WO2015142828A1

WO2015142828A1 - Catalysis in the production of phenols from aromatics

Info

Publication number: WO2015142828A1
Application number: PCT/US2015/020935
Authority: WO
Inventors: Christopher C. Scarborough; Marika WIELICZKO
Original assignee: Emory University
Priority date: 2014-03-18
Filing date: 2015-03-17
Publication date: 2015-09-24

Abstract

This disclosure relates to catalytic complexes for the oxidation of aromatic compounds. In certain embodiments, the disclosure relates to complexes with three coordination centers. Typically, two centers comprise the same metal ion and the third, central coordination center is a different atom. In certain embodiments, the catalytic complexes are used to produce phenolic products from aromatic compounds such as benzene using oxidants such as hydrogen peroxide or oxygen.

Description

CATALYSIS IN THE PRODUCTION OF PHENOLS FROM AROMATIC S

CROSS REFERENCE TO RELATED APPLICATIONS

This Application claims priority to U.S. Provisional Application Number 61/954,665 filed March 18, 2014, and is hereby incorporated by reference in its entirety.

BACKGROUND

Phenol is a valuable commodity. Principal applications for phenol are as an intermediate to bisphenol A (used in turn to make polycarbonates); as a component in phenol-aldehyde resins, coatings, and adhesives; as a precursor to capro lactam (precursor to Nylon-6), detergents, antioxidants, and to a number of other chemicals which are used in diverse applications.

A few commercial processes are used to produce phenol. One method to produce phenol is a multistep process starting from benzene. In this process, benzene is alkylated to cumene with propylene. Then in a second step, cumene is oxidized with air to the hydroperoxide which, in turn, is subsequently decomposed in the presence of acid to an acetone and phenol. Another route to phenol is the "toluene oxidation route." In this route, toluene, not benzene, is catalytically oxidized to benzoic acid. In a second step, the benzoic acid is catalytically decarboxylated to phenol.

U.S. Patent 6,646,167 reports a method of manufacturing phenol with a vanadium-supported alumina catalyst.

U.S. Patent 6,410,805 reports methods wherein benzene is oxidized to phenol in the presence of oxygen, a vanadium catalyst, and hydrogen.

U.S. Patent 5,952,532 reports hydroxylation of aromatics using molecular oxygen as the terminal oxidant without coreductant.

U.S. Patent 4,861,911 reports a process for oxidation of benzene to phenol precursor in the presence of a cobalt salt.

Phenol has been produced from benzene using molecular oxygen (or air) as the oxidant over a variety of catalysts usually at high temperature. Unfortunately, oxidation of benzene at these temperatures leads to ring cleavage products such as carboxylic acids or anhydrides such as maleic anhydride. Thus, there is a need for a commercially viable process for the direct, one-step oxidation of benzene to pure phenol.

Lucy et al. report heterobimetallic Co '/Ca" complexes with aquo and hydroxo ligands. J. Am. Chem. Soc, 2012, 134 (42), pp 17526-17535. Park et al. report heterobimetallic complexes with ΜΙΙΙ-(μ-ΟΗ)-ΜΙΙ cores (Mill = Fe, Mn, Ga; Mil = Ca, Sr, and Ba): structural, kinetic, and redox properties. Chem. Sci., 2013, 4, 717-726. See also Sickerman et al., Polyhedron, 2013, 58, 65-70; Yohei et al., Inorg. Chem., 2013, 52 (18): 10229-10231 ; Sickerman et al. Chem. Commun., 2014, 50, 2515-2517.

References cited herein are not an admission of prior art. SUMMARY

In certain embodiments, the disclosure relates to complexes comprising a first metal cation, a second metal cation, a third metal cation, and two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups. In certain embodiments, the first two metals are transition metals. In certain embodiments, the third metal is an alkali metal, alkaline earth metal, or a transition metal.

