Highly Selective Vapor and Liquid Phase Transfer Hydrogenation of Diaryl and Polycyclic Ketones with Secondary Alcohols in the Presence of Magnesium Oxide As Catalyst

catalysts

Article Highly Selective Vapor and Liquid Phase Transfer Hydrogenation of Diaryl and Polycyclic Ketones with Secondary Alcohols in the Presence of Magnesium Oxide as Catalyst

Marek Gli ´nski*, Anna Markowska, Laura Wro ´nska , Anna Jerzak and Magdalena Tarkowska

Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw, Poland; [email protected] (A.M.); [email protected] (L.W.); [email protected] (A.J.); [email protected] (M.T.) * Correspondence: [email protected]

Abstract: MgO has been shown to catalyze an almost quantitative hydrogen transfer from 2-octanol as the hydrogen donor to benzophenone to form benzhydrol, a useful intermediate product in the pharmaceutical industry. The hydrogen transfer from a series of alcohols to the carbonyl group of benzophenone, its ten derivatives, four polycyclic ketones, and 2-naphthyl phenyl ketone was carried out in liquid (LP) or vapor phase (VP). The dependence of reactivity on the structure of the hydrogen donor, reaction temperature, donor-acceptor ratio, amount of catalyst, and the type and position of substituents has been established. For both reaction modes, optimal conditions for selective synthesis Citation: Gli´nski,M.; Markowska, of the alcohols were determined and side reactions were investigated. The results indicate that the A.; Wro´nska,L.; Jerzak, A.; Tarkowska, M. Highly Selective reactivity of the ketone is suppressed by the presence of a methyl substituent in the ortho position to Vapor and Liquid Phase Transfer a much greater extent in LP mode. A scale-up was demonstrated in the liquid phase mode. Hydrogenation of Diaryl and Polycyclic Ketones with Secondary Keywords: magnesium oxide; transfer hydrogenation; benzophenones; 2-octanol; selective reduction Alcohols in the Presence of Magnesium Oxide as Catalyst. Catalysts 2021, 11, 574. https://doi.org/10.3390/ 1. Introduction catal11050574 Much attention in research is focused on transfer hydrogenation reactions on different catalysts [1–4]. Although multiple studies using complex catalytic systems which Academic Editor: Valeria La Parola include magnesium compounds have been recently reported [5,6] pure MgO is known for its basicity and is therefore able to serve as a catalyst for multiple reactions without any Received: 15 April 2021 additives [7]. It is a cheap, nontoxic solid, which is easily separated from the post reaction Accepted: 27 April 2021 Published: 29 April 2021 mixture and can be reused. MgO has also been shown to catalyze transfer hydrogenation reactions of various carbonyl compounds into alcohols [8–13]. Similarly, other oxides, such

Publisher’s Note: MDPI stays neutral as ZrO2 [14–16] and Al2O3 [17], zeolites [18,19], as well as other systems [20–26] have been with regard to jurisdictional claims in found to be active catalysts in hydrogen transfer. Reviews of the catalysts studied in such published maps and institutional affil- reactions are available in the literature [27,28]. Ethanol is often used as the hydrogen donor iations. because it is cheap and easily available, although other alcohols are good alternatives. In the current paper, only secondary alcohols were studied and the scale-up is performed with 2-octanol, whose industrial synthesis requires the use of a sole raw material; namely, Castor Oil, a product of plant origin. These heterogeneous catalysts are environmentally friendly and can be applied in one-pot organic synthesis reactions which do not require Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. the use of toxic and corrosive solvents, gaseous hydrogen under pressure, or expensive, This article is an open access article moisture-sensitive and often hazardous hydride reagents. Moreover, they do not pro- distributed under the terms and duce inorganic salts as waste and reactions can be carried out in the vapor phase mode conditions of the Creative Commons under flowing conditions which is recommended by the rules of Green Chemistry [29]. Attribution (CC BY) license (https:// An additional benefit of implementing this method, is that the obtained product is pure creativecommons.org/licenses/by/ and the solid catalyst is easily separated from the post-reaction mixture. High selectiv- 4.0/). ity of the reaction and ease of purification of a compound is especially important in the

Catalysts 2021, 11, 574. https://doi.org/10.3390/catal11050574 https://www.mdpi.com/journal/catalysts Catalysts 2021, 11, 574 2 of 16

pharmaceutical industry, in which benzhydrol is commonly used in the production of, e.g., antihistamines. Reduction of carbonyl compounds has been one of the most fundamental processes in organic chemistry [30,31]. It is usually carried out in the presence of catalysts containing transition metals deposited onto a support, and pressurized gaseous dihydrogen is used as a reducing agent. A second common method of reducing a carbonyl group is the use of metal hydrides; mainly sodium borohydride. This compound, due to its mild reactivity, reduces carbonyl compounds in a water-alcohol solution instead of anhydrous ether solutions, which is a very convenient and an important simpliﬁcation of the method of reduction. However, both these methods have disadvantages such as the risks associated with the use of gaseous hydrogen under pressure, expensive, moisture-sensitive and hazardous hydride reagents, inorganic salts as waste, and often the need for toxic and corrosive solvents. The Meerwein–Ponndorf–Verley (MPV) reduction of aldehydes and ketones, a third method, is a classic example of a homogeneous route of hydrogen transfer reaction, which has been implemented to obtain various alcohols synthesized under mild conditions. A big advantage of the method is its selectivity, which enables a chemoselective reduction of α,β-unsaturated carbonyl compounds into unsaturated alcohols [32]. However, a major drawback of the method is the requirement to work in an anhydrous environment and the necessity to use a stoichiometric amount of aluminium alkoxides. In contrast to the previously described methods a heterogeneous route of MPV reduction is freed from the abovementioned disadvantages and truly offers a green procedure for the synthesis of various alcohols. Catalytic transfer hydrogenation has been used in the reduction of many types of aldehydes and ketones: saturated [20,33,34], cyclic [21,35,36] and aralkyl [18,37,38], as well as α,β-unsaturated [8–10,39–42]. Although various carbonyl compounds have been reduced by this method, no systematic study of the reduction of diaryl ketones has been performed. Only benzophenone has been described in literature as the hydrogen acceptor. Ramana and Pillai have studied the reduction of the ketone in gas phase over alumina doped with Na+ cations [43]. At 573 K and with the 2-propanol to benzophenone molar ratio (D/A) of 10, a 70% yield of benzhydrol has been observed. Vapour-phase transfer hydrogenation (TH) of benzophenone with 2-propanol (D/A = 3) has also been studied by Jyothi et al. [44]. At 473 K, in the presence of 6MgO·Al2O3 catalyst, 31% yield of benzhydrol has been noted. Hydrous zirconia, ZrO2·nH2O has shown a very high activity in TH of benzophenone with 2-propanol [45]. In its presence a quantitative yield of benzhydrol has been attained after 10 h of reﬂuxing. On the other hand, very low activity of 2MgO·Al2O3 catalyst in the mentioned reaction with 2-propanol has been observed by Ruiz et al. After 24 h and at D/A = 30, a 4% yield of product has been found [20]. In the present work a thorough investigation of the reactivity of sixteen aromatic carbonyl compounds in the hydrogen transfer reduction by alcohols over magnesium oxide as the catalyst either in liquid or in vapor phase has been performed. The studied compounds were benzophenone and its ten derivatives, as well as four polycyclic ketones containing a benzene moiety, and 2-naphthyl phenyl methanone. The reduction of halogen containing derivatives of benzophenone and also 4-nitrobenzophenone was tested in order to determine if dehalogenation/denitrogenation reaction, which, very often accompanying the reduction of these compounds with a gaseous hydrogen in the presence of metallic catalysts, takes place under these reaction conditions. A broad spectrum of secondary alcohols as hydrogen donors from 2-propanol to 2-octanol was used due to the expected moderate reactivity of diaryl ketones in the liquid phase mode of TH reaction.

2. Results and Discussion 2.1. The Catalyst 2 −1 The speciﬁc surface area of the catalyst precursor, i.e., Mg(OH)2, is 30.4 m ·g and the pore volume is 0.17 cm3·g−1. Structural examination by powder X-ray diffraction has shown that the precursor comprises a single phase: as synthesized, the magnesium Catalysts 2021, 11, 574 3 of 17

2.1. The Catalyst Catalysts 2021, 11, 574 3 of 16 The specific surface area of the catalyst precursor, i.e., Mg(OH)2, is 30.4 m2·g−1 and the pore volume is 0.17 cm3·g−1. Structural examination by powder X-ray diffraction has shown that the precursor comprises a single phase: as synthesized, the magnesium hy- hydroxidedroxide crystalizes crystalizes in thein the trigonal trigonal system, system, in in the the P3m1P3m1 space group group as as exhibited exhibited by by brucite. brucite.The The TG-DTA TG-DTA analysis analysis revealed revealed that that Tmax T formax thefor decomposition the decomposition of Mg(OH) of Mg(OH)2 is 692.22 is K and 692.2 Kthe and weight the weight loss (320–873 loss (320–873 K) 30.61% K) 30.61% (exp), (exp),30.89% 30.89% (calc).(calc). The speciﬁcThe specific surface surface area area and and pore pore volume volume determined determined for for the the calcined calcined catalyst, MgO, MgO,were 129.2 129.2 m m22·g·g−1− and1 and 0.40 0.40 cm cm3·g−31·,g respectively.−1, respectively. The XRD The XRDresults results indicate indicate the presence the of presencea single of a singlephase phasein the incatalyst the catalyst sample. sample. The ob Thetained obtained MgO crystallized MgO crystallized in the cubic in the system cubic systemin the Fm3m in the space Fm3m group space (periclase). group (periclase). The stre Thength strength of the surface of the surface acid-base acid-base sites of MgO sites ofas MgO determined as determined by the indicator by the indicator studies are: studies (H0) are:> + 4.8; (H 07.2) > ≤ + (H 4.8;−) < 7.2 33.0.≤ (HThe− )concentration < 33.0. −1 The concentrationof acidic sites of equals acidic 8 sites μmol·g equals−1 (titrant: 8 µmol Et·g3N), (titrant:whereas Et that3N), of whereas basic sites that is 1360 of basic μmoL·g−1 − sites is(titrant: 1360 µmoL PhCOOH).·g 1 (titrant: PhCOOH).

