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C—H Cyanoalkylation:the Direct C—H Cyanomethylation of Naphthalimide

Xi Chen , Zheyao Li , Yayun Chen , Zhihua Chen , Yan Hu , Chuanxiang Liu

Progress in Chemistry ›› 2021, Vol. 33 ›› Issue (11) : 1947 -1952.

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Progress in Chemistry ›› 2021, Vol. 33 ›› Issue (11) : 1947-1952 DOI: 10.7536/PC201001
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C—H Cyanoalkylation:the Direct C—H Cyanomethylation of Naphthalimide
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Abstract

The cyanoalkylation/cyanomethylation of organic molecules is of great research interest to organic and medicinal chemists due to the wide presence of the cyano group in biologically active molecules and the facile conversion of the cyano group into many other functional groups, such as amides, esters, aldehydes, and primary amines. Although a variety of different synthetic strategies have been developed for the selective introduction of the cyanomethyl group, an attractive approach is to use acetonitrile directly through C—H activation due to the highly efficient atom economy and the avoidance of prefunctionalization. Therefore, this review summarizes the main research progress in C—H cyanoalkylation/cyanomethylation of radical cyanomethylation, Photochemical Cross-coupling reaction, Cross-Dehydrogenative Coupling(CDC) Reaction, Directing group-promoted C—H cyanomethylation and Fluorophore C—H cyanomethylation reported by our group.

Contents

1 Introduction

2 Radical cyanomethylation of activated alkenes with acetonitrile

3 Photochemical cross-coupling reaction of alkene or aroma C(sp2)—H functionalization of acetonitrile

4 Cross-dehydrogenative coupling(CDC)reaction of aromatic ring C(sp2)—H functionalization of acetonitrile

5 Directing group-promoted C—H cyanomethylation

6 Conclusion and outlook

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Keywords

cyanomethylation / C—H functionalization / radical / directing group / naphthalimide

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Xi Chen, Zheyao Li, Yayun Chen, Zhihua Chen, Yan Hu, Chuanxiang Liu. C—H Cyanoalkylation:the Direct C—H Cyanomethylation of Naphthalimide. Progress in Chemistry, 2021, 33(11): 1947-1952 DOI:10.7536/PC201001

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1 Introduction

Cyano-group is widely existed in drug active molecules, and it can be easily converted into amide, ester, aldehyde, primary amine and other functional groups, so the cyanomethylation of organic molecules has been widely concerned by organic and pharmaceutical researchers[1][2]. Acetonitrile generally cannot be used as a cyanide source for the synthesis reaction due to its relatively weak acidity [pKa (MeCN) ≈ 31.3, DMSO][3]. The common organic methods of introducing cyano group usually use cyanomethylation reagents, such as trimethylsilyl acetonitrile, ethyl cyanoacetate salt, chloroacetonitrile and so on. In addition, the C — H bond dissociation of the acetonitrile molecule can be initiated by some basic reagents such as NaH, cesium trimethylacetate, or NaOH.
Aryl acetonitrile derivatives are important intermediates, which can be used as raw materials for the synthesis of amines, carboxylic acids and heterocyclic diaryl ketone derivatives[4,5]. Therefore, arylacetonitrile derivatives have been widely used in the synthesis of drugs, pigments, dyes and heterocycles[6]. The method for preparing the aryl (heterocyclic aryl) acetonitrile derivative mainly comprises the following steps of: (a) carrying out nucleophilic substitution reaction on a benzyl halide and a cyanide; (B) carrying out dehydration reaction on an amide or aldoxime compound;The decarboxylation of aryl fluoride via substitution with ethyl cyanoacetate (C), and the Pd-catalyzed coupling of aryl halides with functionalized acetonitrile derivatives (d), such as bromoacetonitrile, TMS-acetonitrile, Bu3Sn- acetonitrile, cyanoacetate, etc[7][8][9][10⇓~12]. Although these methods are widely used, they still have many disadvantages, including: (1) transition metal catalysts are expensive and may require ligands and various additives; (2) harsh reaction conditions (e.g., high temperature or long reaction time); and (3) the need for a prefunctionalized coupling substrate[13]. In addition, these reactions also produce toxic heavy metal wastes that are harmful to the environment and organisms and poor atom economy. Therefore, it is necessary to develop a practical, easy to operate, low-cost, regioselective and direct C-C bond formation method without transition metal catalysis.
In recent years, targeting group (DG) -directed C — H functionalization has gradually become one of the most effective methods for the synthesis of complex molecules, especially when there are multiple C — H bonds in the molecule, the targeting group can effectively control the regioselectivity[14,15]. The direct cyanomethylation of acetonitrile or substituted acetonitrile via C — H bond activation has attracted the attention of researchers because of its efficient atom economy and the avoidance of pre-functionalization. In this paper, we summarized the literatures on cyanomethylation of C — H in recent years, and summarized the research progress of cyanomethylation of C — H in fluorophores reported by our group in recent years.

