BIS(ARYL)ACETAL COMPOUNDS

A bis(aryl)acetal has the formula wherein Y1 and Y2 are each independently chloro, bromo, iodo, mesylate, tosylate, triflate, or Bx, provided that Y1 and Y2 are not both selected from chloro, bromo, and iodo; each occurrence of Bx is independently a boron-containing functional group bonded to Ar1 or Ar2 via a boron atom; Ar1 and Ar2 are each independently unsubstituted or substituted C6-18 arylene, or unsubstituted or substituted C3-18 heteroarylene; provided that Ar1 and Ar2 are not covalently linked to each other to form a ring structure that includes -Ar1-O—C—O-Ar2-; and R1 and R2 are each independently hydrogen, unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-20 cycloalkyl, unsubstituted or substituted C6-18 aryl, or unsubstituted or substituted C3-20 heteroaryl. The bis(aryl)acetal is useful as a monomer for oligoacetal and polyacetal synthesis via Suzuki polycondensation.

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Description
FIELD

The present invention relates to bis(aryl)acetals useful in the synthesis of polyacetals.

INTRODUCTION

Polyacetals are known polymers that have some use in microlithography. (As used herein, for brevity the term “acetal” shall be understood to be generic to “acetal” and “ketal”, the term “oligoacetal” shall be understood to be generic to “oligoacetal” and “oligoketal”, and the term “polyacetal” shall be understood to be generic to “polyacetal” and “polyketal”.) The synthesis of polyacetals typically relies on a polycondensation reaction to form acetal moieties during the polymerization reaction. The reactants include free or protected hydroxyl groups that are consumed in the acetal formation, so the resulting polymers typically do not contain free hydroxyl groups or other functional groups that would interfere with or be consumed in typical acetal formation reactions.

There is a need for materials and methods than can be used to synthesize oligoacetals and polyacetals. It would be desirable if the methods were general to the formation of oligoacetals and polyacetals with and without free hydroxyl groups and other functional groups that are incompatible with polycondensation conditions for formation of oligoacetals and polyacetals.

SUMMARY

One embodiment is a bis(aryl)acetal having the formula

wherein Y1 and Y2 are each independently chloro, bromo, iodo, mesylate, tosylate, triflate, or Bx, provided that Y1 and Y2 are not both selected from chloro, bromo, and iodo; each occurrence of Bx is independently a boron-containing functional group bonded to Ar1 or Ar2 via a boron atom; Ar1 and Ar2 are each independently unsubstituted or substituted C6-18 arylene, or unsubstituted or substituted C3-18 heteroarylene; provided that Ar1 and Ar2 are not covalently linked to each other to form a ring structure that includes


-Ar1-O—C—O-Ar2-; and

R1 and R2 are each independently hydrogen, unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-20 cycloalkyl; unsubstituted or substituted C6-18 aryl, or unsubstituted or substituted C3-20 heteroaryl; and R1 and R2 are optionally covalently linked to each other to form a ring that includes


—R1—C—R2—.

This and other embodiments are described in detail below.

DETAILED DESCRIPTION

The family of molecules described herein (hereinafter “bis(aryl)acetals”) permits the synthesis of oligoacetals and polyacetals having backbone acetal functionality without having to rely on an acetal formation reaction during the last step of the synthesis. Instead, the bis(aryl)acetals serve as the sole monomer or a comonomer in a transition metal catalyzed cross-coupling reaction (e.g., Suzuki coupling). Because of this characteristic, bis(aryl)acetals permit the synthesis of oligomers and polymers with acetal functional groups in the backbone and that can be further substituted with functional groups that are incompatible with many acetal formation reactions for example, free hydroxyl groups, including free phenols (which would compete in an acetal-forming reaction), and/or acid-labile or base-labile side chains without having to rely on expensive protection/deprotection strategies.

Oligomers and polymers that contain acetal functional groups in the backbone are useful compounds due to their potential to fragment into smaller molecules upon treatment with Brönsted or Lewis acids or upon electron impact or ionization. Such fragmentation can be used to alter the physicochemical properties (including solubility, aggregate state, glass transition temperature, melting point, and vapor pressure) of materials or formulations comprising the oligomers or polymers. For example, acetal-containing oligomers and polymers are useful in photoresist compositions.

One embodiment is a bis(aryl)acetal having the formula

Y1 and Y2 are each independently chloro, bromo, iodo, mesylate, tosylate, triflate, or Bx, provided that Y1 and Y2 are not both selected from chloro, bromo, and iodo; each occurrence of Bx is independently a boron-containing functional group bonded to Ar1 or Ar2 via a boron atom; Ar1 and Ar2 are each independently unsubstituted or substituted C6-18 arylene, or unsubstituted or substituted C3-18 heteroarylene; provided that Ar1 and Ar2 are not covalently linked to each other to form a ring structure that includes -Ar1-O—C—O-Ar2-; and R1 and R2 are each independently hydrogen, unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-18 cycloalkyl; unsubstituted or substituted C6-18 aryl, or unsubstituted or substituted C3-18 heteroaryl; and R1 and R2 are optionally covalently linked to each other to form a ring that includes —R1—C—R2—. The description of Bx as bonded to Ar1 or Ar2 via a boron atom means that the boron atom is directly covalently bonded to an aromatic carbon of Ar1 or Ar2. The description of Ar1 and Ar2 as not covalently linked to each other to form a ring structure that includes -Ar1-O—C—O-Ar2- means that Ar1 and Ar2 are not directly covalently bonded to each other, nor are they linked via a divalent group that completes a ring also containing -Ar1-O—C—O-Ar2-. The description of R1 and R2 as optionally covalently linked to each other to form a ring that includes —R1—C—R2— means that R1 and R2 can be either directly covalently bonded to each other, or linked via a divalent group that completes a ring also containing —R1—C—R2—.

