Patent Application
20230391787
The present application relates to organic compounds with a negative singlet-triplet gap and a positive oscillator strength. The present application further relates to the use of the compounds as emitters and/or dopants in organic light-emitting diodes (OLED) and in photocatalysis.
The design of state-of-the-art organic light-emitting diodes (OLEDs) has focused mainly on molecules consisting of spatially separated but electronically connected, donor and acceptor π-systems. Accordingly, their low-lying electronic excited states are typically of significant charge-transfer character minimizing the associated exchange energy difference leading to vanishing singlet-triplet gaps. This feature allows facile upconversion of excited state triplets to excited state singlets via thermally activated delayed fluorescence (TADF) resulting in OLEDs with internal quantum efficiencies (IQEs) of up to 100% and external quantum efficiencies (EQEs) rivaling those of state-of-the-art organometallic OLEDs. However, the large-scale market deployment of TADF-based OLEDs remains limited, due to a lack of blue and red emitters, of TADF molecules possessing color purity, and of devices with long-term operational stability.
Hund's first rule (1) predicts that the first excited state of closed-shell molecules is a triplet state lower in energy than the first excited singlet state. This prediction holds for all but a handful of all known organic and inorganic compounds. (2,3) Hence, it is the basis for Jablonski diagrams (4) in educational material about electronic spectra of molecules illustrating that it is almost considered a basic truth in chemistry. (5-12) Accordingly, molecules violating Hund's first rule in their first excited singlet and triplet energies, i.e. molecules with excited state triplet(s) higher in energy than excited state singlet(s), are said to possess an “inverted” singlet-triplet gap (herein termed the INVEST property). Very few organic INVEST molecules were predicted previously to exist based on computations alone (2, 17, 18) with little to no experimental evidence (19, 20) and no inorganic INVEST molecule is known to date. Besides inherent INVEST molecules, it has been shown in recent years that the influence of the environment can also invert the gap (13) for instance in exciplexes (14) through strong light-matter coupling in microcavities (15) and polarizable environments. (16)
Nevertheless, recent publications spark new interest in INVEST molecules and their potential applications in photocatalysis, and organic optoelectronics as emissive layer in organic light-emitting diodes (OLEDs). (21, 22) The two molecules reported were both based on phenalene (23) with a distinct degree of nitrogen substitution. However, both molecules have dipole-forbidden S1-S0 transitions (due to spatial symmetry) and are likely very poor emitters.
Accordingly, there is a need to develop organic INVEST molecules.
Molecules with appreciable oscillator strength and inverted singlet-triplet gaps have the potential to become the next generation of OLED materials (13, 24) because of their potential for fast reverse intersystem crossing (i.e., TADF without activation), high emission rates, and a thermodynamic equilibrium that disfavors triplets, and, hence, minimizes triplet annihilation and nonradiative Ti decay processes that shorten device lifetimes. (13)
Based on computational evidence, in the present application, it has been shown that compounds of the present application exhibit appreciable oscillator strength. Overall, it was observed that the singlet-triplet gap, the oscillator strength, and the absorption wavelength can be tuned by modification, including nitrogen substitution, of the phenalene core. It was also observed that the compounds of the present application, azaphenalenes substituted with electron-donating and electron-withdrawing substituents, have increased oscillator strength but still an inverted singlet-triplet gap. Equally, systematic optimization of substituted azaphenalenes was investigated for high oscillator strength, small singlet-triplet gap, and absorption wavelength leading to compounds of the present application with considerable oscillator strength, covering the visible light spectrum.
Accordingly, in one aspect, the present application includes a compound of Formula I
wherein
In another aspect, the present application includes an organic light-emitting diode comprising at least one compound of the present application.
In another aspect, the present application includes a photocatalyst comprising at least one compound of the present application.
In another aspect, the present application includes a triplet quencher comprising at least one compound of the present application.
In another aspect, the present application also includes a use of a compound of the present application in an organic light-emitting diode.
In another aspect, the present application also includes a method of preparing an organic light-emitting diode comprising providing at least one compound of the present application as an emitter or a dopant.
In another aspect, the present application includes a use of a compound of the present application as a photocatalysis.
In another aspect, the present application includes a method of performing photocatalysis comprising providing at least one compound of the present application as a photocatalyst.
In another aspect, the present application includes a use of a compound of the present application in the generation of organic laser.
In another aspect, the present application includes a method of generating organic laser comprising providing at least one compound of the present application as a light emitter.
In another aspect, the present application includes a use of a compound of the present application in the enhancement of photostability.
In another aspect, the present application includes a method of enhancing photostability comprising providing at least one compound of the present application as a triplet quencher.
The embodiments of the application will now be described in greater detail with reference to the attached drawings in which:
Other features and advantages of the present application will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the application, are given by way of illustration only and the scope of the claims should not be limited by these embodiments, but should be given the broadest interpretation consistent with the description as a whole.
Unless otherwise indicated, the definitions and embodiments described in this and other sections are intended to be applicable to all embodiments and aspects of the present application herein described for which they are suitable as would be understood by a person skilled in the art.
The term “compound(s) of the application” or “compound(s) of the present application” and the like as used herein refers to a compound of Formula I.
The term “and/or” as used herein means that the listed items are present, or used, individually or in combination. In effect, this term means that “at least one of” or “one or more” of the listed items is used or present.
As used in the present application, the singular forms “a”, “an” and “the” include plural references unless the content clearly dictates otherwise. For example, an embodiment including “a compound” should be understood to present certain aspects with one compound, or two or more additional compounds.
In embodiments comprising an “additional” or “second” component, such as an additional or second compound, the second component as used herein is chemically different from the other components or first component. A “third” component is different from the other, first, and second components, and further enumerated or “additional” components are similarly different.
As used in this application and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “include” and “includes”) or “containing” (and any form of containing, such as “contain” and “contains”), are inclusive or open-ended and do not exclude additional, unrecited elements or process steps.
The term “consisting” and its derivatives as used herein are intended to be closed terms that specify the presence of the stated features, elements, components, groups, integers, and/or steps, and also exclude the presence of other unstated features, elements, components, groups, integers and/or steps.
The term “consisting essentially of”, as used herein, is intended to specify the presence of the stated features, elements, components, groups, integers, and/or steps as well as those that do not materially affect the basic and novel characteristic(s) of these features, elements, components, groups, integers, and/or steps.
The term “suitable” as used herein means that the selection of the particular compound or conditions would depend on the specific synthetic manipulation to be performed, the identity of the molecule(s) to be transformed and/or the specific use for the compound, but the selection would be well within the skill of a person trained in the art.
In embodiments of the present application, the compounds described herein may have at least one asymmetric center. Where compounds possess more than one asymmetric center, they may exist as diastereomers. It is to be understood that all such isomers and mixtures thereof in any proportion are encompassed within the scope of the present application. It is to be further understood that while the stereochemistry of the compounds may be as shown in any given compound listed herein, such compounds may also contain certain amounts (for example, less than 20%, suitably less than 10%, more suitably less than 5%) of compounds of the present application having an alternate stereochemistry. It is intended that any optical isomers, as separated, pure or partially purified optical isomers or racemic mixtures thereof are included within the scope of the present application.
The compounds of the present application may also exist in different tautomeric forms and it is intended that any tautomeric forms which the compounds form, as well as mixtures thereof, are included within the scope of the present application.
