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K10 montmorillonite catalyzed C–C bond formation of aromatic secondary alcohols and alkynes: A green and convenient approach to β-aryl ketones under solvent-free conditions
Sustainable Chemistry and Pharmacy 15 (2020) 100227
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K10 montmorillonite catalyzed C–C bond formation of aromatic secondary alcohols and alkynes: A green and convenient approach to β-aryl ketones under solvent-free conditions Divya Rohini Yennamaneni a, b, Durgaiah Chevella a, Krishna Sai Gajula a, b, Narender Nama a, b, * a b
Catalysis and Fine Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500 007, India Academy of Scientific and Innovative Research, CSIR-HRDC Campus, Sector 19, Kamala Nehru Nagar, Ghaziabad, UP, 201002, India
A R T I C L E I N F O
A B S T R A C T
Keywords: Alcohols Alkynes C–C coupling Heterogeneous catalyst K10 montmorillonite
The synthesis of β-aryl ketones from aromatic alkynes and secondary alcohols catalyzed by heterogeneous K10 montmorillonite via C–C bond formation has been described. This method presents a green and facile approach for the synthesis of various β-aryl ketones. It is relevant to mention that this approach proceeds under solvent free conditions without any usage of further additives and immobilizations. Effect of amount of catalyst, reaction temperature and time on the yield of product have been investigated by using K10 montmorillonite. This process is sustainable and exhibiting good compatibility among a range of various aromatic alkynes and secondary al cohols affording moderate to excellent yields. The presence of unique layered structure as well as strong acidic sites in the K10 montmorillonite might be responsible for the formation of β-aryl ketones and these acidic sites were validated by temperature programmed desorption of ammonia (NH3-TPD) studies. Based on the in situ HRESI-MS and control experiments a tentative mechanism for the formation of β-aryl ketones using K10 montmorillonite as a catalyst was proposed. The efficacy and viability of scale-up of the present catalytic system was demonstrated with gram scale experiments (up to 10 g scale).
1. Introduction The reactions which involve carbon-carbon (C–C) formation portrays one of the most vigorous tools in the synthesis of complex organic moiety. These reactions play a vital role in the development of agro chemicals and bioactive molecules such as Rucaparib (anticancer, in Phase III), Ruxolitinib (myelofibrosis), Methcathinone (psychoactive stimulant), Methylone (arthritis) etc (Philipp et al., 2017). Traditionally, the C–C bond formation involves the coupling of an electrophile (C-X, X ¼ halide, triflate, tosylate, mesylate etc.) with a nucleophile, generally an organometallic reagent (C-M; M ¼ Mg, Zn, Sn etc.) (Meijere and Diederich, 2004; Mehta and Eycken, 2011; Suzuki, 2011). Though, moisture sensitivity, associated degree of toxicity as well as poor func tional group tolerance of these reagents makes this approach quite un attractive. Hence, coupling of an electrophile (C-X) and inactivated substrate (C–H) with more atom economy have been being extensively exploring. However, commercial unavailability of the C-X species sometimes demands extra steps for their synthesis. Concerning this, the construction and development of new C–C bond from inexpensive and
harmless precursors, for the synthesis of biologically important mole cules which facilitates atom economy, serves as an important pursuit in the perspective of sustainable chemistry (Anastas and Eghbali, 2010). In recent times, numerous alternative strategies have been evinced for the development of C–C bond by employing abundantly available pre cursors via C–H activation, use of aryl hydrazones, decarboxylative coupling etc (Kang et al., 2008; Shao and Zhang, 2012). Accordingly, an ideal process for the formation of C–C bond would be the direct reaction of C–OH bond with C–H bond, as the by-product is only water that is non-toxic and without requirement of any wasteful prefunctionaliza tion. In this process, a new C–C bond was developed with the formal release of water from reacting substrates. The direct dehydrative coupling methodologies have been increasing apparently during the last decade. Among different types of alcohols, possessing active sp3 C–OH bond such as allylic, benzylic and propargylic alcohols had been broadly studied as proelectrophiles (Ackermann et al., 2012). This direct dehy drative coupling of alcohols with several alkynes has been emerging as the potential strategy to form C–C bonds due to its characteristic waste free process. Here it is relevant to mention that the coupling approach of
* Corresponding author. Catalysis and Fine Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500 007, India. E-mail addresses: [email protected], [email protected] (N. Nama). https://doi.org/10.1016/j.scp.2020.100227 Received 25 October 2019; Received in revised form 31 January 2020; Accepted 1 February 2020 Available online 12 February 2020 2352-5541/© 2020 Elsevier B.V. All rights reserved.
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alcohols with alkynes beneath different conditions afforded different products. Value added complex moieties were synthesized by the direct functionalization of C–H to C-E (E ¼ C, O, N). Consequently, function alization of C–H bonds in a direct and catalytic pathway has been an intriguing research topic over the past two decades and has evolved as an indispensable tool in synthetic chemistry (Patai, 1994). Carbonyl compounds are ubiquitous in nature. Out of which, ketone moieties are extensively present in diversified bioactive molecules and functional materials. Despite of many existing methods for the synthesis of ketone compounds, most viable and atom economical process is the hydration of alkynes. As a result, a variety of approaches have been demonstrated for alkynes hydration (Thomas et al., 1938; Mameda et al., 2015). These compounds can be easily transformed into a distinct functional groups and recurrently used as pliable synthetic in termediates. β-Unsaturated carbonyl compounds represents significant building blocks as they stimulate further functionalization by several reactions. In fact, such substrates are renowned reagents for cycload dition reactions and conjugated additions (Imamoto et al., 1989; Huang et al., 2015). To date, an avalanche of innovative approaches has been sprung up for the synthesis of β-substituted ketones which depicts prominent class of typical motifs in bioactive compounds like drug candidatures, antioxidants and pesticides. Amidst of all prevailing re ports, synthesis of β-aryl carbonyl compounds from alcohols and alkynes draws prominence because of its high atom economy, ready availability and reaction feasibility (Thompson, 1991; Thiyagarajan and Gunana than, 2019). Jana and co-workers reported the iron(iii)-chloride cata lyzed addition of benzylic alcohols and aryl alkynes in nitromethane to afford β-substituted ketones (Jana et al., 2008). In order to improve the yield, Latisha et al. have reported using FeCl3 and AgSbF6 as catalysts in dichloroethane (Jefferies and Cook, 2014). Recently, Bhanage et al. disclosed the synthesis of aryl ketones by amberlyst-15 immobilized in [Bmim][PF6] ionic liquid. Ionic liquids are combustible and require careful handling also causes severe aquatic toxicity as or more than many currently employing organic solvents (Wagh and Bhanage, 2015; Zhao et al., 2007; Ranke et al., 2007). Niggemann et al. demonstrated the calcium-catalyzed intermolecular carbohydroxylation of alkynes (Stopka and Niggemann, 2015). More recently, Yang and co-workers developed phosphomolybdic acid-catalyzed synthesis of substituted β-aryl ketones in organic carbonate as a solvent (Yang et al., 2017). However, these methods thus far illustrated often suffer from disad vantages like requirements for transition metal catalysts, harmful organic solvents, tedious workup procedures, difficulty in separation and drastic reaction conditions. The forthcoming area of synthetic chemistry is solvent-free organic chemical transformations overwhelming the earlier belief “No solvent no reaction”. In fact, these reactions are more effective when compared to reactions that take place in solvents. Such reactions are easy to handle, economically cheap, brings down pollution and are of great pinnacle to current industry (Tanaka, 2006). In addition, the develop ment of design and use of catalysts is rapid which provokes sustainable and efficient chemistry. Nevertheless, despite the high interest for such reactions and the expected enhancement of selectivity and reactivity certainly demands search of more efficient catalysts. There occurs a necessity to develop environmentally benign processes that are secure and practical (Clark, 1995; Matlack, 2003). In view of addressing environment blended with economic aspects, heterogeneous catalysts by means of stable and well-defined active sites present on the surface, are currently being paid significant attention, because of their distinc tive properties such as recovery of catalyst, ease of handling and sepa ration. Among many prevailing methods, the use of solid acids derived from soil are the most noteworthy catalysts. Notably, Clays and zeolites, well-known for their acid activity, possess many advantages like com mercial availability, cost effectiveness, easy handling, non-corrosiveness, reusability, have marked their prominence in organic transformations over past decade. In particular, many heterogeneous catalysts act as promising candidates which substitutes liquid acids in
Scheme 1. C–C bond formation between aromatic alkyne and alcohol. Table 1 Optimization of reaction conditionsa.