Also as used herein, “substituted” means including at least one substituent such as a halogen (i.e., F, Cl, Br, I), hydroxyl, amino, thiol, carboxyl, carboxylate, amide, nitrile, sulfide, disulfide, nitro, C1-18 alkyl, C1-18 alkoxyl, C6-18 aryl, C6-18 aryloxyl, C7-18 alkylaryl, or C7-18 alkylaryloxyl. It will be understood that any group or structure disclosed with respect to the formulas herein may be so substituted unless otherwise specified, or where such substitution would significantly adversely affect the desired properties of the resulting structure. Also, “fluorinated” means having one or more fluorine atoms incorporated into the group. For example, where a C1-18 fluoroalkyl group is indicated, the fluoroalkyl group can include one or more fluorine atoms, for example, a single fluorine atom, two fluorine atoms (e.g., as a 1,1-difluoroethyl group), three fluorine atoms (e.g., as a 2,2,2-trifluoroethyl group), or fluorine atoms at each free valence of carbon (e.g., as a perfluorinated group such as —CF3, —C2F5, —C3F7, or —C4F9).

In some embodiments of the bis(aryl)acetal formula above, at least one of Y1 and Y2 is Bx. In some embodiments, one of Y1 and Y2 is Bx, and the other is selected from chloro, bromo, iodo, mesylate, tosylate, and triflate. In such embodiments, the bis(aryl)acetal can be polymerized via Suzuki coupling without the need for a comonomer.

In some embodiments, Y1 and Y2 are each independently selected from mesylate, tosylate, and triflate.

In some embodiments, Y1 and Y2 are each independently Bx, wherein each occurrence of Bx is independently selected from the group consisting of —BF3−M+, wherein each occurrence of M+ is independently an alkali metal cation, or an unsubstituted or substituted ammonium ion; —B(OH)2;

wherein R3 and R4 are each independently C1-18 alkyl, C3-18 cycloalkyl, or C6-18 aryl; and R3 and R4 are optionally covalently linked to each other to form a ring that includes —R3—B—O—R4—; and

wherein R15 and R16 are each independently hydrogen, unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-18 cycloalkyl; unsubstituted or substituted C6-18 aryl, unsubstituted or substituted C3-18 heteroaryl, or

wherein Y2, Ar1, Ar2, R1, and R2 are defined as above.

In some embodiments, each occurrence of Bx is

wherein R3 and R4 are each independently C1-18 alkyl, C3-18 cycloalkyl, or C6-18 aryl; and R3 and R4 are optionally covalently linked to each other to form a ring that includes —R3—O—B—O—R4—.

Examples of Bx species include

In the bis(aryl)acetal structure above, Ar1 and Ar2 are each independently unsubstituted or substituted C6-18 arylene, or unsubstituted or substituted C3-18 heteroarylene, provided that Ar1 and Ar2 are not covalently linked to each other to form a ring structure that includes -Ar1—O—C—O-Ar2-. Specific examples of Ar1 and Ar2 include unsubstituted or substituted 1,2-phenylene, unsubstituted or substituted 1,3-phenylene, unsubstituted or substituted 1,4-phenylene, unsubstituted or substituted 4,4′-biphenylene, unsubstituted or substituted 4,4″-p-terphenylene, unsubstituted or substituted 3,3″-p-terphenylene, unsubstituted or substituted 4,4″-m-terphenylene, unsubstituted or substituted 4,4″-p-terphenylene, unsubstituted or substituted 4,4″-o-terphenylene, unsubstituted or substituted 2,2″-o-terphenylene, unsubstituted or substituted 1,4-naphthylene, unsubstituted or substituted 2,7-naphthylene, unsubstituted or substituted 2,6-naphthylene, unsubstituted or substituted 1,5-naphthylene, unsubstituted or substituted 2,3-naphthylene, unsubstituted or substituted 1,7-naphthylene, unsubstituted or substituted 1,8-naphthylene, unsubstituted or substituted imidazo-2,4-ylene, 2,4-pyridylene, 2,5-pyridylene, unsubstituted or substituted 1,8-anthracenylene, unsubstituted or substituted 9,10-anthracenylene, unsubstituted or substituted 2,7-phenanthrenylene, unsubstituted or substituted 9,10-phenanthrenylene, unsubstituted or substituted 3,6-phenanthrenylene, unsubstituted or substituted 2,7-pyrenylene, unsubstituted or substituted 1,6-pyrenylene, unsubstituted or substituted-1,8-pyrenylene, unsubstituted or substituted 2,5-furanylene, unsubstituted or substituted 3,4-furanylene, unsubstituted or substituted 2,3-furanylene, unsubstituted or substituted 2,5-thiofuranylene, unsubstituted or substituted 3,4-thiofuranylene, unsubstituted or substituted 2,3-thiofuranylene, unsubstituted or substituted 2,5-oxazolylene, unsubstituted or substituted 2,7-fluorenylene, unsubstituted or substituted 2,5-benzofuranylene, unsubstituted or substituted 2,7-benzofuranylene, unsubstituted or substituted 5,7-benzofuranylene, unsubstituted or substituted 5,7-[1,3-benzoxazole], unsubstituted or substituted dithieno[3,2-b:2′,3′-d]thiophene, and unsubstituted or substituted 2,7-xanthenylene.