In certain embodiments, the dis lexes of the formula

and salts or derivatives thereof wherein,

M¹ is a cation of cobalt, scandium, vanandium, chromium, manganese, iron, nickel, copper, zinc, or gallium;

M² is a Group I and II ion such as of calcium, magnesium, aluminium, scandium, vanandium, chromium, manganese, iron, cobalt, nickel, copper, zinc, gallium, barium, strontium, caesium or lanthanum;

S¹ is S0₂;

R¹ is at each occurrence independently selected from alkyl, alkenyl, alkanoyl, formyl, dialkylamino, carbocyclyl, aryl, and heterocyclyl wherein R¹ is optionally substituted with one or more, the same or different, R¹⁰;

R¹⁰ is selected from alkyl, alkenyl, alkanoyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, alkylthio, alkylamino, dialkylamino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, and heterocyclyl wherein R¹⁰ is optionally substituted with one or more, the same or different, R¹¹; and

R¹¹ is selected from halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, propyl, tert-butyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl.methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N- dimethylsulfamoyl, Ν,Ν-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, and heterocyclyl.

In certain embodiments, the disclosure relates to methods of oxidizing an aromatic to be substituted with a phenolic hydroxy comprising mixing an arylic or heteroarylic compound with an oxidizing agent and complexes disclosed herein under conditions such that the arylic or heteroarylic compound substituted with a phenolic hydroxy is formed.

In certain embodiments, the disclosure relates to methods of producing a complex comprising a first metal cation, a second metal cation, a third cation, and two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups comprising mixing ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups with an oxidizing agent and a counterion under conditions such that a complex comprising a first metal, a second metal, a third metal, and a two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups is formed.

In certain embodiments, the first and second metal are cobalt.

In certain embodiments, the third cation is a dication such as calcium²⁺.

In certain embodiments, ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups are [((ArS0₂)₃tren)Coⁿ]^~ wherein Ar is aryl optionally substituted.

In certain embodiments, the oxidizing agent is selected from PhIO, hydrogen peroxide, H₂O₂- urea, and ozone.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1 A illustrates a process of preparing phenol.

Figure IB Illustrates the oxidation of benzene to phenol form certain complexes disclosed herein.

Figure 1 C illustrates the preparation of an embodiment disclosed herein.

Figure 2 illustrates a complex that meets the design criteria for a precursor to a relatively stable Co^-oxo species (top) and its corresponding X-ray crystal structure (bottom).

Figure 3A shows data from experiments - Reactivity of Co₂Ca with PhIO to afford the putative Co^IV-oxo species Co₂0₂Ca, and the O-atom-transfer reactivity of this species with PPh₃. The stoichiometry shown was determined by GC. Co₂Ca also reacts with other O-atom transfer reagents (H₂0₂-urea, tBuOOH, O3) to afford the same putative Co₂0₂Ca species by UV-vis.

Figure 3B shows data from experiments -Reactivity of Co¹¹ ions with non-coordinating Figure 3C shows data from experiments - phosphonium counterions (CoAr₄) with PhIO highlighting the effect of the counter-cation (c.f. (a)). UV-vis/NIR absorption spectra of Co₂0₂Ca and CoⁿⁱOH₂, and their Co¹¹ precursors Co₂Ca and CoPAr₄ (inset).

Figure 3D shows mass spectrum (negative mode) of the deep-green solution of the putative oxo species, (e)

Figure 3E shows IR spectra of Co₂Ca, the aqua complex CoⁿOH₂, Co₂0₂Ca, and Co^mOH₂, revealing the absence of 0-H stretching vibrations in Co₂0₂Ca.

Figure 3F shows frozen-glass (10 K) EPR spectrum of Co₂0₂Ca indicating the presence of S = 3/2 cobalt ions.

Figure 4 A shows data from experiments -selective oxidation of benzene to phenol by H₂0₂ catalyzed by Co₂Ca.

Figure 4B shows sample gas chromatograph of a Co₂Ca/H₂0₂ benzene reaction mixture highlighting the absence of phenol oxidation products. Arrows from benzoquinone, catechol, and hydroquinone indicate the retention times of these species from independent measurements.

Figure 5 illustrates a method for determination of counter-ion effects on both stability of putative Co^IV-oxo species and reactivity/selectivity for benzene oxidation (right) based on H₂O₂ reactivity of CoPAr₄ with added Ca(OTf)₂ (left).

Figure 6 illustrates certain embodiments of this disclosure. DETAILED DISCUSSION

Before the present disclosure is described in greater detail, it is to be understood that this disclosure is not limited to particular embodiments described, and as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, the preferred methods and materials are now described.

All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. Further, the dates of publication provided could be different from the actual publication dates that may need to be independently confirmed.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present disclosure. Any recited method can be carried out in the order of events recited or in any other order that is logically possible.