Entry
Catalyst
Solvent
Time (h)
Yield(b) 3a (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
NaY HY MCM-41 H-ZSM-5 H-mordenite Hβ K10 montmorillonite Amberlyst-15 SiO2–Al2O3 TS-1 PTSA L-Proline K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite Without catalyst
DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE Toluene H2O DCM Methanol No solvent No solvent No solvent No solvent No solvent No solvent No solvent No solvent No solvent
3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 2 4 3 3 3 3 3 3
00 04 00 00 19 11 68 26 00 00 27 00 42 00 34 00 67 60 67 67 c 58 d 36 e 45c,f 67c,g 00
a Reaction conditions: 1a (1 mmol), 2a (1.2 mmol), solvent (2 mL), catalyst (100 mg), 70 � C. b Isolated yields based on 1a. c Catalyst (75 mg). d Catalyst (50 mg). e Catalyst (25 mg). f Temperature-60 � C. g Temperature-80 � C.
many renowned chemical transformations (Laszlo, 1990; Izumi et al., 1992; Balogh and Laszlo, 1993; Surjyakanta et al., 2015, 2019a, 2019b). Clay catalysts being a group of aluminosilicates (Al2Si4O10(OH)2. nH2O) contains both Brønsted and Lewis acid sites, are most widely studied under liquid phase organic transformations (Li et al., 2004; Varadwaj et al., 2014, 2016; Sujit et al., 2015). These are layered sili cates consisting exchangeable interlayer cations and by simple ion-exchange process it allows change in acidic nature of the material (Sartori et al., 2004; Kaur and Kishore, 2012). The increasing demand in support of environmentally benign nature insisted us to develop an alternate synthesis for β-aryl ketones. In continuation to our work on the utility of heterogeneous solid acid catalysts (Chevella et al., 2019a, 2019b), herein we disclose an 2
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D.R. Yennamaneni et al.
Table 2 Alkynes variationa.
Entry
Alkyne
Time (h)
Product
Yield (%)b
1
3
67
2
3
86
3
4
91
4
3
82
5
2
87
6
4
86
7
4
85
8
8
52
9
8
51
10
12
00
11
4
00
(continued on next page)
3
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Table 2 (continued ) Entry
Alkyne
Time (h)
Product
Yield (%)b
12
8
00
13
12
00
14
3
76
a b
Reaction conditions: 1a-1n (1 mmol), 2a (1.2 mmol), K10 montmorillonite (75 mg), 70 � C, sealed vial. Isolated yields based on alkyne (1a-1n).
atom-economical, solvent-free and sustainable carbon-carbon coupling reaction of alkynes with secondary alcohols for the synthesis of β-aryl ketones catalyzed by K10 montmorillonite under feasible conditions (Scheme 1).
to presence of strong acidic sites and distinctive layered structure that might responsible for the formation of our desired product in higher yield. 3.2. Optimization of reaction conditions
2. Material and methods
Directly after, we focused our efforts to enhance the yield of our desired product. We tested this reaction with solvents like toluene, water, DCM, methanol as well as without solvent (Table 1, entries 13–17). To our amuse, 67% yield was obtained under solvent free condition and this is because due to the availability of high concentra tions of reagents which indeed leads to more interactions between these reagent molecules compared to solvent based reactions. However, the yield of our required product was found to be same in the case of aprotic polar solvent DCE but with the environmental consciousnesss and con ept of sustainability we continued to work under solvent-free conditions (Table 1, entry 17). Subsequent studies on reaction time, amount of catalyst found that decrease in reaction time resulted in the low yield and increase in reaction time did not exhibit any remarkable change (Table 1, entries 18 & 19). Later on we turned our attention to the variable amount of catalyst from which we are glad to notice that only 75 mg of catalyst is sufficient to furnish good yield of our desired product (Table 1, entries 20–22). Next we changed the temperature of reaction to 60 � C with this decrease in temperature the yield of required product was reduced and upon increase in temperature to 80 � C no drastic alteration observed (Table 1, entries 23 & 24). When we per formed this reaction in the absence of catalyst the reaction had not undergone and the role of catalyst is justified (Table 1, entry 25). Based on these observations, the optimized conditions were chosen as 1 mmol of phenylacetylene to 1.2 mmol of diphenylmethanol with 75 mg of catalyst and a reaction temperature of 70 � C for 3 h without any solvent.
The alkyne (1 mmol) and alcohol (1.2 mmol) were taken in a 9 mL sealed vial and 75 mg of K10 montmorillonite was added to it. The re action was carried out at 70 � C temperature with stirring. After disap pearance of the substrate (monitored by TLC) or after an appropriate time, the reaction mixture was cooled to room temperature and diluted with ethyl acetate (3 � 5 mL). Simple filtration separated the catalyst (K10 montmorillonite), and the removal of solvent in vacuo yielded crude. The crude was further purified by column chromatography using silica gel (100–200 mesh) to afford pure products and these identified based on 1H, 13C NMR, and mass spectral data. 3. Results and discussion 3.1. Catalyst screening In order to validate our demonstration, we commenced our studies by choosing diphenylmethanol and phenylacetylene as model substrates and the reaction carried out at 70 � C for 3 h in DCE screening different heterogeneous and homogeneous catalysts (Table 1, entries 1–12). Fortunately, this reaction when performed with K10 montmorillonite gave the best yield of corresponding β-aryl ketone among different catalysts (Table 1, entry 7). This might be due to the presence of unique intrinsic inorganic layered structures which are main characteristics of clays and thus these layers enable the mobility of compounds more feasibly when compared to microporous zeolites (NaY, HY, HZSM-5, Hmordenite, Hβ, TS-1). Due to lesser diffusion of reagents and reaction products through these micropores of zeolites results in the low yield of desired product. From NH3-TPD studies (Table S1, Fig. S1), MCM-41 (mesoporous) and SiO2–Al2O3 does not possess strong acidic sites. Whereas in Amberlyst-15 (macroporous) the presence of strong acidic sites were found to be low when compared to K10 montmorillonite. K10 montmorillonite was found to be the most active catalyst probably due
3.3. Variation of aromatic alkynes Following these optimized studies, we then investigated scope of the aromatic alkyne derivatives with diphenyl methanol 2a as the coupling partner under optimized conditions. As depicted in Table 2, an extensive range of alkynes having electron-donating groups at ortho, meta and para positions were well tolerated and afforded the corresponding β-aryl 4
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3ab, 3ac achieved in moderate yields (Table 3, entries 1 & 2). 4-Chlor obenzhydrol also reacted smoothly to provide the respective product 3ad in 61% yield (Table 3, entry 3). Similarly, 1-phenylethanol also reacted well and our required product 3ae obtained in 68% yield (Table 3, entry 4). 4-Fluoro-α-methylbenzyl alcohol and 4-bromoα-methylbenzyl alcohol were tolerated well under standard reaction conditions and gave the desired products 3af, 3ag in 62% and 48% yields, respectively (Table 3, entries 5 & 6).
