Novel ferroelectric nematic liquid crystal materials and compositions thereof

Abstract

The present application relates to ferroelectric nematic liquid crystal (FNLC) compounds characterized by chemical structures having electron donor–acceptor chromophores connected via linkers. The compounds have a general structure of A1–L1–A2–L2–(Ax–Ly)n–B, where A and B are aryl or heteroaryl groups, and L are linkers selected to promote spontaneous polar alignment in the nematic phase. The FNLCs enable enhanced second-order nonlinear optical properties and electro-optic coefficients (r33), with values exceeding, e.g., 30 pm / V in some embodiments. The FNLC compounds also exhibit absorption maxima above 400 nm, indicating extended π-conjugation and strong intramolecular charge transfer. The present application also includes compositions and mixtures of such compounds, which may form glassy ferroelectric nematic phases suitable for integration into nonlinear optical devices.

Description

POLA.P2010WO (00642386) NOVEL FERROELECTRIC NEMATIC LIQUID CRYSTAL MATERIALS AND COMPOSITIONS THEREOF CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application Serial No.63 / 667,693 filed July 3, 2024, the entire content of which is hereby incorporated by reference. BACKGROUND

[0002] Ferroelectric nematic liquid crystals (FNLC) are a recently discovered class of liquid crystals that have intrinsically large second order nonlinear optical (NLO) susceptibility χ(2) due to their lack of center symmetry and the alignment of their polar axis with the polarizable long axis. DESCRIPTION OF EMBODIMENTS

[0003] Although the following detailed description contains many specifics for the purpose of illustration, a person of ordinary skill in the art will appreciate that many variations and alterations to the following details can be made and are considered included herein. Accordingly, the following embodiments are set forth without any loss of generality to, and without imposing limitations upon any claims set forth. It is also to be understood that the terminology used herein is for describing particular embodiments only and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skills in the art to which this disclosure belongs. Also, the same reference numerals appearing in different drawings represent the same element. Numbers provided in flow charts and processes are provided for clarity in illustrating steps and operations and do not necessarily indicate a particular order or sequence.

[0004] Furthermore, the described features, structures, or characteristics can be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided, such as examples of formulas, procedures, ingredients, etc., to provide a thorough understanding of various embodiments. One skilled in the relevant art will recognize, however, that such detailed embodiments do not limit the overall concepts articulated herein but are merely representative thereof. One skilled in the relevant art will also recognize that the technology can be practiced without one or more of the specific details, or with other methods, components, formulas, etc. In other instances, well-known structures, materials, or operations may not be shown or described in detail to avoid obscuring aspects of the disclosure.

[0005] In this application, “comprises,” “comprising,” “containing” and “having” and the like can have the meaning ascribed to them in U.S. Patent law and can mean “includes,” “including,” and the like, and are generally interpreted to be open ended terms. The terms “consisting of” or “consists of” are closed terms, and include only the components, structures, steps, or the like specifically listed in conjunction with such terms, as well as that which is in accordance with U.S. Patent law. “Consisting essentially of” or “consists essentially of” have the meaning generally ascribed to them by U.S. Patent law. In particular, such terms are generally closed terms, with the exception of allowing inclusion of additional items, materials, components, steps, or elements, which do not materially affect the basic and 1POLA.P2010WO (00642386) novel characteristics or function of the item(s) used in connection therewith. For example, trace elements present in a composition, but not affecting the composition’s nature or characteristics would be permissible if present under the “consisting essentially of” language, even though not expressly recited in a list of items following such terminology. When using an open-ended term in this written description, like “comprising” or “including,” it is understood that direct support should be afforded also to “consisting essentially of” language as well as “consisting of” language as if stated explicitly and vice versa.

[0006] As used herein, the term “substantially” refers to the complete or nearly complete extent or degree of an action, characteristic, property, state, structure, item, or result. For example, an object that is “substantially” enclosed would mean that the object is either completely enclosed or nearly completely enclosed. The exact allowable degree of deviation from absolute completeness may in some cases depend on the specific context. However, generally speaking the nearness of completion will be so as to have the same overall result as if absolute and total completion were obtained. The use of “substantially” is equally applicable when used in a negative connotation to refer to the complete or near complete lack of an action, characteristic, property, state, structure, item, or result. For example, a composition that is “substantially free of” particles would either completely lack particles, or so nearly completely lack particles that the effect would be the same as if it completely lacked particles. In other words, a composition that is “substantially free of” an ingredient or element may still actually contain such item as long as there is no measurable effect thereof.