In some embodiments, at least one of Ar1 and Ar2 is substituted with at least one functional group selected from the group consisting of hydroxyl, acetals, ketals, esters, and lactones. The acetals can be monovalent acetals having the structure


—O—C(H)(R5)—OR6,

wherein R5 and R6 are independently selected from the group consisting of unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-18 cycloalkyl, unsubstituted or substituted C6-18 aryl, and unsubstituted or substituted C3-18 heteroaryl; optionally R5 or R6 is covalently connected to the polymer backbone such that the acetal is part of a ring structure, provided that the ring structure does not include


Ar1-O—C—O-Ar2.

In some embodiments, R5 and R6 are covalently connected to each others to form a ring structure. Specific examples of monovalent acetals having the structure —O—C(H)(R5)—OR6 include

The acetals can also be divalent cyclic acetals attached via oxygen atoms to Ar1 or Ar2 as shown in the structure

wherein Arn is Ar1 or Ar2, or a combination of Ar1 and Ar2 (for example, when one acetal oxygen is bonded directly to Ar1 and the other directly to Ar2); R10 is selected from the group consisting of unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-18 cycloalkyl, unsubstituted or substituted C6-18 aryl, and unsubstituted or substituted C3-18 heteroaryl; and —O—C(H)(R10)—O is part of a ring structure provided that the ring structure does not include


—Ar1—O—C(R1)(R2)—O-Ar2.

The ketals can be monovalent ketals having the structure


—O—C(R7)(R8)—OR9,

wherein R7, R8, and R9 are independently selected from the group consisting of unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-18 cycloalkyl, unsubstituted or substituted C6-18 aryl, and unsubstituted or substituted C3-18 heteroaryl; optionally R7, R8, or R9 is covalently connected to the polymer backbone such that the acetal is part of a ring structure, provided that the ring structure does not include


Ar1-O—C—O-Ar2.

The ketals can also be cyclic ketals attached via oxygen atoms to Ar1 or Ar2 as shown in the structure

wherein Arn is Ar1 or Ar2, or a combination of Ar1 and Ar2 (for example, when one ketal oxygen is bonded directly to Ar1 and the other directly to Ar2); R11 and R12 are independently selected from the group consisting of unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-18 cycloalkyl, unsubstituted or substituted C6-18 aryl, and unsubstituted or substituted C3-18 heteroaryl; and
O—C(R11)(R12)—O is part of a ring structure provided that the ring structure does not include


Ar1-O—C(R1)(R2)—O-Ar2.

The esters can have the structure


—(O)a-(L1)b-C(═O)—OR13,

wherein a is 0 or 1 and b is 0 or 1, provided that when a is 1 then b is 1; R13 is selected from the group consisting of unsubstituted or substituted C1-20 linear or branched alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, diphenylmethyl, 2-phenylpropan-2-yl, 1,1-diphenylethan-1-yl, triphenylmethyl), unsubstituted or substituted C3-20 cycloalkyl (e.g., cyclopentyl, cyclohexyl, methylcyclohexan-1-yl, ethylcyclohexan-1-yl, 1-norbornyl, 1-adamantlyl, 2-methylbicyclo[2.2.1]heptan-2-yl, 1-adamantlyl, 2-methyladamantan-2-yl), unsubstituted or substituted C6-20 aryl (e.g., phenyl, 1-naphthyl, and 2-naphthyl), and unsubstituted or substituted C3-20 heteroaryl (e.g., 2-imidazolyl, 4-imidazolyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl); and wherein L1 is selected from the group consisting of unsubstituted or substituted C1-20 linear or branched alkylene (e.g., methane-1,1-diyl (—CH2—), ethane-1,2-diyl (—CH2CH2—), ethane-1,1-diyl (—CH(CH3)—), propane-2,2-diyl(—C(CH3)2—)), unsubstituted or substituted C3-20 cycloalkylene (e.g., 1,1-cyclopentanediyl, 1,2-cyclopentanediyl, 1,1-cyclohexanediyl, 1,4-cyclohexanediyl), unsubstituted or substituted C6-20 arylene (e.g., 1,3-phenylene, 1,4-phenylene, 1,4-naphthylene, 1,5-naphthylene, 2,6-naphthylene), and unsubstituted or substituted C3-20 heteroarylene (e.g., imidazo-2,4-ylene, 2,4-pyridylene, 2,5-pyridylene). In some embodiments, R13 and L1 are covalently connected to each others to form a lactone. In some embodiments, R13 is bonded to the adjacent ester oxygen atom via a tertiary carbon atom, for example,