Table 3 Aromatic alcohols variationa.
3.5. Gram scale reactions Entry
Alcohol
Time (h)
product
Yield (%)b
1
5
69
2
3
46
3
4
61
4
5
68
5
8
62
6
6
48
To highlight the practical viability of this protocol, we have con ducted large-scale reactions (10, 30, 60 mmol) of phenylacetylene 1a and diphenylmethanol 2a under optimized conditions. All the preparative-scale reactions proceeded smoothly and were outlined in Scheme 2. 3.6. Reusability studies We also tested the reusability of K10 montmorillonite by performing the reaction with phenyl acetylene and diphenyl methanol under stan dard reaction conditions. After the reaction, K10 montmorillonite was recovered by simple filtration then washed with ethyl acetate and dried at 120 � C for 6 h in an oven. This dried catalyst was reused for next cycle of reaction. There was gradual decrease observed in the yield of product for the consecutive 5 cycles (Table S2). XRD study was done to validate the crystalline structure of K10 montmorillonite before and after the reaction (Fig. S2 (a) and Fig. S2 (b)). From the figures, it is clear that the intensity as well as the sharpness of the XRD peaks confirmed the high crystallinity of the material and shown similar diffraction peaks that indicate the structure has been retained during and after the reaction (Nur Fatin et al., 2015). Similarly, SEM analysis of K10 montmorillonite shows irregular structures with non-uniform size distribution of flakes. SEM analysis of used catalyst had similar appearance compared to fresh catalyst (Fig. S3). To explore the thermal stability we have characterized TG-DTA of fresh and used catalysts that are shown in Fig. S4. The thermal analysis of fresh catalyst shows a weight loss about 10% at the temperature of 25–250 � C due to physically adsorbed water molecules. The weight loss about 3% at the temperature of 250–550 � C is due to the loss of water molecules bonded to the clay. The weight loss about 2% at the temperature of 550–800 � C is due to the loss of hydroxyl groups of the clay (Gustavo et al., 2018). The thermal analysis of used catalyst shows similar weight loss trends compared to fresh catalyst and there is no significant difference in the TG-DTA data of fresh and used catalyst. This result confirms that there is no significant amount of reactants or products remains adsorbed on the used catalyst (Fig. S4). In order to come by with perception of reaction mechanism, we have performed in situ HRESI-MS experiment (Fig. S5) and few control ex periments (Scheme 3) to gain the experimental evidence about the reactive intermediates formed in situ under standard reaction conditions.
a Reaction conditions: 1a (1 mmol), 2ab-2ag (1.2 mmol), K10 montmoril lonite (75 mg), 70 � C, sealed vial. b Isolated yields based on alkyne (1a).
ketones 3b-3e in excellent yields (Table 2, entries 2–5). Strong electronwithdrawing group present on aryl ring of phenyl acetylene 1j upon increasing reaction time also did not furnish desired product (Table 2, entry 10). These results shows that the presence of activating groups on aromatic ring of phenyl acetylene facilitates the reaction, whereas electron deactivating groups were found to be dormant. Halogen sub stituents like fluorine, chlorine and bromine were fine compatible, facilitating the products 3f-3i in 86%, 85%, 52% and 51% yields, respectively (Table 2, entries 6–9). This might be due to the inductive and resonance phenomena of halogen groups present on the aryl ring of phenyl acetylene. Disappointingly, naphthalene and anthracene derived compounds did not react with diphenyl methanol even after extension of reaction time (Table 2, entries 11 & 12). Terribly, electron-poor het erocyclic compound i.e. 3-ethynylpyridine did not react even after prolonged reaction time, whereas electron-rich heterocycle like 2-ethy nylthiophene reacted and produced the corresponding product 3n in 76% yield under standard conditions (Table 2, entries 13 & 14).
3.7. Control experiments When phenylacetylene 1a reacted with K10 montmorillonite under solvent free conditions at 70 � C for 3 h no reaction observed [Eq. (1)]. Whereas, diphenylmethanol was easily converted into dimeric ether 2a′ under the standard conditions anticipating that this reaction proceeds via an ether intermediate [Eq. (2)]. This dimeric ether was isolated and characterized by NMR (spectral data given in SI). We have also con ducted a reaction of phenylacetylene with dimeric ether in the presence of these standard reaction conditions and afforded the desired product in 52% yield [Eq. (3)]. Based on the literature precedent, in situ HRESI-MS and control ex periments, it is assumed that diphenylmethanol 2a is quick in conver sion to carbocation A (detected by in situ HRESI-MS) and forms dimeric ether 2a′ by self-coupling in the presence of Brønsted acidic sites of K10
3.4. Variation of aromatic alcohols Succeeding, we then turned our attention to extend the scope of this reaction to several alcohols coupled with phenylacetylene under stan dard reaction conditions. From Table 3, we can depict typical aromatic alcohols such as electron donating methyl groups on different sub stitutions of benzhydrol were screened and our desired β-aryl ketones 5
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Scheme 2. Large-scale experiments for the synthesis of 1,3,3-triphenylpropan-1-one (3a) from phenylacetylene (1a) and diphenylmethanol (2a).
Scheme 3. Control experiments for mechanistical studies.
montmorillonite followed by nucleophilic attack of alkyne 1a leads to alkenyl cation B (detected by in situ HRESI-MS). Lastly, addition of water within onto the alkenyl cation generated in situ undergoes deprotonation followed by tautomerism furnishes required product 3a (Scheme 4).
the structure of the catalyst along with the acidity plays a crucial role for the establishment of reaction. This protocol provides a good range of β-aryl ketones in shorter reaction times under non-toxic environment. The scope and limitations of this method were investigated with various alkynes containing halo, electron withdrawing and electronic donating groups on an aromatic ring and different substituted like methyl and halo secondary alcohols. The recyclability studies showed a gradual decrease in the activity of catalyst. The in situ HRMS detection of reac tive intermediates and control experiments provided the firm support for the reaction mechanism. Moreover, the synthetic utility of this method has been presented by performing scale up experiments (5 g, 10 g) beneath standard conditions. Notable advantages offered by this
4. Conclusions In conclusion, we have demonstrated a facile approach for the syn thesis of β-aryl ketones by using simple and readily available K10 montmorillonite as heterogeneous catalyst without any immobilized solutions and additives under solvent-free conditions. Comparison of the catalytic properties of various solid heterogeneous catalysts shows that 6
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Scheme 4. Probable mechanism for the formation of β-aryl ketones.
method are absence of organic solvent, good substrate scope, high atom economy, use of non-hazardous catalysts, simple work-up procedure and mild reaction conditions, water as by-product which makes it significant and useful alternative to the existing methods.