[0007] As used herein, the term “about” is used to provide flexibility to a given term, metric, value, range endpoint, or the like. The degree of flexibility for a particular variable can be readily determined by one skilled in the art. However, unless otherwise expressed, the term “about” generally provides flexibility of less than 1%, and in some cases less than 0.01%. It is to be understood that, even when the term “about” is used in the present specification in connection with a specific numerical value, support for the exact numerical value recited apart from the “about” terminology is also provided.

[0008] As used herein, a plurality of items, structural elements, compositional elements, and / or materials may be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no individual member of such list should be construed as a de facto equivalent of any other member of the same list solely based on their presentation in a common group without indications to the contrary.

[0009] Concentrations, amounts, and other numerical data may be expressed or presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. As an illustration, a numerical range of “about 1 to about 5” should be interpreted to include not only the explicitly recited 2POLA.P2010WO (00642386) values of about 1 to about 5, but also include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 3, and 4 and sub-ranges such as from 1-3, from 2-4, and from 3-5, etc., as well as 1, 1.5, 2, 2.3, 3, 3.8, 4, 4.6, 5, and 5.1 individually.

[0010] This same principle applies to ranges reciting only one numerical value as a minimum or a maximum. Furthermore, such an interpretation should apply regardless of the breadth of the range or the characteristics being described.

[0011] Reference throughout this specification to “an example” means that a particular feature, structure, or characteristic described in connection with the example is included in at least one embodiment. Thus, appearances of phrases including “an example” or “an embodiment” in various places throughout this specification are not necessarily all referring to the same example or embodiment.

[0012] An initial overview of embodiments is provided below, and specific embodiments are then described in further detail. This initial summary is intended to aid readers in understanding the disclosure more quickly and is not intended to identify key or essential technological features, nor is it intended to limit the scope of the claimed subject matter.

[0013] As described above, FNLC materials are a recently discovered class of liquid crystals that have intrinsically large second order nonlinear optical (NLO) susceptibility χ(2)by virtue of lacking a center symmetry and having the polar axis coincidence with the polarizable long axis.

[0014] Materials with nonzero χ(2)are valuable for frequency conversion, optical rectification, and electro-optic (Pockels) modulation. For electro-optic applications, the component of the χ(2)tensor that describes the efficiency of transduction between the electrical and optical domains is the electro-optic coefficient or r33. It describes the change in refractive index of a material in response to an applied electric field and is typically measured in units of m / V or pm / V. The larger χ(2)or r33 is for a given material, the more valuable it is for these applications. The values of χ(2)and r33are macroscopic coefficients, and for FNLCs their magnitudes are proportional to the molecular hyperpolarizability (β). The inventors have developed numerous FNLC compounds and compositions according to the present disclosure with large χ(2)and r33 and increased molecular parameter β.

[0015] Large β is achieved in organic molecules by incorporation of charge-transfer electronic structures. These charge transfer chromophores have strong electron donors and acceptors connected by efficient pi conjugated bridges. Incorporation of efficient charge-transfer chromophores into a molecule that spontaneously forms an FNLC phase would yield an acentrically ordered material with enhanced NLO coefficients.

[0016] The FNLC materials of the present disclosure have the distinct characteristic of structural alignment in a ferroelectric nematic phase in the absence of an electric field and without an alignment 3POLA.P2010WO (00642386) layer being present, although both can be utilized, either alone or together in embodiments of the present disclosure and still be within the present intended scope.