The compounds of the present application may further exist in varying polymorphic forms and it is contemplated that any polymorphs, or mixtures thereof, which form are included within the scope of the present application.
The present description refers to a number of chemical terms and abbreviations used by those skilled in the art. Nevertheless, definitions of selected terms are provided for clarity and consistency.
The terms “about”, “substantially” and “approximately” as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed as including a deviation of at least ±5% of the modified term if this deviation would not negate the meaning of the word it modifies or unless the context suggests otherwise to a person skilled in the art.
The term “alkyl” as used herein, whether it is used alone or as part of another group, means straight or branched chain, saturated alkyl groups. The number of carbon atoms that are possible in the referenced alkyl group are indicated by the prefix “Cn1-n2”. For example, the term C1-10alkyl means an alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.
The term “alkylene”, whether it is used alone or as part of another group, means straight or branched chain, saturated alkylene group, that is, a saturated carbon chain that contains substituents on two of its ends. The number of carbon atoms that are possible in the referenced alkylene group are indicated by the prefix “Cn1-n2”. For example, the term C2-6alkylene means an alkylene group having 2, 3, 4, 5 or 6 carbon atoms.
The term “alkenyl” as used herein, whether it is used alone or as part of another group, means straight or branched chain, unsaturated alkyl groups containing at least one double bond. The number of carbon atoms that are possible in the referenced alkylene group are indicated by the prefix “Cn1-n2”. For example, the term C2-6alkenyl means an alkenyl group having 2, 3, 4, 5 or 6 carbon atoms and at least one double bond.
The term “alkynyl” as used herein, whether it is used alone or as part of another group, means straight or branched chain, unsaturated alkynyl groups containing at least one triple bond. The number of carbon atoms that are possible in the referenced alkyl group are indicated by the prefix “Cn1-n2”. For example, the term C2-6alkynyl means an alkynyl group having 2, 3, 4, 5 or 6 carbon atoms.
The term “cycloalkyl,” as used herein, whether it is used alone or as part of another group, means a saturated carbocyclic group containing from 3 to 20 carbon atoms and one or more rings. The number of carbon atoms that are possible in the referenced cycloalkyl group are indicated by the numerical prefix “Cn1-n2”. For example, the term C3-10cycloalkyl means a cycloalkyl group having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms.
The term “aryl” as used herein, whether it is used alone or as part of another group, refers to carbocyclic groups containing at least one aromatic ring and contains either 6 to 20 carbon atoms.
The term “heterocycloalkyl” as used herein, whether it is used alone or as part of another group, refers to cyclic groups containing at least one non-aromatic ring containing from 3 to 20 atoms in which one or more of the atoms are a heteroatom selected from O, S and N and the remaining atoms are C. Heterocycloalkyl groups are either saturated or unsaturated (i.e. contain one or more double bonds). When a heterocycloalkyl group contains the prefix Cn1-n2 this prefix indicates the number of carbon atoms in the corresponding carbocyclic group, in which one or more, suitably 1 to 5, of the ring atoms is replaced with a heteroatom as selected from O, S and N and the remaining atoms are C. Heterocycloalkyl groups are optionally benzofused.
The term “heteroaryl” as used herein, whether it is used alone or as part of another group, refers to cyclic groups containing at least one heteroaromatic ring containing 5-20 atoms in which one or more of the atoms are a heteroatom selected from O, S and N and the remaining atoms are C. When a heteroaryl group contains the prefix Cn1-n2 this prefix indicates the number of carbon atoms in the corresponding carbocyclic group, in which one or more, suitably 1 to 5, of the ring atoms is replaced with a heteroatom as defined above. Heteroaryl groups are optionally benzofused.
The term “heterocycle” as used herein, whether it is used alone or as a part of another group, refers to cyclic groups containing at least one heterocycloalkyl ring or at least one heteroaromatic ring.
All cyclic groups, including aryl, heteroaryl, heterocycloalkyl and cycloalkyl groups, contain one or more than one ring (i.e. are polycyclic). When a cyclic group contains more than one ring, the rings may be fused, bridged, spirofused or linked by a bond.
The term “benzofused” as used herein refers to a polycyclic group in which a benzene ring is fused with another ring.
A first ring being “fused” with a second ring means the first ring and the second ring share two adjacent atoms there between.
A first ring being “bridged” with a second ring means the first ring and the second ring share two non-adjacent atoms there between.
A first ring being “spirofused” with a second ring means the first ring and the second ring share one atom there between.
The term “fluorosubstituted” refers to the substitution of one or more, including all, available hydrogens in a referenced group with fluoro.
The terms “halo” or “halogen” as used herein, whether it is used alone or as part of another group, refers to a halogen atom and includes fluoro, chloro, bromo and iodo.
The term “available”, as in “available hydrogen atoms” or “available atoms” refers to atoms that would be known to a person skilled in the art to be capable of replacement by a substituent.
The term “amine” or “amino,” as used herein, whether it is used alone or as part of another group, refers to groups of the general formula NR′R″, wherein R′ and R″ are each independently selected from hydrogen or C1-10alkyl.
The term “protecting group” or “PG” and the like as used herein refers to a chemical moiety which protects or masks a reactive portion of a molecule to prevent side reactions in those reactive portions of the molecule, while manipulating or reacting a different portion of the molecule. After the manipulation or reaction is complete, the protecting group is removed under conditions that do not degrade or decompose the remaining portions of the molecule. The selection of a suitable protecting group can be made by a person skilled in the art. Many conventional protecting groups are known in the art, for example as described in “Protective Groups in Organic Chemistry” McOmie, J. F. W. Ed., Plenum Press, 1973, in Greene, T. W. and Wuts, P. G. M., “Protective Groups in Organic Synthesis”, John Wiley & Sons, 3rd Edition, 1999 and in Kocienski, P. Protecting Groups, 3rd Edition, 2003, Georg Thieme Verlag (The Americas).
In one aspect, the present application includes a compound of Formula I
wherein
In some embodiments, the oscillator strength is greater than or equal to about 0.03. In some embodiments, the oscillator strength is greater than or equal to about 0.05. In some embodiments, the oscillator strength is greater than or equal to about 0.1. In some embodiments, the oscillator strength is greater than or equal to about 0.2. In some embodiments, the oscillator strength is greater than or equal to about 0.3. In some embodiments, the oscillator strength is greater than or equal to about 0.4. In some embodiments, the oscillator strength is greater than or equal to about 0.5. In some embodiments, the oscillator strength is greater than or equal to about 0.6. In some embodiments, the oscillator strength is greater than or equal to about 0.7. In some embodiments, the oscillator strength is greater than or equal to about 0.8. In some embodiments, the oscillator strength is greater than or equal to about 0.9. In some embodiments, the oscillator strength is greater than or equal to about 1.
In some embodiments, R1 and R9 are not all H.
In some embodiments, 2 to 4 of X1 to X6 are N
In some embodiments, each halo is independently selected from F, Br, and Cl.
In some embodiments, each C1-10alkyl is independently selected from linear and branched C1-6alkyl. In some embodiments, the linear and branched C1-6alkyl is selected from methyl, ethyl, propyl, butyl, isopropyl, secpropyl, secbutyl, and tertbutyl.