Chevella, D., Macharla, A.K., Kodumuri, S., Banothu, R., Gajula, K.S., Amrutham, V., Gennadievna, G.N., Nama, N., 2019a. Catal. Commun. 123, 114–118. https://doi. org/10.1016/j.catcom.2019.01.027. Chevella, D., Macharla, A.K., Banothu, R., Gajula, K.S., Amrutham, V., Boosa, M., Nama, N., 2019b. Green Chem. 21, 2938–2945. https://doi.org/10.1039/ c9gc00541b. Clark, J.H., 1995. Chemistry of Waste Minimization. Chapman and Hall, London, ISBN 978-94-011-0623-8. Gustavo, R.P., Cristina, M.S., Ramon, Z.N., Rafael, R.T., Raul, M.A., 2018. Instrum. Sci. Technol. 46, 676–692. https://doi.org/10.1080/10739149.2018.1443121. Huang, Z., Nam Lim, H., Mo, F., Young, M.C., Dong, G., 2015. Chem. Soc. Rev. 44, 7764–7786. https://doi.org/10.1039/C5CS00272A. Imamoto, T., Takiyama, N., Nakamura, K., Hatajima, T., Kamiya, Y., 1989. J. Am. Chem. Soc. 111, 4392–4398. https://doi.org/10.1021/ja00194a037. Izumi, Y., Urabe, K., Onaka, M., 1992. Zeolite, Clay and Heteropoly Acid in Organic Chemistry. Kodansha-VCH, Tokyo-Weinheim, ISBN 3-527-29011-7. Jana, U., Biswas, S., Maiti, S., 2008. Eur. J. Org Chem. 5798–5804. https://doi.org/ 10.1002/ejoc.200800713. Jefferies, L.R., Cook, S.P., 2014. Tetrahedron 70, 4204–4207. https://doi.org/10.1016/j. tet.2014.03.072. Kang, F.A., Sui, Z., Murray, W.V., 2008. J. Am. Chem. Soc. 130, 11300–11302. https:// doi.org/10.1021/ja804804p. Kaur, N., Kishore, D., 2012. J. Chem. Pharmaceut. Res. 4, 991–1015. ISSN: 0975-7384. Laszlo, P., 1990. Pure Appl. Chem. 62, 2027–2030. https://doi.org/10.1351/ pac199062102027. Li, J., Xing, C., Li, T., 2004. J. Chem. Technol. Biotechnol. 79, 1275–1278. https://doi. org/10.1002/jctb.1123. Mameda, N., Peraka, S., Marri, M.R., Kodumuri, S., Chevella, D., Gutta, N., Nama, N., 2015. Appl. Catal., A 505, 213–216. https://doi.org/10.1016/j.apcata.2015.07.038. Matlack, A., 2003. Green Chem. G7 https://doi.org/10.1039/B300501C. Mehta, V.P., Eycken, E.V.V., 2011. Chem. Soc. Rev. 40, 4925–4936. https://doi.org/ 10.1039/C1CS15094D. Meijere, A.D., Diederich, F., 2004. Metal-Catalyzed Cross-Coupling Reactions, second ed. Wiley VCH, Weinheim. https://doi.org/10.1002/9783527619535. Nur Fatin, D.C.H., Farah, W.H., Juliana, J., Siti, S.O., 2015. J. Ind. Eng. Res. 1, 8–13. ISSN: 2077-4559. Patai, S., 1994. Chemistry of Triple-Bonded Functional Groups. Wiley, New York, NY, ISBN 978-0-470-77156-3, pp. 689–737. Philipp, S., Thomas, P., Mireia, S., Stephen, P.F., 2017. Nat. Commun. 8, 1–12. https:// doi.org/10.1038/ncomms15762. Ranke, J., Stolte, S., Stormann, R., Arning, J., Jastorff, B., 2007. Chem. Rev. 107, 2183–2206. https://doi.org/10.1021/cr050942s. Sartori, G., Ballini, R., Bigi, F., Bosica, G., Maggi, R., Righi, P., 2004. Chem. Rev. 104, 199–250. https://doi.org/10.1021/cr0200769. Shao, Z., Zhang, H., 2012. Chem. Soc. Rev. 41, 560–572. https://doi.org/10.1039/ C1CS15127D. Stopka, T., Niggemann, M., 2015. Org. Lett. 17, 1437–1440. https://doi.org/10.1021/ acs.orglett.5b00312. Sujit, P.C., Varadwaj, G.B.B., Kulamani, P., Bhalchandra, M.B., 2015. Appl. Catal., A 506, 237–245. https://doi.org/10.1016/j.apcata.2015.09.019. Surjyakanta, R., Suresh, M., Kotaiah, Y., Sreekantha, B.J., 2015. Appl. Catal., A 505, 539–547. https://doi.org/10.1016/j.apcata.2015.07.018. Surjyakanta, R., Varadwaj, G.B.B., Jonnalagadda, S.B., 2019a. Nanoscale Adv. 1, 1527–1530. https://doi.org/10.1039/c8na00245b.
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CRediT authorship contribution statement Divya Rohini Yennamaneni: Methodology, Investigation, Writing original draft. Durgaiah Chevella: Conceptualization, Investigation. Krishna Sai Gajula: Writing - review & editing, Resources. Narender Nama: Supervision, Project administration, Funding acquisition. Acknowledgements We thank the DST, New Delhi for financial support under Indo-Russia (DST-RSF) (No. INT/RUS/RSF/P-7) programme. Y. D., Ch. D. and G. K. acknowledge the CSIR, India for financial support in the form of fellowship. We thank Director CSIR-IICT (IICT/Pubs./2019/309) for providing all the required facilities to carry out the work. Also we appreciate support from Rammurthy Banothu for validation, Murali Boosa for visualization and Sai Krishna Ganji for in situ HRESI-MS studies. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi. org/10.1016/j.scp.2020.100227. References Ackermann, L., Pospech, J., Potukuchi, H.K., 2012. Org. Lett. 14, 2146–2149. https:// doi.org/10.1021/ol300671y. Anastas, P., Eghbali, N., 2010. Chem. Soc. Rev. 39, 301–312. https://doi.org/10.1039/ B918763B. Balogh, M., Laszlo, P., 1993. Organic Chemistry Using Clays. Springer Verlog, New York, ISBN 978-3-540-55710-4.
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Surjyakanta, R., Varadwaj, G.B.B., Sreekantha, B.J., 2019b. RSC Adv. 9, 13332–13335. https://doi.org/10.1039/C9RA01715A. Suzuki, A., 2011. Angew. Chem. Int. Ed. 50, 6723–6737. https://doi.org/10.1002/ anie.201101379. Tanaka, K., 2006. Solvent Free Organic Synthesis. John Wiley & Sons, ISBN 978-3-52760536-1. Thiyagarajan, S., Gunanathan, C., 2019. J. Am. Chem. Soc. 141, 3822–3827. https://doi. org/10.1021/jacs.9b00025. Thomas, R.J., Campbell, K.N., Hennion, G.F., 1938. J. Am. Chem. Soc. 60, 718–720. https://doi.org/10.1021/ja01270a061. Thompson, D.J., 1991. In: Trost, B.M., Fleming, I. (Eds.), Comprehensive Organic Synthesis, vol. 3. Pergamon, Oxford, pp. 1015–1043. https://doi.org/10.1016/B9780-08-052349-1.00088-3.
Varadwaj, G.B.B., Surjyakanta, R., Kulamani, P., 2014. J. Phys. Chem. C 118, 1640–1651. https://doi.org/10.1021/jp410709n. Varadwaj, G.B.B., Kulamani, P., Vincent, O.N., 2016. Inorg. Chem. Front. 3, 1100–1111. https://doi.org/10.1039/C6QI00179C. Wagh, K.V., Bhanage, B.M., 2015. Synlett 26, 759–764. https://doi.org/10.1055/s-00341380142. Yang, G.P., Zhang, N., Ma, N.N., Yu, B., Hu, C., 2017. Adv. Synth. Catal. 359, 926–932. https://doi.org/10.1002/adsc.201601231. Zhao, D., Liao, Y., Zhang, Z., 2007. Clean 35, 42–48. https://doi.org/10.1002/ clen.200600015.