2.2. Liquid-Phase2.2. Liquid-Phase Transfer Transfer Tydrogenation Tydrogenation of Diaryl of KetonesDiaryl Ketones For ourFor studies our studies on hydrogen on hydrogen transfer transfer in the liquid in the phase liquid conducted phase conducted in the presence in the presence of magnesiumof magnesium oxide as oxide a catalyst as a catalyst from secondary from secondary alcohols alcohols to diaryl to ketones,diaryl ketones, unsubstituted unsubstituted diphenyldiphenyl methanone methanone (benzophenone) (benzophenone) was selected was select alonged along with ten with of ten its derivativesof its derivatives con- con- tainingtaining the following: the following: alkyl-, alkyl-, halo-, hydroxy-,halo-, hydroxy-, methoxy- methoxy- and nitro- and groups.nitro- groups. The course The course of of the reaction is exempliﬁed by the following equation: the reaction is exemplified by the following equation: O OH OH O (1) + + (1)

The dependenceThe dependence of the structure of the structure of the hydrogen of the hydr donor,ogen the donor, reactant the molar reactant ratio molar and theratio and catalystthe weight catalyst on weight the conversion on the conversion of benzophenone, of benzophenone, and the and yield the of yield the productof the product have have been determined.been determined. The resultsThe results of the of the activity activity measurements measurements when when different different isomers isomers of of hep- heptan-x-olstan-x-ols (x (x = 2,= 2, 3 3 or or 4) 4) were were used used asas thethe hydrogenhydrogen donordonor are collected in Figure Figure 11.. In the In the casecase ofof heptan-2-ol, heptan-2-ol, the the yield yield of benzhydrolof benzhydrol after after 1 h of1 h reaction of reaction was 45%,was whereas45%, whereas when when heptan-3-olheptan-3-ol and heptan-4-ol and heptan-4-ol were used, were the used, yield the of theyield product of the was product 14 and was 2%, 14 respectively. and 2%, respec- Therefore,tively. it can Therefore, be concluded it can that be theconcluded shift of the that hydroxy the shift group of the to hydroxy the middle group of the to molecule the middle of Catalysts 2021, 11, 574 the molecule causes a decrease in its reactivity. This trend is maintained4 of 17 for all three stud- causes a decrease in its reactivity. This trend is maintained for all three studied times of the reaction.ied After times 6 hof of the reaction, reaction. the After differences 6 h of in reaction the reactivity, the differences were less pronounced, in the reactivity with thewere less yield ofpronounced, benzhydrol equalwith the to 73, yield 69 and of benzhydrol 39% for x = 2,equa 3, andl to 473, in 69 heptan-x-ol and 39% (Figurefor x =1 2,). 3, and 4 in heptan-x-ol (Figure 1).

Figure 1. Liquid phase transfer hydrogenation of benzophenone with heptan-x-ols (x = 2, 3 or 4) in Figure 1. Liquid phase transfer hydrogenation of benzophenone with heptan-x-ols (x = 2, 3 or 4) in the presence of MgO. Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8, the presence of MgO. Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8, se- selectivity >98%. lectivity >98%. The results obtained with heptan-x-ols show that the most meaningful comparison The results obtained with heptan-x-ols show that the most meaningful comparison betweenbetween donors donors which which differ differ in the in length the length of the ofaliphatic the aliphatic chain wo chainuld be would between be between alco- alcohols hols with the OH group in the same position. Therefore, seven straight chain secondary aliphatic alcohols with the OH group attached to the second carbon atom were used as hydrogen donors in the reaction with benzophenone. Since they all have much lower boiling points than benzophenone itself (b.p. 579 K) and they were added in substantial excess, their boiling points determined the reaction temperature. The results reveal that there is a strong dependence of the product yield on the boiling point of the donor. Previ- ous studies in which the activity of some donors was tested at the same temperature, i.e., for two of them the temperature was lower than their boiling points, in order to ensure separation of the effect of donor from the reaction temperature have shown that the yield is the highest at the boiling point temperature of the donor and negligible at lower temperatures [38]. Therefore, in the present work, as well as in most of the literature on LP transfer hydrogenation, all liquid phase activity tests were carried out at the boiling point of each donor, which means that it is not possible to separate the effect of the type of donor and reaction temperature. The yield of benzhydrol after 1 h of reaction are shown in Fig- ure 2 and indicate that by increasing the length of the chain, and therefore the reaction temperature, the yield increases. Under the studied reaction conditions with 2-octanol as the hydrogen donor (D/A = 8, 6 h) an almost quantitative yield of benzhydrol has been observed. It is noteworthy that the order of introduction of substrates and the catalyst into the reaction chamber plays an important role in the reaction. When the catalyst is first dosed with the donor, and then the acceptor is introduced, a much higher yield of the product is observed. A reversed order of introducing of reactants, first acceptor then 2- octanol, leads to a yield of benzhydrol equal to 75% after 1 h of reaction, as opposed to 97% (Figure 2).

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with the OH group in the same position. Therefore, seven straight chain secondary aliphatic alcohols with the OH group attached to the second carbon atom were used as hydrogen donors in the reaction with benzophenone. Since they all have much lower boiling points than benzophenone itself (b.p. 579 K) and they were added in substantial excess, their boiling points determined the reaction temperature. The results reveal that there is a strong dependence of the product yield on the boiling point of the donor. Previous studies in which the activity of some donors was tested at the same temperature, i.e., for two of them the temperature was lower than their boiling points, in order to ensure separation of the effect of donor from the reaction temperature have shown that the yield is the highest at the boiling point temperature of the donor and negligible at lower temperatures [38]. Therefore, in the present work, as well as in most of the literature on LP transfer hydrogenation, all liquid phase activity tests were carried out at the boiling point of each donor, which means that it is not possible to separate the effect of the type of donor and reaction temperature. The yield of benzhydrol after 1 h of reaction are shown in Figure2 and indicate that by increasing the length of the chain, and therefore the reaction temperature, the yield increases. Under the studied reaction conditions with 2-octanol as the hydrogen donor (D/A = 8, 6 h) an almost quantitative yield of benzhydrol has been observed. It is noteworthy that the order of introduction of substrates and the catalyst into the reaction chamber plays an important role in the reaction. When the catalyst is ﬁrst dosed with the Catalysts 2021, 11, 574 5 of 17 donor, and then the acceptor is introduced, a much higher yield of the product is observed. A reversed order of introducing of reactants, ﬁrst acceptor then 2-octanol, leads to a yield of benzhydrol equal to 75% after 1 h of reaction, as opposed to 97% (Figure2).

Figure 2. Liquid phase transfer hydrogenation of benzophenone with different 2-alkanols at normal

Figurepressure 2. Liquid in the phase presence transfer of MgO hydrogenation catalyst. Reaction of benz conditions:ophenone W withMgO =differen 250 ± 5t 2-alkanols mg, 3.125 mmol at nor- of malketone, pressure D/A in =the 8, selectivitypresence of >98%. MgO catalyst. Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8, selectivity >98%. The results of activity measurements carried out with 2-octanol as the hydrogen donor andThe seven results different of activity donor-acceptor measurements ratios carrie on thed out yield with of 2-octanol benzhydrol as arethe presentedhydrogen indo- norFigure and seven3. It can different be seen donor-acceptor that when the D:Aratios ratio on isthe 4, yield a yield of ofbenzhydrol 86% is noted are afterpresented 1 h of in Figurereaction. 3. It Acan higher be seen yield that is noted when for the the D:A donor-acceptor ratio is 4, a ratios yieldof of 6 86% and 8,is i.e.,noted 93% after and 97%,1 h of reaction.respectively. A higher The yield maximum is noted yield for the of benzhydrol donor-acceptor (99%) ratios was attained of 6 and after 8, i.e., 6 h93% of reactionand 97%, respectively.with 250 mg The of MgOmaximum for a ratioyield equal of benzhydrol to 8. Further (99%) increase was ofattained the D/A after parameter 6 h of reaction leads withto slightly250 mg lowerof MgO yields for a (98–90%) ratio equal of the to 8. product Further although increase the of high the D/A selectivity parameter (>98%) leads was to retained. In light of these results, the optimal donor to acceptor ratio is 8:1. slightly lower yields (98–90%) of the product although the high selectivity (>98%) was retained. In light of these results, the optimal donor to acceptor ratio is 8:1.

Figure 3. Influence of the donor-acceptor molar ratio on the reaction yield in liquid phase transfer hydrogenation of benzophenone with 2-octanol in the presence of MgO. Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, selectivity >98%.

Figure 4 contains the results of studies performed to determine the effect of the weight of the catalyst used on the yield of benzhydrol. When 25 mg of MgO are used, the yield of the desired product is only 35% after 1 h of reaction. After two more hours, a yield of 55% is noted, which shows that the additional time is needed. However, the yield of benzhydrol after 6 h of reaction is only 5% higher than that observed after 3 h. This shows

Catalysts 2021, 11, 574 5 of 17

Figure 2. Liquid phase transfer hydrogenation of benzophenone with different 2-alkanols at normal pressure in the presence of MgO catalyst. Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8, selectivity >98%.

The results of activity measurements carried out with 2-octanol as the hydrogen do- nor and seven different donor-acceptor ratios on the yield of benzhydrol are presented in Figure 3. It can be seen that when the D:A ratio is 4, a yield of 86% is noted after 1 h of reaction. A higher yield is noted for the donor-acceptor ratios of 6 and 8, i.e., 93% and 97%, respectively. The maximum yield of benzhydrol (99%) was attained after 6 h of reaction with 250 mg of MgO for a ratio equal to 8. Further increase of the D/A parameter leads to Catalysts 2021, 11, 574 slightly lower yields (98–90%) of the product although the high selectivity (>98%) was5 of 16 retained. In light of these results, the optimal donor to acceptor ratio is 8:1.

FigureFigure 3. 3.InfluenceInﬂuence of the of the donor-acceptor donor-acceptor molar molar ratio ratio on the on reaction the reaction yield yield in liquid in liquid phase phase transfer trans- hydrogenationfer hydrogenation of benzophenone of benzophenone with 2-octanol with 2-octanol in the presence in the presence of MgO. of Reaction MgO. Reaction conditions: conditions: WWMgOMgO = 250= 250 ± 5 ±mg,5 mg, 3.125 3.125 mmol mmol of ketone, of ketone, selectivity selectivity >98%. >98%.