In some embodiments, each heterocycle and heterocyclocycloalkyl is independently selected from azetidine, aziridine, pyrrolidine, pipperidine, morpholine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, indolinone, and quinolinone.
In some embodiments, each aryl is independently selected from phenyl and naphthyl. In some embodiments, each aryl is phenyl.
In some embodiments, each heterocycle and heteroaryl is independently selected from pyrrole, pyrazole, pyridine, indole, carbazole, indazole, imidazole, oxazole, isoxazole, thiazole, thiophene, furan, pyridazine, isothiazole, pyrimidine, benzofuran, benzothiophene, benzoimidazole, and quinoline.
In some embodiments, R1-R9 are independently selected from H, F, Br, Cl, NO2, CN, isonitrile, C(O)H, NH2, OH, SH, C1-6alkyl, C3-8cycloalkyl, C2-4alkenyl, C2-4alkynyl, OC1-6alkyl, NHC1-6alkyl, N(C1-6alkyl)(C1-6alkyl), C(O)C1-6alkyl, SC1-6alkyl, S(O)C1-6alkyl, OC(O)C1-6alkyl, aryl, N(aryl)(aryl), S-aryl, heteroaryl, C(O)NH2. In some embodiments, R1-R9 are independently selected from H, F, Br, Cl, NO2, CN, isonitrile, C(O)H, NH2, OH, SH, CF3, methyl, ethyl, propyl, butyl, isopropyl, secpropyl, secbutyl, tertbutyl, C3-6cycloalkyl, CH═CH2, C≡CH, OCH3, OEt, Oisopropyl, Otertbutyl, OCF3, NHCH3, NHCH2CH3, NHisopropyl, NHtertbutyl, N(CH3)2, NH(CH2CH3)2, C(O)CH3, C(O)CH2CH3, SCH3, SCH2CH3, S(O)CH3, S(O)CH2CH3, OC(O)CH3, OC(O)CH2CH3, phenyl, naphthyl, N(phenyl)(phenyl), S-phenyl, S-naphthyl, NH-phenyl, O-pehynl, pyrrole, pyrazole, indole, indazole, benzoimidazole, pyridine, carbazole, benzofuran, benzothiophene, furan, thiophene, imidazole, oxazole, isoxazole, thiazole, C(O)NH2.
In some embodiments, R10 is selected from F, Br, Cl, NO2, CN, NH2, OH, SH, C1-6alkyl, OC1-6alkyl, NHC1-6alkyl, N(C1-6alkyl)(C1-6alkyl), N(aryl)(aryl), NH(C3-10cycloalkyl), 3- to 8-membered heterocycloalkyl, NHC(O)H, NHC(O)C1-6alkyl, aryl, NH-aryl, C(O)-aryl, heteroaryl, NH-heteroaryl, wherein all alkyl, cycloalkyl, alkenyl, alkynyl, aryl, C1-10akyl substituted aryl, heterocycle, and heteroaryl groups are each unsubstituted or substituted with one or more substituents independently selected from halo, NO2, CN, NH2, OH, C3-6cycloalkyl, C1-6alkyl, OC1-6alkyl, N(C1-6alkyl)(C1-6alkyl), trialkylsilanyl, heteroaryl.
In some embodiments, R10 is selected from F, Br, Cl, NO2, CN, NH2, OH, SH, CF3, methyl, ethyl, propyl, butyl, isopropyl, secpropyl, secbutyl, tertbutyl, OCH3, OEt, Oisopropyl, Otertbutyl, OCF3, NHCH3, NHCH2CH3, NHisopropyl, NHtertbutyl, N(CH3)2, N(isopropyl)2, N(phenyl)(phenyl), NH(C3-6cycloalkyl), azetidine, aziridine, pyrrolidine, pipperidine, morpholine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, NHC(O)H, NHC(O)CH3, NHC(O)CH2CH3, phenyl, naphthyl, NH-phenyl, NH-naphthyl, C(O)-phenyl, pyrrole, imidazole, pyrazole, carbazole, indole, NH-pyridine, NH-pyrrole, NH-furan, NH-imidazole, NH-thiophene, NH-pyridazine, NH-pyrimidine, NH-isoxazole, NH-oxazole, NH-pyrazole, NH-isothiazole, NH-thiazole, NH-indole, wherein all alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocycle, and heteroaryl groups are each unsubstituted or substituted with one or more substituents independently selected from F, NO2, CN, NH2, OH, C3-6cycloalkyl, methyl, ethyl, propyl, butyl, isopropyl, secpropyl, secbutyl, tertbutyl, OCH3, OEt, N(CH3)2, N(CH2CH3)2, triethylsilanyl, trimethylsilanyl phenyl, pyrazine.
In some embodiments, the compound of the present application is selected from
In some embodiments, the compound has a structure of Formula I-a
wherein
In some embodiments, R11 and R12 are each independently selected from H, NH2, NH(alkyl), NH(aryl), and NH-heteroaryl. In some embodiments, R11 and R12 are H or NH2.
In some embodiment, the compound is selected from
In some embodiments, the compound has a structure of Formula I-b
wherein ring A and ring B are each independently a 5-membered or 6-membered carbocycle or heterocycle, optionally an aromatic or heteroaromatic cycle, unsubstituted or substituted with one or more substituents independently selected from R10.
In some embodiments, the heterocycle is a nitrogen-containing heterocycle.
In some embodiments, R11 and R12 are nitrogen.
In some embodiment, the compound is selected from
In some embodiments, the compound has a structure of Formula I-c
wherein ring C and ring D are each independently a 5-membered or 6-membered carbocycle or heterocycle, optionally an aromatic or heteroaromatic cycle, unsubstituted or substituted with one or more substituents independently selected from R10.
In some embodiments, ring C and ring D are each independently selected from nitrogen-containing heterocycles and sulfur-containing heterocycles.
In some embodiments, the compound is
In some embodiments, the compound has a structure of Formula I-d
and wherein R1 and R2 are each independently selected from aryl and heteroaryl, each unsubstituted or substituted with one or more substituents independently selected from R10.
In some embodiments, R1 and R2 are each independently selected from phenyl, pyrrole, furan, thiophene, indole, benzofuran, benzothiophene, benzoimidazole, indazole, indoline, quinolinone, and pyridine.
In some embodiments, the compound is selected from
In another aspect, the present application includes an organic light-emitting diode comprising at least one compound of the present application.
In another aspect, the present application includes a photocatalyst comprising at least one compound of the present application.
In another aspect, the present application includes a triplet quencher comprising at least one compound of the present application.
Compounds of the present application can be prepared by various synthetic processes. The choice of particular structural features and/or substituents may influence the selection of one process over another. The selection of a particular process to prepare a given compound of Formula I is within the purview of the person of skill in the art. Some starting materials for preparing compounds of the present application are available from commercial chemical sources. Other starting materials, for example as described below, are readily prepared from available precursors using straightforward transformations that are well known in the art. In the Schemes below showing the preparation of compounds of the application, all variables are as defined in Formula I, unless otherwise stated.
The compounds of Formula I generally can be prepared according to the processes illustrated in the Schemes below. In the structural formulae shown below the variables are as defined in Formula I unless otherwise stated. A person skilled in the art would appreciate that many of the reactions depicted in the Schemes below would be sensitive to oxygen and water and would know to perform the reaction under an anhydrous, inert atmosphere if needed. Reaction temperatures and times are presented for illustrative purposes only and may be varied to optimize yield as would be understood by a person skilled in the art.