Terms

Embodiments of the present disclosure will employ, unless otherwise indicated, techniques of medicine, organic chemistry, biochemistry, molecular biology, pharmacology, and the like, which are within the skill of the art. Such techniques are explained fully in the literature.

It must be noted that, as used in the specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

As used herein, the term "derivative" refers to a structurally similar compound that retains sufficient functional attributes of the identified analogue. The derivative may be structurally similar because it is lacking one or more atoms, substituted, a salt, in different hydration/oxidation states, or because one or more atoms within the molecule are switched, such as, but not limited to, replacing an oxygen atom with a sulfur atom or replacing an amino group with a hydroxy group. Contemplated derivative include switching carbocyclic, aromatic or phenyl rings with heterocyclic rings or switching heterocyclic rings with carbocyclic, aromatic or phenyl rings, typically of the same ring size. Derivatives may be prepare by any variety of synthetic methods or appropriate adaptations presented in synthetic or organic chemistry text books, such as those provide in March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Wiley, 6th Edition (2007) Michael B. Smith or Domino Reactions in Organic Synthesis, Wiley (2006) Lutz F. Tietze, all hereby incorporated by reference.

The term "substituted" refers to a molecule wherein at least one hydrogen atom is replaced with a substituent. When substituted, one or more of the groups are "substituents." The molecule may be multiply substituted. In the case of an oxo substituent ("=0"), two hydrogen atoms are replaced. Example substituents within this context may include halogen, hydroxy, alkyl, alkoxy, nitro, cyano, oxo, carbocyclyl, carbocycloalkyl, heterocarbocyclyl, heterocarbocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -NRaRb, -NRaC(=0)Rb, -NRaC(=0)NRaNRb, -NRaC(=0)ORb, - NRaS0₂Rb, -C(=0)Ra, -C(=0)ORa, -C(=0)NRaRb, -OC(=0)NRaRb, -ORa, -SRa, -SORa, - S(=0)₂Ra, -OS(=0)₂Ra and -S(=0)₂0Ra. Ra and Rb in this context may be the same or different and independently hydrogen, halogen hydroxy, alkyl, alkoxy, alkyl, amino, alkylamino, dialkylamino, carbocyclyl, carbocycloalkyl, heterocarbocyclyl, heterocarbocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl. As used herein, "alkyl" means a noncyclic straight chain or branched, unsaturated or saturated hydrocarbon such as those containing from 1 to 10 carbon atoms. Representative saturated straight chain alkyls include methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-septyl, n-octyl, n-nonyl, and the like; while saturated branched alkyls include isopropyl, sec -butyl, isobutyl, tert-butyl, isopentyl, and the like. Unsaturated alkyls contain at least one double or triple bond between adjacent carbon atoms (referred to as an "alkenyl" or "alkynyl", respectively). Representative straight chain and branched alkenyls include ethylenyl, propylenyl, 1 -butenyl, 2-butenyl, isobutylenyl, 1 -pentenyl, 2- pentenyl, 3 -methyl- 1 -butenyl, 2-methyl-2 -butenyl, 2,3- dimethyl-2 -butenyl, and the like; while representative straight chain and branched alkynyls include acetylenyl, propynyl, 1 -butynyl, 2- butynyl, 1-pentynyl, 2-pentynyl, 3- methyl- 1 -butynyl, and the like.

Non-aromatic mono or polycyclic alkyls are referred to herein as "carbocycles" or

"carbocyclyl" groups. Representative saturated carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like; while unsaturated carbocycles include cyclopentenyl and cyclohexenyl, and the like.

"Heterocarbocycles" or heterocarbocyclyl" groups are carbocycles which contain from 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur which may be saturated or unsaturated (but not aromatic), monocyclic or polycyclic, and wherein the nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quatemized. Heterocarbocycles include morpholinyl, pyrrolidinonyl, pyrrolidinyl, piperidinyl, hydantoinyl, valerolactamyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydroprimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, and the like.

"Aryl" means an aromatic carbocyclic monocyclic or polycyclic ring such as phenyl or naphthyl. Polycyclic ring systems may, but are not required to, contain one or more non-aromatic rings, as long as one of the rings is aromatic.