2 Free Radical Cyanomethylation of Activated Alkenes by Acetonitrile

In general, due to the electron-withdrawing effect of the cyano group and its ability to stabilize free radical intermediates, it is easy to cleave the α-C — H bond in the acetonitrile molecule from other types of sp3C—H bonds, and the resulting α-cyanocarbon radical can easily participate in various free radical reactions.
In 2011, Liu et al. Used N-arylacrylamide (1) as the raw material for the more effective direct cyanomethylation reaction of olefins.In this paper, we report the direct synthesis of cyano-substituted indolone derivatives (2) with acetonitrile via a Pd-catalyzed ligand-involved C(sp2)-H and C(sp3)-H tandem activation, which involves metal Pd reagents and N-containing ligands, and requires appropriate oxidant PhI(OPiv)2 and necessary AgF catalysis[16]. The reaction conditions are harsh and the applicability of the substrate is limited.
In 2014, You et al. Reported the preparation of cyano-substituted oxindole derivatives by free radical tandem cyanomethylation of activated alkenes[17]. In that presence of a DTBP free radical initiator, the reaction generate an activated cyanomethyl free radical, and then carries out addition and cyclization reaction on the olefin substrate (3) to efficiently generate the indolone derivative (4). The reaction has the advantages of simple operation, simple and easily obtained raw materials, wide substrate range and the like. They examined the expansion of substrates such as benzene ring and heterocyclic pyridine, and prepared nitro-substituted indolone derivatives for the first time.
Liu et al reported in 2015 that a class of free radicals initiated the selective activation of the α-C(sp3)—H bond in arylacetonitrile (6), and then anti-Markovikov addition with the unactivated substrate double bond (5) to prepare a series of acetonitrile derivatives (7)[18]. After the condition screening, it was found that the conversion of the reaction could be efficiently completed in the presence of CuI and DCP initiator, and various substituted nitrile derivatives could be prepared. The method has the advantages of being suitable for simple olefins, simple in raw materials, mild in operation, suitable for industrial scale-up and the like.
In 2015, Zhu et al. Reported the direct preparation of indole derivatives (9) from N-arylacrylamide (8) and acetonitrile by Fe-promoted radical cyanomethylation[19]. The reaction involves a one-step C(sp3)—H and the functionalization of the double C-H bond of the C(sp2)—H. The reaction has good functional group compatibility to methoxy, ethoxyacyl, chlorine, bromine, iodine, nitro, trifluoromethoxy and trifluoromethyl and the like, and the reaction condition is mild.
In 2015, Zhu et al. reported the copper-catalyzed alkylation and epoxidation of allyl alcohol (10) with non-activated alkylacetonitrile derivatives (11) to prepare functionalized epoxides (12)[20]. The free radical initiator induces the generation of alkyl cyanide free radicals, and then adds to the double bond, and forms C(sp3)—O bonds with the help of copper-assisted catalysis to form epoxy compounds. This reaction provides an efficient route to the preparation of difunctionalized tri- or tetrasubstituted epoxides through the formation of C(sp3)—C(sp3) and C(sp3)—O bonds.
In 2015, Zhu et al. reported that Cu-catalyzed cyanomethylated allyl alcohol derivatives (13) efficiently synthesized functionalized ketone derivatives (15) containing α-quaternary carbon centers by accompanying 1,2-aryl migration[21]. The reaction mechanism involves radical initiation and ketone-catalyzed concomitant neophyl rearrangement. This reaction also provides a route for the preparation of bifunctional derivatives containing ketones and cyano-acetonitrile.
In 2017, Li et al. reported a method for one-step construction of γ-aminoalkyl cyanide derivatives (18) by oxidative intramolecular 1,2-alkylamination with the participation of free radicals through three components of alkyl acetonitrile derivatives (17), amine and alkene derivatives (16). This reaction uses simple silver carbonate and iron Lewis salt as catalysts to efficiently and concisely construct acetonitrile derivatives containing C-C and C-N bonds in one step[22].
Zhang et al. 2018 reported that a series of novel 3,4-dihydroquinolinone derivatives (20) were prepared by AgOAc-promoted free radical cyanomethylation reaction, which generated cyanomethyl free radicals with the help of initiators, and the addition of double bonds in the substrate (19) was accompanied by intramolecular cyclization and aromatization[23]. The reaction is simple to operate, has good functional group compatibility, and is suitable for scale-up preparation of gram-level products.