Alternatively, the esters can have the structure


—(O)c-(L2)d-O—C(═O)—R14,

wherein c is 0 or 1 and d is 0 or 1, provided that when c is 1 then d is 1; R14 is selected from the group consisting of unsubstituted or substituted C1-20 linear or branched alkyl (e.g., methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, diphenylmethyl, 2-phenylpropan-2-yl, 1,1-diphenylethan-1-yl, and triphenylmethyl), unsubstituted or substituted C3-20 cycloalkyl (e.g., cyclopentyl, cyclohexyl, 1-norbornyl, 1-adamantlyl, 2-methylbicyclo[2.2.1]heptan-2-yl, 2-methyladamantan-2-yl), unsubstituted or substituted C6-20 aryl (e.g., phenyl, 1-naphthyl, 2-naphthyl), and unsubstituted or substituted C3-20 heteroaryl (e.g., 2-imidazolyl, 4-imidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl); and wherein L2 is selected from the group consisting of unsubstituted or substituted C1-20 linear or branched alkylene (e.g., methane-1,1-diyl (—CH2—), ethane-1,2-diyl (—CH2CH2—), ethane-1,1-diyl (—CH(CH3)—), propane-2,2-diyl (—C(CH3)2—), 2-methylpropane-1,2-diyl(—CH2C(CH3)2—), diphenylmethylene (—C(C6H5)2—), 1-phenylmethane-1,1-diyl (—CH(C6H5)—), 2-phenylpropane-1,2-diyl (—CH2C(CH3)(C6H5)—), 1,1-diphenylethane-1,2-diyl (—CH2C(C6H5)2)—), unsubstituted or substituted C3-20 cycloalkylene (e.g., 1,1-cyclopentanediyl, 1,2-cyclopentanediyl, 1,1-cyclohexanediyl, 1,4-cyclohexanediyl, ethylcyclohexane-1,4-diyl, 4-methyladamantane-1,4-diyl), unsubstituted or substituted C6-20 arylene (e.g., 1,3-phenylene, 1,4-phenylene, 1,4-naphthylene, 1,5-naphthylene, 2,6-naphthylene), and unsubstituted or substituted C3-20 heteroarylene (e.g., imidazo-2,4-ylene, 2,4-pyridylene, 2,5-pyridylene). In some embodiments, R14 and L2 are covalently connected to each others to form a lactone. A specific example of an ester having the structure —(O)c-(L2)d-O—C(═O)—R14 is

The lactones can have the structure

wherein e is 0 or 1; f is 0 or 1; g is 1, 2, 3, or 4 (specifically 2); R50 is hydrogen, unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-18 cycloalkyl, unsubstituted or substituted C6-18 aryl, or unsubstituted or substituted C3-18 heteroaryl; and L3 is selected from the group consisting of unsubstituted or substituted C1-20 linear or branched alkylene (e.g., unsubstituted or substituted C3-20 cycloalkylene (e.g., 1,1-cyclopentanediyl, 1,2-cyclopentanediyl, 1,1-cyclohexanediyl, 1,4-cyclohexanediyl), unsubstituted or substituted C6-20 arylene (e.g., 1,3-phenylene, 1,4-phenylene, 1,4-naphthylene, 1,5-naphthylene, 2,6-naphthylene), and unsubstituted or substituted C3-20 heteroarylene (e.g., imidazo-2,4-ylene, 2,4-pyridylene, 2,5-pyridylene).

In some embodiments, at least one of Ar1 and Ar2 is substituted with hydroxyl in at least 40 mole percent of the plurality of repeat units. In other embodiments, each occurrence of Ar1 and Ar2 is independently 1,3-phenylene or 1,4-phenylene.

When used in applications in which the polymer is exposed to acid to promote its fragmentation, it may be desirable for the polymer to exclude robust linkages between the Ar1 and Ar2 rings. Thus, in some embodiments, Ar1 and Ar2 are not covalently linked with one another to form a ring structure that includes -Ar1-O—C—O-Ar2-.

In some embodiments of the bis(aryl)acetal formula above, Ar1 and Ar2 are each independently 1,3-phenylene or 1,4-phenylene, specifically 1,4-phenylene. In other embodiments, at least one of Ar1 and Ar2 is substituted with hydroxyl.

In the bis(aryl)acetal structure above, R1 and R2 are each independently hydrogen, unsubstituted or substituted C1-18 linear or branched alkyl (e.g., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 1 methyl-2-propyl, diphenylmethyl, 2-phenylpropan-2-yl, 1,1-diphenylethan-1-yl, and triphenylmethyl), unsubstituted or substituted C3-20 cycloalkyl (e.g., cyclopentyl, cyclohexyl, 1-norbornyl, 1-adamantlyl, 2-methylbicyclo[2.2.1]heptan-2-yl, 2-methyladamantan-2-yl); unsubstituted or substituted C6-18 aryl (e.g., phenyl, 1-naphthyl, 2-naphthyl, anthracenyl), or unsubstituted or substituted C3-18 heteroaryl (e.g., 2-imidazolyl, 4-imidazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl); and R1 and R2 are optionally covalently linked to each other to form a ring that includes —R1—C—R2—. In some embodiments, at least one of R1 and R2 is hydrogen or methyl. In some embodiments, R1 is hydrogen, and R2 is selected from phenyl, ortho-methoxyphenyl, meta-methoxyphenyl, and para-methoxyphenyl. In some embodiments, R1 is hydrogen and R2 is unsubstituted or substituted phenyl. When R2 is substituted phenyl, it can be substituted with a hydroxyl group, an acetal group, an ester group (including a lactone), or other such group that would be incompatible with polyacetal formation via acetal-generating polycondensation or would cause undesired polymer crosslinking. As described in a co-filed application, the present inventors have determined that such groups are tolerated in the Suzuki coupling reaction in which polyacetals are synthesized from the bis(aryl)acetal. Two specific examples of bis(aryl)acetal compounds in which R1 and R2 are covalently linked to each other to form a ring that includes —R1—C—R2— are

Specific examples of bis(aryl)acetals include

In a very specific embodiment of the bis(aryl)acetal formula above, Y1 and Y2 are each Bx; each occurrence of Bx is

Ar1 and Ar2 are 1,4-phenylene; R1 is hydrogen; and R2 is selected from phenyl, ortho-methoxyphenyl, meta-methoxyphenyl, and para-methoxyphenyl.