Catalysts 2021, 11, 574 FigureFigure 44 contains thethe resultsresults of of studies studies performed performed to determineto determine the effectthe effect of the of weight6 ofthe 17

weightof the of catalyst the catalyst used on used the on yield the ofyield benzhydrol. of benzhydrol. When When 25 mg 25 of MgOmg of areMgO used, are theused, yield the of yieldthe desiredof the desired product product is only is 35% only after 35% 1 after h of reaction.1 h of reaction. After twoAfter more two hours,more hours, a yield a ofyield 55% is noted, which shows that the additional time is needed. However, the yield of benzhydrol ofthat 55% doubling is noted, the which time doesshows not that help the to additi increaonalse the time yield is needed.of the product. However, In contrast,the yield the of benzhydrolafter 6 h of after reaction 6 h of is onlyreaction 5% higheris only than 5% hi thatgher observed than that after observed 3 h. This after shows 3 h. thatThis doubling shows usethe of time 100 doesmg of not the help catalyst to increase instead the of yield25 mg of leads the product. to a substantial In contrast, increase the use of the of 100product mg of yieldthe catalyst(Figure instead4). It can of be 25 seen mg leadsthat even to a substantialafter 1 h of increasethe test, ofa 91% the productyield of yieldbenzhydrol (Figure is4). attained,It can be which seen that is substantially even after 1 more h of the than test, afte a 91%r 6 h yieldof reaction of benzhydrol with the issmaller attained, amount which of is catalyst.substantially It can more be stated than afterthat the 6 h ofyield reaction of be withnzhydrol the smaller increases amount with ofan catalyst. increase It of can the be amountstated thatof the the catalyst yield of until benzhydrol reaching increases a plateau with (98–99%), an increase which of thestarts amount at 250 of mg the of catalyst MgO (Figureuntil reaching 4). a plateau (98–99%), which starts at 250 mg of MgO (Figure4).

Figure 4. Inﬂuence of the weight of MgO on the reaction yield in liquid phase transfer hydrogenation Figure 4. Influence of the weight of MgO on the reaction yield in liquid phase transfer hydrogena- of benzophenone with 2-octanol in the presence of MgO catalyst. Reaction conditions: WMgO = var, tion of benzophenone with 2-octanol in the presence of MgO catalyst. Reaction conditions: WMgO = 3.125 mmol of ketone, D/A = 8, selectivity >98%. var, 3.125 mmol of ketone, D/A = 8, selectivity >98%. The catalyst was tested repeatedly with a total of 4 batches of benzophenone. Under theThe reaction catalyst conditions was tested MgO repeatedly does not with react a tototal form of any4 batches soluble of magnesium-containingbenzophenone. Under thecompounds reaction conditions and it is not MgO soluble does itself.not react Therefore, to form the any same soluble portion magnesium-containing of MgO was used in compoundsconsecutive and tests it directlyis not soluble after separationitself. Therefore, from reactants.the same portion In each of cycle, MgO the was yield used of thein consecutive tests directly after separation from reactants. In each cycle, the yield of the desired product was determined after 1, 3 and 6 h of reaction. It was observed that in the second cycle, the efficiency of the reduction of benzophenone slightly decreased from 99 to 97% after 6 h of reaction (Figure 5). Further drops in activity were noticed in each of the two subsequent cycles, but overall, this parameter did not have as great of an impact on the yield of benzhydrol as the other studied variables. In the fourth repetition of the cycle under these conditions, benzhydrol was obtained with a yield of 91%.

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desired product was determined after 1, 3 and 6 h of reaction. It was observed that in the second cycle, the efﬁciency of the reduction of benzophenone slightly decreased from 99 to 97% after 6 h of reaction (Figure5). Further drops in activity were noticed in each of the Catalysts 2021, 11, 574 two subsequent cycles, but overall, this parameter did not have as great of an impact7 of 17 on

the yield of benzhydrol as the other studied variables. In the fourth repetition of the cycle under these conditions, benzhydrol was obtained with a yield of 91%.

Figure 5. Recycling test of MgO in liquid phase transfer hydrogenation of Ph2CO with 2-octanol. Figure 5. Recycling test of MgO in liquid phase transfer hydrogenation of Ph2CO with 2-octanol. Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8, selectivity >98%. Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8, selectivity >98%. The results of activity tests of some derivatives of benzophenone under the optimized conditions,The results i.e., of 250 activity mg of tests MgO of used,some 2-octanolderivatives as of the benzophenone hydrogen donor, under D:A the = 8,optimized are shown conditions,in Table1 .i.e., The 250 presence mg of MgO of a used, methyl 2-octano substituentl as the inhydrogen the 2-position donor, D:A of one = 8, of are the shown rings in resultedTable 1. inThe a significantpresence ofdecrease a methyl (Table substitu1 linesent in 1 andthe 2-position 2) in the reactivityof one of ofthe the rings ketone, re- sultedmanifested in a significant by a 27% decrease yield of (Table the alcohol 1 lines after 1 and 3 h 2) of in reaction. the reactivity Extending of the the ketone, reaction man- time ifestedto 6 hby allowed a 27% yield us to of obtain the alcohol (2-methylphenyl) after 3 h of reaction. phenyl Extending methanol withthe reaction 75% yield. time Itto can6 h allowedbe seen thatus to the obtain presence (2-methylphenyl) of a methyl groupphenyl in methanol the 3 or 4with positions 75% yield. of one It ofcan the be ketoneseen thatrings the (Tablepresence1 lines of a 3methyl and 4) group had a in very the slight 3 or 4 effectpositions on its of reactivity;one of the ketone after 3 rings h of reaction, (Table 1 linesthe yields 3 and of4) thehad alcohols a very slight were effect 88 and on 94% its reactivity; for (3-methylphenyl) after 3 h of phenylreaction, methanone the yields andof the(4-methylphenyl) alcohols were phenyl88 and methanone, 94% for (3-m respectively.ethylphenyl) phenyl methanone and (4- methylphenyl)As shown phenyl in the methanone, catalytic test, respectively. the presence of two methyl substituents in ortho positions in one of the ketone rings ((2,4,6-trimethylphenyl) phenyl methanone; TableTable 1. 1Liquid line 5) phase leads transfer to a lack hydr ofogenation reactivity of ofsubstituted the ketone Ph2 duringCO with 62-octanol h under in reaction the presence condi- of tions.MgO catalyst. The reason for such behavior is undoubtedly the presence of a steric hindrance in

the close vicinity of the carbonyl group. This isYield similar of Alcohol to the a,b [%]/Reaction case of the Time non-reactivity [h] of Line No. Substituent 1-(2,4,6-trimethylphenyl)-1-ethanone (acetylmesitylene)1 in reaction3 with secondary 6 alcohols in the liquid1 phase in the presence- of MgO described97 in our previous98 work [38]. 99 2 2-Me 5 27 75 The3 transfer hydrogenation3-Me of benzophenone74 derivatives88 containing96 halogens (Table41 lines 6–8) in the4-Me para position was carried81 out with94 a donor:acceptor99 ratio of 16. Under5 such conditions,2,4,6-triMe the yield of benzhydrol 0 from the unsubstituted0 ketone 0 was 87% 6 4-F c 68 d 88 87 e after 17 h of reaction. It4-Cl can c be seen that the82 type f of halogen85 used has an impact 83 g on the yield8 of benzhydrol with4-Br valuesc of 68%, 82%87 h,i and 87% noted84 for fluorine, chlorine 79 and bromine,9 respectively. Thesej values indicate3 k that the extent10 of the electron withdrawing 18 10 4-OMe 43 76 78 effect11 plays a role in the4-OH interaction of the ketone 0 with the catalyst0 and/or the0 donor. 12 4-NO2 - 6 l,m 20 l,n 13 2-NpPh ° 39 87 94 a—Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8; b—Selectivity > 98% or stated otherwise; c—D/A = 16; d—For 1, 3 and 6 h the conversions of 69, 90 and 91% were noted, respectively; e—Formation of Ph2CO was not observed during 6 h; f—For 1, 3 and 6 h the conversions 84, 87 and 89% were noted, respectively; g—After 6 h 0.2% yield of Ph2CO was noted; h—For 1, 3 and 6h the conversions 92, 93 and 96% were noted, respectively; i—Yields of Ph2CO were 3.4, 3.8 and 4.4% after 1, 3 and 6 h, respectively; j—2-PrOH as hydrogen donor, D/A = 16; k—For 1, 3 and 6 h yields of Ph2CO 1.4, 1.7 and 2.0% were noted, respectively; l—PhCH(OH)Ph-NO2; m—Also 1.1% PhCOPh-NH2 and 1.3% of mixture of Ph2CO and PhCH(OH)Ph; n—Also 1.5% PhCOPh-NH2 and 2.3% of mixture of Ph2CO and PhCH(OH)Ph; °—2-Naphthyl phenyl ketone as hydrogen acceptor.

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Table 1. Liquid phase transfer hydrogenation of substituted Ph2CO with 2-octanol in the presence of MgO catalyst.

Yield of Alcohol a,b [%]/Reaction Time [h] Line No. Substituent 1 3 6 1 - 97 98 99 2 2-Me 5 27 75 3 3-Me 74 88 96 Catalysts 2021, 11, 574 4 4-Me 81 94 99 8 of 17