3 Photochemical Coupling Reaction of Acetonitrile with Olefin or Aromatic C(sp2)—H Functionalization

Yoshida et al. reported in 2013 that a class of palladium and titanium dioxide catalysts were used in combination to cyanomethylate benzene rings. Titanium dioxide activated acetonitrile to form cyanomethyl radicals, and palladium catalysts promoted continuous substitution to form C — C bonds[24]. The reaction is carried out under mild conditions, which reduces the treatment of harmful leaving groups and embodies the concept of green and sustainable chemistry.
In 2014, Li et al. reported the synthesis of a series of indolone derivatives by a photopromoted pair activated alkene bifunctionalization strategy[25]. The 1,2-alkylarylation of various N-arylacrylamides (21) with acetonitrile or acetone in the presence of a ligand [Ru(bpy)3Cl2], a radical initiator ArN2BF4, and a base under irradiation with a 36 W fluorescent lamp afforded a series of indolone derivatives (22) in high yields.
In 2017, Yoshida et al. Reported that cyanomethylation of aliphatic or aromatic rings C — H (23) with acetonitrile was directly catalyzed by (Pt/TiO2) photocatalysts[26]. Compared with (Pd/TiO2) photocatalyst, (Pt/TiO2) photocatalyst was found to be more effective in catalyzing the cyanomethylation of aliphatic ring C — H, while the participation of metal Pd was required for catalyzing the cyanomethylation of aryl ring C — H. In this process, titanium dioxide photocatalysts supported on metal Pt and Pd nanoparticles can act as acceptors of photoexcited electrons to enhance the photocatalytic reaction rate.

4 Dehydrocoupling of Acetonitrile Functionalized Aromatic C(sp2)—H

In 2016, Li et al. Reported a novel radical initiated site-specific coupling dehydrogenation reaction to prepare heterocyclic aromatic acetonitrile derivatives[27]. The substrates of this reaction can be furan, pyrrole, thiophene and other heterocyclic molecules (24). They explored radical initiators, monovalent copper derivatives and so on, and finally found that heterocyclic aromatic acetonitrile derivatives (25) could be prepared in high yield under the action of DCP and CuCl. For the first time, aromatic acetonitrile was developed to heterocyclic molecules.
In 2017, Xu et al reported a class of dehydrogenation sp3-sp2 coupling reaction of 2-aryl imidazopyridine (26) and acetonitrile under the catalysis of iron, which can efficiently and directly dehydrogenate and oxidize sp2C—H to prepare heterocyclic aromatic acetonitrile derivatives (27) under the catalysis of divalent iron ligand under the initiator of DCP free radical, and has the advantages of wide substrate expansion range, high yield and mild conditions[28].
Yan et al. 2018 reported that a series of coumarin-acetonitrile derivatives (29) were prepared by the cross-dehydrocoupling reaction of a class of coumarin-based compounds (28) with acetonitrile in the presence of TBPB and potassium fluoride through the non-metal catalysis of direct oxidation activation C(sp3)—H[29]. The reaction has good functional group tolerance and good yield, and a new strategy of C — H activation of acetonitrile oxidation by free radical pathway is proposed.