Below is an example of a synthesis of a bis(aryl)acetal of the formula above, in which Y1 and Y2 are each independently selected from chloro, bromo, iodo, mesylate, tosylate, and triflate, provided that Y1 and Y2 are not both selected from chloro, bromo, and iodo. Two equivalents of phenol substituted with chloro, bromo, iodo, mesylate, tosylate, or triflate (provided that both equivalents of phenol are not selected from chlorophenol, bromophenol, and iodophenol) are reacted with one equivalent of an R1-substituted 1,1-dihalomethane and two equivalents of sodium hydride to yield the desired product.

To form a bis(aryl)acetal of the formula above, in which Y1 is Bx and Y2 is selected from chloro, bromo, iodo, mesylate, tosylate, and triflate, the product, a corresponding bis(aryl)acetal in which Y1 and Y2 are each independently selected from chloro, bromo, iodo, mesylate, tosylate, and triflate, can be reacted with one equivalent of butyl lithium followed by one equivalent of a boronic ester, as shown below, to form the desired product. As an alternative to the use of butyl lithium and boronic ester, palladium-catalyzed borylation with bis(picolinato)diboron can be used.

To form a bis(aryl)acetal of the formula above, in which Y1 and Y2 are both Bx, the previous reaction is modified to use two equivalents each of butyl lithium followed by two equivalents of boronic ester, as shown below. Again, palladium-catalyzed borylation with bis(picolinato)diboron can be used as an alternative to the use of butyl lithium and boronic ester.

The invention is further illustrated by the following examples.

General Procedures

All solvents and reagents were obtained in commercially available qualities purum, puriss. or p.a. Dry solvents were obtained from in-house purification/dispensing system (hexane, toluene, tetrahydrofuran and diethyl ether) or purchased from Sigma-Aldrich, Fisher Scientific, or Acros. All experiments involving water sensitive compounds were conducted in oven dried glassware under nitrogen atmosphere or in a glovebox. Reactions were monitored by analytical thin-layer chromatography (TLC) on precoated aluminum plates (VWR 60 F254), visualized by UV light and/or potassium permanganate staining. Flash chromatography was performed on an Isco COMBIFLASH™ system with GRACERESOLV™ cartridges.

Proton nuclear magnetic resonance (1H-NMR) spectra (500 megahertz (MHz) or 400 MHz) were obtained on a Varian VNMRS-500 or VNMRS-400 spectrometer at 30° C. unless otherwise noted. The chemical shifts were referenced to tetramethylsilane (TMS) (δ=0.00) in CDCl3, Benzene-d5 (7.15) in Benzene-d6 or tetrahydrofuran-d7 (THF-d7; δ 3.58 (used) and 1.73) in THF-d8. If necessary, peak assignment was carried out with the help of COSY, HSQC or NOESY experiments. 13C-NMR spectra (125 MHz or 100 MHz) were obtained on a Varian VNMRS-500 or VNRMS-400 spectrometer, chemical shifts were solvent or standard signals (0.0—TMS in CDCl3, 128.02—Benzene-d6, 67.57 (53.37)—THF-d8). If NMR was used for quantification purposes, single scan experiments or relaxation delays of ≧30 seconds were used.

If not otherwise noted, high resolution mass spectrometry was carried out as follows. For ESUMS and EST/LC/MS/MS studies, three microliter aliquots of the samples as 1 milligram/milliliter solutions in methanol were injected on an Agilent 1200SL binary gradient liquid chromatograph coupled to an Agilent 6520 QToF, quadrupole-time of flight mass spectrometry system via a dual spray electrospray (ESI) interface operating in the positive ion (PI) mode. The following analysis conditions were used: Column: None flow injection; Column temperature: 40° C.; Mobile phase: 0.3 M ammonium acetate in methanol; Flow: 0.25 milliliter/min; UV detection: Diode Array 210 to 600 nanometers; ESI conditions: Gas Temp 350° C., Gas Flow 8 milliliters/minute, Capillary-3.5 kilovolt, Nebulizer 45 pounds per square inch, Fragmentor—145 volts; AutoMSMS conditions: Mode—±TOFMS and ±TOFMSMS; Centroid Resolution 12000(+) 2 Ghz Extended Dynamic Range, Scan-100 to 1700 atomic mass units (amu) (±MS), Rate—4 scan/sec, Scan-50 to 1700 atomic mass units (±MS/MS), Rate—4 scans/second, Collision Energy: 5 volts+5 volts/100 atomic mass units, Collision Gas: Nitrogen, Isolation Width about 4 atomic mass units, Reference Ions: 121.050873: 922.009798 (+); 112.985587, 1033.988109.

Infrared spectra were acquired with a Perkin Elmer Spectrum One FT-IR and Universal ATR Sampling Accessory at a nominal resolution of 4 centimeter−1 and 16 scans (approximate acquisition time of 90 seconds). The Universal ATR Sampling Accessory was equipped with a single bounce diamond/ZnSe crystal.

Melting points were obtained by differential scanning calorimetry (DSC) measurement in crimped aluminum pans. The samples (about 8 milligrams) were weighed and sealed in an aluminum hermetic (P/N 900793.901 pan and 900794.901 lid) DSC pan and scanned in a TA Instruments Q2000 DSC (Differential Scanning calorimeter) (P/N 970001.901) equipped with an autosampler, nitrogen purge of 50 milliliters/minute and mechanical cooling accessory. The run parameters were 20° C. to 300° C. at 10° C./min. for a single heat. The scans were analyzed using Universal Analysis V4.3A software.

