Acidity Scale of N-Heterocyclic Carbene Precursors: Can We Predict

Letter Cite This: Org. Lett. 2018, 20, 6041−6045

pubs.acs.org/OrgLett

Acidity Scale of N‑Heterocyclic Carbene Precursors: Can We Predict the Stability of NHC−CO2 Adducts? Zhen Wang,†,§ Fang Wang,† Xiao-Song Xue,*,†,§ and Pengju Ji*,‡ †

School of Chemical and Environmental Engineering, Anyang Institute of Technology, Anyang 455000, China State Key Laboratory on Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China ‡ Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 100084, China §

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S Supporting Information *

ABSTRACT: The acidity scale (∼14 pK units) of more than 90 triazolium, imidazolium, and imidazolinium based NHC precursors in DMSO was established systematically by a well-developed computational model. The substituent effects on the acidities of these NHC precursors were analyzed through acidity comparison and Hammett correlation. The binding energy (ΔG1) of the reaction between NHC and CO2 was also calculated and linearly correlates with the basicity of the corresponding NHC, which implies that the stability of the NHC−CO2 adduct is essentially dictated by the basicity of NHC.

ince the isolation of the first stable N-heterocyclic carbene (NHC) by Arduengo,1 NHCs have been widely used as organocatalysts or as ligands in organometallic catalysis.2 To date, there are hundreds of NHCs which have been successfully prepared and applied in various organic reactions as effective catalysts,2c and this number continues to grow. No doubt NHCs equip chemists with a powerful synthetic tool box with diverse catalytic modes, which have promoted the art of catalysis into a brand new stage. Despite the tremendous research attention that has been given to the catalytic application of NHCs in synthetic chemistry, our knowledge of some essential aspects, such as thermodynamic properties and kinetic behaviors, of the NHCs is rather limited, which may later become a “bottleneck” for the rational design and development of NHCs. The basicities of NHCs are among those fundamental aspects which are crucial for the evaluation of stability, reactivity, catalytic performance of NHCs, etc. However, in stark contrast with the rapid progression of methodology development in using NHCs as catalysts to achieve various synthetic purposes, only a little work has been dedicated to the determination of acidities for the precursors of NHCs (conjugate acid form of NHC).3−5 In addition, apart from sporadic work which endeavored to establish a correlation between the basicity and nucleophilicity of NHCs,6 to the best of our knowledge, the correlation between the thermodynamic property of an NHC and its catalytic efficiency or related experimental observations is very rare.7 In recent years, NHCs have been employed as a promising catalytic system, either metal-based or metal-free, for the activation and transformation of greenhouse gas carbon dioxide.8 For the metal-free catalysis, one of the most concerned processes is the forming of NHC−CO2 adducts9

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© 2018 American Chemical Society

which can be further converted into some value-added chemicals.10 Furthermore, the NHC−CO2 adducts are frequently employed as the precatalyst or surrogate of NHC in many catalytic processes, which later can be conveniently decarboxylated to in situ generate the desired free NHC under mild conditions.11 In this connection, the thermodynamic stability of NHC−CO2 adducts is essential to evaluate the ability of NHCs for CO2 capture and can be an effective indicator for the activity of NHC−CO2 adducts as a precatalyst. In light of this, previously the stability of NHC− CO2 adducts have been studied by thermogravimetric analysis,12 in situ FTIR,13 and theoretical calculations.14 These critical studies reveal that the stability of an NHC− CO2 adduct is dictated by the structure and substituent (both electronic and steric factors) of the NHC, as well as the polarity of the solvent. Although the basicities for some NHCs have been experimentally3,4 made available and can be used as a benchmark for the theoretical calculation, there were only a few computational studies in this respect.5 The calculated acidity scale of NHC precursors has a relative narrow pK span and was based on only one or two experimental values. In addition, the involved NHC precursors were limited and mainly concentrated on imidazolium derivatives.5 Furthermore, there has been practically no work focused on the effect of basicity of NHCs on the stability of NHC−CO2 adducts.15 We envisage that a systematic investigation of the acidities for various NHCs may provide insights into the acid−base chemistry of NHCs and, more importantly, generate some Received: July 30, 2018 Published: September 14, 2018 6041