5 C-H Cyanomethylation Promoted by Directing Group

In 2016, Ge et al. reported a Pd-catalyzed ligand-promoted site-selective cyanomethylation reaction using an unactivated C(sp3)—H bond (30) and acetonitrile directly[30]. The mechanism involves coordination of metal Pd with bidentate aminoquinoline, distal activation of the C(sp3)—H bond under alkaline conditions to form a cyclometalated Pd complex, transmetallation with the cyanomethyl Cu2+, and release of metal Pd to form the C(sp3)—H bond acetonitrilation product (31). In this reaction, the potential C — H bond was activated by intramolecular targeting group regulation and Pd complexation, and then a direct cyanomethylation method was successfully constructed.
Guo et al reported a cyanomethylation reaction of indole or pyrrole molecules at (32) C-2, which was catalyzed by divalent iron acetate and pyrimidinyl as a guide group, and successfully constructed sp3-sp2 oxidative coupling reactions to prepare a series of acetonitrile derivatives (33)[31]. The results show that the N atom in the pyrimidine molecule of the guiding group is coordinated with the activated iron-containing atom, and then the cyanomethyl radical is attacked by addition, releasing ferrous iron to form cyanomethyl products. The reaction requires a free radical initiator and a high temperature of 120.d egree. C. to complete. And the pyrimidinyl group of the directing group can be easily removed at high temperature in NaOEt/DMSO to afford a series of 2-acetonitrile-substituted indole derivatives (34).
To sum up, the direct use of acetonitrile or substituted acetonitrile for cyanomethylation is mainly a free radical strategy to prepare highly active cyanomethyl radicals, and then to the double bonds, aromatic hydrocarbons, and even the unactivated C(sp3)—H bonds in the substrate molecules.By means of metal coordination catalysis or guiding group induced activation, the C-C bond formation reaction is constructed, and then a series of transformations occur to prepare cyanomethyl products.
Pizzini et al. First reported the reaction of nitroalkenes with phenylacetonitrile carbanions, which gave 5-chloro-3-phenylbenzoxazole (36) in ethanol-water solution of potassium hydroxide, while in the presence of aprotic solvent pyridine, the nucleophilic substitution SNAr reaction took place to give the arylacetonitrile substituted product (37)[32]. Subsequently, M M kosza et al. Made a detailed review on the nucleophilic substitution ArH-CH reaction of electron-deficient aromatic hydrocarbons or heterocycles in 2004[33]. The mechanism of cyanomethylation of nucleophilic substituted aromatic C-H is systematically expounded. It is considered that electron-deficient aromatic hydrocarbons, especially nitro aromatic hydrocarbons, can undergo addition reaction with nucleophilic reagents to form δH-adducts, which can undergo rapid transformation.They defined this process as oxidative nucleophilic substitution of hydrogen (ONSH), and this reaction can be applied to various organic synthetic reactions[34]. Obviously, this is also a method of cyanomethylation of aromatic rings, but it has not received much attention in the subsequent literature.
In the process of creating novel anion receptors and modifying the structure of fluorophores, we have done some exploratory work on the construction of CHCN-containing action sites for electron-deficient fluorophores and the development of potential cyanomethylation methods[35,36]. In particular, in the construction of 1,8-naphthalimide fluorophores for the design of chemical sensors and biological probe materials, the common method to modify 1,8-naphthalimides is to introduce a functional group at the C3, C4 or C5 site, and then obtain a strong fluorescence signal for the detection of molecules to be detected in the environment and cells, however, the C2 and C7 site in 1,8-naphthalimides are rarely used[37,38][39,40]. And that CH2CN introduce at the C2 or C7 site may form an intramolecular C=O…H-CCN hydrogen bond with the carbonyl group of the 1, 8-naphthalimide. Therefore, we successfully introduced trifluoromethylpyridine-methanol group at the C4 position as a directing group or an electron-withdrawing group to assist the activation of the aromatic ring C — H bond (35), and then realized the cyanomethylation at the C2 or C7 position through the nucleophilic substitution of acetonitrile carbanion on the aromatic ring C — H, thus obtaining cis-36 and trans-36 ion probes with cis-trans isomerism characteristics[41].
Furthermore, the -CF3 was used as a directing group to enhance the electron-deficient nature of the aromatic ring, and the C4- (37) of the aromatic ring of 1,8-naphthalimide was introduced to activate the C — H functionalization at the C2 or C7 position on the fluorophore skeleton.In addition, by introducing halogen bromine (38) at the C6 position, the functional group position isomerization generated by the reaction is inhibited, and the cyanomethylation occurs at the C2 position specifically and efficiently. Compared with the previous work, this synthesis strategy has better regioselectivity and mild reaction conditions, and only NaH is needed to catalyze the direct arylation of naphthalimide C2 at room temperature.And the pyridine ring and the carbonyl in the product (39) can effectively stabilize the carbanion generated by the action of the probe 39 and the anion, so that the probe 39 has a better recognition effect on the anion[42].
Naphthalimide (40) and phenylacetonitrile were used as the model reaction to study the reaction concentration, alkali equivalent, reaction time and other factors.C — H arylacetonitriles can be conveniently prepared at room temperature for 6 H under mild conditions, especially in the absence of transition metal catalysts, to afford a series of α-diarylacetonitrile derivatives (41), which broaden the structural diversity of naphthalic anhydride dyes or chromophores[43].