5 2,4,6-triMe 0 0 0 6 4-F c 68 d 88 87 e 7 4-Cl c 82 f 85 83 g As shown in the catalytic test, the presence of two methyl substituents in ortho posi- 8 4-Br c 87 h,i 84 79 tions9 in one of the ketonej rings ((2,4,6-trimet3hylphenyl)k phenyl10 methanone; Table 18 1 line 5) leads10 to a lack of reactivity 4-OMe of the ketone during 43 6 h under reaction 76 conditions. 78 The reason for such11 behavior is undoubtedly 4-OH the presence 0 of a steric hindrance 0 in the close 0 vicinity of l,m l,n the 12carbonyl group. 4-NOThis 2is similar to the -case of the non-reactivi6 ty of 1-(2,4,6-trime-20 ◦ thylphenyl)-1-ethanone13 2-NpPh (acetylmesitylene) in39 reaction with secondary 87 alcohols 94 in the liq- a—Reactionuid phase conditions: in the presence WMgO = 250 of ±MgO5 mg, described 3.125 mmol in of our ketone, previous D/A = 8; workb—Selectivity [38]. > 98% or stated otherwise; c—D/A = 16; d—For 1, 3 and 6 h the conversions of 69, 90 and 91% were noted, respectively; e The transfer hydrogenation of benzophenonef derivatives containing halogens (Table —Formation of Ph2CO was not observed during 6 h; —For 1, 3 and 6 h the conversions 84, 87 and 89% were 1 lines 6–8) ing the para position was carried outh with a donor:acceptor ratio of 16. Under noted, respectively; —After 6 h 0.2% yield of Ph2CO was noted; —For 1, 3 and h the conversions 92, 93 and 96% i j weresuch noted, conditions, respectively; the—Yields yield ofof Ph benzhydrol2CO were 3.4, from 3.8 and the 4.4% unsubstituted after 1, 3 and 6 keto h, respectively;ne was 87%—2-PrOH after 1 h k as hydrogenof reaction. donor, It D/Acan =be 16; seen—For that 1, 3the and type 6 h yieldsof halogen of Ph2CO used 1.4, 1.7has and an 2.0%impact were on noted, the respec-yield of l m tively; —PhCH(OH)Ph-NO2; —Also 1.1% PhCOPh-NH2 and 1.3% of mixture of Ph2CO and PhCH(OH)Ph; n benzhydrol with values of 68%, 82% and 87% noted for fluorine,◦ chlorine and bromine, —Also 1.5% PhCOPh-NH2 and 2.3% of mixture of Ph2CO and PhCH(OH)Ph; —2-Naphthyl phenyl ketone as hydrogenrespectively. acceptor. These values indicate that the extent of the electron withdrawing effect plays a role in the interaction of the ketone with the catalyst and/or the donor. It hasIt has been been observed observed that for that (4-bromophenyl) for (4-bromophenyl) phenyl methanone,phenyl methanone, the yield ofthe the yield alcohol of the decreasedalcohol indecreased time. The in corresponding time. The corresponding conversions conversions of the substrate of the were substrate 92, 93 were and 96% 92, 93 for and 1, 396% and for 6 h 1, of 3 the and reaction 6 h of (Tablethe reaction1 point (Table h). It was 1 point determined h). It was that determined a dehalogenation that a reactiondehalogen- was occurring, in which 3.4, 3.8 and 4.4% of the substrate were converted to Ph CO (Table1 ation reaction was occurring, in which 3.4, 3.8 and 4.4% of the substrate were2 converted point i). The course of the dehalogenation reaction on the example of 4-bromobenzophenone to Ph2CO (Table 1 point i). The course of the dehalogenation reaction on the example of 4- is described by Equation (2): bromobenzophenone is described by Equation (2): O O OH O (2)(2) + + + HBr Br Hydrogen bromide formed in the reaction is chemically bonded to magnesium oxide. Hydrogen bromide formed in the reaction is chemically bonded to magnesium oxide. In contrast, in the case of the F-substituted ketone the formation of Ph2CO was not ob- In contrast, in the case of the F-substituted ketone the formation of Ph CO was not observed served during 6 h under reaction conditions (Table 1 point e).2 When (4-bromophenyl) during 6 h under reaction conditions (Table1 point e). When (4-bromophenyl) phenyl phenyl methanone reacted with 2-propanol instead of 2-octanol, the yield of the alcohol methanone reacted with 2-propanol instead of 2-octanol, the yield of the alcohol was only was only 3% after 1 h of reaction (Table 1 line 9). Additional 2 h of reaction led to an overall 3% after 1 h of reaction (Table1 line 9). Additional 2 h of reaction led to an overall alcohol alcohol yield of 10%, and after a total of 6 h of reaction the value reached 18%. yield of 10%, and after a total of 6 h of reaction the value reached 18%. Significant differences in the reactivity of (4-methoxyphenyl) phenyl methanone and Significant differences in the reactivity of (4-methoxyphenyl) phenyl methanone and (4-hydroxyphenyl) phenyl methanone were observed in the tested reaction (Table 1 lines (4-hydroxyphenyl) phenyl methanone were observed in the tested reaction (Table10 and1 lines 11). 10The and former 11). compound The former was compound reduced to was the reduced corresponding to the correspondingalcohol with a 76% alcoholyield, with whereas a 76% the yield, latter whereaswas non-reactive. the latter The was reason non-reactive. for the observed The reason lack for of thereactivity ob- servedis undoubtedly lack of reactivity the presence is undoubtedly of a phenolic the presence hydroxy of group a phenolic in the hydroxy molecule group of the in thelatter, moleculewhose ofacidic the latter,properties whose in acidicconjunction properties with inthe conjunction high basicity with of the magnesium high basicity oxide of the sur- magnesiumface resulted oxide in surfacean acid-base resulted reaction in an and acid-base catalyst reaction deactivation. and catalyst deactivation. In theIn the reduction reduction of 4-nitrobenzophenone,of 4-nitrobenzophenone, next next to theto the main main product, product, an an equimolar equimolar mixturemixture of benzophenoneof benzophenone and and benzhydrol benzhydrol was was formed formed (Table (Table1 line 1 line 12). 12). The The yield yield of of PhCH(OH)Ph-NO2 was 6 and 20% after 3 and 6 h of reaction, respectively. The other com- PhCH(OH)Ph-NO2 was 6 and 20% after 3 and 6 h of reaction, respectively. The other componentsponents of of the the reactant reactant stream werewere alsoalso identiﬁed. identified. After After 3 3 h h under unde reactionr reaction conditions, conditions, the liquid phase also contained 1.1% PhCOPh-NH2 and 1.3% of mixture of Ph2CO and PhCH(OH)Ph, whereas after 6 h, the corresponding values were: 1.5% PhCOPh-NH2 and 2.3% of mixture of Ph2CO and PhCH(OH)Ph. In order to determine if a heavier ketone, i.e., one with more rings in its structure can be reduced using this method, a test was conducted with 2-naphthyl phenyl ketone as the hydrogen acceptor (Table 1 line 13). It has been shown that the yield of the appropriate alcohol was 39%, 87% and 94% after 1, 3 and 6 h of reaction, respectively. The occurrence of dehalogenation of (4-halophenyl) phenyl methanones during the course of the hydrogen transfer reaction in the liquid phase was taken up in further research. (4-Bromophenyl) phenyl methanone was selected for the test, i.e., the ketone which underwent the above-mentioned side reaction with the highest yield. Catalytic tests were carried out with three hydrogen donors: 2-propanol, 2-pentanol and 2-octanol. The

Catalysts 2021, 11, 574 8 of 16

the liquid phase also contained 1.1% PhCOPh-NH2 and 1.3% of mixture of Ph2CO and PhCH(OH)Ph, whereas after 6 h, the corresponding values were: 1.5% PhCOPh-NH2 and 2.3% of mixture of Ph2CO and PhCH(OH)Ph. In order to determine if a heavier ketone, i.e., one with more rings in its structure can be reduced using this method, a test was conducted with 2-naphthyl phenyl ketone as the hydrogen acceptor (Table1 line 13). It has been shown that the yield of the appropriate alcohol was 39%, 87% and 94% after 1, 3 and 6 h of reaction, respectively. The occurrence of dehalogenation of (4-halophenyl) phenyl methanones during the course of the hydrogen transfer reaction in the liquid phase was taken up in further research. (4-Bromophenyl) phenyl methanone was selected for the test, i.e., the ketone which underwent the above-mentioned side reaction with the highest yield. Catalytic tests were carried out with three hydrogen donors: 2-propanol, 2-pentanol and 2-octanol. The test results are summarized in Table2. It can be seen that the occurrence of the ketone debromination reaction was found in the case of all the hydrogen donors used and the yield of the tested reaction increased slightly with temperature. It was shown that at the highest reaction temperature (454 K) the dehalogenation product yield did not exceed the value of 5% after 6 h, with a hydrogen transfer reaction product yield of 67%.

Table 2. Liquid phase transfer hydrogenation of 4-bromobenzophenone with various secondary alcohols in the presence of MgO catalyst.

Yield of PhCH(OH)Ph-Br a [%]/Reaction Time [h] Donor T [K] 1 3 6 2-PrOH 355 2.5/1.4 b 10.2/1.7 17.9/2.0 2-PeOH 393 31.1/2.3 b 59.5/2.5 73.7/2.7 2-OcOH 454 66.7/3.4 b 70.7/3.8 66.5/4.4 a b —Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 16; —Yield of PhCOPh.

2.3. Vapour-Phase Transfer Hydrogenation of Diaryl Ketones The study of the hydrogen transfer reaction to diphenyl methanones in the gas phase was limited to the unsubstituted ketone and its monosubstituted methyl derivatives. The reason was the high boiling point of ketones under normal pressure (benzophenone, b.p. 579 K) and the need to work in the temperature regime in which they occur in the gas phase. Therefore, the choice of reaction temperatures was rather limited and the catalytic tests were performed in the temperature range of 573–723 K (Table3).

Table 3. Liquid phase transfer hydrogenation of polycyclic derivatives of cyclopentanone with secondary alcohols in the presence of MgO catalyst.

Conversion [%]/Yield of Alcohol [%] a Line No. Substituents 573 K 623 K 673 K 723 K 1 - 90/89 90/89 76/68 72/43 2 - b 89/88 91/89 - - 3 - c 62/62 68/67 54/51 39/16 4 - d 52/52 61/57 66/59 60/44 5 2-Me 75/74 75/73 69/62 67/44 6 3-Me 90/89 88/83 81/78 74/46 7 4-Me 89/88 85/80 78/56 78/41 a −1 3 −1 b —Reaction conditions: D/A = 8, LHSV = 3 h ,N2 = 3 dm h ; —Repeated test with a spent catalyst; c—D/A = 6; d—Ethanol as hydrogen donor.