[0017] In some embodiments, the present application relates to FNLC compounds and compositions having an electro-optic coefficient greater than 5 pm / V, e.g., greater than 5.5 pm / V, greater than 6 pm / V, greater than 6.5 pm / V, greater than 7 pm / V, greater than 7.5 pm / V, greater than 8 pm / V, greater than 8.5 pm / V, greater than 9 pm / V, greater than 9.5 pm / V, greater than 10 pm / V, greater than 10.5 pm / V, greater than 11 pm / V, greater than 11.5 pm / V, greater than 12 pm / V, greater than 12.5 pm / V, greater than 13 pm / V, greater than 13.5 pm / V, greater than 14 pm / V, greater than 14.5 pm / V, greater than 15 pm / V, greater than 15.5 pm / V, greater than 16 pm / V, greater than 17 pm / V, greater than 18 pm / V, greater than 19 pm / V, greater than 20 pm / V, greater than 21 pm / V, greater than 22 pm / V, greater than 23 pm / V, greater than 24 pm / V, greater than 25 pm / V, greater than 26 pm / V, greater than 27 pm / V, greater than 28 pm / V, greater than 29 pm / V, greater than 30 pm / V, greater than 31 pm / V, greater than 32 pm / V, greater than 33 pm / V, greater than 34 pm / V, greater than 36 pm / V, greater than 38 pm / V, greater than 40 pm / V, greater than 42 pm / V, greater than 44 pm / V, greater than 46 pm / V, greater than 48 pm / V, greater than 50 pm / V, greater than 52 pm / V, greater than 54 pm / V, greater than 56 pm / V, greater than 58 pm / V, greater than 60 pm / V, greater than 62 pm / V, greater than 64 pm / V, greater than 66 pm / V, greater than 68 pm / V, greater than 70 pm / V, greater than 72 pm / V, greater than 74 pm / V, greater than 76 pm / V, greater than 78 pm / V, greater than 80 pm / V, greater than 82 pm / V, greater than 84 pm / V, greater than 86 pm / V, greater than 88 pm / V, greater than 90 pm / V, greater than 92 pm / V, greater than 94 pm / V, greater than 96 pm / V, greater than 98 pm / V, or greater than 100 pm / V.

[0018] In some embodiments, the present application relates to FNLC compounds and compositions having an electro-optic coefficient less than 100 pm / V, e.g., less than 98 pm / V, less than 96 pm / V, less than 94 pm / V, less than 92 pm / V, less than 90 pm / V, less than 88 pm / V, less than 86 pm / V, less than 84 pm / V, less than 82 pm / V, less than 80 pm / V, less than 78 pm / V, less than 76 pm / V, less than 74 pm / V, less than 72 pm / V, less than 70 pm / V, less than 68 pm / V, less than 66 pm / V, less than 64 pm / V, less than 62 pm / V, less than 60 pm / V, less than 58 pm / V, less than 56 pm / V, less than 54 pm / V, less than 52 pm / V, less than 50 pm / V, less than 48 pm / V, less than 46 pm / V, less than 44 pm / V, less than 42 pm / V, less than 40 pm / V, less than 38 pm / V, less than 36 pm / V, less than 34 pm / V, less than 32 pm / V, less than 30 pm / V, less than 28 pm / V, less than 26 pm / V, less than 24 pm / V, less than 22 pm / V, less than 20 pm / V, less than 18 pm / V, less than 16 pm / V, less than 14 pm / V, less than 12 pm / V, or less than 10 pm / V.

[0019] In some embodiments, the present application relates to FNLC compounds and compositions having an electro-optic coefficient that falls under a numeric range based on the electro-optic coefficient combinations described herein, e.g., greater than 30 pm / V and less than 80 pm / V.

[0020] Achieving this value presents significant challenges. While such values are common in inorganic crystals like lithium niobate, replicating or exceeding this performance in organic or liquid crystalline materials requires overcoming multiple barriers. 4POLA.P2010WO (00642386)

[0021] For example, as briefly mentioned above, high electro-optic activity in organic materials typically relies on the incorporation of charge-transfer chromophores with strong donor–acceptor pairs and extended π-conjugation. However, designing such chromophores to be compatible with FNLC self- assembly while maintaining thermal stability, solubility, and phase behavior is nontrivial. The chromophore must not only exhibit a large molecular hyperpolarizability (β) but also align effectively within the FNLC matrix to contribute to macroscopic order.

[0022] FNLCs require spontaneous polar alignment of molecules along a common axis. Introducing bulky or highly polarizable chromophores can disrupt this delicate balance, destabilizing the ferroelectric nematic phase or leading to phase separation. Achieving both high electro-optic response and stable FNLC behavior demands precise molecular engineering and formulation strategies.

[0023] Even if individual molecules possess high β values, the bulk electro-optic coefficient depends on the degree of polar alignment across the material. Achieving uniform, defect-free alignment over large areas such as in thin films or device architecture is a major challenge. Additionally, maintaining this alignment under operational electric fields and thermal cycling is critical for device reliability.

[0024] Materials with high electro-optic coefficients are desirable for low-voltage operation. However, FNLCs must also exhibit low dielectric loss, and compatibility with standard fabrication processes. Ensuring that the material can be integrated into real-world devices without degradation or performance loss is a key hurdle.