DOI: 10.1021/acs.orglett.8b02290 Org. Lett. 2018, 20, 6041−6045

Letter

Organic Letters

Figure 1. Calculated pKa’s for three different families of NHC precursors in DMSO (Mes = 2,4,6-trimethylphenyl, Dipp = 2,6-diisopropylphenyl, and experimental pKa values4 are marked in red).

respectively. This could be understood by the presence of an additional electronegative nitrogen atom in the triazolium ring (A1), compared with imidazolium (B1); due to the lack of aromatic stabilization of the incipient carbene upon deprotonation, the N-alkyl substituted imidazolinium (C1) is the weakest acid among the three. It is worth noting that the acidity of phenyl substituted imidazolinium C9 (19.1) shows 0.9 pK units stronger than its imidazolium analogue B10 (20.0), which is not in line with the acidity trend found above. However, as shown in Scheme 1,

necessary information from the thermodynamic point of view for the assessment of the stability of NHC−CO2 adducts. In the present work, the acidities of three families of commonly seen precursors of NHCs in DMSO (Figure 1), i.e., triazolium (A, including several frequently used chiral substrates), imidazolium (B), and imidazolinium (C), with distinctive core structures and substituents were systematically calculated first. This was achieved via a well-developed theoretical method, i.e., the SMD/M06-2x/6-311++G(2df,2p)//B3LYP/6-31+G(d) method, for the absolute acidity calculation in solution (the Supporting Information provides details for the establishment and calibration of the methods).16 Next, as a proof-of-concept investigation, the binding energies for the reactions between NHCs and CO2 (ΔG1) were calculated in order to explore whether there exists a correlation between the stability of the NHC−CO2 adduct and the basicity of the NHC. As shown in Figure 1, the pKa values of NHC precursors cover a wide range from 10.7 to 25.0 (∼14 pK units) in DMSO. In addition, the NHC precursors are more acidic (0.2−5.0 pK units) in DMSO than those in water (Table S2), which is mainly due to a larger Gibbs solvation energy of proton in DMSO than in water.17 A closer survey reveals that the pKa values of three kinds of NHC precursors follow the order triazolium (A) < imidazolium (B) < imidazolinium (C). These results reveal that the basicities of NHCs are closely dependent on the structure of their precursors. For example, an acidity comparison of three representative NHC precursors from each family, i.e., 1,4-dimethyl-1,2,4-triazolium (A1), 1,3dimethyl-imidazolium (B1) and 1,3-dimethyl-imidazolinium (C1), shows an increased pKa value of 16.1, 21.5, and 22.7,

Scheme 1. Calculated Geometries of C9, A10, A13, and B10 in DMSOa

In parentheses is the Hammett ρ value of their phenyl substituted derivatives (vide infra). a

this could be rationalized by considering a much smaller dihedral angle (a better coplanarity) between the phenyl substituent and the parent imidazolinium ring of C9 (19.1°) than that of B10 (43.5°), which leads to a better resonance stabilization of the NHC of the former. Conversely, the pKa of N-mesityl substituted imidazolinium C13 is 1.2 pK units higher than that of B13, which should be a result of losing the planar structure due to the steric hindrance caused by the bulky trimethylphenyl group.18 6042

