m was the main process in the absence of a good nucleophile (HCRC-CH 2 Cl 2 ), while ipso-substitution took place as well (Table 4, entry 2).The addition of alcohols extensively retarded transformation of 1m (Table 7, entries 1-3); the proportion of substitution is decreasing with the growing sterical hindrance and the reducing nucleophilicity of the solvent.A noteworthy modulation of the reactivity was noted in the case of more acidic and low nucleophilic 2,2,2-trifluoroethanol (TFE) and HFIP.Starting 1m displayed a strong tendency of polymerization in the latter two alcohols, and after too long reaction time, the tar material was only isolated.The reaction time was consequently limited to one hour and dimerization and ipso-substitu-tion were the only processes (entries 4 and 5).Both alcohols are poor nucleophiles, and no substitution took place.
An additional methyl group contributed to the substantially higher reactivity of 1-(4-methoxyphenyl)ethanol 1h in comparison with 1m, dimerization and substitution became the only reaction channels.Dimerization was the exclusive transformation in the absence of a good nucleophile (HCRC-CH 2 Cl 2 ) (Table 3, entry 9).In the presence of MeOH, EtOH and i-PrOH substitution and dimerization took place (Table 7, entries 7, 9 and 11), exhibiting a similar reactivity pattern as in the case of 1m.It is evident that Jereb and Vražič: Iodine-catalyzed Transformation of Aryl-substituted ... the dimeric ether 2 is a kinetically controlled product (entries 6-11), and iodine could catalyze its transetherification. 69Transformations of 1h were faster in presence of the fluorinated solvents; in the case of a better nucleophile TFE, substitution almost completely prevailed (entries 12 and 13), while in the presence of HFIP dimerization was the only process (entry 14).It could be concluded that reactivity patterns of 1m and 1h in the presence of iodine under SFRC and HCRC are similar.Dimerization of both alcohols is the key process in the absence of a good nucleophile, while substitution took place predominantly in the presence of a good nucleophile.It is evident in the Table 7 that dimerization is followed by transetherification, and we decided to further investigate this rather unexplored process, Table 8.
Functionalization of 2h in the presence of methanol under HCRC yielded the corresponding methyl ether 6ha (97%) and 3% of the alcohol 1h (entry 1).This is an indication that relation between 1h and 2h is reversible.The conversion roughly corresponds with the nucleophilicity of the alcohols (entries 1-3); in the case of the most sterically hindered and least nucleophilic i-PrOH the lowest conversion was achieved.A surprising turning point was observed in CF 3 CH 2 OH (entry 4).Although considerably more acidic and worse nucleophile than ethanol, the highest conversion was achieved in CF 3 CH 2 OH.The result reflects the much stronger stabilization of the reaction intermediates in comparison with the simple alkyl alcohols.Transformation of 2h in the presence of acetic acid yielded the corresponding acetate ester 6he (entry 5), demonstrating the carboxylic acids are suitable nucleophiles in this reaction.Products 6 were considerably more stable than 2h, and remained intact in the presence of iodine.
The Hammett correlation 70,71 is a convenient tool for the estimation of the nature of the reaction intermediates and the type of bond cleavage, and in the case of ionic in-termediates, the degree of the charge developed.It is determined under homogenous conditions in diluted solution; however, we decided to examine the relative reactivity of the substituted 1-phenylethanols in I 2 -catalyzed dimerization under SFRC (Figure 1).The SFRC conditions are challenging, and therefore the Hammett correlation has been rarely studied. 72he relative reactivity of 1-phenylethanol 1a toward its substituted 4-F 1o, 3-Me 1p, 3-MeO 1q, 4-Cl 1r and 4-Br 1s derivatives was studied at 55 °C, all the alcohols are liquid at given temperature.In all cases, dimeric ethers 2a and 2o-s were formed and good Hammett correlation (r 2 = 0.98) was obtained utilizing σ + substituent constants.The slope ρ + = −2.8suggests the transition state involving electron-deficient intermediates with a partial developed charge in a rate-determining step.A similar value of ρ = −2.76 was obtained in I 2 -catalyzed dihydroperoxidation of benzaldehydes in acetonitrile at 22 °C. 73It can be summarized that iodine has a remarkable feature of generation of species that would normally require the use of a strong acid.
In order to demonstrate the role of iodine, reactivity of different catalytic systems were examined on an exceedingly acid-sensitive substrate 9H-xanthene-9-ol 10, giving 11a and 11b smoothly, 74 Table 9.
Entries 1 and 2 were added from Table 6 for easier comparison.Transformation of 10 in the presence of phosphomolybdic acid hydrate under SFRC was much less effective in comparison with the I 2 -catalyzed reaction (entry 3), while reaction in the presence of methanol yielded the methoxy ether 11c with 84% selectivity (entry 4).Expectedly, disproportionation of 10 in the presence of 57 % aqueous solution of HI was the only process 75 (entry 5), whereas in the presence of methanol 80% of 11c was formed (entry 6); displaying similar reactivity in the presence of heteropoly acid and HI (entries 3-6).Reaction of   ).In reactions in entries 3 and 10 an unidentified product appeared, seemingly a dimeric ether of 10.There is often speculated, though not experimentally proven, that the in-situ formed HI is the actual catalyst in the iodine-catalyzed transformations. 77A potential formation of HI would probably result in a loss of the reaction selectivity (comparison of entries 2 and 6).
The results indicate that iodine was the active catalyst, where complexation changed the reaction pathway considerably.Additionally, iodine was titrated with a standard solution of Na 2 S 2 O 3 after the end of the disproportionation of 10.The entire amount of iodine was present at the end of the reaction.Similar observation was made in the case of dimerization of a secondary alcohol and substitution reaction with methanol, strongly indicating iodine as the active catalyst in these reactions.A tentative explanation of the reaction pathways is presented on Scheme 2. The driving force in all cases is presumably polarization of the reactants by iodine.We proposed such halogen bond 78 activation in disproportionation of ethers under SFRC 39 , which is in agreement with recent computational 37 and experimental studies. 38A simultaneous TS-1 or two separated activation processes TS-2, including carbenium ion TS-3 could be proposed as the key steps in the dimerization process.In the absence of a better nucleophile, the starting alcohol took over a role of an attacking nucleophile, affording the dimer 2. The dehydration process of the tertiary alcohols might be initiated by polarization of the starting alcohol as shown in TS-4.The substitution step is suggested as a concomitant activation TS-5 or a divided activation TS-6 or by carbenium ion TS-7.
In the presence of added stronger nucleophile, substitution products 6 and 7 substantially prevailed over the dimerization products 2.