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K10 montmorillonite catalyzed C–C bond formation of aromatic secondary alcohols and alkynes: A green and convenient approach to β-aryl ketones under solvent-free conditions Divya Rohini Yennamaneni a, b, Durgaiah Chevella a, Krishna Sai Gajula a, b, Narender Nama a, b, * a b
Catalysis and Fine Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500 007, India Academy of Scientific and Innovative Research, CSIR-HRDC Campus, Sector 19, Kamala Nehru Nagar, Ghaziabad, UP, 201002, India
A R T I C L E I N F O
A B S T R A C T
Keywords: Alcohols Alkynes C–C coupling Heterogeneous catalyst K10 montmorillonite
The synthesis of β-aryl ketones from aromatic alkynes and secondary alcohols catalyzed by heterogeneous K10 montmorillonite via C–C bond formation has been described. This method presents a green and facile approach for the synthesis of various β-aryl ketones. It is relevant to mention that this approach proceeds under solvent free conditions without any usage of further additives and immobilizations. Effect of amount of catalyst, reaction temperature and time on the yield of product have been investigated by using K10 montmorillonite. This process is sustainable and exhibiting good compatibility among a range of various aromatic alkynes and secondary al cohols affording moderate to excellent yields. The presence of unique layered structure as well as strong acidic sites in the K10 montmorillonite might be responsible for the formation of β-aryl ketones and these acidic sites were validated by temperature programmed desorption of ammonia (NH3-TPD) studies. Based on the in situ HRESI-MS and control experiments a tentative mechanism for the formation of β-aryl ketones using K10 montmorillonite as a catalyst was proposed. The efficacy and viability of scale-up of the present catalytic system was demonstrated with gram scale experiments (up to 10 g scale).
1. Introduction The reactions which involve carbon-carbon (C–C) formation portrays one of the most vigorous tools in the synthesis of complex organic moiety. These reactions play a vital role in the development of agro chemicals and bioactive molecules such as Rucaparib (anticancer, in Phase III), Ruxolitinib (myelofibrosis), Methcathinone (psychoactive stimulant), Methylone (arthritis) etc (Philipp et al., 2017). Traditionally, the C–C bond formation involves the coupling of an electrophile (C-X, X ¼ halide, triflate, tosylate, mesylate etc.) with a nucleophile, generally an organometallic reagent (C-M; M ¼ Mg, Zn, Sn etc.) (Meijere and Diederich, 2004; Mehta and Eycken, 2011; Suzuki, 2011). Though, moisture sensitivity, associated degree of toxicity as well as poor func tional group tolerance of these reagents makes this approach quite un attractive. Hence, coupling of an electrophile (C-X) and inactivated substrate (C–H) with more atom economy have been being extensively exploring. However, commercial unavailability of the C-X species sometimes demands extra steps for their synthesis. Concerning this, the construction and development of new C–C bond from inexpensive and
harmless precursors, for the synthesis of biologically important mole cules which facilitates atom economy, serves as an important pursuit in the perspective of sustainable chemistry (Anastas and Eghbali, 2010). In recent times, numerous alternative strategies have been evinced for the development of C–C bond by employing abundantly available pre cursors via C–H activation, use of aryl hydrazones, decarboxylative coupling etc (Kang et al., 2008; Shao and Zhang, 2012). Accordingly, an ideal process for the formation of C–C bond would be the direct reaction of C–OH bond with C–H bond, as the by-product is only water that is non-toxic and without requirement of any wasteful prefunctionaliza tion. In this process, a new C–C bond was developed with the formal release of water from reacting substrates. The direct dehydrative coupling methodologies have been increasing apparently during the last decade. Among different types of alcohols, possessing active sp3 C–OH bond such as allylic, benzylic and propargylic alcohols had been broadly studied as proelectrophiles (Ackermann et al., 2012). This direct dehy drative coupling of alcohols with several alkynes has been emerging as the potential strategy to form C–C bonds due to its characteristic waste free process. Here it is relevant to mention that the coupling approach of
* Corresponding author. Catalysis and Fine Chemicals Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, Telangana, 500 007, India. E-mail addresses: [email protected], [email protected] (N. Nama). https://doi.org/10.1016/j.scp.2020.100227 Received 25 October 2019; Received in revised form 31 January 2020; Accepted 1 February 2020 Available online 12 February 2020 2352-5541/© 2020 Elsevier B.V. All rights reserved.
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alcohols with alkynes beneath different conditions afforded different products. Value added complex moieties were synthesized by the direct functionalization of C–H to C-E (E ¼ C, O, N). Consequently, function alization of C–H bonds in a direct and catalytic pathway has been an intriguing research topic over the past two decades and has evolved as an indispensable tool in synthetic chemistry (Patai, 1994). Carbonyl compounds are ubiquitous in nature. Out of which, ketone moieties are extensively present in diversified bioactive molecules and functional materials. Despite of many existing methods for the synthesis of ketone compounds, most viable and atom economical process is the hydration of alkynes. As a result, a variety of approaches have been demonstrated for alkynes hydration (Thomas et al., 1938; Mameda et al., 2015). These compounds can be easily transformed into a distinct functional groups and recurrently used as pliable synthetic in termediates. β-Unsaturated carbonyl compounds represents significant building blocks as they stimulate further functionalization by several reactions. In fact, such substrates are renowned reagents for cycload dition reactions and conjugated additions (Imamoto et al., 1989; Huang et al., 2015). To date, an avalanche of innovative approaches has been sprung up for the synthesis of β-substituted ketones which depicts prominent class of typical motifs in bioactive compounds like drug candidatures, antioxidants and pesticides. Amidst of all prevailing re ports, synthesis of β-aryl carbonyl compounds from alcohols and alkynes draws prominence because of its high atom economy, ready availability and reaction feasibility (Thompson, 1991; Thiyagarajan and Gunana than, 2019). Jana and co-workers reported the iron(iii)-chloride cata lyzed addition of benzylic alcohols and aryl alkynes in nitromethane to afford β-substituted ketones (Jana et al., 2008). In order to improve the yield, Latisha et al. have reported using FeCl3 and AgSbF6 as catalysts in dichloroethane (Jefferies and Cook, 2014). Recently, Bhanage et al. disclosed the synthesis of aryl ketones by amberlyst-15 immobilized in [Bmim][PF6] ionic liquid. Ionic liquids are combustible and require careful handling also causes severe aquatic toxicity as or more than many currently employing organic solvents (Wagh and Bhanage, 2015; Zhao et al., 2007; Ranke et al., 2007). Niggemann et al. demonstrated the calcium-catalyzed intermolecular carbohydroxylation of alkynes (Stopka and Niggemann, 2015). More recently, Yang and co-workers developed phosphomolybdic acid-catalyzed synthesis of substituted β-aryl ketones in organic carbonate as a solvent (Yang et al., 2017). However, these methods thus far illustrated often suffer from disad vantages like requirements for transition metal catalysts, harmful organic solvents, tedious workup procedures, difficulty in separation and drastic reaction conditions. The forthcoming area of synthetic chemistry is solvent-free organic chemical transformations overwhelming the earlier belief “No solvent no reaction”. In fact, these reactions are more effective when compared to reactions that take place in solvents. Such reactions are easy to handle, economically cheap, brings down pollution and are of great pinnacle to current industry (Tanaka, 2006). In addition, the develop ment of design and use of catalysts is rapid which provokes sustainable and efficient chemistry. Nevertheless, despite the high interest for such reactions and the expected enhancement of selectivity and reactivity certainly demands search of more efficient catalysts. There occurs a necessity to develop environmentally benign processes that are secure and practical (Clark, 1995; Matlack, 2003). In view of addressing environment blended with economic aspects, heterogeneous catalysts by means of stable and well-defined active sites present on the surface, are currently being paid significant attention, because of their distinc tive properties such as recovery of catalyst, ease of handling and sepa ration. Among many prevailing methods, the use of solid acids derived from soil are the most noteworthy catalysts. Notably, Clays and zeolites, well-known for their acid activity, possess many advantages like com mercial availability, cost effectiveness, easy handling, non-corrosiveness, reusability, have marked their prominence in organic transformations over past decade. In particular, many heterogeneous catalysts act as promising candidates which substitutes liquid acids in
Scheme 1. C–C bond formation between aromatic alkyne and alcohol. Table 1 Optimization of reaction conditionsa.