DOI: 10.1021/acs.orglett.8b02290 Org. Lett. 2018, 20, 6041−6045

Letter

Organic Letters Changing the N-methyl group with a longer or sterically flexible alkyl group (such as A2 vs A3, A4; B1 vs B2, B3 and C1 vs C3, C4) has a very limited effect (0.5 pK units) on the acidity of these NHC precursors. However, varying the Nmethyl group with a bulky alkyl substituent, such as tert-butyl (A2 vs A5; B1 vs B4 and C1 vs C5), brings about a 1 pK unit or more attenuation in the acidity and a further decrease in acidity is found with another bulky group installed (such as A6, B5, and C6). Presumably, this is due to the steric inhibition of solvation.19 However, on the contrary the replacement of Nmethyl with a N-aryl group generally increases the acidity from 1.1 to 10.1 pK units, depending on the nature and number of aryl substituent(s). The monosubstituted phenyl and mesityl at the N-1 position leads to the increase in acidity from 1.4 to 3.6 pK units. For example, in comparison with A2, B1, and C1, a phenyl substitution on nitrogen in A7, B10, and C9 leads to a 2.5, 1.5, and 3.6 pK unit increase in acidity, respectively. Further introduction of another aryl shows a notable addictive effect on the acidity. The 1,3-diphenyl substituted B11 and C12 are more acidic than B10 and C9 by about 1.8 and 2.2 pK units, respectively. The presence of strong electron-withdrawing pentafluorophenyl group(s) has a pronounced acidifying effect. For example, A16 is 3.2 pK units more acidic than its analogue A13, while, under the influence of two pentafluorophenyl groups, the acidity of B16 is 6.8 pK units stronger than B11. Due to the electron donation, the incorporation of an additional methyl group(s) on the 5-position of triazolium or the 4,5-position of imidazolium or imidazolinium brings about a 1−2 pK units decrease in the acidity (such as A1 vs A2, B1 vs B6, C1 and C2). This indicates that the substitution made on the parent NHC ring has a stronger effect on the acidity of the NHC precursor than those made on the side arms. Pyrrolidine and piperidine based triazoliums exhibit similar acidities with the rest of the family. For example, the acidity difference between A7 and its bicyclic analogues A10 and A12 is within 0.5 pK units. Introducing an O atom to A10 and A12 leads to a pronounced increase in acidity (1.5 pK units) of the resulting oxazolidine and morpholine based triazoliums (A11 and A13). Substituent effects on the acidities of NHC precursors were also systemically investigated in the present work. As shown in Figure 2, as the para-position of the flanking phenyl group varies from the electron-donating p-MeO to the withdrawing p-CN group, the acidity of the selected phenyl-substituted NHC precursors accordingly increases 1.7−2.3 pK units.

Moreover, as expected, the 1,3-diphenyl substituted series (B11, B22, and C12 series) also exhibits a distinct additive substituent effect.20 The Hammett analyses show good linear correlations (Figure 3) for all the selected NHC precursors

Figure 3. Hammett plots for the acidities of selected NHC precursor series.

series, and the Hammett ρ values change along with the trend of imidazolium (1.82) < triazolium (2.16 or 2.29) < imidazolinium (2.40). This, again, could be understood by considering the dihedral angle between the substituted benzene ring and the parent NHC ring, as shown in Scheme 1; the ρ value decreases with the increasing dihedral angle for the representative NHC precursor. ΔG1 NHC + CO2 ⎯⎯⎯⎯⎯→ NHC−CO2

(1)

With the acidity scale of 93 NHC precursors in our hands, next the binding energy (ΔG1), i.e., Gibbs energy change of the reaction between NHC and CO2 to form the NHC−CO2 adducts in DMSO (1), were investigated to estimate the stability of NHC−CO2 adducts (see SI for calculation details). The results show that ΔG1 values decrease as the pKa of the NHC precursor increases (Table S3), and interestingly, an excellent linear correlation (Figure 4, R2 = 0.956, without the

Figure 4. Correlation between the pKa of NHC precursors and ΔG1 of reaction between NHC and CO2 (eq 1).