The conversion of benzophenone and yield of alcohol observed for vapor phase transfer hydrogenation with 2-propanol as the donor at 573 K, with a donor-acceptor ratio of 8, were 90 and 89% (Table3 line 1), respectively. When the test was performed again with Catalysts 2021, 11, 574 9 of 16

recycled MgO, the results were 89 and 88% (Table3 line 2), respectively. When the donor- acceptor ratio was 6, the conversion of benzophenone and yield of benzhydrol dropped substantially; both were equal to 62% (Table3 line 3). The lowest benzophenone conversion and alcohol yield (both 52%) were noted when the hydrogen donor was changed from 2-propanol to ethanol (Table3 line 4). However, unlike the results obtained with 2-propanol, the values noted in the reaction with ethanol did not exhibit a drop at 673 K. In fact, both went up. Upon further increase in temperature (to 723 K), the conversion and the alcohol yield dropped with ethanol as the hydrogen donor. The inﬂuence of the presence of a methyl group in the ortho position was pronounced regardless of the reaction temperature. For example, at 573 K the conversion of benzophe- Catalysts 2021, 11, 574 10 of 17 none dropped from 90% to 75% and the yield of alcohol decreased from 89% to 74% (Table3 line 5). However, the discrepancy was much smaller than in the case of that observed in the liquid phase (Table1). It is noteworthy that in the case of (3-methylphenyl) phenylmethanone methanone (Table (Table3 line 36), line no 6),effect no effectof the ofmethyl the methyl substituent substituent on the on conversion the conversion and al- andcohol alcohol yield yieldis detected is detected in the in thevapor vapor phase. phase. A similar A similar observation observation was was made made for for (4- (4-methylphenyl)methylphenyl) phenyl phenyl methanone, methanone, which which indica indicatestes that onlyonly thethe orthoortho positionposition causes causes a a stericsteric hindrance hindrance which which impedes impedes the the reaction reaction (Table (Table3 line3 line 7). 7). TheThe effect effect of of the the temperature temperature on on the the conversion conversion and and yield yield of of alcohol alcohol for for the the studied studied compoundscompounds is is presentedpresented inin TableTable3 3 (lines (lines 1–7).1–7). When 2-propanol 2-propanol is is used used as as the the hydrogen hydrogendonor, donor, the thehighest highest conversions conversions in the in reaction the reaction for all for tested all tested ketones ketones were were observed observed at the attemperature the temperature of 623 of K. 623 They K. reached They reached 85–90%, 85–90%, except exceptfor the for2-methyl the 2-methyl derivative derivative (Table 3 (Tableline 5)3 forline which 5) for 75% which conversion 75% conversion was recorded. was recorded. Moreover, Moreover, very high very (>94%) high selectivities (>94%) selectivitieswere found were in the found reduction in the of reduction ketones to of the ketones corresponding to the corresponding alcohols at this alcohols temperature. at this temperature.As the reaction As thetemperature reaction temperature increased, the increased, conversion the conversionof all ketones of alldropped ketones and dropped the se- andlectivity the selectivity of reduction of reduction to alcohols to significantly alcohols signiﬁcantly decreased, decreased, especially especially at the temperature at the tem- of perature723 K; it of has 723 been K; it shown has been to be shown caused to beby caused a side reaction by a side in reaction which inthe which primary the reduction primary reductionproduct, product,diphenylmethanol, diphenylmethanol, undergoes undergoes a subsequent a subsequent reaction reactionwith the withparticipation the participa- of the tionhydrogen of the hydrogendonor, hydrogenolysis, donor, hydrogenolysis, in which init is which converted it is converted to diphenylmethane to diphenylmethane according accordingto the equation to the equationshown below: shown below: OH OH O (3)(3) + + + H2O

TheThe water water formed formed in in the the reaction reaction interacts interacts with with the the catalyst catalyst causing causing its partialits partial tempo- tem- raryporary deactivation, deactivation, which which in turn in turn reduces reduces the conversion the conversion of the of ketone. the ketone. It was It calculated was calculated that forthat the for two the higher two higher temperatures, temperatures, i.e., 673 i.e., K 673 and K 723 and K, 723 the K, amount the amount of water of water forming forming was −1 −1 87wasµmol 87 ·μh−mol·h1 and 319andµ 319mol μ·hmol·h−1, respectively., respectively. Despite Despite a similar a similar conversion, conversion, a substantially a substan- lowertially yieldlower of yield benzhydrol of benzhydrol was noted was noted for the fo higherr the higher temperature. temperature. Catalyst Catalyst deactivation deactiva- hastion been has been shown shown to be to reversible be reversible in the in the catalytic catalytic test; test; upon upon returning returning to to lower lower reaction reaction temperatures,temperatures, the the catalyst catalyst regained regained its its previous previous high high activity. activity. ItIt was was observed observed that that the the selectivity selectivity of of the the reaction reaction at at the the two two higher higher temperatures temperatures is is stronglystrongly influenced influenced by by the the donor. donor. When When 2-propanol 2-propanol was was used, used, a a substantial substantial drop drop of of the the selectivityselectivity to to the the alcohol alcohol noted noted when when the the temperature temperature waswas changed changed fromfrom 673 673 K K to to 723 723 K. K. AA smaller smaller dropdrop of selectivity selectivity was was observed observed wh whenen ethanol ethanol was was used used as the as hydrogen the hydrogen donor. donor.Although Although the selectivity the selectivity to the alcohol to the alcohol with both with studied both studied donors donorswere the were same the (89%) same at (89%)673 K, at the 673 selectivities K, the selectivities noted at noted723 K were at 723 60% K were and 73% 60% for and 2-propanol 73% for 2-propanol and ethanol, and re- ethanol,spectively. respectively. TheThe time-on-stream time-on-stream tests tests carried carried out out at at 573 573 K K with with benzophenone benzophenone as as the the hydrogen hydrogen acceptor,acceptor, 2-propanol 2-propanol asas thethe donor, and a D/A D/A = =8, 8,have have shown shown that that magnesium magnesium oxide oxide was washighly highly active active in the in thereaction reaction for for6 h 6in h the in thereactant reactant stream stream (Figure (Figure 6). 6The). The determined determined con- conversionversion over over time time was was 90 and 90 and 88% 88% after after 1 and 1 and6 h of 6 the h of test, the respectively. test, respectively. A similar A similar profile proﬁlewas noted was notedfor the for yield the of yield diphenylmethanol, of diphenylmethanol, after 6 after h the 6 product h the product was obtained was obtained with a yield of 87%. It should be emphasized that the selectivity of the hydrogen transfer reaction was equal to 99% throughout the entire test.

Catalysts 2021, 11, 574 10 of 16

Catalysts 2021, 11, 574 11 of 17 with a yield of 87%. It should be emphasized that the selectivity of the hydrogen transfer reaction was equal to 99% throughout the entire test.

Figure 6. Vapor phase transfer hydrogenation of benzophenone with 2-propanol in the presence of MgO Figure 6. Vapor phase transfer hydrogenation of benzophenone with 2-propanol−1 in the presence3 −of1 catalyst. Time-on-stream test. Reaction conditions: T = 573 K, D/A = 8, LHSV = 3 h ,VN2 = 3 dm h . MgO catalyst. Time-on-stream test. Reaction conditions: T = 573 K, D/A = 8, LHSV = 3 h−1, VN2 = 3 3 −1 dm2.4. h Liquid-Phase. Transfer Hydrogenation of Polycyclic Ketones

2.4. Liquid-PhaseIn the part ofTransfer the research Hydrog devotedenation of to Polycyclic the transfer Ketones of hydrogen to polycyclic ketones, two groups of ketones were selected as research objects: In the part of the research devoted to the transfer of hydrogen to polycyclic ketones, - cyclopentanone derivatives with one or two fused benzene rings: benzocyclopen- two groups of ketones were selected as research objects: tenone (1-indanone) and dibenzocyclopentadienone (ﬂuorenone); -- cyclopentanonecyclohexanone derivativesderivatives with with one one or or two two fused fused benzene benzene rings: rings: benzocyclohexenone benzocyclopentenone(1-tetralone) (1-indanone) and dibenzocyclohexadienone and dibenzocyclopentadienone (anthrone). (fluorenone); - cyclohexanone derivatives with one or two fused benzene rings: benzocyclohex- It was expected that this change in the structure of ketone molecules, i.e., hydrogen enone (1-tetralone) and dibenzocyclohexadienone (anthrone). acceptors, would have an inﬂuence on the reactivity of their carbonyl groups in the reaction. Moreover,It was theexpected lower aciditythat this of change hydrogen in the atoms structure in the αofposition ketone molecules, in the case ofi.e., monobenzo- hydrogen acceptors,cycloalkenones, would was have expected an influence to cause on anthe increase reactivity in theof their selectivity carbonyl of the groups reaction in the towards reaction.the formation Moreover, of the the lower appropriate acidity of carbinols. hydrogen In atoms order toin assessthe α position the reactivity in the ofcase the of selected mono- benzocycloalkenones,ketones, their reactivity was in expected the hydrogen to cause transfer an increase reaction in wasthe selectivity carried out of inthe the reaction liquid towardsphase and the itformation was compared of the appropriate with the reactivity carbinols. of In cyclopentanone order to assess andthe reactivity cyclohexanone, of the selectedrespectively, ketones, under their these reactivity conditions. in the hydrogen transfer reaction was carried out in the liquidTable phase4 contains and it was the value compared obtained with for the group reactivity I polycyclic of cyclopentanone ketones, i.e., the and ones cyclohexa- containing none,the cyclopentanone respectively, core.under In these the case conditions. of cyclopentanone, the conversion was 25, 39 and 48% after 1, 3, andTable 6 h4 ofcontains reaction, the respectively. value obtained The yield for group of alcohol, I polycyclic however, ketones, was only i.e., 1, 2the and ones 3% con- after taining1, 3 and the 6 h cyclopentanone under reaction conditions. core. In the This case shows of cyclopentanone, very poor selectivity the conversion towards the was alcohol. 25, 39 In andcontrast, 48% bothafter of1, the3, and ketones 6 h withof reaction, fused benzene respectively. rings exhibit The yield a much of alcohol, higher selectivity however, of was the onlyreaction 1, 2 towardsand 3% after the corresponding 1, 3 and 6 h under carbinol. reac Thetion selectivityconditions. determined This shows for very benzocyclopen- poor selec- tivitytenone towards and dibenzocyclopentadienone the alcohol. In contrast, wasboth 98% of the compared ketones to with only fused 6% for benzene cyclopentanone. rings exhibit It is anoteworthy much higher that selectivity a lack of by-products of the reaction was observed towards in the the corresponding case of benzocyclopentenone, carbinol. The despiteselec- tivitythe fact determined that its molecule for benzocyclopentenone contains hydrogen and atoms dibenzocyclopentadienone in the α position to the carbonyl was 98% group, com- paredwhich to could only potentially 6% for cyclopentanone. undergo acid-base It is transformations. noteworthy that Itis a highlylack of probable by-products that the was fusion ob- servedof cyclopentanone in the case of and benzocyclopentenone, the benzene rings results despite in such the a fact change that in its the molecule charge distribution contains hy- in drogenthe newly atoms formed in the compound α position that to the the hydrogen carbonyl atoms group, in thewhichα position could topotentially the carbonyl undergo group acid-baselose their acidictransformations. properties. It is highly probable that the fusion of cyclopentanone and the benzene rings results in such a change in the charge distribution in the newly formed compound that the hydrogen atoms in the α position to the carbonyl group lose their acidic properties.