Accordingly, in some embodiments, the compounds of the present application can be prepared as shown in the retrosynthetic Schemes below. The term “Hal” as used in the Schemes refers to halogen. For example, it can refer to Br, Cl, or I. Each Re is independently selected from C1-3alkyl.
Accordingly, in some embodiments, certain compounds of Formula I (shown as compound of Formula A, wherein X1 and X6 are CR4 and CR9, respectively, and X2, X3, X4 and X5 are N) are prepared as shown in retrosynthetic Scheme 1. Therefore, 2,6-diaminopyridine compound D can react as a nucleophile with the acyl halide compounds of Formulae E and F to provide intermediate compound of Formula B. Intermediate compound of Formula B can produce compound A through cyclization with cyanamide C.
In some embodiments, the certain compounds of Formula I (shown as compound of Formula G, wherein X1, X2, X5 and X6 are CR4, CR5, CR8 and CR9, respectively, and X3 and X4 are N) are prepared as shown in retrosynthetic Scheme II. Therefore, the carbonyl compounds of Formulae K and L can undergo an aromatic nucleophilic substitution with the dihalopyridine compound of Formula J to provide the intermediate compound of Formula H. The intermediate compound of Formula H can cyclize with cyanamide of Formula C to produce the compound of Formula G.
In some embodiments, the certain compounds of Formula I (shown as compound of Formula G, wherein X1, X2, X5 and X6 are CR4, CR5, CR8 and CR9, respectively, and X3 and X4 are N) are prepared as shown in retrosynthetic Scheme Ill. Therefore, the compounds of Formulae N and O can undergo cyclization with the compound of Formula M to produce the compound of Formula G.
In some embodiments, certain compounds of Formula I (shown as compound of Formula P, wherein X1, X2 and X6 are CR4, CR5 and CR9, respectively, and X3, X4 and X5 are N) are prepared as shown in retrosynthetic Scheme IV. Therefore, the compounds of Formulae N and O can undergo cyclization with the aminopyridine compound of Formula Q to produce the compound of Formula P.
In some embodiments, certain compounds of Formula I (shown as compound of Formula P, wherein X1, X2 and X6 are CR4, CR5 and CR9, respectively, and X3, X4 and X5 are N) are prepared as shown in retrosynthetic Scheme V. Therefore, the acyl halide compound of Formula F can react with the halogenated aminopyridine compound of Formula T to obtain the intermediate compound of Formula S. The intermediate compound of Formula S can undergo aromatic nucleophilic substitution with the carbonyl compound of Formula K to produce the intermediate compound of Formula R. The intermediate compound of Formula R can then cyclize with cyanamide of Formula C to obtain the compound for Formula P.
In some embodiments, certain compounds of Formula I (shown as compound of Formula U, wherein X1 and X2 are CR4 and CR5, respectively, and X3, X4, X5 and X6 are N) are prepared as shown in retrosynthetic Scheme VI. Therefore, the acyl halide compound of Formula F can react with the halogenated aminopyrimidine compound of Formula X to obtain the intermediate compound of Formula W. The intermediate compound of Formula W can undergo aromatic nucleophilic substitution with the carbonyl compound of Formula K to produce the intermediate compound of Formula V. The intermediate compound of Formula V can then cyclize with cyanamide of Formula C to obtain the compound for Formula U.
In some embodiments, certain compounds of Formula I (shown as compound of Formula U, wherein X1 and X2 are CR4 and CR5, respectively, and X3, X4, X5 and X6 are N) are prepared as shown in retrosynthetic Scheme VII. Therefore, the compounds of Formulae N and O can cyclize with the aminopyrimidine compound of Formula Y to produce the compound of Formula U.
In some embodiments, certain compounds of Formula I (shown as compound of Formula Z, wherein X3 and X4 are CR6 and CR7, respectively, and X1, X2, X5 and X6 are N) are prepared as shown in retrosynthetic Scheme VIII. Therefore, the enamine compounds of Formulae AC and AD can undergo aromatic nucleophilic substitution with the dihalogenated triazine compound of Formula AB to obtain the intermediate compound of Formula AA, which can then undergo intramolecular cyclization and sequential decarboxylation to generate the compound for Formula Z.
In some embodiments, certain compounds of Formula I (shown as compound of Formula Z, wherein X3 and X4 are CR6 and CR7, respectively, and X1, X2, X5 and X6 are N) are prepared as shown in retrosynthetic Scheme IX. Therefore, the compound of Formula AF can condense with the diaminotriazine compound of Formula AE to produce the compound of Formula Z.
In some embodiments, certain compounds of Formula I-a (shown as compound of Formula AG, wherein X3 and X4 are CR6 and CR7, respectively, R6 and R7 are linked to form CH═CH and X1, X2, X5 and X6 are N) are prepared as shown in retrosynthetic Scheme X. Therefore, the cyclopentanone compound of Formula AH can condense with the compound of Formula AE to produce the compound of Formula AG.
In some embodiments, certain compounds of Formula I-a (shown as compound of Formula AG, wherein X3 and X4 are CR6 and CR7, respectively, R6 and R7 are linked to form CH═CH and X1, X2, X5 and X6 are N) are prepared as shown in retrosynthetic Scheme XI. Therefore, the compounds of Formulae AJ and O can cyclize with the bicyclic compound of Formula AI to generate the compound of Formula AG.
In some embodiments, certain compounds of Formula I-a (shown as compound of Formula AG, wherein X3 and X4 are CR6 and CR7, respectively, R6 and R7 are linked to form CH═CH and X1, X2, X5 and X6 are N) are prepared as shown in retrosynthetic Scheme XII. Therefore, the halogenated pyrimidine compound of Formula AN can undergo nucleophilic attack of the hydroxamic acid ester compound of Formula AO to produce the intermediate compound of Formula AL. The intermediate compound of Formula AL can undergo aromatic nucleophilic substitution with the compound of Formula AM to generate the intermediate compound of Formula AK. The intermediate compound of Formula AK can cyclize with cyanamide of Formula C to produce the compound of Formula AG.
In some embodiments, certain compounds of Formula I-a (shown as compound of Formula AG, wherein X3 and X4 are CR6 and CR7, respectively, R6 and R7 are linked to form CH═CH and X1, X2, X5 and X6 are N) are prepared as shown in retrosynthetic Scheme XIII. Therefore, the dicarbonyl compound of Formula AS can cyclise with the tricarbonyl compound of Formula AR to produce the furanone compound of Formula AQ, which can condense with diaminotriazine compound of Formula AE to obtain the intermediate compound of Formula AP. The intermediate compound of Formula AP can undergo alkene metathesis to produce the compound of Formula AG.