[0025] Strong charge-transfer chromophores are often associated with absorption in visible or near- infrared regions, which can reduce material transparency and introduce optical losses. This presents a design challenge in balancing high electro-optic activity with a broad optical window, an essential consideration for practical implementation in photonic systems. In the context of FNLCs, one key molecular feature that supports spontaneous polar ordering is the presence of a strong intramolecular charge-transfer interaction. This interaction is typically evidenced by an absorption band in the visible region, generally above 400 nanometers, indicating extended π-conjugation and effective donor– acceptor separation. These characteristics contribute to a large molecular dipole moment and promote enhanced polar alignment in the nematic phase. By contrast, many previously reported FNLC compounds exhibit absorption maximum below 400 nanometers, reflecting limited charge-transfer character and reduced electronic asymmetry. While such materials may still exhibit ferroelectric behavior, they often lack the electronic features necessary for strong dipolar coupling and efficient molecular organization. Therefore, the presence of a visible-region charge-transfer band serves as a distinguishing molecular signature for FNLC materials with improved polar responsiveness and phase stability.

[0026] In some embodiments, the FNLC compound and composition demonstrate an absorption maximum (λmax) greater than 400 nm, e.g., greater than 410 nm, greater than 420 nm, greater than 430 nm, greater than 440 nm, greater than 450 nm, greater than 460 nm, greater than 470 nm, greater than 5POLA.P2010WO (00642386) 480 nm, greater than 490 nm, greater than 500 nm, greater than 510 nm, greater than 520 nm, greater than 530 nm, greater than 540 nm, greater than 550 nm, greater than 560 nm, greater than 570 nm, greater than 580 nm, greater than 590 nm, greater than 600 nm, greater than 610 nm, greater than 620 nm, greater than 630 nm, greater than 640 nm, greater than 650 nm, greater than 660 nm, greater than 670 nm, greater than 680 nm, greater than 690 nm, greater than 700 nm, greater than 710 nm, greater than 720 nm, greater than 730 nm, greater than 740 nm, greater than 750 nm, greater than 775 nm, greater than 800 nm, greater than 825 nm, greater than 850 nm, greater than 875 nm, and greater than 900 nm.

[0027] In some embodiments, the FNLC compound and composition demonstrate an absorption maximum (λmax) less than 900 nm, e.g., less than 875 nm, less than 850 nm, less than 825 nm, less than 800 nm, less than 775 nm, less than 750 nm, less than 740 nm, less than 730 nm, less than 720 nm, less than 710 nm, less than 700 nm, less than 690 nm, less than 680 nm, less than 670 nm, less than 660 nm, less than 650 nm, less than 640 nm, less than 630 nm, less than 620 nm, less than 610 nm, less than 600 nm, less than 590 nm, less than 580 nm, less than 570 nm, less than 560 nm, less than 550 nm, less than 540 nm, less than 530 nm, less than 520 nm, less than 510 nm, less than 500 nm, less than 490 nm, less than 480 nm, less than 470 nm, less than 460 nm, less than 450 nm, less than 440 nm, less than 430 nm, less than 420 nm, or less than 400 nm.

[0028] In some embodiments, the present application relates to FNLC compounds and compositions having a λmax that falls under a numeric range based on the λmax combinations described herein, such as greater than 450 nm and less than 900 nm.

[0029] In some embodiments, an FNLC composition comprises at least one compound of having a structure of A1-L1-A2-L2-(Ax-Ly)n-B, where n is from 0 to 5, preferably from 0 to 3. When n is 0, the FNLC composition comprises a compound having a structure of Formula (IA), namely A1-L1-A2-L2-B, and when n is from 1-5 the FNLC composition comprises a compound having a structure of Formula (IIA), namely A1-L1-A2-L2-(Ax-Ly)n-B, where Ax can be, e.g., A3, A4, A5, A6, and A7; and Ly can be L3, L4, L5, L6, and L7. It is noted that (Ax -Ly)n may represent a unit that repeats itself for n times, or it can be a total of n units, each unit having a different (Ax -Ly) chemical structure.