Conclusions
To summarize, we have studied iodine-catalyzed transformations of aryl-substituted alcohols under SFRC and under HCRC, the concentration was proved to have an exceptional impact on the transformation.Achieving a pasty aggregate state of solid substrates in the presence of I 2 was of vital importance for the reaction progress.Primary and secondary alcohols underwent two main transformations, depending on the reaction conditions.Dimerization took place in absence of the good nucleophiles under SFRC and HCRC, while substitution prevailed in presence of the good nucleophiles.The tertiary alcohols exhibited a strong tendency of dehydration into alkenes, which is in sharp contrast with the reactivity of primary and second-ary alcohols.The difference in thermodynamic stability of the alkenes, derived from the tertiary and the secondary alcohols, is supposedly a driving force for the observed selectivity.Substitution was another process observed in the presence of the hydroxylic solvents; their acidity, nucleophilicity and hydrophobicity were important parameters for studying the reactivity of those alcohols.4-Methoxyphenyl-substituted alcohols possessed higher reactivity than phenyl analogues; their pentafluorophenyl counterparts were unreactive under the studied conditions.The results indicated the electron-deficient intermediates to be likely involved in these processes, the geometries of the molecule and heteroatom share an important part in reactivity.4-Methoxybenzyl alcohol yielded its dimeric ether and bis(4-methoxyphenyl)methane, a product derived via the I 2 -catalyzed ipso-substitution.4-Methoxybenzyl alcohol exhibited higher reactivity in TFE and HFIP than in EtOH and in i-PrOH under HCRC, thus indicating stronger stabilization of the reaction intermediates in the fluorinated alcohols.A tertiary benzylic alcohol 1n was demonstrated to possess a special reactivity.It appears that upon its dehydration all three possible alkenes were obtained.The thermodynamically less stable alkene unexpectedly reacted with the initially formed intermediate, furnishing two dimeric alkenes.It is worth mentioning that certain processes take place under SFRC and HCRC, but not under the classical diluted conditions.This is an indication that reacting species have to be in close vicinity.Iodine catalyzed the disproportionation of 9H-xanthene-9-ol 10 under SFRC and HCRC, and in contrast, the substitution took place in the presence of MeOH.Iodine is a convenient catalyst for transetherification under mild conditions, it has a potential for interconversion of ether to ester.The Hammett correlation analysis of the I 2 -catalyzed dimerization of substituted 1-phenylethanols under SFRC (T = 55 °C) furnished straight-line ρ + = −2.8(r 2 = 0.98).This fact strongly suggests the involvement of the electron-deficient intermediates with a certain degree of the developed charge in the transition state.
a SFRC: 1 mmol of 1m and 0.03 mmol of I 2 , HCRC: 1 mmol of 1m, 3 mmol of solvent and 0.03 mmol of I 2 stirred at 25 °C.b Conversion and product distribution determined by 1 H NMR spectroscopy.c Dimerization vs. Ipso substitution vs. Substitution.