Throughout the processes described herein it is to be understood that, where appropriate, suitable protecting groups will be added to, and subsequently removed from, the various reactants and intermediates in a manner that will be readily understood by one skilled in the art. Conventional procedures for using such protecting groups as well as examples of suitable protecting groups are described, for example, in “Protective Groups in Organic Synthesis”, T. W. Green, P. G. M. Wuts, Wiley-Interscience, New York, (1999). It is also to be understood that a transformation of a group or substituent into another group or substituent by chemical manipulation can be conducted on any intermediate or final product on the synthetic path toward the final product, in which the possible type of transformation is limited only by inherent incompatibility of other functionalities carried by the molecule at that stage to the conditions or reagents employed in the transformation. Such inherent incompatibilities, and ways to circumvent them by carrying out appropriate transformations and synthetic steps in a suitable order, will be readily understood to one skilled in the art. Examples of transformations are given herein, and it is to be understood that the described transformations are not limited only to the generic groups or substituents for which the transformations are exemplified. References and descriptions of other suitable transformations are given in “Comprehensive Organic Transformations—A Guide to Functional Group Preparations” R. C. Larock, VHC Publishers, Inc. (1989). References and descriptions of other suitable reactions are described in textbooks of organic chemistry, for example, “Advanced Organic Chemistry”, March, 4th ed. McGraw Hill (1992) or, “Organic Synthesis”, Smith, McGraw Hill, (1994). Techniques for purification of intermediates and final products include, for example, straight and reversed phase chromatography on column or rotating plate, recrystallisation, distillation and liquid-liquid or solid-liquid extraction, which will be readily understood by one skilled in the art.
In some embodiments, the present application also includes a use of a compound of the present application in an organic light-emitting diode.
In some embodiments, the compound of the present application is used as an emitter or a dopant.
In some embodiments, the present application also includes a method of preparing an organic light-emitting diode comprising providing at least one compound of the present application as an emitter or a dopant.
In some embodiments, the present application also includes an organic-light emitting diode comprising at least one compound of the present application.
In some embodiments, the present application includes a use of a compound of the present application as a photocatalysis.
In some embodiments, the present application includes a method of performing photocatalysis comprising contacting at least one compound of the present application with a mixture requiring a photocatalyst and performing a photocatalytic transformation on the mixture.
In some embodiments, the present application includes a use of a compound of the present application in the generation of organic laser.
In some embodiments, the present application includes a method of generating organic laser comprising providing at least one compound of the present application as a light emitter.
In some embodiments, the present application also includes an organic-laser comprising at least one compound of the present application.
In some embodiments, the present application includes a use of a compound of the present application in the enhancement of photostability.
In some embodiments, the compound is used as a triplet quencher.
In some embodiments, the present application includes a method of enhancing photostability comprising providing at least one compound of the present application as a triplet quencher.
The following non-limiting examples are illustrative of the present application.
Ground state conformational ensembles were generated using crest (25) (version 2.10.1) with the iMTD-GC (26, 27) workflow (default option) at the GFN0-xTB (28) level of theory. The lowest energy conformers were first reoptimized using xtb (29) (version 6.3.0) at the GFN2-xTB (30, 31) level of theory, followed by another reoptimization using Orca (32, 33) (version 4.2.1) at the B3LYP (34-36)/cc-pVDZ (37) level of theory. The corresponding geometries were used for subsequent ground and excited state single-point calculations. Single points at the ωB2PLYP (38)/def2-SVP (39), and DLPNO-NEVPT2(6,6) (40)/def2-SV(P) (39) levels of theory were performed using Orca (32, 33) (version 4.2.1), single points at the ADC(2) (41-47)/cc-pVDZ (37), ADC(3) (41-47)/cc-pVDZ (37), EOM-CCSD (48-52)/cc-pVDZ (37), FNO-EOM-CCSD (48-56)/cc-pVDZ (37) with 98.85% of the total natural population, and SA-SF-PBE50 (57-62)/def2-SVP (37) levels of theory were performed using Q-Chem (63) (version 5.2). Ground and excited geometry optimizations for adiabatic state energy differences at the ωB2PLYP (38)/def2-SV(P) (39) level of theory were performed using Orca (32, 33) (version 4.2.1). For all excited state single point calculations, four roots were chosen each for both the singlet and the triplet manifold. For the ground and excited state geometry optimizations, two roots were chosen each.
Gaussian process regression was carried out using Python (version 3.6.9) together with the scikit-learn package (version 0.21.2). First, data was transformed linearly to be within the interval [0,1]. As kernel, we used a sum of the Matérn kernel with v=5/2 and the White kernel.
Methods have been developed to predict the singlet-triplet inversion, which are suitable for high-throughput virtual screening. Several efficient methods were compared against benchmark methods for molecules 1 and 2 (Scheme 1). It was shown previously that single-excitation calculations, including time-dependent density functional approximations (TD-DFA) with GGA, meta-GGA and hybrid functionals, are unable to describe singlet-triplet inversion. (21, 22) Table 1 shows the results of excited state computations for several methods of varying computational cost including two particularly efficient families of methods that include double excitations, namely double-hybrid TD-DFAs (64-67) (ωB2PLYP (38)) and spin-flip TD-DFAs (57, 58) (SA-SF-PBE50 (57-62)). Using ωB2PLYP, vibrational contributions to the singlet-triplet gap were estimated by performing excited singlet and triplet geometry optimizations. Due to their rigid structures, the energy difference between singlet and triplet minima (sometimes termed adiabatic gap) is almost identical to the singlet-triplet gap at the Franck-Condon point (sometimes termed vertical gap) for both 1 and 2. Hence, the latter was used as an approximation to the gap between minima. It was noted that ωB2PLYP only reproduced an inverted singlet-triplet gap for 2, but not for 1. As shown below, this may be the result of a systematic and correctable offset compared to benchmark correlated methods like ADC(2) or EOM-CCS D.
Compounds 1 and 2 are isoelectronic and differ only by substitution of C—H with N. Hence, all structures resulting from systematic permutations of such nitrogen substitutions were investigated (Scheme 2).
Next, the impact of both electron-donating and electron-withdrawing substituents on the properties was assessed. Both mesomeric and inductive effects were also investigated. Hence, a set of 18 both common and small substituents was selected and the properties for all distinct monosubstituted analogues of compounds 1-6 computed, as depicted in Scheme 4. The corresponding property map, at the EOM-CCSD/cc-pVDZ level of theory, is shown in
To start optimizing oscillator strength while keeping the singlet-triplet gap negative, a computational protocol was established that predicted trends in the INVEST property, as well as the oscillator strength, and could be efficiently applied to larger molecules. Hence, all EOM-CCSD/cc-pVDZ results, both singlet-triplet gaps and oscillator strengths, of the core structures and monosubstituted compounds were compiled as a benchmark dataset.
To correct for the systematic offset in the ωB2PLYP/def2-SVP singlet-triplet gaps, Gaussian process regression was performed, and the offset-estimate was determined at an EOM-CCSD/cc-pVDZ singlet-triplet gap of 0 eV. The offset-estimate equals 0.15±0.05 eV. Hence, molecules were optimized by keeping the ωB2PLYP/def2-SVP singlet-triplet gap below 0.15 eV, while maximizing the oscillator strength simultaneously. Without wishing to be bound by theory, outliers in the oscillator strength diagrams (cf.
Consequently, INVEST molecules were optimized by systematic structural modification and fine-tuning of properties. The corresponding progress is depicted in
The previous optimization turned out no potential blue INVEST emitters, a color of particular importance in optoelectronic applications (24). Before carrying out a more focused investigation towards INVEST molecules with appreciable oscillator strength, a few modifications of molecules 1 and 2 were tested to find out what structural features revert the inverted singlet-triplet gap. One change that did not revert it, but also increased the vertical excitation energy, is azacyclopenta[cd]phenalene (85) 18, shown in Scheme 5. Hence, analogously to above, all structures resulting from systematic permutations of all possible substitutions of C—H with N were explored (Scheme 5).