Entry
Catalyst
Solvent
Time (h)
Yield(b) 3a (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
NaY HY MCM-41 H-ZSM-5 H-mordenite Hβ K10 montmorillonite Amberlyst-15 SiO2–Al2O3 TS-1 PTSA L-Proline K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite K10 montmorillonite Without catalyst
DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE Toluene H2O DCM Methanol No solvent No solvent No solvent No solvent No solvent No solvent No solvent No solvent No solvent
3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 2 4 3 3 3 3 3 3
00 04 00 00 19 11 68 26 00 00 27 00 42 00 34 00 67 60 67 67 c 58 d 36 e 45c,f 67c,g 00
a Reaction conditions: 1a (1 mmol), 2a (1.2 mmol), solvent (2 mL), catalyst (100 mg), 70 � C. b Isolated yields based on 1a. c Catalyst (75 mg). d Catalyst (50 mg). e Catalyst (25 mg). f Temperature-60 � C. g Temperature-80 � C.
many renowned chemical transformations (Laszlo, 1990; Izumi et al., 1992; Balogh and Laszlo, 1993; Surjyakanta et al., 2015, 2019a, 2019b). Clay catalysts being a group of aluminosilicates (Al2Si4O10(OH)2. nH2O) contains both Brønsted and Lewis acid sites, are most widely studied under liquid phase organic transformations (Li et al., 2004; Varadwaj et al., 2014, 2016; Sujit et al., 2015). These are layered sili cates consisting exchangeable interlayer cations and by simple ion-exchange process it allows change in acidic nature of the material (Sartori et al., 2004; Kaur and Kishore, 2012). The increasing demand in support of environmentally benign nature insisted us to develop an alternate synthesis for β-aryl ketones. In continuation to our work on the utility of heterogeneous solid acid catalysts (Chevella et al., 2019a, 2019b), herein we disclose an 2
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Table 2 Alkynes variationa.
Entry
Alkyne
Time (h)
Product
Yield (%)b
1
3
67
2
3
86
3
4
91
4
3
82
5
2
87
6
4
86
7
4
85
8
8
52
9
8
51
10
12
00
11
4
00
(continued on next page)
3
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Table 2 (continued ) Entry
Alkyne
Time (h)
Product
Yield (%)b
12
8
00
13
12
00
14
3
76
a b
Reaction conditions: 1a-1n (1 mmol), 2a (1.2 mmol), K10 montmorillonite (75 mg), 70 � C, sealed vial. Isolated yields based on alkyne (1a-1n).
atom-economical, solvent-free and sustainable carbon-carbon coupling reaction of alkynes with secondary alcohols for the synthesis of β-aryl ketones catalyzed by K10 montmorillonite under feasible conditions (Scheme 1).
to presence of strong acidic sites and distinctive layered structure that might responsible for the formation of our desired product in higher yield. 3.2. Optimization of reaction conditions
2. Material and methods
Directly after, we focused our efforts to enhance the yield of our desired product. We tested this reaction with solvents like toluene, water, DCM, methanol as well as without solvent (Table 1, entries 13–17). To our amuse, 67% yield was obtained under solvent free condition and this is because due to the availability of high concentra tions of reagents which indeed leads to more interactions between these reagent molecules compared to solvent based reactions. However, the yield of our required product was found to be same in the case of aprotic polar solvent DCE but with the environmental consciousnesss and con ept of sustainability we continued to work under solvent-free conditions (Table 1, entry 17). Subsequent studies on reaction time, amount of catalyst found that decrease in reaction time resulted in the low yield and increase in reaction time did not exhibit any remarkable change (Table 1, entries 18 & 19). Later on we turned our attention to the variable amount of catalyst from which we are glad to notice that only 75 mg of catalyst is sufficient to furnish good yield of our desired product (Table 1, entries 20–22). Next we changed the temperature of reaction to 60 � C with this decrease in temperature the yield of required product was reduced and upon increase in temperature to 80 � C no drastic alteration observed (Table 1, entries 23 & 24). When we per formed this reaction in the absence of catalyst the reaction had not undergone and the role of catalyst is justified (Table 1, entry 25). Based on these observations, the optimized conditions were chosen as 1 mmol of phenylacetylene to 1.2 mmol of diphenylmethanol with 75 mg of catalyst and a reaction temperature of 70 � C for 3 h without any solvent.
The alkyne (1 mmol) and alcohol (1.2 mmol) were taken in a 9 mL sealed vial and 75 mg of K10 montmorillonite was added to it. The re action was carried out at 70 � C temperature with stirring. After disap pearance of the substrate (monitored by TLC) or after an appropriate time, the reaction mixture was cooled to room temperature and diluted with ethyl acetate (3 � 5 mL). Simple filtration separated the catalyst (K10 montmorillonite), and the removal of solvent in vacuo yielded crude. The crude was further purified by column chromatography using silica gel (100–200 mesh) to afford pure products and these identified based on 1H, 13C NMR, and mass spectral data. 3. Results and discussion 3.1. Catalyst screening In order to validate our demonstration, we commenced our studies by choosing diphenylmethanol and phenylacetylene as model substrates and the reaction carried out at 70 � C for 3 h in DCE screening different heterogeneous and homogeneous catalysts (Table 1, entries 1–12). Fortunately, this reaction when performed with K10 montmorillonite gave the best yield of corresponding β-aryl ketone among different catalysts (Table 1, entry 7). This might be due to the presence of unique intrinsic inorganic layered structures which are main characteristics of clays and thus these layers enable the mobility of compounds more feasibly when compared to microporous zeolites (NaY, HY, HZSM-5, Hmordenite, Hβ, TS-1). Due to lesser diffusion of reagents and reaction products through these micropores of zeolites results in the low yield of desired product. From NH3-TPD studies (Table S1, Fig. S1), MCM-41 (mesoporous) and SiO2–Al2O3 does not possess strong acidic sites. Whereas in Amberlyst-15 (macroporous) the presence of strong acidic sites were found to be low when compared to K10 montmorillonite. K10 montmorillonite was found to be the most active catalyst probably due
3.3. Variation of aromatic alkynes Following these optimized studies, we then investigated scope of the aromatic alkyne derivatives with diphenyl methanol 2a as the coupling partner under optimized conditions. As depicted in Table 2, an extensive range of alkynes having electron-donating groups at ortho, meta and para positions were well tolerated and afforded the corresponding β-aryl 4
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3ab, 3ac achieved in moderate yields (Table 3, entries 1 & 2). 4-Chlor obenzhydrol also reacted smoothly to provide the respective product 3ad in 61% yield (Table 3, entry 3). Similarly, 1-phenylethanol also reacted well and our required product 3ae obtained in 68% yield (Table 3, entry 4). 4-Fluoro-α-methylbenzyl alcohol and 4-bromoα-methylbenzyl alcohol were tolerated well under standard reaction conditions and gave the desired products 3af, 3ag in 62% and 48% yields, respectively (Table 3, entries 5 & 6).