As used herein, "heteroaryl" or "heteroaromatic" refers an aromatic heterocarbocycle having 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and containing at least 1 carbon atom, including both mono- and polycyclic ring systems. Polycyclic ring systems may, but are not required to, contain one or more non-aromatic rings, as long as one of the rings is aromatic. Representative heteroaryls are furyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrrolyl, indolyl, isoindolyl, azaindolyl, pyridyl, quinolinyl, isoquinolinyl, oxazolyl, isooxazolyl, benzoxazolyl, pyrazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, cinnolinyl, phthalazinyl, and quinazolinyl. It is contemplated that the use of the term "heteroaryl" includes N-alkylated derivatives such as a l-methylimidazol-5-yl substituent.

As used herein, "heterocycle" or "heterocyclyl" refers to mono- and polycyclic ring systems having 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and containing at least 1 carbon atom. The mono- and polycyclic ring systems may be aromatic, non-aromatic or mixtures of aromatic and non-aromatic rings. Heterocycle includes heterocarbocycles, heteroaryls, and the like.

"Alkylthio" refers to an alkyl group as defined above attached through a sulfur bridge. An example of an alkylthio is methylthio, (i.e., -S-CH₃).

"Alkoxy" refers to an alkyl group as defined above attached through an oxygen bridge.

Examples of alkoxy include, but are not limited to, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n- pentoxy, and s-pentoxy. Preferred alkoxy groups are methoxy, ethoxy, n- propoxy, i- propoxy, n-butoxy, s-butoxy, t-butoxy.

"Alkylamino" refers an alkyl group as defined above attached through an amino bridge. An example of an alkylamino is methylamino, (i.e., -NH-CH₃).

"Alkanoyl" refers to an alkyl as defined above attached through a carbonyl bridge (i.e., - (C=0)alkyl).

"Alkylsulfonyl" refers to an alkyl as defined above attached through a sulfonyl bridge (i.e., - S(=0)₂alkyl) such as mesyl and the like, and "Arylsulfonyl" refers to an aryl attached through a sulfonyl bridge (i.e., - S(=0)₂aryl).

"Alkylsulfamoyl" refers to an alkyl as defined above attached through a sulfamoyl bridge (i.e., -S(=0)₂NHalkyl), and an "Arylsulfamoyl" refers to an alkyl attached through a sulfamoyl bridge (i.e., - S(=0)₂NHaryl).

"Alkylsulfinyl" refers to an alkyl as defined above with the indicated number of carbon atoms attached through a sulfinyl bridge (i.e. -S(=0)alkyl).

The terms "halogen" and "halo" refer to fluorine, chlorine, bromine, and iodine.

The term "aroyl" refers to an aryl group (which may be optionally substituted as described above) linked to a carbonyl group (e.g., -C(O)-aryl).

The term "sulfamoyl" refers to the amide of sulfonic acid (i.e, -S(=0)₂NRR')

An unspecified "R" group may be a hydrogen, lower alkyl, aryl, or heteroaryl, which may be optionally substituted with one or more, the same or different, substituents.

Throughout the specification, groups and substituents thereof may be chosen to provide stable moieties and compounds. Methods of Oxidation

In certain embodiments, the mixing is done at a temperature above 40, 50, 60, 70, 80 degrees

Celsius. In certain embodiments, the oxidizing agent is hydrogen peroxide, nitrous oxide, ozone, or oxygen.

In certain embodiments, the arylic is benezene.

An industrial route for producing phenol is through Friedel-Crafts alkylation of benzene to cumene, radical oxygenation of cumene to cumyl hydroperoxide, and acid-catalyzed cleavage of cumyl hydroperoxide to phenol and acetone (Figure l a). Beyond the inefficiencies associated with this multi-step protocol, each individual step has its drawbacks. A direct route to phenol from benzene using an inexpensive oxidant is needed.

The increased oxidative susceptibility of phenol compared to benzene has hindered attempts to produce phenol directly by benzene oxidation. Nonetheless, it is conceivable that kinetic suppression of phenol oxidation could be achieved through catalyst design, and insights into the origin of selectivity could pave the way for development of new catalysts for a variety of selective oxidation protocols.

A molecular catalyst has been identified with the metals cobalt and calcium that exhibits selectivity against over-oxidation in the conversion of benzene to phenol (Figure lb). Although it is not intended that embodiments of this disclosure be limited by any particular mechanism, a couple principals have guided our design of catalysts for selective oxidation of benzene to phenol: 1.