Consequently, compound 21 was used as a basis for further substitution optimization because it offers the best trade-off of all these four structures and studied all distinct monosubstituted analogues with the same set of 18 substituents used with the azaphenalenes, as depicted in Scheme 7. The corresponding property maps at the EOM-CCSD/cc-pVDZ level of theory are shown in
Having identified compound 21 as the most promising azacyclopenta[cd]phenalene core structure and studied the effect of small substituents on its properties, systematic optimization was done to find substituted analogues of 21 with inverted singlet-triplet gaps, appreciable oscillator strength and vertical excitation energies suitable for blue emitters. Hence, this time three target properties were to be optimized simultaneously. The optimization progress is illustrated in
To validate the structures generated, minimal analogues of promising structures identified above were used to confirm their properties using higher-level theory. Furthermore, vibrational contributions to the singlet-triplet gaps were evaluated as above and tested for the possibility of excited-state intramolecular proton transfer (ESIPT) (89-97) in hydrogen-bonded INVEST molecules. The minimal analogues selected are defined in Scheme 8. The results of high-level theory methods, as well as the comparison between Franck-Condon (vertical) and minima-to-minima (adiabatic) singlet-triplet gaps, are illustrated in
Finally, the possibility of ESIPT was tested in all validation compounds with intramolecular hydrogen bonds, namely 31, 33, 35, 37, 39, 41, 42 and 44. Both single and double proton transfer from the aniline to the respective hydrogen-bonded core nitrogen atom were tested by displacing the hydrogen atom accordingly and optimizing the resulting structures in the S0, S1 and T1 manifolds, respectively. The corresponding results are provided in Table 6. For almost all compounds, neither single (1 PT), nor double (2 PT) proton transfer results in a stable state in the S1 manifold as geometry optimization reversed the proton transfer(s) back to the original structures. In the S0 manifold, proton transfer never resulted in a stable state. In the T1 manifold, single proton transfer generally resulted in stable states, which were energetically uphill for all validation compounds except 42. Nevertheless, for 42, single proton transfer was energetically downhill only by about 0.08 eV. Double proton transfer resulted in a stable state in the T1 manifold only for 44. Hence, ESIPT is unlikely to cause significant property changes to the INVEST molecules studied herein.
The table entries provide the energy differences of the proton transfer states (PT) to the corresponding initial states in the respective state manifolds (S0, S1 or T1) at the ωB2PLYP/def2-SV(P) level of theory. Unstable structures, denoted as “-,” showed reverse proton transfer during geometry optimization.
It has been shown that modification of phenalene cores results in a rich chemical space of INVEST molecules as the singlet-triplet gap, oscillator strength and absorption wavelength can be tuned over wide property intervals.
Further, it has been shown that INVEST molecules with appreciable oscillator strength are possible, and can be realized by careful modification of substituents on azaphenalenes.
Moreover, it has been shown that INVEST molecules with appreciable oscillator strength based on azaphenalenes cores cover substantially the entire visible light spectrum and thus can be used as organic electronic materials for various applications, especially OLED materials.
In the present application, organic molecules with inverted singlet-triplet gaps based on nitrogen-substituted phenalenes have been explored computationally. Through substitution of azaphenalenes with a combination of π-substituents, donor, and acceptor groups, a number of INVEST molecules with appreciable oscillator strength was revealed. In addition, by modifying the phenalene core, and investigating azacyclopenta[cd]phenalenes, blue INVEST emitters with considerable oscillator strength were identified. These molecules are synthetically accessible and offer various advantages for optoelectronic applications, including potentially fast reverse intersystem crossing, increased device lifetime and high color purity.
Table 7 provides the data used for calibrating for the solvatochromic shift with the corresponding references. Table 8 provides the results of linear regressions carried out for that purpose. These linear regressions were used to estimate the absorption wavelength for the compounds investigated in the course of this study.
The solvents used in experiment, if known, are added in parenthesis. Computations were carried out without solvent model.
The above computational results were confirmed using a more robust method as described below.
Error! Reference source not found.9 shows the results of several computational excited state techniques of varying computational cost including two particularly efficient families of methods that include double excitations, namely double-hybrid TD-DFAs (ωB2PLYP′110) and spin-flip TD-DFAs111,112 (SA-SF-PBE50111-116). As no currently available program can compute the perturbative doubles correction for the excited triplet energies of range-separated double-hybrid functionals such as ωB2PLYP,117 the singlet-triplet gap was computed by subtracting the first excited triplet energy without the doubles correction from the first excited singlet energy, which includes the doubles correction. In this study, this method is denoted by ωB2PLYP′. It is noted that ωB2PLYP′ only reproduces an inverted singlet-triplet gap for 2, but not for 1. Without wishing to be bound theory, this is the result of a systematic and correctable offset compared to benchmark methods like ADC(2) or EOM-CCSD (vide infra).
To obtain an estimate of the impact of omitting the doubles correction for the excited triplets, RI-CIS(D)/def2-SVP calculations were performed for the benchmark dataset. The results show that the doubles correction, in principle, can be both stabilizing and destabilizing for the first excited triplet, but tends to be stabilizing with a median of about −0.1 eV. For the first excited singlet, the doubles correction is always strongly stabilizing, and its median is about ten times as large. This suggests that the impact of omitting the doubles correction for the excited triplets is likely not large.
Finally, extensive simulations were performed evaluating the properties of 1 in amorphous solid-state thin films using a mixed QM/MM approach. Table provides the average and standard deviations of oscillator strength and singlet-triplet gap, respectively, of conformers of 1 extracted from the thin film simulations carried out, both the results with and without accounting for the point charge clouds approximating the environment within the thin films. The results show that the effect of the environment in thin films does not affect the inverted singlet-triplet gaps.
It was found that in none of the thin-films simulated the spectroscopic properties of 1 changed significantly, both singlet-triplet gaps and oscillator strengths were largely unaffected. This suggests that the inverted singlet-triplet gaps are at least not intrinsically affected by the solid-state environment.
Comparison of Vertical and Adiabatic Singlet-Triplet Gaps. The comparison of vertical and adiabatic gaps from ωB2PLYP′ calculations was also investigated for the benchmark set. The corresponding results are illustrated in Error! Reference source not found.9. It shows that the deviation between adiabatic and vertical singlet-triplet gaps generally is larger in magnitude the larger the singlet-triplet gap. Hence, for molecules with inverted singlet-triplet gaps, the corresponding corrections tend to be very small. However, there are a few outliers with significantly more positive adiabatic singlet-triplet gaps, which all correspond to monosubstituted derivatives of 2 with oxygen-containing functional groups (one ketone, one aldehyde and one nitro group). Notably, there are also compounds for which the corresponding corrections can lead to significantly smaller singlet-triplet gaps. Importantly, the associated deviation tends to be negligible for INVEST molecules and over the entire benchmark set the average difference between adiabatic and vertical singlet-triplet gaps only surmounts to 0.02 eV. This shows that the vertical singlet-triplet gaps are generally a good approximation of the adiabatic singlet-triplet gaps in the INVEST emitters studied in this work.