Table 3 Aromatic alcohols variationa.
3.5. Gram scale reactions Entry
Alcohol
Time (h)
product
Yield (%)b
1
5
69
2
3
46
3
4
61
4
5
68
5
8
62
6
6
48
To highlight the practical viability of this protocol, we have con ducted large-scale reactions (10, 30, 60 mmol) of phenylacetylene 1a and diphenylmethanol 2a under optimized conditions. All the preparative-scale reactions proceeded smoothly and were outlined in Scheme 2. 3.6. Reusability studies We also tested the reusability of K10 montmorillonite by performing the reaction with phenyl acetylene and diphenyl methanol under stan dard reaction conditions. After the reaction, K10 montmorillonite was recovered by simple filtration then washed with ethyl acetate and dried at 120 � C for 6 h in an oven. This dried catalyst was reused for next cycle of reaction. There was gradual decrease observed in the yield of product for the consecutive 5 cycles (Table S2). XRD study was done to validate the crystalline structure of K10 montmorillonite before and after the reaction (Fig. S2 (a) and Fig. S2 (b)). From the figures, it is clear that the intensity as well as the sharpness of the XRD peaks confirmed the high crystallinity of the material and shown similar diffraction peaks that indicate the structure has been retained during and after the reaction (Nur Fatin et al., 2015). Similarly, SEM analysis of K10 montmorillonite shows irregular structures with non-uniform size distribution of flakes. SEM analysis of used catalyst had similar appearance compared to fresh catalyst (Fig. S3). To explore the thermal stability we have characterized TG-DTA of fresh and used catalysts that are shown in Fig. S4. The thermal analysis of fresh catalyst shows a weight loss about 10% at the temperature of 25–250 � C due to physically adsorbed water molecules. The weight loss about 3% at the temperature of 250–550 � C is due to the loss of water molecules bonded to the clay. The weight loss about 2% at the temperature of 550–800 � C is due to the loss of hydroxyl groups of the clay (Gustavo et al., 2018). The thermal analysis of used catalyst shows similar weight loss trends compared to fresh catalyst and there is no significant difference in the TG-DTA data of fresh and used catalyst. This result confirms that there is no significant amount of reactants or products remains adsorbed on the used catalyst (Fig. S4). In order to come by with perception of reaction mechanism, we have performed in situ HRESI-MS experiment (Fig. S5) and few control ex periments (Scheme 3) to gain the experimental evidence about the reactive intermediates formed in situ under standard reaction conditions.
a Reaction conditions: 1a (1 mmol), 2ab-2ag (1.2 mmol), K10 montmoril lonite (75 mg), 70 � C, sealed vial. b Isolated yields based on alkyne (1a).
ketones 3b-3e in excellent yields (Table 2, entries 2–5). Strong electronwithdrawing group present on aryl ring of phenyl acetylene 1j upon increasing reaction time also did not furnish desired product (Table 2, entry 10). These results shows that the presence of activating groups on aromatic ring of phenyl acetylene facilitates the reaction, whereas electron deactivating groups were found to be dormant. Halogen sub stituents like fluorine, chlorine and bromine were fine compatible, facilitating the products 3f-3i in 86%, 85%, 52% and 51% yields, respectively (Table 2, entries 6–9). This might be due to the inductive and resonance phenomena of halogen groups present on the aryl ring of phenyl acetylene. Disappointingly, naphthalene and anthracene derived compounds did not react with diphenyl methanol even after extension of reaction time (Table 2, entries 11 & 12). Terribly, electron-poor het erocyclic compound i.e. 3-ethynylpyridine did not react even after prolonged reaction time, whereas electron-rich heterocycle like 2-ethy nylthiophene reacted and produced the corresponding product 3n in 76% yield under standard conditions (Table 2, entries 13 & 14).
3.7. Control experiments When phenylacetylene 1a reacted with K10 montmorillonite under solvent free conditions at 70 � C for 3 h no reaction observed [Eq. (1)]. Whereas, diphenylmethanol was easily converted into dimeric ether 2a′ under the standard conditions anticipating that this reaction proceeds via an ether intermediate [Eq. (2)]. This dimeric ether was isolated and characterized by NMR (spectral data given in SI). We have also con ducted a reaction of phenylacetylene with dimeric ether in the presence of these standard reaction conditions and afforded the desired product in 52% yield [Eq. (3)]. Based on the literature precedent, in situ HRESI-MS and control ex periments, it is assumed that diphenylmethanol 2a is quick in conver sion to carbocation A (detected by in situ HRESI-MS) and forms dimeric ether 2a′ by self-coupling in the presence of Brønsted acidic sites of K10
3.4. Variation of aromatic alcohols Succeeding, we then turned our attention to extend the scope of this reaction to several alcohols coupled with phenylacetylene under stan dard reaction conditions. From Table 3, we can depict typical aromatic alcohols such as electron donating methyl groups on different sub stitutions of benzhydrol were screened and our desired β-aryl ketones 5
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Scheme 2. Large-scale experiments for the synthesis of 1,3,3-triphenylpropan-1-one (3a) from phenylacetylene (1a) and diphenylmethanol (2a).
Scheme 3. Control experiments for mechanistical studies.
montmorillonite followed by nucleophilic attack of alkyne 1a leads to alkenyl cation B (detected by in situ HRESI-MS). Lastly, addition of water within onto the alkenyl cation generated in situ undergoes deprotonation followed by tautomerism furnishes required product 3a (Scheme 4).
the structure of the catalyst along with the acidity plays a crucial role for the establishment of reaction. This protocol provides a good range of β-aryl ketones in shorter reaction times under non-toxic environment. The scope and limitations of this method were investigated with various alkynes containing halo, electron withdrawing and electronic donating groups on an aromatic ring and different substituted like methyl and halo secondary alcohols. The recyclability studies showed a gradual decrease in the activity of catalyst. The in situ HRMS detection of reac tive intermediates and control experiments provided the firm support for the reaction mechanism. Moreover, the synthetic utility of this method has been presented by performing scale up experiments (5 g, 10 g) beneath standard conditions. Notable advantages offered by this
4. Conclusions In conclusion, we have demonstrated a facile approach for the syn thesis of β-aryl ketones by using simple and readily available K10 montmorillonite as heterogeneous catalyst without any immobilized solutions and additives under solvent-free conditions. Comparison of the catalytic properties of various solid heterogeneous catalysts shows that 6
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Scheme 4. Probable mechanism for the formation of β-aryl ketones.
method are absence of organic solvent, good substrate scope, high atom economy, use of non-hazardous catalysts, simple work-up procedure and mild reaction conditions, water as by-product which makes it significant and useful alternative to the existing methods.