Table 6 .
The effect of the reaction conditions on iodine-catalyzed transformation of 10 of 10, 0.03 mmol of I 2 , T = 25 °C.b 1 mmol of 10, 3 mmol of solvent, 0.03 mmol I 2 , T = 25 °C.c Conversion and product distribution determined by 1 H NMR spectroscopy.
H NMR spectroscopy.Results are presented in Tables, Figures and Schemes.Isolation procedure is given for the best yield.

Table 1 .
The effect of the alcohol structure 1 and reaction conditions (SFRC vs. HCRC) on the type of iodine-induced transformation a A: SFRC; 1 mmol of 1 and 0.03 mmol of I 2 ; B: HCRC; 1 mmol of 1, 3 mmol of CH 2 Cl 2 and 0.03 mmol of I 2 .b Conversion and product distribution determined by 1 H NMR spectroscopy.c 4% of (Z)-isomer relatively to (E)-alkene, traces of the Hofmann alkene.d 5% of (Z)-isomer relatively to (E)-alkene, Zaitsev vs. Hofmann = 85/15.1c remained intact without iodine under conditions A and B. e Reaction temperature was 55 °C, in all other cases was 25 °C.

Table 2 .
The effects of geometry, ring size and substituents on the iodine-catalyzed dehydration of tertiary alcohols 4 a Reaction conditions: 1 mmol of 4, 3 mmol of CH 2 Cl 2 and 0.03 mmol of I 2 stirred at 25 °C.b Determined by 1 H NMR spectroscopy.

Table 3 .
The effect of hydroxy-substituted solvent on the iodine-catalyzed transformations of alcohols 1 under HCRC a 1 mmol of 1, 3 mmol of solvent and 0.03 mmol of I 2 stirred at 25 °C.b Conversion and product distribution determined by 1 H NMR spectroscopy.c Dimerization vs. Dehydration vs. Substitution.d A ratio 2/7 without I 2 was 23/77.

Table 4 .
The effect of the reaction conditions on the iodine-catalyzed transformation of 4-methoxybenzyl alcohol

Table 5 .
The effect of the reaction conditions on the iodine-catalyzed transformations of 1n a SFRC; 1 mmol of 1n and 0.03 mmol of I 2 , HCRC; 1 mmol of 1n, 3, 30 or 300 mmol of solvent and 0.03 mmol of I 2 stirred at 25 °C for 30 min.b Conversion determined by 1 H NMR spectroscopy.c Data refer to the sum of 3na and 3na', with (E)/(Z) = 95/5 (entries 1, 5, 8-10) and (E)/(Z) = 90/10 in entries 2 and 3. d Methoxy ether 6na in the case of MeOH and ethoxy ether 6nb in the case of EtOH were formed.

Table 7 .
The effect of the HCRC on the transformation of 1m and 1h 3 mmol of R 2 OH, 0.03 mmol of I 2 , T = 25 °C.b Conversion and product distribution determined by 1 H NMR spectroscopy.

Table 8 .
The effect of the hydroxy-substituted solvent on the conversion of 2h under HCRC a Reaction conditions: 1 mmol of 2h, 3 mmol ROH, 0.03 mmol of I 2 , T = 25 °C, R. t. (reaction time).b Conversion and product distribution determined by 1 H NMR spectroscopy.c The product is 1-(4-methoxyphenyl)ethyl acetate 6he.
product (entry 9).Additional complexation of I 2 with Bu 4 NI almost completely suppressed disproportionation, suggesting that formation of triiodide was a key (entry 10).Reaction of 10 with I 2 /Bu 4 NI in the presence of methanol yielded the methoxy ether 11c only, while no disproportionation took place (entry 11 Jereb and Vražič: Iodine-catalyzed Transformation of Aryl-substituted ... sole