Preparative Example 1

Bis(4-bromophenoxy)methane

To a stirred solution of 4-bromophenol (17.3 grams, 100 millimoles, 1.0 equivalent) in N-methylpyrrolidone (NMP; 120 milliliters) at 0° C. under nitrogen atmosphere was added sodium hydride (NaH; 2.50 grams, 104 millimoles, 1.04 equivalent) in four installments over a period of 1 hour. This solution was stirred for another hour at 0° C. and to this methylene chloride (25 milliliters) was added slowly. After stirring for 1 hour at 0° C., the mixture was warmed to room temperature and then heated to 40° C. for 18 hours. This mixture was poured into cold water (200 milliliters). The mixture was extracted with 5% ethyl acetate in hexanes (3×150 milliliters) and the combined organic layer was washed with water and brine. After drying over anhydrous magnesium sulfate the solvent was removed and the residue was purified by flash chromatography using 10% ethyl acetate in hexanes to yield the product (16.1 grams, 45.0 millimoles, 90%) in the form of a white solid. 1H-NMR (CDCl3) δ 7.40 (dd, J=6.8 Hz and 2.2 Hz, 4H), 6.97 (dd, J=6.8 Hz and 2.2 Hz, 4H) and 5.66 (s, 2H); 13C-NMR (CDCl3) δ 155.84, 132.48, 118.28, 115.10, and 91.18.

Preparative Example 2

Bis(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methane

To a stirred solution of bis(4-bromophenoxy)methane (4.00 grams, 11.2 millimoles, 1.00 equivalent) in THF (50 mL) at −78° C. under nitrogen atmosphere, n-butyllithium (n-BuLi; 13.6 milliliters, 2.5 M solution in hexane, 33.5 millimoles, 3.00 equivalents) was added slowly. After an hour 2-iso-propoxy-4,4,5,5-tetramethyl-1,3-2-dioxaborolane (6.8 milliliters, 33 millimoles, 3.0 equivalents) was added and stirring was continued at −78° C. for three more hours. The reaction mixture allowed to warm to room temperature and further stirred for 18 hours. The volatiles were removed by rotary evaporation and the residue was treated with crushed ice and extracted with methylene chloride. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. Removal of the solvent followed by recrystallization from pentane gave the diboronate ester (4.11 grams, 9.09 millimoles, 81%) in the form of a white solid. 1H-NMR (CDCl3) δ 7.76 (d, J=8.6 Hz, 4H0, 7.08 (d, J=8.6 Hz, 4H), 5.77 (s, 2H) and 1.33 (s, 24H); 13C-NMR (CDCl3) δ 159.38, 136.53, 115.61, 90.32, 83.62 and 24.83.

Preparative Example 3

1-Bromo-4-(vinyloxy)benzene

Under nitrogen, a 250 milliliter round bottom flask was charged with 4-bromophenol (8.00 grams, 46.2 millimoles, 1.0 equivalent), sodium acetate (2.28 grams, 27.7 millimoles, 0.6 equivalent) and bis(1,5-cyclooctadiene)diiridium(I) dichloride (233 milligram, 347 micromoles, 0.0075 equivalent). Toluene (75 milliliter) was added to this and vinyl acetate (8.5 milliliter, 92 millimoles, 2.0 equivalents) was added via syringe. The reaction was heated to 102° C. for 3 hours and then allowed to cool to room temperature. The crude reaction was concentrated on a rotary evaporator and filtered through a plug of silica. The solvent was removed by rotary evaporation and the product dried under high vacuum. The final compound was obtained in form of a colorless to slightly yellow oil (6.97 gram, 35.0 millimoles, 76%). 1H NMR (500 MHz, CDCl3) δ 7.44-7.37 (m, 2H), 6.91-6.84 (m, 2H), 6.56 (dd, J=13.7, 6.1 Hz, 1H), 4.77 (dd, J=13.7, 1.8 Hz, 1H), 4.45 (dd, J=6.1, 1.8 Hz, 1H).

Preparative Example 4

4,4′-(Ethane-1,1-diylbis(oxy)bis(bromobenzene)

Under nitrogen, a 250 milliliter round bottom flask was charged with 1-bromo-4-(vinyloxy)benzene (6.97 grams, 35.0 millimoles, 1.00 equivalent), dioxane (50 milliliters), 4-bromophenol (6.67 grams, 38.5 millimoles, 1.10 equivalent), and a stir bar. Trifluoroacetic acid (1.21 milliliter, 15.75 millimoles, 0.45 equivalent) was added and the flask was equipped with a condenser while maintaining an inert atmosphere. The reaction mixture was heated to reflux overnight, allowed to cool, and quenched with triethylamine (2.00 milliliters). The mixture was separated via automated flash column chromatography using 220 grams Grace normal phase silica column (5% ethyl acetate in hexanes). Concentration gave the product in form of a colorless oil (9.69 grams, 26.0 millimoles, 74%). 1H NMR (400 MHz, CDCl3) δ 7.41-7.32 (m, 4H), 6.91-6.81 (m, 4H), 5.86 (q, J=5.3 Hz, 1H), 1.62 (dd, J=5.3, 0.4 Hz, 3H); 13C-NMR (101 MHz, CDCl3) δ 154.71, 132.46, 119.59, 115.19, 98.44, 20.10.