Chevella, D., Macharla, A.K., Kodumuri, S., Banothu, R., Gajula, K.S., Amrutham, V., Gennadievna, G.N., Nama, N., 2019a. Catal. Commun. 123, 114–118. https://doi. org/10.1016/j.catcom.2019.01.027. Chevella, D., Macharla, A.K., Banothu, R., Gajula, K.S., Amrutham, V., Boosa, M., Nama, N., 2019b. Green Chem. 21, 2938–2945. https://doi.org/10.1039/ c9gc00541b. Clark, J.H., 1995. Chemistry of Waste Minimization. Chapman and Hall, London, ISBN 978-94-011-0623-8. Gustavo, R.P., Cristina, M.S., Ramon, Z.N., Rafael, R.T., Raul, M.A., 2018. Instrum. Sci. Technol. 46, 676–692. https://doi.org/10.1080/10739149.2018.1443121. Huang, Z., Nam Lim, H., Mo, F., Young, M.C., Dong, G., 2015. Chem. Soc. Rev. 44, 7764–7786. https://doi.org/10.1039/C5CS00272A. Imamoto, T., Takiyama, N., Nakamura, K., Hatajima, T., Kamiya, Y., 1989. J. Am. Chem. Soc. 111, 4392–4398. https://doi.org/10.1021/ja00194a037. Izumi, Y., Urabe, K., Onaka, M., 1992. Zeolite, Clay and Heteropoly Acid in Organic Chemistry. Kodansha-VCH, Tokyo-Weinheim, ISBN 3-527-29011-7. Jana, U., Biswas, S., Maiti, S., 2008. Eur. J. Org Chem. 5798–5804. https://doi.org/ 10.1002/ejoc.200800713. Jefferies, L.R., Cook, S.P., 2014. Tetrahedron 70, 4204–4207. https://doi.org/10.1016/j. tet.2014.03.072. Kang, F.A., Sui, Z., Murray, W.V., 2008. J. Am. Chem. Soc. 130, 11300–11302. https:// doi.org/10.1021/ja804804p. Kaur, N., Kishore, D., 2012. J. Chem. Pharmaceut. Res. 4, 991–1015. ISSN: 0975-7384. Laszlo, P., 1990. Pure Appl. Chem. 62, 2027–2030. https://doi.org/10.1351/ pac199062102027. Li, J., Xing, C., Li, T., 2004. J. Chem. Technol. Biotechnol. 79, 1275–1278. https://doi. org/10.1002/jctb.1123. Mameda, N., Peraka, S., Marri, M.R., Kodumuri, S., Chevella, D., Gutta, N., Nama, N., 2015. Appl. Catal., A 505, 213–216. https://doi.org/10.1016/j.apcata.2015.07.038. Matlack, A., 2003. Green Chem. G7 https://doi.org/10.1039/B300501C. Mehta, V.P., Eycken, E.V.V., 2011. Chem. Soc. Rev. 40, 4925–4936. https://doi.org/ 10.1039/C1CS15094D. Meijere, A.D., Diederich, F., 2004. Metal-Catalyzed Cross-Coupling Reactions, second ed. Wiley VCH, Weinheim. https://doi.org/10.1002/9783527619535. Nur Fatin, D.C.H., Farah, W.H., Juliana, J., Siti, S.O., 2015. J. Ind. Eng. Res. 1, 8–13. ISSN: 2077-4559. Patai, S., 1994. Chemistry of Triple-Bonded Functional Groups. Wiley, New York, NY, ISBN 978-0-470-77156-3, pp. 689–737. Philipp, S., Thomas, P., Mireia, S., Stephen, P.F., 2017. Nat. Commun. 8, 1–12. https:// doi.org/10.1038/ncomms15762. Ranke, J., Stolte, S., Stormann, R., Arning, J., Jastorff, B., 2007. Chem. Rev. 107, 2183–2206. https://doi.org/10.1021/cr050942s. Sartori, G., Ballini, R., Bigi, F., Bosica, G., Maggi, R., Righi, P., 2004. Chem. Rev. 104, 199–250. https://doi.org/10.1021/cr0200769. Shao, Z., Zhang, H., 2012. Chem. Soc. Rev. 41, 560–572. https://doi.org/10.1039/ C1CS15127D. Stopka, T., Niggemann, M., 2015. Org. Lett. 17, 1437–1440. https://doi.org/10.1021/ acs.orglett.5b00312. Sujit, P.C., Varadwaj, G.B.B., Kulamani, P., Bhalchandra, M.B., 2015. Appl. Catal., A 506, 237–245. https://doi.org/10.1016/j.apcata.2015.09.019. Surjyakanta, R., Suresh, M., Kotaiah, Y., Sreekantha, B.J., 2015. Appl. Catal., A 505, 539–547. https://doi.org/10.1016/j.apcata.2015.07.018. Surjyakanta, R., Varadwaj, G.B.B., Jonnalagadda, S.B., 2019a. Nanoscale Adv. 1, 1527–1530. https://doi.org/10.1039/c8na00245b.
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. CRediT authorship contribution statement Divya Rohini Yennamaneni: Methodology, Investigation, Writing original draft. Durgaiah Chevella: Conceptualization, Investigation. Krishna Sai Gajula: Writing - review & editing, Resources. Narender Nama: Supervision, Project administration, Funding acquisition. Acknowledgements We thank the DST, New Delhi for financial support under Indo-Russia (DST-RSF) (No. INT/RUS/RSF/P-7) programme. Y. D., Ch. D. and G. K. acknowledge the CSIR, India for financial support in the form of fellowship. We thank Director CSIR-IICT (IICT/Pubs./2019/309) for providing all the required facilities to carry out the work. Also we appreciate support from Rammurthy Banothu for validation, Murali Boosa for visualization and Sai Krishna Ganji for in situ HRESI-MS studies. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi. org/10.1016/j.scp.2020.100227. References Ackermann, L., Pospech, J., Potukuchi, H.K., 2012. Org. Lett. 14, 2146–2149. https:// doi.org/10.1021/ol300671y. Anastas, P., Eghbali, N., 2010. Chem. Soc. Rev. 39, 301–312. https://doi.org/10.1039/ B918763B. Balogh, M., Laszlo, P., 1993. Organic Chemistry Using Clays. Springer Verlog, New York, ISBN 978-3-540-55710-4.
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Surjyakanta, R., Varadwaj, G.B.B., Sreekantha, B.J., 2019b. RSC Adv. 9, 13332–13335. https://doi.org/10.1039/C9RA01715A. Suzuki, A., 2011. Angew. Chem. Int. Ed. 50, 6723–6737. https://doi.org/10.1002/ anie.201101379. Tanaka, K., 2006. Solvent Free Organic Synthesis. John Wiley & Sons, ISBN 978-3-52760536-1. Thiyagarajan, S., Gunanathan, C., 2019. J. Am. Chem. Soc. 141, 3822–3827. https://doi. org/10.1021/jacs.9b00025. Thomas, R.J., Campbell, K.N., Hennion, G.F., 1938. J. Am. Chem. Soc. 60, 718–720. https://doi.org/10.1021/ja01270a061. Thompson, D.J., 1991. In: Trost, B.M., Fleming, I. (Eds.), Comprehensive Organic Synthesis, vol. 3. Pergamon, Oxford, pp. 1015–1043. https://doi.org/10.1016/B9780-08-052349-1.00088-3.
Varadwaj, G.B.B., Surjyakanta, R., Kulamani, P., 2014. J. Phys. Chem. C 118, 1640–1651. https://doi.org/10.1021/jp410709n. Varadwaj, G.B.B., Kulamani, P., Vincent, O.N., 2016. Inorg. Chem. Front. 3, 1100–1111. https://doi.org/10.1039/C6QI00179C. Wagh, K.V., Bhanage, B.M., 2015. Synlett 26, 759–764. https://doi.org/10.1055/s-00341380142. Yang, G.P., Zhang, N., Ma, N.N., Yu, B., Hu, C., 2017. Adv. Synth. Catal. 359, 926–932. https://doi.org/10.1002/adsc.201601231. Zhao, D., Liao, Y., Zhang, Z., 2007. Clean 35, 42–48. https://doi.org/10.1002/ clen.200600015.
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