data points highlighted in red) was found between the pKa’s of NHC precursors (over 14 pK units) and the ΔG1 values for most of NHCs involved in this work (Figure S2). From a thermodynamic point of view, this suggests that the reactions are basically driven by the thermodynamic difference between reactants and products, as indicated by a recent study which shows that the formation of NHC−CO2 adducts, in most cases, is exothermic.14c Hence, it is reasonable to deduce that an NHC with a higher basicity, normally coinciding with a stronger nucleophilicity,21 is more favorable to bind CO2,

Figure 2. Substituent effect on the acidities of selected NHC precursors; in square brackets marked in red are experimental values.4 6043

DOI: 10.1021/acs.orglett.8b02290 Org. Lett. 2018, 20, 6041−6045

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which very likely leads to a better stability of the corresponding NHC−CO2 adduct. However, it should be noted that the steric and electronic factors also have a notable influence. As shown in Figure 4, the NHCs flanked with tert-butyl (but not mesityl) group(s) are distinctly deviated above the line (A5, A6, B4, B5, C5, and C7), and also those with electronwithdrawing pentafluorophenyl groups as side arms are far below the line (A16, A17, B15, B16, C11, and C15). The steric effects are known to have a pronounced effect on the reactivity of NHCs6 and stability of NHC−CO2 adducts,14 and the positive deviation caused by the flanking pentafluorophenyl group(s), as our calculation suggests, should be due to the fact that the carboxylate moieties of these NHC−CO2 adducts are more planar with the parent NHC rings, which are favorable for delocalizing the negative charge on carboxylate to the NHC ring, thus leading to better product stability. With A17 and A10 as typical examples, the dihedral angle between the triazolium ring and carboxylate plane is 0.8° in pentafluorophenyl based NHC(A17)−CO2 but 46.5° in phenyl based NHC(A10)−CO2 (Figure S3). In summary, we utilized a mature theoretical model for the systematical calculation of the pKas of more than 90 NHC precursors in DMSO. The calculated binding energies (ΔG1) of reactions between NHCs and CO2 in DMSO exhibit a good linear relationship with the basicity of NHC, which suggests that an NHC with stronger basicity will lead to a more stable NHC−CO2 adduct. We believe these results may provide a useful guide to a rational design of novel NHCs for CO2 capture and conversion, and also shed some light on the mechanism of reactions using NHC−CO 2 adducts as precatalysts to generate free NHCs.