Preparative Example 5

2,2′-((Ethane-1,1-diylbis(oxy))bis(4,1-phenylene))bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)

Under nitrogen, a 250 milliliter round bottom flask was charged with 4.4-(ethane-1,1-diylbis(oxy)bis(bromobenzene) (9.56 gram, 25.7 millimoles, 1.00 equivalent), tetrahydrofuran (50 milliliters), and a stir bar and cooled to −78° C. in a dry ice/acetone bath. n-Butyllithium (2.5 M in hexane, 25.7 milliliters, 64.2 millimoles, 2.50 equivalents) was added while maintaining an internal temperature between −78 and −70° C. The reaction mixture was then further stirred for one hour at −78° C. Dioxaborolane (15.7 milliliters, 77.1 millimoles, 3.00 equivalents) was added to the solution over a thirty minute period and the reaction mixture was stirred overnight and allowed to gradually warm to ambient temperature. The solution was concentrated, dissolved in ethyl acetate, and filtered through a plug of CELITE™ 545 using ethyl acetate as an eluent. The crude product was concentrated, dissolved in a minimal amount of hot acetonitrile (˜150-200 milliliters), filtered hot, and recrystallized by cooling gradually to −20° C. The crystals were isolated by filtration, washed with cold acetonitrile, and dried in a vacuum oven to yield the final product in form of colorless crystalline powder (6.56 grams, 14.7 millimoles, 55%). The mother liquor was concentrated, dissolved a minimum amount of hot acetonitrile. Crystallization at −20° C., followed by isolation by filtration, washing with cold acetonitrile and drying under high vacuum yielded a second crop of product (547 mg) bringing the total yield to 7.10 g (15.2 millimoles, 59%). 1H NMR (400 MHz, CDCl3) δ 7.75-7.67 (m, 4H), 6.97-6.89 (m, 4H), 6.05 (q, J=5.2 Hz, 1H), 1.68 (d, J=5.2 Hz, 3H), 1.32 (s, 24H); 13C NMR (101 MHz, cdcl3) δ 158.50, 136.51, 116.50, 97.43, 83.63, 24.86, 20.42.

Preparative Example 6

4,4′-((phenylmethylene)bis(oxy))bis(bromobenzene)

Inside a nitrogen purged glove box, to a solution of 4-bromophenol (12.0 grams, 69.4 millimoles, 2.5 equivalents) dissolved in anhydrous 1-methyl-2-pyrrolidinone (100 milliliters), was added 95% sodium hydride (1.82 grams, 72.1 millimoles, 2.6 equivalents) in small portions over a 30 minute period. The reaction was stirred for an additional 90 minutes at room temperature. α,α-Dichlorotoluene (4.13 milliliters, 27.7 millimoles, 1.0 equivalent) was added and the reaction was heated to 70° C. overnight. The reaction was quenched by addition to water (200 milliliters). The aqueous phase was extracted with a 1:1 mixture of diethyl ether and ethyl acetate (3×120 milliliters). The combined organic phases were then washed with de-ionized water (5×100 milliliters), brine (1×100 milliliters) and dried over magnesium sulfate. After filtration and concentration on the rotary evaporator, the residue was taken up in diethyl ether (60 milliliters) and filtered through a plug of basic alumina. The product was fully eluted with additional diethyl ether (700 milliliters) and concentrated on the rotary evaporator. Further drying under high vacuum for several days yielded the product quantitatively in form of a yellow oil that crystallizes over time to give an off-white solid (12.0 grams, 27.7 millimoles, 100%). m.p.: 50.8° C.; 1H-NMR (400 MHz, CDCl3) δ 7.59-7.51 (m, 2H), 7.44-7.37 (m, 3H), 7.37-7.29 (m, 4H), 6.93-6.82 (m, 4H), 6.59 (s, 1H); 13C-NMR (101 MHz, CDCl3) δ 155.07, 136.58, 132.59, 129.65, 128.86, 126.78, 119.60, 115.42, 100.77; FTIR: 605, 658, 674, 694, 741, 792, 816, 848, 886, 928, 984, 1031, 1060, 1100, 1115, 1167, 1178, 1210, 1242, 1280, 1304, 1363, 1449, 1483, 1584, 1689, 3033, 3065 cm−1; UV/Vis 223 (shoulder), 237, 278 nm; GC/MS/EI+: 432, 434, 436 [M+] (2×Br isotope pattern); 261, 263 [Br—C6H4—O—CHPh]+ (1×Br isotope pattern); 182 [C6H4—O—CHPh] HRMS (EST): calc. for C19H13Br2O2− [M+Na]+ 430.9288, found 430.9287.

Preparative Example 7

2,2′-(((phenylmethylene)bis(oxy))bis(4,1-phenylene))-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)