Catalysts 2021, 11, 574 11 of 16

Catalysts 2021, 11, 574 12 of 17 Catalysts 2021, 11, 574 12 of 17 Catalysts 2021, 11, 574 12 of 17 Table 4. Liquid phase transfer hydrogenation of polycyclic derivatives of cyclopentanone with secondaryTable 4. Liquid alcohols phase in the transfer presence hydrogenation of MgO. of polycyclic derivatives of cyclopentanone with Table 4. Liquid phase transfer hydrogenation of polycyclic derivatives of cyclopentanone with secondaryTable 4. Liquid alcohols phase in thetransfer presence hydrogenation of MgO. of polycyclic derivatives ofa cyclopentanone with secondary alcohols in the presence of MgO. Yield of Alcohol [%] /Reaction Time [h] secondaryKetone alcohols in the presence Donor of MgO. Yield1 of Alcohol [%] 3 a/Reaction Time 4 [h] Ketone Donor Yield of Alcohol [%] a/Reaction Time [h] Ketone Donor Yield1 of Alcohol [%]3 a/Reaction Time 4 [h] Ketone Donor 1 3 4 O 1 3 4 O O 2-PrOH 11b b 2 3 3 2-PrOH 1 b 2 3 2-PrOH 1 b 2 3

O c 2-PrOH 8c 12 14 O 2-PrOH 88 c 1212 14 14 O 2-PrOH 8 c 12 14 2-OcOH 43 c 45 45 2-OcOH 43 c 45 45 2-OcOH 43 c 45 45 c O 2-OcOH 43 d 45c 45 2-PrOH 49 74 78 O 2-PrOH 49 d 74 c 78 O 2-PrOH 4949d d 7474 cc 7878 2-OcOH 82 c 82 78 c 2-OcOH 82 c 82 78 2-OcOH 82 82 78 a b —Reaction conditions: W MgO = 2502-OcOH ± 5 mg, 3.125 mmol 82 c of ketone, D/A82 = 8; —Conversion 78 of cyclo- a MgO c b pentanonea—Reaction was conditions: 25, 39 and W 48%= after250 ± 1, 5 3mg, and 3.125 6 h of mmol reaction, of ketone, respectively; D/A = 8; —Selectivity b—Conversion into of car- cyclo- a—Reaction—Reaction conditions: conditions: W WMgO= 250 = 250± 5 mg,± 5 mg, 3.125 3.125 mmol mmol of ketone, of ketone, D/A = 8;D/Ab—Conversion = 8; —Conversion of cyclopentanone of cyclopentanone was 25, 39 andMgO 48%d after 1, 3 and 6 h of reaction, respectively; c—Selectivity into car- wasbinolpentanone 25, 39was and higher was 48% 25, after than 39 1, and98%; 3 and 48% 6—Yield h after of reaction, 1,after 3 and 30 respectively; 6min h of of reaction, reaction.c—Selectivity respectively; into carbinol c—Selectivity was higher into than car- 98%; binol was higher than 98%; d—Yield after 30 min of reaction. d—Yieldbinol was after higher 30 min than of reaction. 98%; d—Yield after 30 min of reaction. Fluorenone, in which two benzene rings are fused with the cyclopentanone ring, Fluorenone, in which two benzene rings are fused with the cyclopentanone ring, showsFluorenone,Fluorenone, a much higher inin which which reactivity two two benzene inbenzene the hydrogen rings rings are ar transfere fused fused reaction with with the the to cyclopentanone cyclopentanoneform the correspond- ring, ring, shows a much higher reactivity in the hydrogen transfer reaction to form the correspond- showsingshows carbinol a a much much than higher higher benzocyclopentenone reactivity reactivity in in the the hydrogen hydrogen (Table transfer 4). transfer In the reaction reaction latter to case, form to form after the the corresponding 6 h correspond- of reaction ing carbinol than benzocyclopentenone (Table 4). In the latter case, after 6 h of reaction carbinolwithing carbinol 2-propanol, than benzocyclopentenonethan abenzocyclopentenone carbinol yield of (Table 14% (Table4 was). In obtained the4). In latter the compared case,latter after case, 6to after h a of 78% reaction6 h yield of reaction within the with 2-propanol, a carbinol yield of 14% was obtained compared to a 78% yield in the 2-propanol,reductionwith 2-propanol, of a carbinolfluorenone. a carbinol yield of yield 14% wasof 14% obtained was obtained compared compared to a 78% yield to a in78% the yield reduction in the reduction of fluorenone. ofreduction ﬂuorenone.The impact of fluorenone. of the hydrogen donor on the reactivity and selectivity of the reaction The impact of the hydrogen donor on the reactivity and selectivity of the reaction withThe Thethe impact groupimpact ofI ofketones the the hydrogen hydrogen was also donor donor studied. on theon Both reactivitythe reactivity 2-propanol and selectivityand and selectivity 2-octanol of the of reaction were the reactionused with as with the group I ketones was also studied. Both 2-propanol and 2-octanol were used as Catalysts 2021, 11, 574 thedonorswith group the for Igroup ketonesthe reaction I ketones was alsowith was studied. the also two studied. Bothcyclopentanone 2-propanol Both 2-propanol andderivatives 2-octanol and (Table2-octanol were 4). used Inwere asboth donorsused cases,13 of as 17 donors for the reaction with the two cyclopentanone derivatives (Table 4). In both cases, forthedonors the yield reaction for of the the withreaction alcohol the twowaswith cyclopentanonemuch the two higher cyclopentanone in derivativesthe reaction derivatives (Table with 42-octanol.). In (Table both cases,4). In both the yield cases, the yield of the alcohol was much higher in the reaction with 2-octanol. ofthe the yieldThe alcohol inverseof the was alcohol relationship much was higher much of in reactivity the higher reaction in to thestructure with reaction 2-octanol. was with noted 2-octanol. for group II ketones (Ta- The inverse relationship of reactivity to structure was noted for group II ketones (Ta- ble 5).TheThe Benzocyclohexenone inverse inverseO relationshiprelationship showed of reactivity reactivity four timesto to structure structure lower reactivitywas was noted noted with for for group 2-propanol group II ketones II ketones than (Ta- cy- ble 5). Benzocyclohexenone showed four times lower reactivity with 2-propanol than cy- (Tableclohexanoneble 5).5). Benzocyclohexenone Benzocyclohexenone under the same showed conditions. showed four four After times times 6 lowerh lowerof reaction reactivity reactivity with with with2-propanol, 2-propanol 2-propanol only than thana 14% cyclohexanone under the same conditions. After 6 h of reaction with 2-propanol, only a 14% cyclohexanoneyieldclohexanone of benzocyclohexenol under under the the same same was 2-OcOHconditions. conditions. recorded. After AfterA simi 6 h0 6 larof h ofreactionyield reaction of withthis with - alcohol 2-propanol, 2-propanol, (59%) only as 0 only that a 14% aof yield of benzocyclohexenol was recorded. A similar yield of this alcohol (59%) as that of 14%cyclohexanolyield yield of benzocyclohexenol of benzocyclohexenol (61%) was obtained was wasrecorded. by recorded. replacin A simig A2-propanollar similar yield yieldof as this the of alcohol thisdonor alcohol (59%)with (59%)theas that much as of cyclohexanol (61%) was obtained by replacing 2-propanol as the donor with the much thathighercyclohexanol of cyclohexanol boiling (61%) 2-octanol. (61%)was obtainedOn was the obtained other by replacinhand by replacing, benzocyclohexenoneg 2-propanol 2-propanol as the as wasdonor the reduced donor with withthe to themuch the al- highera—Reaction boiling conditions: 2-octanol. WMgO On = 250the ±other 5 mg, hand 3.125, mmolbenzocyclohexenone of ketone, D/A = 8. was b—Conversion reduced to of the cyclo- al- muchcoholhigher higher with boiling a boiling higher 2-octanol. 2-octanol.selectivity On theOn (>98%) other the other handthan , hand,cyclohexanone benzocyclohexenone benzocyclohexenone (81%). wasThis reduced wasproves, reduced toas thein to theal- coholhexanone with was a higher58, 68 and selectivity 75% after (>98%) 1, 3 and than 6 h of cyclohexanone reaction, respectively. (81%). c—Selectivity This proves, into as carbinol in the thecasecohol alcohol of with benzocyclopentenone, witha higher a higher selectivity selectivity that (>98%) the (>98%) fusion than thancyclohexanone of the cyclohexanone cyclohexanone (81%). (81%). moleculeThis proves, This and proves, asthe in ben- asthe casewas higherof benzocyclopentenone, than 98%. that the fusion of the cyclohexanone molecule and the ben- inzenecase the ofring case benzocyclopentenone, reduces of benzocyclopentenone, the acidity ofthat the the hydrogens that fusion the fusionof atthe the cyclohexanone of α the-carbon, cyclohexanone thus molecule inhibiting molecule and the the possi- and ben- thezene benzene ring reduces ring reduces the acidity the acidity of the ofhydrogens the hydrogens at the at α-carbon, the α-carbon, thus inhibiting thus inhibiting the possi- the bilityzene ringItof was the reduces foundsubstrate thethat aldolacidity dibenzocyclohexadienone condensation of the hydrogens reaction. at (anthrone)the α-carbon, had thus no measurable inhibiting the reactivity possi- possibilitybility of the of substrate the substrate aldol aldol condensation condensation reaction. reaction. bilitywhen of reacting the substrate with 2-propanol aldol condensation in the presence reaction. of magnesium oxide as the catalyst (Table TableIt was5. Liquid found phase that dibenzocyclohexadienonetransfer hydrogenation of polycyclic (anthrone) derivative had no measurables of cyclohexanone reactivity with when sec- Table5). It 5.was Liquid also phase impossible transfer to hydrogen observeation its reactivityof polycyclic at derivativea much highers of cyclohexanone temperature with (454 sec- K) reactingondaryTable 5. alcohols with Liquid 2-propanol phasein the transferpresence in the hydrogen of presence MgO. ation of magnesium of polycyclic oxide derivative as thes of catalyst cyclohexanone (Table5). with It was sec- ondaryobtained alcohols by changing in the presence the hydrogen of MgO. donor from 2-propanol to 2-octanol. The reason for alsoondary impossible alcohols toin observethe presence its reactivityof MgO. at a much higher temperature (454 K) obtained by the lack of reactivity of the ketone is its transformationYield of Alcohol in the presence[%] a/Reaction of the Time catalyst [h] with changing theKetone hydrogen donor fromDonor 2-propanol to 2-octanol.Yield of Alcohol The reason [%] a for/Reaction the lack Time of reactivity [h] basic properties,Ketone into its enolDonor form that is not Yieldsusceptible1 of Alcohol to reduction, [%]3 a/Reaction which Time is 4described [h] of the ketoneKetone is its transformationDonor in the presence of1 the catalyst with3 basic properties, 4 into its by EquationO (4): 1 3 4 enol form thatO is not susceptible to reduction, which is described by Equation (4): O O2-PrOH 52 b OH 58 61 b 2-PrOH 52 b 58 61 2-PrOH 52 58 61 (4) (4) O c 2-PrOH 10 13 14 O 2-PrOH 10 c 13 14 O 2-PrOH 10 c 13 14 2-OcOH 53 c 58 59 c 3. Materials and Methods 2-OcOH 53 c 58 59 2-OcOH 53 58 59

3.1. Preparation of MgO and Its2-PrOH Characterization 0 - 0 2-PrOH 0 - 0 The method of preparation2-PrOH of the catalyst 0can be found in - [12]. The fraction 0 of MgO used for the tests carried out in these studies was 0.40–0.63 mm for vapor and 0.16–0.40 mm for the liquid phase.