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REFERENCES

(1) Arduengo, A. J.; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991, 113, 361. (2) For representative reviews and monographs, see: (a) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606. (b) DíezGonzález, S., Ed. N-Heterocyclic Carbenes: From Laboratory Curiosities to Efficient Synthetic Tools; RSC Catalysis Series, Vol. 6; Royal Society of Chemistry: Cambridge, 2010. (c) Nolan, S. P., Ed. N-Heterocyclic Carbenes: Effective Tools for Organometallic Synthesis; Wiley-VCH: Weinheim, 2014. (d) Flanigan, D. M.; Romanov-Michailidis, F.; White, N. A.; Rovis, T. Chem. Rev. 2015, 115, 9307. (3) (a) Alder, R. W.; Allen, P. R.; Williams, S. J. J. Chem. Soc., Chem. Commun. 1995, 1267. (b) Kim, Y. J.; Streitwieser, A. J. Am. Chem. Soc. 2002, 124, 5757. (c) Amyes, T. L.; Diver, S. T.; Richard, J. P.; Rivas, F. M.; Toth, K. J. Am. Chem. Soc. 2004, 126, 4366. (d) Higgins, E. M.; Sherwood, J. A.; Lindsay, A. G.; Armstrong, J.; Massey, R. S.; Alder, R. W.; O’Donoghue, A. C. Chem. Commun. 2011, 47, 1559. (e) Massey, R. S.; Collett, C. J.; Lindsay, A. G.; Smith, A. D.; O’Donoghue, A. C. J. Am. Chem. Soc. 2012, 134, 20421. (4) (a) Chu, Y.; Deng, H.; Cheng, J.-P. J. Org. Chem. 2007, 72, 7790. (b) Li, Z.; Li, X.; Cheng, J.-P. J. Org. Chem. 2017, 82, 9675. iBond 2.0 database: http://ibond.chem.tsinghua.edu.cn or http://ibond.nankai. edu.cn. (d) Dunn, M. H.; Konstandaras, N.; Cole, M. L.; Harper, J. B. J. Org. Chem. 2017, 82, 7324. (5) (a) Magill, A. M.; Cavell, K. J.; Yates, B. F. J. Am. Chem. Soc. 2004, 126, 8717. (b) Magill, A. M.; Yates, B. F. Aust. J. Chem. 2004, 57, 1205. (6) (a) Maji, B.; Breugst, M.; Mayr, H. Angew. Chem., Int. Ed. 2011, 50, 6915. (b) Levens, A.; An, L.; Breugst, M.; Mayr, H.; Lupton, D. W. Org. Lett. 2016, 18, 3566. (7) Niu, Y.; Wang, N.; Muñoz, A.; Xu, J.; Zeng, H.; Rovis, T.; Lee, J. K. J. Am. Chem. Soc. 2017, 139, 14917. (8) (a) Yang, L.-H.; Wang, H.-M. ChemSusChem 2014, 7, 962. (b) Wang, S.-B.; Wang, X.-C. Angew. Chem., Int. Ed. 2016, 55, 2308 and reference cited therein. (9) Kuhn, N.; Steimann, M.; Weyers, G. Z. Naturforsch., B: J. Chem. Sci. 1999, 54, 427. (10) (a) Duong, H. A.; Cross, M. J.; Louie, J. Org. Lett. 2004, 6, 4679. (b) Tommasi, I.; Sorrentino, F. Tetrahedron Lett. 2005, 46, 2141. (c) Kayaki, Y.; Yamamoto, M.; Ikariya, T. Angew. Chem., Int. Ed. 2009, 48, 4194. (d) Gu, L.; Zhang, Y. J. Am. Chem. Soc. 2010, 132, 914. (e) Zhou, H.; Wang, Y.-M.; Zhang, W.-Z.; Qu, J.-P.; Lu, X.-B. Green Chem. 2011, 13, 644. (f) Ueno, A.; Kayaki, Y.; Ikariya, T. Green Chem. 2013, 15, 425. (g) Fèvre, M.; Vignolle, J.; Taton, D. Polym. Chem. 2013, 4, 1995. (h) Talapaneni, S. N.; Buyukcakir, O.; Je, S. H.; Srinivasan, S.; Seo, Y.; Polychronopoulou, K.; Coskun, A. Chem. Mater. 2015, 27, 6818. (i) Hoshimoto, Y.; Asada, T.; Hazra, S.; Kinoshita, T.; Sombut, P.; Kumar, R.; Ohashi, M.; Ogoshi, S. Angew. Chem., Int. Ed. 2016, 55, 16075. (11) (a) Voutchkova, A. M.; Appelhans, L. H.; Chianese, A. R.; Crabtree, R. H. J. Am. Chem. Soc. 2005, 127, 17624. (b) Voutchkova, A. M.; Feliz, M.; Clot, E.; Eisenstein, O.; Crabtree, R. H. J. Am. Chem. Soc. 2007, 129, 12834. (c) Olszewski, T. K.; Jaskólska, D. E. Heteroat. Chem. 2012, 23, 605. (d) Hans, M.; Delaude, L.; Rodriguez, J.; Coquerel, Y. J. Org. Chem. 2014, 79, 2758. (e) Papadaki, E.; Delaude, L.; Magrioti, V. Tetrahedron 2017, 73, 7295. (f) Tintori, G.; Nabokoff, P.; Buhaibeh, R.; Bergé-Lefranc, D.; Redon, S.; Broggi, J.; Vanelle, P. Angew. Chem., Int. Ed. 2018, 57, 3148. (12) (a) Duong, H. A.; Tekavec, T. N.; Arif, A. M.; Louie, J. Chem. Commun. 2004, 0, 112. (b) Van Ausdall, B. R.; Glass, J. L.; Wiggins, K. M.; Aarif, A. M.; Louie, J. J. Org. Chem. 2009, 74, 7935. (13) Zhou, H.; Zhang, W.-Z.; Liu, C.-H.; Qu, J.-P.; Lu, X.-B. J. Org. Chem. 2008, 73, 8039. (14) (a) Ajitha, M. J.; Suresh, C. H. J. Org. Chem. 2012, 77, 1087. (b) Denning, D. M.; Falvey, D. E. J. Org. Chem. 2014, 79, 4293. (c) Alkorta, I.; Montero-Campillo, M. M.; Elguero, J. Chem. - Eur. J. 2017, 23, 10604. (d) Denning, D. M.; Falvey, D. E. J. Org. Chem. 2017, 82, 1552. (e) Nziko, V. D. N.; Shih, J. L.; Jansone-Popova, S.; Bryantsev, V. S. J. Phys. Chem. C 2018, 122, 2490.