For further validation, RI-ADC(2)/cc-pVDZ calculations were performed for compounds 8-15 and 17. The corresponding results are provided in Table 11. They show that all the compounds are predicted to have inverted singlet-triplet gaps confirming our ωB2PLYP′/def2-SVP results and showing that the systematic offset seen in the benchmark data is valid for larger compounds as well. In addition, the observed trends in the oscillator strengths at the ωB2PLYP′/def2-SVP level of theory were well reproduced with RI-ADC(2)/cc-pVDZ.
Finally, the impact of excited state relaxation on both emission energies was evaluated and compared to vertical transition energies, and fluorescence rates. To do this, absorption and emission spectra including Franck-Condon factors were computed using a path integral approach118-119 at the B3LYP/6-31G* level of theory (
Influence of the Environment in an Emitter. Moreover, the influence of the environment in an emitter at the ωB2PLYP′/def2-SVP/C-PCM level of theory was also investigated on the same compound series (Table 12).
The corresponding influence was evaluated for the molecules used for benchmarking. Solvent environment effects on the minimal analogues of the structures described herein were also assessed. The corresponding results are depicted in Error! Reference source not found.11. It shows that the influence of the solid-state solvation is very small with the largest adverse correction only surmounting to 0.09 eV and on average only to 0.03 eV. Interestingly, as illustrated in Error! Reference source not found.11B, the oscillator strength tends to be increased by the solid-state solvation by about 18%. Hence, the small adverse effects observed for the singlet-triplet gaps are compensated for by higher oscillator strength values facilitating emission.
Ground state conformational ensembles were generated using crest120 (version 2.10.1) with the iMTD-GC121-122 workflow (default option) at the GFN0-xTB123 level of theory. The lowest energy conformers were first reoptimized using xtb124 (version 6.3.0) at the GFN2-xTB125-126 level of theory, followed by another reoptimization using Orca127-128 (version 4.2.1) at the B3LYP129-131/cc-pVDZ132 level of theory. The corresponding geometries were used for subsequent ground and excited state single-point calculations. Single points at the ωB2PLYP′110/def2-SVP,133 and DLPNO-NEVPT2(6,6)134/def2-SV(P)133 levels of theory were performed using Orca128-128 (version 4.2.1), single points at the RI-ADC(2)135-141/cc-pVDZ,132 RI-ADC(2)135-141/aug-cc-pVDZ,132, 142 RI-ADC(3)135-141/cc-pVDZ,132 RI143-145-CIS(D)146-147/def2-SVP, RI-EOM-CCSD148-152/cc-pVDZ,132 RI-FNO-EOM-CCSD148-156/cc-pVDZ132 and RI-FNO-EOM-CCSD143-151/aug-cc-pVDZ132,142 with 98.85% of the total natural population, and SA-SF-PBE50111-116/def2-SVP132 levels of theory were performed using Q-Chem157 (version 5.2). RI-ADC(2)135-141/cc-pVDZ132 calculations for large molecules (8-15 and 17) were performed using TURBOMOLE158, 159 (version 7.4.1). Ground and excited geometry optimizations for adiabatic state energy differences at the ωB2PLYP′110/def2-SV(P)133 level of theory were performed in Orca127-128 (version 4.2.1) using numerical gradients. Single point calculations with implicit solvent corrections at the ωB2PLYP′110/def2-SVP133/C-PCM160 level of theory were performed using Orca127-128 (version 4.2.1) and at the ADC(2)135-141/cc-pVDZ132/IEFPCM161-162 level of theory using Q-Chem157 (version 5.2) assuming a dielectric constant of 4.0163-164 and a refractive index of 1.8.165-167 Importantly, in the Orca version used (version 4.2.1), the perturbative doubles correction is not applied to the excited triplet states.117 Hence, to indicate this explicitly, the corresponding method was termed ωB2PLYP′ as opposed to ωB2PLYP. For all excited state single point calculations, four roots were chosen each for both the singlet and the triplet manifold. For the ground and excited state geometry optimizations, two roots were chosen each. Fluorescence rate estimates provided in the tables in the main text are based on absorption oscillator strengths and vertical excitation energies, which are used first to compute transition dipole moments, and converted to fluorescence rates based on well-established equations from the literature.119 These values are intended to convey an idea as to the order of magnitude of the emission rate168 and to help compare the brightness of INVEST emitters with, for example, those of well-known emitters.
More sophisticated emission wavelength and fluorescence rate calculations were performed using Franck-Condon calculations via a gradient-based method, which was described previously,118-119 at the previously benchmarked168-169 B3LYP129-131/6-31G*170-172 level of theory using Q-Chem157 (version 5.3). For each molecule, a geometry optimization was performed to obtain the minimum energy geometry of the electronic ground state R0 and the Hessian matrix H0(R0) was calculated. Excited-state minimum energy geometries Ri were estimated using energy gradients gi(R0) computed with TD-DFT,68 Ri=R0+[H0(R0)]−1gi(R0). Vibronic time-dependent correlation functions were evaluated using the displaced harmonic oscillator equations.174 The correlation functions were multiplied by a broadening factor, Γ(t)=e−σ
To evaluate the effect of solid state embedding on the inverted singlet-triplet gap, a multiscale simulation protocol based on molecular dynamics was used for the generation of amorphous thin film morphologies and a quantum mechanical embedding scheme that self-consistently evaluates the partial charges of each (polarized) molecule in the thin film. The point charge clouds were used as an embedding to compute the excited S1 and T1 states. In detail, atomistically resolved amorphous thin films were generated using the Metropolis Monte Carlo based vapor deposition simulation protocol Deposit,176 based on a DFT parameterized dihedral force field, using B3LYP129-131/def2-SV(P)133 as reference. For mixed guest-host systems, 2000 1,3-bis(N-carbazolyl)benzene (mCP) or bis[2-(diphenylphosphino)phenyl]ether oxide (DPEPO) host molecules and 200 molecules of 1 were used. For each molecule in the system, partial charges were computed using the self-consistent embedding protocol Quantum Patch, at the B3LYP129-131/def2-SV(P)133 level of theory.177 These partial charges were then used in ωB2PLYP′110/def2-SVP133 computations to emulate a polarized solid-state environment at the QM level.
Exemplary compound I-428 was prepared as described below.
A mixture of Compound 9-1 (1.00 g, 1.75 mmol), Compound 9-1A (622 mg, 3.15 mmol), SPhos-Pd-G3 (273 mg, 0.35 mmol) and t-BuONa (337 mg, 3.50 mmol) in 2-methylbutan-2-ol (15 mL) was degassed and purged with N2 for 3 times, and then the mixture was stirred at 100° C. for 8 h under N2 atmosphere. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, Petroleum ether/Ethyl acetate=30/1 to 5/1) to give Compound 9-2 (0.40 g, 0.50 mmol, 28% yield) was obtained as a black-brown solid.
To a mixture of Compound 9-2 (56 mg, 0.07 mmol) in EtOH (3 mL) and H2O (1 mL) was added Fe (16 mg, 0.28 mmol) and NH4Cl (15 mg, 28 mmol). The mixture was stirred at 85° C. for 1 h. The organic volatiles were removed under reduced pressure to give a residue. The residue was purified by Prep-TLC (DCM) to give Compound 9-3 (20 mg, 0.03 mmol, 39% yield) as a gray solid.