4,4′-((phenylmethylene)bis(oxy))bis(bromobenzene) (12.0 grams, 27.6 millimoles, 1.0 equivalent) in anhydrous THF (120 milliliter) under nitrogen was cooled to −78° C. using an acetone/dry ice bath. n-Butyllithium (1.6 M in hexanes, 42 milliliters, 65.5 millimoles, 2.4 equivalents) was added over a 60 minute period. The reaction was stirred at −78° C. for 90 minutes. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (17 milliliters, 83.1 millimoles, 3.00 equivalents) was added to the reaction drop-wise over a course of 30 minutes. The reaction was allowed to warm to room temperature overnight. The reaction was carefully quenched by drop-wise addition of water (2 milliliters), followed by stirring for 10 minutes. Dichloromethane (200 milliliters) was added and the reaction mixture was dried over magnesium sulfate. The solids were filtered off and the organic phase was concentrated. The residue was dissolved in dichloromethane (100 milliliters) and filtered through a plug of silica covered with a layer of CELITE™. The produced was fully eluted with additional dichloromethane (400 milliliters) and the combined organic phases concentrated. The plug filtration process was repeated two additional times. After the final concentration, the residue was recrystallized from a minimum amount of boiling acetonitrile that was gradually cooled to 5° C. overnight. The colorless crystals were isolated by filtration, washed with a small aliquot of cold acetonitrile, and dried in under vacuum at 65° C. overnight. The final product was obtained in a yield of 70% (10.2 grams, 19.3 millimoles). 1H-NMR (400 MHz, CDCl3) δ 7.72-7.66 (m, 4H), 7.63-7.58 (m, 2H), 7.43-7.35 (m, 3H), 7.00-6.92 (m, 4H), 6.76 (s, 1H), 1.31 (s, 24H); 13C NMR (101 MHz, cdcl3) δ 158.67, 137.10, 136.46, 129.27, 128.62, 126.69, 116.53, 99.72, 83.63, 24.86, 24.85 (one overlapping peak); FTIR: 578, 632, 651, 697, 733, 756, 832, 855, 884, 919, 964, 996, 1065, 1084, 1096, 1141, 1173, 1210, 1247, 1272, 1322, 1359, 1400, 1458, 1573, 1604, 2927, 2977 cm−1; UV/Vis: 242 nm; ESI+): 549, 550, 551, 552, 553 [M+Na]+ (isotope pattern consistent with 2×B and 31×C), 308, 309 (bp), 310 [pinB-C6H4—O—CHPh]+ (isotope pattern consistent with B and 19×C); HRMS (ESI+): calc. for C31H38B2NaO6+ [M+Na]+551.2752, found 551.2762.

Claims

1. A bis(aryl)acetal having the formula

wherein
Y1 and Y2 are each independently chloro, bromo, iodo, mesylate, tosylate, triflate, or Bx, provided that Y1 and Y2 are not both selected from chloro, bromo, and iodo;
each occurrence of Bx is independently a boron-containing functional group bonded to Ar1 or Ar2 via a boron atom;
Ar1 and Ar2 are each independently unsubstituted or substituted C6-18 arylene, or unsubstituted or substituted C3-18 heteroarylene; provided that Ar1 and Ar2 are not covalently linked to each other to form a ring structure that includes -Ar1-O—C—O-Ar2-; and
R1 and R2 are each independently hydrogen, unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-20 cycloalkyl; unsubstituted or substituted C6-18 aryl, or unsubstituted or substituted C3-20 heteroaryl; and R1 and R2 are optionally covalently linked to each other to form a ring that includes —R1—C—R2—.

2. The bis(aryl)acetal of claim 1, wherein at least one of Y1 and Y2 is Bx.

3. The bis(aryl)acetal of claim 1, wherein Y1 and Y2 are each independently Bx.

4. The bis(aryl)acetal of any of claims 1-3, wherein each occurrence of Bx is independently selected from the group consisting of BF3−M+, wherein each occurrence of M+ is independently an alkali metal cation, or an unsubstituted or substituted ammonium ion;

—B(OH)2;
wherein R3 and R4 are each independently C1-18 alkyl, C3-18 cycloalkyl, or C6-18 aryl; and
R3 and R4 are optionally covalently linked to each other to form a ring that includes —R3—O—B—O—R4—; and
wherein R15 and R16 are each independently hydrogen, unsubstituted or substituted C1-18 linear or branched alkyl, unsubstituted or substituted C3-18 cycloalkyl; unsubstituted or substituted C6-18 aryl, unsubstituted or substituted C3-18 heteroaryl, or
wherein Y2, Ar1, Ar2, R1, and R2 are defined as above in claim 1.

5. The bis(aryl)acetal of any of claims 1-4, wherein each occurrence of Bx is

wherein R3 and R4 are each independently C1-18 alkyl, C3-18 cycloalkyl, or C6-18 aryl; and
R3 and R4 are optionally covalently linked to each other to form a ring that includes —R3—O—B—O—R4—.

6. The bis(aryl)acetal of any of claims 1-5, wherein Ar1 and Ar2 are each independently 1,3-phenylene or 1,4-phenylene.

7. The bis(aryl)acetal of any of claims 1-6, wherein Ar1 and Ar2 are each independently 1,4-phenylene.

8. The bis(aryl)acetal of any of claims 1-7, wherein

R1 is hydrogen; and
R2 is unsubstituted or substituted phenyl.

9. The bis(aryl)acetal of any of claims 1-8, wherein

R1 is hydrogen; and
R2 is selected from phenyl, ortho-methoxyphenyl, meta-methoxyphenyl, and para-methoxyphenyl.

10. The bis(aryl)acetal of claim 1, selected from the group consisting of

Patent History
Publication number: 20150025262
Type: Application
Filed: Jul 16, 2013
Publication Date: Jan 22, 2015
Inventors: Matthias S. OBER (Midland, MI), Duane R. ROMER (Midland, MI), John B. ETIENNE (Mount Pleasant, MI), Pulikkottil J. THOMAS (Midland, MI)
Application Number: 13/943,232
Classifications
Current U.S. Class: Plural Rings Each Having Boron, Carbon And Oxygen As Ring Members (558/290); Benzene Ring Containing (568/592)
International Classification: C07C 43/225 (20060101); C07F 5/04 (20060101);