The procedures of the following characterization, such as nitrogen physisorption, X- Ray Diffraction, TG-DTA-MS measurements and determination of the acid-base sites (types and concentration [46]), along with details of the instruments, are provided in our previous publication [10].

3.2. Hydrogen Acceptors Benzophenone (99%, Aldrich, Munich, Germany) was crystallized twice from ethanol. The purified product was 99.7% (GC) pure. The following derivatives of benzophenone were used: 2-methyl- (98%), 3-methyl- (99%), 4-methyl- (99%), 4-chloro- (99%), 4-bromo- (98%), 4-hydroxy- (98%) and 4-methoxybenzophenone (97%), all from Aldrich. For purification, they were crystallized from ethanol or distilled under reduced pressure. 4-Fluorobenzophenone was prepared by dropping benzoyl chloride to a suspension of AlCl3 as catalyst in boiling fluorobenzene (an excess) and heating the reaction mixture under reflux for 13 h. Yield of distilled product 84%, b.p. 427-9 K/15 hPa (exp), 432-4 K/17 hPa (lit), purity 99.4% (GC) (including 2.2% of 2-fluorobenzophenone), m.p. 314–318 K (exp), 320-2 K (lit). 2,4,6-Trimethylbenzophenone was synthesized in our laboratory in the reaction of benzoyl chloride with mesitylene in the presence of anhydrous AlCl3 and purified by distillation under reduced pressure. Yield 73%, m.p. 308 K (exp), 307-8 K (lit), purity 99.4% (GC). 4-Nitrobenzophenone was prepared by acylation of benzene with 4-nitrobenzoyl chloride in the presence of anhydrous AlCl3. A crude product was mixed with charcoal and crystallized thrice from methanol-toluene solution. Yield 54%, m.p. 408–409 K (exp), 404-6 K (lit), purity 99.0% (GC). Fluorenone (98%, Aldrich) (dibenzocyclopentadienone) was crystallized twice from ethanol, mp. 355 K (exp), 355-6 K (lit), purity 99.1% (GC).

Catalysts 2021, 11, 574 12 of 17

Table 4. Liquid phase transfer hydrogenation of polycyclic derivatives of cyclopentanone with secondary alcohols in the presence of MgO.

a Yield of Alcohol [%] a/Reaction Time [h] Ketone Donor 1 3 4 O

b 2-PrOH 1 b 2 3

O c O 2-PrOH 8 c 12 14

c 2-OcOH 43 c 45 45

O d c O 2-PrOH 49 d 74 c 78

c 2-OcOH 82 c 82 78

a b a—Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8; b—Conversion of cyclo- —Reaction conditions: WMgO = 250 ± 5 mg, 3.125 mmol of ketone, D/A = 8; —Conversion of cyclo- c pentanone was 25, 39 and 48% after 1, 3 and 6 h of reaction, respectively; c—Selectivity into car- d binol was higher than 98%; d—Yield after 30 min of reaction.

Fluorenone, in which two benzene rings are fused with the cyclopentanone ring, shows a much higher reactivity in the hydrogen transfer reaction to form the corresponding carbinol than benzocyclopentenone (Table 4). In the latter case, after 6 h of reaction with 2-propanol, a carbinol yield of 14% was obtained compared to a 78% yield in the reduction of fluorenone. The impact of the hydrogen donor on the reactivity and selectivity of the reaction with the group I ketones was also studied. Both 2-propanol and 2-octanol were used as donors for the reaction with the two cyclopentanone derivatives (Table 4). In both cases, the yield of the alcohol was much higher in the reaction with 2-octanol. The inverse relationship of reactivity to structure was noted for group II ketones (Ta- ble 5). Benzocyclohexenone showed four times lower reactivity with 2-propanol than cyclohexanone under the same conditions. After 6 h of reaction with 2-propanol, only a 14% yield of benzocyclohexenol was recorded. A similar yield of this alcohol (59%) as that of cyclohexanol (61%) was obtained by replacing 2-propanol as the donor with the much higher boiling 2-octanol. On the other hand, benzocyclohexenone was reduced to the alcohol with a higher selectivity (>98%) than cyclohexanone (81%). This proves, as in the Catalysts 2021, 11, 574 cohol with a higher selectivity (>98%) than cyclohexanone (81%). This proves, as 12in ofthe 16 case of benzocyclopentenone, that the fusion of the cyclohexanone molecule and the benzene ring reduces the acidity of the hydrogens at the α-carbon, thus inhibiting the possi- bility of the substrate aldol condensation reaction. Table 5. Liquid phase transfer hydrogenation of polycyclic derivatives of cyclohexanone with Tablesecondary 5. Liquid alcohols phase in transfer the presence hydrogen of MgO.ation of polycyclic derivatives of cyclohexanone with secondary alcohols in the presence of MgO. Yield of Alcohol [%] a/Reaction Time [h] a Ketone Donor Yield of Alcohol [%] a/Reaction Time [h] Ketone Donor 1 3 4 1 3 4 O

bb 2-PrOH 5252 b 5858 61 61

O c O 2-PrOH 10 10 c c 1313 14 14

Catalysts 2021, 11, 574 13 of 17 c 2-OcOH 53 c 58 59 c 2-OcOH 53 58 59 2-PrOH 0 - 0 O 2-PrOH 0 0 - - 0 0

2-OcOH 0 - 0

2-OcOH 0 - 0 aa MgO b b —Reaction—Reaction conditions:conditions: W WMgO == 250 250± ±5 5 mg, mg, 3.125 3.125 mmol mmol of ketone, of ketone, D/A D/A = 8. =—Conversion 8. —Conversion of cyclohexanone of cyclo- hexanonewas 58, 68 andwas 75% 58, after68 and 1, 375% and 6after h of 1, reaction, 3 and respectively.6 h of reaction,c—Selectivity respectively. into carbinolc—Selectivity was higher into than carbinol 98%. was higher than 98%. 3. Materials and Methods 3.1. PreparationIt was found of that MgO dibenzocyclohexadienone and Its Characterization (anthrone) had no measurable reactivity whenThe reacting method with of preparation2-propanol ofin thethe catalystpresence can of be magnesium found in [12 oxide]. The as fraction the catalyst of MgO (Table used 5).for It the was tests also carried impossible out in these to observe studies its was reactivity 0.40–0.63 at mm a much for vapor higher and temperature 0.16–0.40 mm (454 for theK) obtainedliquid phase. by changing the hydrogen donor from 2-propanol to 2-octanol. The reason for the lackThe of procedures reactivity of of the the ketone following is its tran characterization,sformation in suchthe presence as nitrogen of the physisorption, catalyst with basicX-Ray properties, Diffraction, into TG-DTA-MS its enol form measurements that is not susceptible and determination to reduction, of which the acid-base is described sites by(types Equation and concentration (4): [46]), along with details of the instruments, are provided in our previous publication [10].O OH

3.2. Hydrogen Acceptors (4) Benzophenone (99%, Aldrich, Munich, Germany) was crystallized twice from ethanol. The puriﬁed product was 99.7% (GC) pure. The following derivatives of benzophenone were used: 2-methyl- (98%), 3-methyl- 3.(99%), Materials 4-methyl- and Methods (99%), 4-chloro- (99%), 4-bromo- (98%), 4-hydroxy- (98%) and 3.1.4-methoxybenzophenone Preparation of MgO and (97%),Its Characterization all from Aldrich. For puriﬁcation, they were crystallized from ethanol or distilled under reduced pressure. The method of preparation of the catalyst can be found in [12]. The fraction of MgO 4-Fluorobenzophenone was prepared by dropping benzoyl chloride to a suspen- used for the tests carried out in these studies was 0.40–0.63 mm for vapor and 0.16–0.40 sion of AlCl as catalyst in boiling fluorobenzene (an excess) and heating the reaction mm for the liquid3 phase. mixture under reflux for 13 h. Yield of distilled product 84%, b.p. 427-9 K/15 hPa (exp), The procedures of the following characterization, such as nitrogen physisorption, X- 432-4 K/17 hPa (lit), purity 99.4% (GC) (including 2.2% of 2-fluorobenzophenone), m.p. Ray314–318 Diffraction, K (exp), TG-DTA-MS 320-2 K (lit). measurements and determination of the acid-base sites (types2,4,6-Trimethylbenzophenone and concentration [46]), along was with synthesized details of in the our instruments, laboratory in are the provided reaction ofin ben-our previous publication [10]. zoyl chloride with mesitylene in the presence of anhydrous AlCl3 and purified by distillation under reduced pressure. Yield 73%, m.p. 308 K (exp), 307-8 K (lit), purity 99.4% (GC). 3.2. Hydrogen4-Nitrobenzophenone Acceptors was prepared by acylation of benzene with 4-nitrobenzoyl chlorideBenzophenone in the presence (99%, of Aldrich, anhydrous Munich, AlCl 3Germ. A crudeany) productwas crystallized was mixed twice with from charcoal ethanol.and The crystallized purified thriceproduc fromt was methanol-toluene 99.7% (GC) pure. solution. Yield 54%, m.p. 408–409 K (exp), 404-6The K (lit),following purity derivatives 99.0% (GC). of benzophenone were used: 2-methyl- (98%), 3-methyl- (99%),Fluorenone 4-methyl- (99%), (98%, Aldrich)4-chloro- (dibenzocyclopentadienone) (99%), 4-bromo- (98%), 4-hydroxy- was crystallized (98%) and twice4-methox- from ybenzophenoneethanol, mp. 355 (97%), K (exp), all 355-6from Aldrich. K (lit), purity For pu 99.1%rification, (GC). they were crystallized from ethanol or distilled under reduced pressure. 4-Fluorobenzophenone was prepared by dropping benzoyl chloride to a suspension of AlCl3 as catalyst in boiling fluorobenzene (an excess) and heating the reaction mixture under reflux for 13 h. Yield of distilled product 84%, b.p. 427-9 K/15 hPa (exp), 432-4 K/17 hPa (lit), purity 99.4% (GC) (including 2.2% of 2-fluorobenzophenone), m.p. 314–318 K (exp), 320-2 K (lit). 2,4,6-Trimethylbenzophenone was synthesized in our laboratory in the reaction of benzoyl chloride with mesitylene in the presence of anhydrous AlCl3 and purified by distillation under reduced pressure. Yield 73%, m.p. 308 K (exp), 307-8 K (lit), purity 99.4% (GC). 4-Nitrobenzophenone was prepared by acylation of benzene with 4-nitrobenzoyl chloride in the presence of anhydrous AlCl3. A crude product was mixed with charcoal and crystallized thrice from methanol-toluene solution. Yield 54%, m.p. 408–409 K (exp), 404-6 K (lit), purity 99.0% (GC). Fluorenone (98%, Aldrich) (dibenzocyclopentadienone) was crystallized twice from ethanol, mp. 355 K (exp), 355-6 K (lit), purity 99.1% (GC).