1H NMR (EC1230-58-P1) (400 MHz, DMSO-d6) δ 7.84 (d, J=9.2 Hz, 2H), 7.41 (t, J=8.4 Hz, 1H), 7.35-7.09 (m, 12H), 7.00 (d, J=8.0 Hz, 8H), 6.18 (d, J=8.4 Hz, 2H), 6.07-5.94 (m, 4H), 2.29 (s, 12H)
To a solution of Compound 9-3 (200 mg, 0.27 mmol) and Py (149 mg, 1.88 mmol, 0.2 mL) in dioxane (6 mL) was added Cu(OAc)2 (166 mg, 0.91 mmol) and stirred at 25° C. for 0.25 h, then Compound 9-3A (48 mg, 0.81 mmol) was added to the mixture and stirred at 100° C. for 11.75 h. The organic volatiles were remove under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO2, DCM) to give Compound I-428 (45 mg, 0.05 mmol, 20% yield, 94% purity) as a brown solid.
LCMS: EC1230-113-P1B, tR=0.794 min, MS (ESI+) m/z=772.4[M+1].
HPLC: EC1230-112-P1D, tR=2.727 min, Purity=94.86%.
1H NMR (EC1230-113-P1D) (400 MHz, DMSO-d6) δ 8.97-8.90 (m, 2H), 7.98 (d, J=9.2 Hz, 2H), 7.47-7.43 (m, 1H), 7.21-7.14 (m, 8H), 7.06 (d, J=8.4 Hz, 8H), 6.24 (d, J=8.0 Hz, 2H), 6.03 (dd, J=2.2, 8.8 Hz, 2H), 5.96 (d, J=2.0 Hz, 2H), 2.61 (s, 6H), 2.32 (s, 12H)
Exemplary Compound I-432 was prepared as described below.
A mixture of Compound 10-1 (2.00 g, 8.13 mmol) in SOCl2 (10 mL) was degassed and purged with N2 for 3 times and the mixture was stirred at 80° C. for 2 h under N2 atmosphere. TLC (PE/EA=4/1) showed Compound 10-1 was consumed completely. The reaction mixture was concentrated under reduced pressure to give a residue, which was used directly. To a solution of Compound 10-1A (0.43 g, 3.97 mmol) in DCM (10 mL) was added Pyridine (0.94 g, 11.91 mmol) at 0° C. Then the former residue in DCM (5 mL) was slowly added to the reaction mixture and the mixture was stirred at 0° C. for 2 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: 330 g Flash Coulmn Welch Ultimate XB_C18 20-40 μm; mobile phase: [water-ACN]; B %: 5-40% 30 min; 40% 5 min) to give Compound 10-2 (0.40 g, 70.71 mmol, 18% yield) as a brown solid.
1H NMR (EC1230-41-P1) (400 MHz, DMSO-d6) δ 11.00 (s, 2H), 8.36 (d, J=2.0 Hz, 2H), 8.08 (dd, J=2.0, 8.0 Hz, 2H), 7.97-7.80 (m, 3H), 7.71 (d, J=8.0 Hz, 2H)
A mixture of Compound 10-2 (350 mg, 0.92 mmol), PCl5 (388 mg, 1.86 mmol) in toluene (3 mL) was degassed and purged with N2 for 3 times, and then the mixture was stirred at 120° C. for 3 h under N2 atmosphere. TLC (PE/EA=4/1) showed Compound 10-2 was consumed and one main spot formed. The reaction mixture was concentrated under reduced pressure to give Compound 10-3 (390 mg, crude) as a brown oil, which was used into the next step without further purification.
To a solution of Compound 10-3 (1.80 g, 2.99 mmol) in DCM (20 mL) was added NH2CN (1.51 g, 35.88 mmol) in i-Pr2O (10 mL), then the reaction mixture was stirred at 40° C. for 12 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was triturated with MeOH (40 mL) for 30 min to give Compound 10-4 (1.15 g, 2.01 mmol, 67% yield) as a green solid.
1H NMR (EC1230-58-P1) (400 MHz, DMSO-d6) δ 8.21 (d, J=2.0 Hz, 2H), 7.99 (dd, J=2.0, 8.4 Hz, 2H), 7.86 (d, J=8.4 Hz, 2H), 7.54 (t, J=8.4 Hz, 1H), 6.23 (d, J=8.4 Hz, 2H)
A mixture of Compound 10-4 (1.00 g, 1.75 mmol), Compound 10-4A (0.72 g, 3.15 mmol), Sphos-Pd-G3 (0.27 g, 0.35 mmol) and t-BuONa (0.34 g, 3.50 mmol) in 2-methylbutan-2-ol (15 mL) was degassed and purged with N2 for 3 times and then the mixture was stirred at 100° C. for 8 h under N2 atmosphere. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, DCM) to give Compound 10-5 (0.40 g, 0.46 mmol, 26% yield) as a brown solid.
A mixture of Compound 10-5 (200 mg, 0.23 mmol), Fe (128 mg, 2.30 mmol) and NH4Cl (123 mg, 2.30 mmol) in dioxane (12 mL) and H2O (4 mL) was heated to 85° C. and the mixture was stired at 85° C. for 1 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by Prep-TLC (SiO2, DCM) to give Compound 10-6 (40 mg, 0.05 mmol, 21% yield) as a red solid.
To a solution of Compound 6 (150 mg, 0.19 mmol) and Py (103 mg, 1.30 mmol, 0.1 mL) in dioxane (6 mL) was added Cu(OAc)2 (115 mg, 0.63 mmol). The mixture was stirred at 25° C. for 0.25 h, then Compound 6A (33 mg, 0.56 mmol) was added to the mixture and the mixture was stirred at 100° C. for 11.75 h. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-TLC (SiO2, DCM) to give Compound UT20201112B (57 mg, 0.06 mmol, 35% yield, 95% purity) as a brown solid.
LCMS: EC1230-112-P1E, tR=0.700 min, MS (ESI+) m/z=836.3[M+1].
HPLC: EC1230-112-P1F, tR=3.248 min, Purity=95.37%.
1H NMR (EC1230-112-P1A) (400 MHz, DMSO-d6) δ 9.10-8.96 (m, 2H), 7.93 (d, J=9.2 Hz, 2H), 7.44 (t, J=8.4 Hz, 1H), 7.20-7.09 (m, 8H), 7.00-6.92 (m, 8H), 6.23 (d, J=8.4 Hz, 2H), 5.91 (dd, J=2.4, 9.2 Hz, 2H), 5.77-5.75 (m, 2H), 3.76 (s, 12H), 2.56 (d, J=4.8 Hz, 6H)
While the present application has been described with reference to examples, it is to be understood that the scope of the claims should not be limited by the embodiments set forth in the examples, but should be given the broadest interpretation consistent with the description as a whole.
All publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety. Where a term in the present application is found to be defined differently in a document incorporated herein by reference, the definition provided herein is to serve as the definition for the term.
The present application claims the benefit of priority from U.S. patent application No. 63/090,024, filed Oct. 9, 2020, the contents of which are incorporated herein by reference in their entirety.
This invention was made with government support under Contract No. HR00111920027 awarded by Defense Advanced Research Projects Agency (DARPA). The government has certain rights in the invention.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/CA2021/051423 | 10/8/2021 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63090024 | Oct 2020 | US |