6 Conclusion and prospect

In this paper, we mainly summarized the recent research on the CH cyanomethylation/alkylation reaction and the C — H cyanomethylation reaction developed by our group on the fluorophore skeleton of 1,8-naphthalic anhydride and its successful application to the detection of anions. To sum up, the most studied strategy is to generate stable cyanomethyl radicals through free radical initiators or irradiation, and then to generate C-C bonds in the double bonds of the substrate molecules, thus obtaining the target products. There are few studies on the use of targeting group strategy for cyanomethylation, so we continue to explore the targeting group strategy to construct useful C — H cyanomethylation reactions and broaden the applicability of substrates.It will be an interesting and important research direction in the field of synthetic chemistry to develop efficient and green strategies to discover more beautiful functional molecules for application in the field of drugs or probes.

References

Publishing order | Descend order by publishing year | Descend order by cited within
[1]

Mᶏkosza M. Chem. Soc. Rev., 2010, 39(8): 2855.
[2]

Rappoport Z.[M]. Chichester, UK: John Wiley & Sons, Ltd., 1970.
[3]

Dénès F, Pérez-Luna A, Chemla F. Chem. Rev., 2010, 110(4): 2366.
[4]

Weiberth F J, Hall S S. J. Org. Chem., 1987, 52(17): 3901.
[5]

Trivedi B K, Holmes A, Stoeber T L, Blankley C J, Roark W H, Picard J A, Shaw M K, Essenburg A D, Stanfield R L, Krause B R. J. Med. Chem., 1993, 36(22): 3300.
[6]

Culkin D A, Hartwig J F. Acc. Chem. Res., 2003, 36(4): 234.
[7]

Chen G, Wang Z, Wu J, Ding K L. Org. Lett., 2008, 10(20): 4573.
[8]

Narsaiah A, Nagaiah K. Adv. Synth. Catal., 2004, 346(11): 1271.
[9]

Bacchi S, Stazi F, Maton W, Castoldi D, Westerduin P, Curcuruto O. Synthesis, 2010, 2010(19): 3332.
[10]

Yang Y Y, Tang S, Liu C, Zhang H M, Sun Z X, Lei A W. Org. Biomol. Chem., 2011, 9(15): 5343.
[11]

Wu L Y, Hartwig J F. J. Am. Chem. Soc., 2005, 127(45): 15824.
[12]

Shang R, Ji D S, Chu L, Fu Y, Liu L. Angew. Chem. Int. Ed., 2011, 50(19): 4470.
[13]

Lovato K, Guo L R, Xu Q L, Liu F T, Yousufuddin M, Ess D H, Kürti L, Gao H Y. Chem. Sci., 2018, 9(41): 7992.
[14]

Dong Z, Wang J C, Dong G B. J. Am. Chem. Soc., 2015, 137(18): 5887.
[15]

Cornella J, Righi M, Larrosa I. Angew. Chem. Int. Ed., 2011, 50(40): 9429.
[16]