[0030] It is noted that, while single compounds are described herein for convenience, an FNLC composition can include one, two, three, four, or more compounds, either according to Formula (IA), Formula (IIA), or other compounds having FNLC properties, including combinations thereof. In some embodiments, A1has a chemical structure of. 6POLA.P2010WO (00642386)

[0032] In some embodiments, the present application relates to an FNLC compound having an amine moiety as the electron donor in the A1position, and having the RA,B-N-Ar structure illustrated above. The inclusion of such a donor group is advantageous due to its strong electron-donating character, which, when paired with an electron-withdrawing acceptor group, facilitates the formation of a push- pull electronic structure. This configuration enhances the molecular dipole moment along the longitudinal axis, thereby promoting spontaneous polarization and stabilizing the ferroelectric nematic phase. Surprisingly, it has been found that such amine-functionalized donor systems yield enhanced nonlinear optical responses and improved electro-optic switching behavior not previously reported in the art. The resulting materials exhibit unexpectedly high second-order nonlinear optical coefficients, particularly in thin-film geometries, and demonstrate efficient dipole alignment under low-voltage conditions. These effects are not anticipated based on prior studies of conventional nematic or ferroelectric liquid crystals, and thus represent a novel and non-obvious advancement in the field. In alternative embodiments, the use of amine donors may be omitted where thermal stability or synthetic simplicity is prioritized, as excessive donor strength may lead to aggregation or mesophase disruption under certain conditions.

[0033] In some embodiments, RA and RB are independently selected from the group consisting of -H and C1-C10 alkyl, either of which may optionally form fused cyclic structure with Ar.

[0034] In some embodiments, Ar is selected from the group consisting of thienylene, fused thienylene, phenylene, naphthalene, fused heterocyclics, azabenzene, and combinations thereof, each of which may be optionally substituted with one or more substituents RC, wherein RC is selected from the group consisting of -H, -F, C1–C10 alkoxy, C1–C10 alkyl, -NO2, -CN, and -CF3.

[0035] In certain more specific examples, A1 has a structure selected from the group consisting ofZ is independently C or N, V is independently CH or N, and A is independently -H, -F, -O-(CH2)(0-10)- (CH3), -(CH2)(0-10)-(CH3), -NO2, -CN, or -CF3. Furthermore, in certain examples A2has a structure selected from 7POLA.P2010WO (00642386)N, V is independently CH or N, and A is independently -H, -F, -O-(CH2)(0-10)-(CH3), -(CH2)(0-10)-(CH3), -NO2, -CN, or -CF3. In yet other examples, A3, when present according to Formula (IIA), has a structureC or N, V is independently CH or N, and A is independently -H, -F, -O-(CH2)(0-10)-(CH3), -(CH2)(0-10)- (CH3), -NO2, -CN, or -CF3. In yet further examples, B has a structure selected fromR4 are independently H or F, and D, E, and J are independently -H, -F, -CN, -CF3, -NO2, or - CH=C(CN)2.Different linkers, L1, L2, and Ly, used between specific structural moieties, A1, A2, and Ax, and B, as well as linkers used relative to one another at different sites (L1, L2, and Ly) can alter the functional characteristics of an FNLC molecule due to the differences in dipole moments of different linkers and how the dipole moments interact with one another.

[0039] As such, the behavior of a liquid crystal material can be adapted to a desired behavior depending on the selection FNLC molecules making up the liquid crystal layer and the specific linkers that are present at specific locations within the FNLC molecules. As such, the functional characteristics of a given FNLC composition can be designed for specific applications that produce desired effects when FNLC materials are stimulated with a signal, for example, an applied electromagnetic signal as well as modulations to that electromagnetic signal.

[0040] In certain example compounds, a linker such as L1bonding A1to A2has a structure selected fromindependently CH or N and R3 and R4 are independently -H or -F. In certain compound examples, L2 bonding A2 to either A3 (Formula IIA) or B (Formula IA) has a structure selected from, where V is independently CH or N and R3 and R4 are independently -H or -F. 8POLA.P2010WO (00642386)

[0041] In other compound examples, L3, when present as per Formula (IIA) bonding A3to B, has a structure selected fromindependently CH or N and R3and R4are independently -H or -F. In some examples of Formula ( IA), L3is bonded to B.The following exemplifies various example compounds having structures of Formula ( IA) (A1-L1-A2-L2-B), where n=0 and the structural subunit A3and linker L3are not present.

[0042] For example, when, Formula (IA) can include a variety of compounds depending on the selected structural subunits such as, for example, where A2 is selected from9POLA.P2010WO (00642386)(

[0043] Additionally, L1 is selected fromand L2 is selected froms described above.