Promoting two-electron (e.g. O-atom transfer) oxidation of benzene over one-electron (e.g. hydroxyl radical) pathways. Phenyl and hydroxyl radicals are often present under one-electron oxidizing conditions, which can decompose through catalyst-independent pathways. The design of catalysts that react by O-atom transfer to benzene to form benzene oxide, which rearranges to phenol by the NIH shift, e.g., take inspiration from Cytochrome P450 enzymes and other reactive O -atom-transfer oxidants. Kinetic suppression of phenol oxidation is another consideration. Phenol is more electron- rich than that of benzene, so even if two-electron oxidants are employed, phenol is still likely to be more reactive to an O-atom-transfer oxidant than benzene in the absence of catalyst control.

Suppressing phenol oxidation will likely involve tuning the catalyst coordination sphere to repel phenol, which could be accomplished through compartmentalization and/or electronic tuning of the outer coordination sphere.

These design concepts led us to evaluate homogeneous transition-metal catalysts with controlled coordination environments that involve the intermediacy of electrophilic metal- oxo species. A series of cobalt catalysts for the oxidation of water into 0₂ and protons have been reported that proceed through putative Co^IV-oxo species, which are active towards O atom transfer. The reactive oxidant in Cytochrome P450 enzymes, which is active for benzene oxygenation, is also a metal-oxo species (M = Fe^w).

An isolable molecular Co^IV-oxo complex was synthesized. (Figure lb) Maximizing the Co- oxo bond order and minimizing electrophilicity at the cobalt and oxo centers might improve the chances of observing, and perhaps isolating, a Co^IV-oxo species. Trigonal symmetry could provide optimal Co-0 bond order; however, trigonal bipyramidal geometry might be preferable to pseudo- tetrahedral because increased coordination number might decrease Co^IV-oxo electrophilicity. Use of trianionic tetradentate tripodal ligands may be decreasing electrophilicity of the Co^-O group. A molecular orbital analysis predicts an inverse correlation between donor strength of the in-plane ligands and Co-oxo bond order, and we have therefore targeted tetradenate tripodal ligands with weak anionic arms to provide maximum bond order and minimal electrophilicity of the Co^-oxo moiety.

Achieving kinetic suppression of phenol oxidation may benefit from caging the reactive putative CoIV-oxo moiety in an electron-rich pocket. Such caging could be improved by bridging two electron-rich environments with a redox-inert metal ion, which is likely to have the added benefit of electrostatically stabilizing the oxo ligand. Incorporation of redox-inert cations is most notably recognized in the incorporation of a calcium ion in the active site of the oxygen-evolving complex of Photosystem II.

As illustrated in Figure lb, trianionic tren-derived ligands (tren = tris(2-aminoetheyl)amine) have electron-withdrawing sulfonyl groups on the terminal nitrogens. The sulfonyl oxygens have the added benefit of providing an electron-rich second coordination sphere. Furthermore, these trianionic ligands necessitate a counter-cation for charge-balance of either a Co^-oxo complex or its precursor Co¹¹ complex, enabling the use of redox-inert metal ions that bridge two anionic [((RSC^trenjCo¹¹]- groups through the electron-rich sulfonyl oxygens, providing an electron-rich pocket that might both repel phenol and provide the electrostatic stabilization of a putative Co^-oxo moiety.

An example of a complex contemplated is shown in Figure 2; this species is indeed active for the catalytic (TON up to 27,000) selective oxidation of benzene to phenol using hydrogen peroxide as the terminal oxidant.

Catalytic Complexes

In certain embodiments, the disclosure relates to complexes comprising a first metal cation, second metal cation, a third metal cation, and two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups. In certain embodiments, the first two metals are transition metals. In certain embodiments, the third metal is an alkali metal, alkaline earth metal, or a transition metal.

In certain embodiments, the di lexes of the formula

and salts or derivatives thereof wherein, M¹ is a cation of cobalt, scandium, vanandium, chromium, manganese, iron, nickel, copper, zinc, or gallium;

S¹ is S0₂;

R¹¹ is selected from halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, propyl, tert-butyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, Ν,Ν-dimethylcarbamoyl, N,N- diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl.methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N- dimethylsulfamoyl, Ν,Ν-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, carbocyclyl, aryl, and heterocyclyl.

In certain embodiments, R¹ is aryl and heteroaryl.

In certain embodiments, M¹ is cobalt and wherein M² is calcium.