Wu T, Mu X, Liu G S. Angew. Chem. Int. Ed., 2011, 50(52): 12578.
[17]

Li J, Wang Z G, Wu N J, Gao G, You J S. Chem. Commun., 2014, 50(95): 15049.
[18]

Li Z J, Xiao Y X, Liu Z Q. Chem. Commun., 2015, 51(49): 9969.
[19]

Pan C D, Zhang H L, Zhu C J. Org. Biomol. Chem., 2015, 13(2): 361.
[20]

Bunescu A, Wang Q, Zhu J P. Org. Lett., 2015, 17(8): 1890.
[21]

Chatalova-Sazepin C, Wang Q, Sammis G M, Zhu J P. Angew. Chem. Int. Ed., 2015, 54(18): 5443.
[22]

Liu Y Y, Yang X H, Song R J, Luo S L, Li J H. Nat. Commun., 2017, 8: 14720.
[23]

Wang K C, Chen X, Yuan M, Yao M, Zhu H C, Xue Y B, Luo Z W, Zhang Y H. J. Org. Chem., 2018, 83(3): 1525.
[24]

Yoshida H, Fujimura Y, Yuzawa H, Kumagai J, Yoshida T. Chem. Commun., 2013, 49(36): 3793.
[25]

Zhang J L, Liu Y, Song R J, Jiang G F, Li J H. Synlett., 2014, 25: 1031.
[26]

Wada E, Takeuchi T, Fujimura Y, Tyagi A, Kato T, Yoshida H. Catal. Sci. Technol., 2017, 7(12): 2457.
[27]

Liu Z Q, Li Z J. Chem. Commun., 2016, 52(99): 14278.
[28]

Su H M, Wang L Y, Rao H H, Xu H. Org. Lett., 2017, 19(9): 2226.
[29]

Zhang R X, Jin S Z, Liu Q, Lin S, Yan Z H. J. Org. Chem., 2018, 83(21): 13030.
[30]

Liu Y B, Yang K, Ge H B. Chem. Sci., 2016, 7(4): 2804.
[31]

Qiao K, Zhang D, Zhang K, Yuan X, Zheng M W, Guo T F, Fang Z, Wan L, Guo K. Org. Chem. Front., 2018, 5(7): 1129.
[32]

Davis R B, Pizzini L C. J. Org. Chem., 1960, 25(11): 1884.
[33]

Mᶏkosza M, Wojciechowski K. Chem. Rev., 2004, 104(5): 2631.
[34]

Mᶏkosza M, Staliński K. Tetrahedron, 1998, 54(30): 8797.
[35]

Chen J J, Liu C X, Zhang J L, Ding W, Zhou M, Wu F H. Chem. Commun., 2013, 49(92): 10814.
[36]

Wu H W, Chen Y Y, Rao C H, Liu C X. Prog. Chem., 2016, 28(10): 1501.
[37]

(伍宏伟, 陈亚运, 饶才辉, 刘传祥. 化学进展, 2016, 28(10): 1501).
[38]

Duke R M, Veale E B, Pfeffer F M, Kruger P E, Gunnlaugsson T. Chem. Soc. Rev., 2010, 39(10): 3936.
[39]

Zhou L, Xie L J, Liu C H, Xiao Y. Chin. Chem. Lett., 2019, 30(10): 1799.
[40]

McDonald K P, Ramabhadran R O, Lee S, Raghavachari K, Flood A H. Org. Lett., 2011, 13(23): 6260.
[41]

Xu Z C, Xiao Y, Qian X H, Cui J N, Cui D W. Org. Lett., 2005, 7(5): 889.
[42]

Chen Y Y, Hu X X, Rao C H, Li Z Y, Chen L, Fu C, Liu C X. Anal., 2018, 143(19): 4655.
[43]

Li Z Y, Rao C H, Chen L, Fu C, Zhu T T, Chen X, Liu C X. J. Org. Chem., 2019, 84(11): 7518.
[44]

Li Z Y, Rao C H, Chen L, Fu C, Zhu T T, Chen X, Liu C X. Dyes Pigments, 2020, 173: 107967.

Funding

Natural Science Foundation of Shanghai(17ZR1429900)

Opening Fund of Shanghai Key Laboratory of Chemical Biology.

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