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b02290.

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Letter

Detailed description and calibration of computational methods; the calculated Gibbs energies for NHC precursors, NHCs, and NHC−CO2 adducts; Cartesian coordinates of optimized structures (PDF)

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Xiao-Song Xue: 0000-0003-4541-8702 Pengju Ji: 0000-0003-3605-1910 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful for the financial grants from the National Natural Science Foundation of China (Nos. 21702005, 21672124, 21406002). P.J. would like to dedicate this work to his former PhD supervisor Prof. Michael I Page of University of Huddersfield, U.K. 6044

DOI: 10.1021/acs.orglett.8b02290 Org. Lett. 2018, 20, 6041−6045

Letter

Organic Letters (15) There is only one example of attempting to explain the thermostability of two NHC−CO2 adducts by using pKa values of the corresponding NHC precursors; for details, see ref 12b. (16) (a) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113, 6378. (b) Yang, C.; Xue, X.-S.; Jin, J.-L.; Li, X.; Cheng, J.-P. J. Org. Chem. 2013, 78, 7076. (c) Yang, C.; Xue, X.-S.; Li, X.; Cheng, J.-P. J. Org. Chem. 2014, 79, 4340. (d) Wang, Z.; Zheng, Y.; Zheng, Y.; Xue, X.-S.; Ji, P. J. Phys. Chem. A 2018, 122, 5750. (17) (a) Bernales, V. S.; Marenich, A. V.; Contreras, R.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2012, 116, 9122. (b) Himmel, D.; Goll, S.; Leito, I.; Krossing, I. Angew. Chem., Int. Ed. 2010, 49, 6885. (18) (a) Li, Z.; Liu, L.; Sun, H.; Shen, Q.; Zhang, Y. Dalton Trans 2016, 45, 17739. (b) Imbrich, D. A.; Frey, W.; Naumann, S.; Buchmeiser, M. R. Chem. Commun. 2016, 52, 6099. (19) Reichardt, C.; Welton, T. Solvents and Solvent Effects in Organic Chemistry, 4th ed.; Wiley-VCH: Weinheim, 2011. (20) (a) Stubbs, F. J.; Hinshelwood, C. J. Chem. Soc. 1949, S71. (b) Jones, B.; Robinson, J. Nature 1950, 165, 453. (21) Although in some cases, there does exist discrepancies between the nucleophilicity and basicity of the nucleophile and the traditional Brönsted analysis fails (c.f.: Mayr, H.; Ofial, A. R. Acc. Chem. Res. 2016, 49, 952 ). However, for NHCs, a recent study shows that the gas phase acidities of precursors of NHCs correlate well with the stereoselectivity; for details, see ref 7.

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DOI: 10.1021/acs.orglett.8b02290 Org. Lett. 2018, 20, 6041−6045