Catalysts 2021, 11, 574 13 of 16

1-Indanone (>99%, Aldrich) (benzocyclopentenone) was distilled under reduced pressure b.p 390-1 K/15 hPa (exp), 387-8 K/13 hPa (lit), solidiﬁes upon standing, m.p. 313-4 K (exp), 314-6 K (lit), purity 99.3% (GC). 1-Tetralone (>97%, Aldrich) (benzocyclohexenone) was distilled under reduced pressure, b.p. 396-8 K/15 hPa (exp), 394-5 K/13 hPa (lit), ﬁnal purity 98.3% (GC). Anthrone (dibenzocyclohexadienone) was obtained by reduction of anthraquinone (97%, Aldrich) with metallic tin and hydrochloric acid in boiling acetic acid as a solvent according to procedure described in [47]. The crude product mixed with charcoal was crystallized twice from a mixture of benzene-n-hexane (3: 1 v/v), m.p. 427-9 K (exp), 429 K (lit), purity 98.9% (GC).

3.3. Hydrogen Donors The hydrogen donor in each reaction was one of the following commercially available alcohols: ethanol (anhydrous, p.a., 99.8%), propan-2-ol (p.a., 99.8%) both from POCh Poland (Gliwice, Poland), 2-butanol (>99%), 2-pentanol (98%) and 2-octanol (97%), all three from Aldrich. Their puriﬁcation has been described by us before [12]. The ﬁnal purities of the last two alcohols were 98.9 and 98.4%, respectively. 2-Heptanol, 3-heptanol and 4-heptanol were prepared by the reduction of the appropriate ketones with sodium borohydride in a water-methanol solution. After fractional distillation through a 50 cm long Vigreux column their purities exceeded 99.5, 98.9 and 99.4% (GC), respectively. All distilled alcohols were kept dry in Schlenk–type containers under nitrogen.

3.4. Catalytic Activity Measurements In both modes of reaction, the transfer of the hydrogen is reversible. The values obtained from the GC determinations are therefore the resultant numbers of both the forward and backward reaction. Vapor phase. The experiments were carried out in a tubular glass reactor which contained a ﬁxed-bed with 250 ± 5 mg of MgO. A protective atmosphere was used when placing the catalyst in the reactor, as well as when ramping the temperature. The measurements were conducted between 573–723 K. After the desired temperature stabilized, the reagents were supplied to the reactor with a microdosing pump (LHSV = 3 h−1). The molar ratio of the hydrogen acceptor and hydrogen donor in the solution was 1:8. The conversion was determined based on the composition of the reaction products after 60 min of reaction. The reason for the delay was the fact that the catalyst is very active at the beginning and produces approximately 10% of products of aldol condensation of 2-octanone, but decreases sharply with the time of reaction and after 30 or so minutes it is no more than 1% and a steady state is reached. In order to get a representative sample, the products were collected for 30 min and then tested. Liquid phase. The tests were performed in a glass reactor, whose description has been given elsewhere [38], into which approximately 250 mg (±5 mg) of MgO was poured. Also for this mode of reaction a protective atmosphere was used when introducing the catalyst into the reactor. Next, the alcohol, ketone (usually 3.125 mmol) and internal standard were sequentially added to the reactor along with a magnetic bar, and the reactor was placed in a hot oil bath thermostat. The time of the beginning of the reaction was determined based on when the boiling point of the stirred mixture was reached. The side arm of the reactor was used to obtain samples for analysis (c.a. 0.05 cm3). After centrifuging (20 min, 3200 rpm) the liquid from above the catalyst was introduced into the gas chromatograph. Tests with recycled catalyst. In order to determine if the catalyst loses its activity in the reaction over time, the catalyst was recycled. After performing a 6 h test, the reactor was emptied and its content was centrifuged in order to remove as much of the liquid as possible. Without any additional treatment, the spent catalyst was suspended in a known volume of hydrogen donor and transferred back to the reactor. A known amount of benzophenone was added and the test was repeated. Such procedure was applied three times. Catalysts 2021, 11, 574 14 of 16

Scaling-up. In a two-necked round-bottomed flask equipped with a mechanical stirrer and a reflux condenser, 10.1 g (0.25 moles) of a freshly calcined MgO catalyst (0.10–0.25 mm of grain diameter) was loaded and mixed with 130.2 g (1 mole, 159 cm3) of 2-octanol. Benzophenone (22.8 g, 0.125 moles) was added in one portion to the suspension under stirring. The flask was heated in an electric mantle and the mixture was refluxed for 6 h. The extent of reaction was monitored by GC. After cooling to room temperature, the reaction mixture was separated by centrifuging and the catalyst was washed with diethyl ether (3 × 20 cm3). The washings were added to a main organic fraction and the solvent was distilled off. The residue was distilled under reduced pressure until the temperature of the vapors reached 383 K at 27 hPa. The crude product (23.5 g) was crystallized from ethanol, yield 20.5 g (89%), m.p. 336-7 K (exp), 338 K (lit).

3.5. Analytical Determinations The identification and quantification of each of the reaction products was performed by GC using a high-resolution gas chromatograph (KONIK, Barcelona, Spain) with a TRACER WAX capillary column (l = 30 m, i.d. = 0.25 mm) and Flame Ionized Detector. High boiling ketones like 4-nitrobenzophenone, 2-naphthyl phenyl ketone, anthrone and fluorenone, and the products derived from them were analyzed using a chromatograph (HP-6890, Hewlett-Packard, Palo Alto, CA, USA.) equipped with HP-1 column (length 60 m, 0.25 mm i.d.), FID. The compounds were identified by GC-MS (HP-6890N with a 5973N mass detector, Palo Alto, CA, USA.) and by comparison of the retention time with that of a standard sample. Tetradecane, t-butylbenzene or 1,3,5-tri-i-propylbenzene were used as the internal standard for quantitative analysis.

4. Conclusions Both vapor and liquid phase transfer hydrogenation of aromatic ketones with the use of secondary alcohols as the hydrogen donors has been successfully performed. It has been found that in the presence of MgO benzophenone is selectively reduced in a liquid phase by secondary aliphatic alcohols to benzhydrol with the yield, which itself depends strongly on several factors. Various secondary alcohols from 2-propanol to 2-octanol, whose boiling points range from 355 to 454 K have been investigated in this reaction. Quantitative yields of benzhydrol (98–99%) have only been observed for 2-octanol, the highest boiling hydrogen donor used. By changing the 2-octanol-benzophenone molar ratio, at a given duration of reaction (6 h), it was found that the maximum yield of benzhydrol is reached for D/A equal to 8. Altering the amount of catalyst used, the optimal mass was determined to be 250 mg for 3.125 mmol of the starting ketone. These conditions were used for the scale up. It has also been shown that the catalyst can be reused up to four times with no substantial loss of conversion or selectivity. Different derivatives of benzophenone with single substituents were used to study the impact of the type and position of the substituent on the activity and selectivity of the reaction. In short, the highest activity was noted for the unsubstituted ketone and all substituents lower the activity to a different extent. From the three studied halogens, ﬂuorine exerted the most pronounced effect on the yield of the alcohol. The presence of a methoxy group in the para position caused a decrease of the yield of alcohol, whereas the presence of an OH group renders the ketone completely unreactive. The side reactions were studied in detail for the Br-substituted benzophenone. It was shown that the choice of the hydrogen donor had a pronounced inﬂuence on the selectivity. The highest activity and selectivity were observed for 2-octanol. In the vapor phase studies it was demonstrated that in the lower region of the studied reaction temperatures (573–623 K) high conversions of benzophenone and its 3- and 4-methyl derivatives (85–90%), as well as high selectivities to the appropriate carbinols can be attained. The time-on-stream test showed that magnesium oxide exhibits stable activity and excellent selectivity in vapor phase transfer hydrogenation of benzophenone with 2-propanol. Catalysts 2021, 11, 574 15 of 16

Author Contributions: Conceptualization, M.G.; methodology, M.G.; formal analysis, M.G.; investigation, A.M., L.W., A.J. and M.T.; resources, M.G.; data curation, M.G.; writing—original draft preparation, M.G.; writing—review and editing, M.G.; supervision, M.G.; funding acquisition, M.G. All authors have read and agreed to the published version of the manuscript. Funding: The APC was funded by the Warsaw University of Technology. Data Availability Statement: Data is contained within the article. Acknowledgments: The work performed within the scope of the paper was funded by the Warsaw University of Technology. Conﬂicts of Interest: The authors declare no conﬂict of interest.

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