In certain embodiments, M¹ and M² are the same metal. In certain embodiments, M¹ and M² are not the same metal. In certain embodiments, M¹ and M² are a transition metal dication.

In certain embodiments, the disclosure relates to methods of producing a complex comprising a first metal cation, a second metal cation, a third metal cation, and a two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups comprising mixing ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups with an oxidizing agent and a counterion under conditions such that a complex comprising a first metal cation, a second metal cation, a third metal cation, and a two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups is formed.

In certain embodiments, the first and second metal are cobalt.

In certain embodiments, the third metal is a dication such as calcium²⁺.

In certain embodiments, the oxidizing agent is selected from PhIO, hydrogen peroxide, H₂0₂- urea, and ozone. EXPERIMENTAL

Catalyst Synthesis and Oxidation Studies

Oxo-precursor Co¹¹ species bearing trianionic tren-derived (tren = tris(2-aminoethyl)amine) trisulfonamido ligands was generated. The Borovik group has reported studies on trianionic sulfonylated tren ligands. Group I and II counterions that bind in the secondary coordination sphere as well as non-coordinating tetraalkylammonium and tetraarylphosphonium counterions for were explored for comparative purposes. Such compounds were accessible from the routes to representative compounds CoPAr₄ and Co₂Ca shown in Figure lc.

[((ArS0₂)₃tren)Coⁿ]- units (Ar = p-tolyl and p-tBuC₆H₄) gave rise to products consistent with a Co^-oxo formulation upon addition of various oxidants, including PhIO, H₂0₂-urea, and 0₃ when calcium counterions were employed (Figure 3a). On the other hand, non-coordinating ammonium or phosphonium ions did not lead to clean formation of a related species, instead furnishing a Co^mOH₂ species (Figure 3b) similar to those reported by the Borovik group.

These results indicate that an ionic oxo-calcium interaction is important for stabilizing a Co^-oxo unit both by alleviating anionic charge density at the oxo and by sterically blocking the reactive Co^-oxo unit from decomposition. Half-life measurements of this reactive deep-green putative Co^IV-oxo species revealed similar stability in benzene and toluene and very high stability in THF (Table 1).

Table 1. Half-lives of the putative CoIV-oxo species Co₂0₂Ca in various solvents at 25° C

These data were inconsistent with decomposition by H-atom abstraction because of the absence of a correlation between weakest solvent C-H bond strength and half-life. Whether benzene was a viable oxidation substrate for this cobalt species was examined. Furthermore, these data may account for the differences in compounds produced in the Borovik group.

The properties of this putative Co^IV-oxo species was evaluated. When PhIO is used as the oxidant, one equivalent of iodobenzene is generated per cobalt ion, consistent with oxidation of both Co¹¹ centers to Co^. Addition of Ph₃P to this putative oxo generated approximately one equivalent of Ph₃PO per cobalt ion (Figure 3a). Based on these stoichiometry data, the putative Co^IV-oxo species was designate as Co₂0₂Ca in Figure 3 a and throughout this document. Co₂0₂Ca is reactive to excess dihydroanthracene, producing anthracene as the sole product; this process is much slower than Ph₃P oxidation, which is consistent with a preference for two-electron oxidation pathways. This putative oxo species is characterized by an electronic absorption spectrum (Figure 3c) that is very similar to related iron and manganese oxo species, and has been described as a "signature" for formation of a terminal oxo complex.

Mass spectrometric analysis of this species in negative mode reveals two dominant species, [((ArS0₂)₃tren)Co]^~ and [((ArS0₂)₃tren)Co⁺0]^~ (Figure 3d). The ratio of the two species increasingly favors the latter with decreasing injection temperature and potential, suggesting that the former may be formed during injection of the latter. Precipitation of the putative deep-green Co^-oxo species, the color of which is similar to oxidized cobalt oxide films containing putative Co^IV-oxo groups that are active for water oxidation, provides a sample that does not show O-H stretches by IR spectroscopy (Figure 3 e);

however, over the course of days, this species begins to develop O-H bands. Allowing the putative oxo

species to decompose over time in solution provides [Ca(solvent)_n((Ts3tren)CoII(OH₂))2], which we have isolated in multiple cases and prepared independently and accounts for the development of O-H bands from Co₂0₂Ca over time by IR. A clean S = 3/2 EPR signal is obtained when Co₂0₂Ca is prepared from H₂0₂-urea in THF (Figure 3f), suggesting the presence of either high-spin Coll or intermediate-spin CoIV. A putative transient trigonal CoIV-oxo species reported was also described as intermediate spin.

S = 3/2 is consistent with our predictions from an MO analysis for a trigonal bipyramidal Co^-oxo ion.

Oxidation of Benzene to Phenol.

Heating [Ca((Ts₃tren)Coⁿ)₂] in benzene in the presence of H₂0₂-urea or aqueous H₂0₂ led to clean formation of phenol (Figure 4a). However, disproportionation of H₂0₂ was evident from the vigorous bubbling observed. Nonetheless, phenol was formed as the sole product based on gas chromatography; ortho-quinone, 1 ,4-benzoquinone, biphenyl, hydroquinone, catechol, maleic anhydride, maleic acid, and trihydroxybenzene, common phenol oxidation products, were all undetectable by gas chromatography and GC-MS. The yield of phenol revealed that the cobalt species was catalytically active, providing 10 turnovers in this initial test. The initial yield of phenol based on hydrogen peroxide was only 0.4% because of competitive disproportionation.

Conditions for benzene oxidation were improved by altering catalyst and H₂0₂ concentration as well as temperature to achieve 27,000 turnovers in 72 hours with phenol as the sole detectable product. This selectivity for oxidation of benzene to phenol was encouraging. Addition of 100,000 equivalents of phenol based on catalyst at the start of the reaction resulted in continued formation of phenol without

concomitant formation of phenol oxidation products, showcasing an unprecedented selectivity against over-oxidation (Figure 4a).

A protocol to investigate the effect of counterions are shown in Figure 5. Addition of Ca(OTf)₂ to a solution of [PAr₄] [(Ts₃tren)Coⁿ] (CoPAr₄) in the presence of H₂0₂-urea generates the deep-green

Co₂0₂Ca species proposed to be the active oxidant in benzene oxidation; in the absence of Ca(OTf)₂, CoPAr₄ and H₂0₂-urea are unreactive at room temperature. Based on this observation, metal triflates are screened to provide new species that are similar to Co₂0₂Ca by absorption spectroscopy - corresponding Co₂M_n complexes as synthetic targets.

Co₂Li₂, Co₂Na2, and Co₂K₂ complexes were synthesized and crystallographically characterized. Of this series the potassium ions react with H₂0₂-urea to afford a deep-green species analogous to Co₂0₂Ca.

Claims

CLAIMS What we claim:

1. A complex comprising a first metal cation, a second metal cation, a third cation, and two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups.

2. The complex of Claim 1 of the rmula

and salts or derivatives thereof wherein,

S¹ is S0₂;

3. The complex of Claim 2, wherein R¹ is aryl and heteroaryl.

4. The complex of Claim 2, wherein M¹ is cobalt and wherein M² is calcium.

5. The complex of Claim 2, wherein M¹ and M² are not the same metal.

6. A method of oxidizing an aromatic to be substituted with a phenolic hydroxy comprising mixing an arylic or heteroarylic compound with an oxidizing agent and a complex of Claims 1 -6 under conditions such that the arylic or heteroarylic compound substituted with a phenolic hydroxy is formed.

7. The method of Claim 6, wherein the mixing is done at a temperature above 40, 50, 60, 70, 80 degrees Celsius.

8. The method of Claim 6, wherein the oxidizing agent is hydrogen peroxide, nitrous oxide, ozone, or oxygen.

9. The method of Claim 6, wherein the arylic is benezene.

10. A method of producing a complex comprising a first metal cation, a second metal cation, a third cation, and two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups comprising mixing ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups with an oxidizing agent and a counterion under conditions such that a complex comprising a first metal, a second metal, a third metal, and a two ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups is formed.

11. The method of Claim 10, wherein the first and second metal are cobalt.

12. The method of Claim 10, wherein the third cation is a dication such as calcium²⁺.

13. The method of Claim 10, wherein ligands comprising nitrogen tetradentate and tripodal sulfamoyl groups are [((ArS0₂)₃tren)Coⁿ]^_ wherein Ar is aryl optionally substituted.

14. The method of Claim 10, wherein the oxidizing agent is selected from PhIO, hydrogen peroxide, H₂0₂-urea, and ozone.