[0044] Further examples of various compounds having structures of Formula ( IA) (A1-L1-A2-L2-B)include thoseFormula (IA) can include a variety of compounds dependingon the selected structural subunits such as, for example, where A2 is selected from , 10POLA.P2010WO (00642386)(( (11POLA.P2010WO (00642386) (

[0045] Further examples of various compounds having structures of Formula (IA) (A1-L1-A2-L2-B)include thoseFormula (IA) can include a variety of compounds depending(12POLA.P2010WO (00642386)(Formula IA-47) (Formula IA-48)

[0046] Further examples of various compounds having structures of Formula ( IA) (A1-L1-A2-L2-B)include those, Formula (IA) can include a variety of compounds dependingon the selected structural subunits such as, for example, where A2 is selected from ,13POLA.P2010WO (00642386)(Formula IA-59) (Formula IA-60) ( (14POLA.P2010WO (00642386)

[0047] Further examples of various compounds having structures of Formula ( IA) (A1-L1-A2-L2-B) include those, Formula (IA) can include a variety of compounds depending on the selected structural subunits such as, for example, where A2is selected from,(Formula IA-71) (Formula IA-72) 15POLA.P2010WO (00642386)(Formula IA-79) (Formula IA-80)

[0048] Further examples of various compounds having structures of Formula ( IA) (A1-L1-A2-L2-B)include thoseFormula (IA) can include a variety of compoundsdepending on the selected structural subunits such as, for example, where A2 is selected from16POLA.P2010WO (00642386)17POLA.P2010WO (00642386)

[0049] Further examples of various compounds having structures of Formula (IA) (A1-L1-A2-L2-B)include thoseFormula (IA) can include a variety of compoundsdepending on the selected structural subunits such as, for example, where A2 is selected from18POLA.P2010WO (00642386)

[0050] Turning to Formula (IIA), having a structure of A1-L1-A2-L2-(Ax-Ly)n-B, A1, L1, A2, L2, and B are essentially the same as what was described in relation to Formula (IA), with the primary difference between the formulas being the presence of -(Ax-Ly)n bonded between L2 and B. Similarly, accordingtructure, and L2 has a structure selected from 19POLA.P2010WO (00642386)are independently -H, or – (CH2)(0-10-)-(CH3), Z is independently C or N, V is independently CH or N, A is independently -H, -F, - O-(CH2)(0-10)-(CH3), -(CH2)(0-10)-(CH3), -NO2, -CN, or -CF3. R3and R4are independently H or F, and D, E, and J are independently -H, -F, -CN, -CF3, -NO2, or -CH=C(CN)2.

[0051] In certain example FNLC composition from Formula (IIA), Axhas a structure selected fromindependently C or N, V is independently CH or N, and A is independently -H, -F, -O-(CH2)(0-10)-(CH3), -(CH2)(0-10)-(CH3), -NO2, -CN, or -CF3. Additionally, in certain examples L3has a structure selected from ,independently CH or N and R3and R4are independently -H or -F.

[0052] A3and L3are present in Formula (IIA) FNLC molecules in one or more groups characterized

[0053] The following exemplifies various compounds having structures of Formula (IIA) (A1-L1-A2- L2-(A3-L3)M-B), where M is at least one. Note that A1, B, and L1 are not being shown for brevity. As one example, when, Formula (IIA) can include a variety of compounds depending on the selected structural subunits such as, for example, such as when A2 has a structure selected fromshown in Formula (IIA-1) toFormula (IIA-4). 20POLA.P2010WO (00642386)(Formula IIA-3) (Formula IIA-4)

[0054] Certain other example molecules having A3 structures are shown below i,(Formula IIA-11) (Formula IIA-12) 21POLA.P2010WO (00642386)(Formula IIA-15) (Formula IIA-16)

[0055] In some embodiments, the linker L1, L2, and Ly each is independently selected from the group consisting of azo, azo oxygen complex, ethene, fluoro-substituted ethene, acetylene, and ester.

[0056] In some embodiments, the linker L1, L2, and Ly each is independently selected from the group consisting of

[0057] In some embodiments, the linker L1is not an ester.

[0058] In some embodiments, A2 and Ax each is independently selected from the group consisting of thienylene, fused thienylene, thiazolylene, phenylene, naphthalene, azabenzene, fused heterocyclic, and combinations thereof, each of which may be optionally substituted with one or more substituents RC.

[0059] In some embodiments, B is selected from the group consisting of phenylene, naphthalene, thienylene, and fused thienylene, fused heterocyclics, and combinations thereof, each of which may be optionally substituted with one or more substituents RD.

[0060] In some embodiments, RC is selected from the group consisting of -H, -F, C1–C10 alkoxy, C1–C10 alkyl, -NO2, -CN, and -CF3.

[0061] In some embodiments, RC is selected from the group consisting of -H, -F, C1–C5 alkoxy, C1–C5 alkyl, -NO2, -CN, and -CF3.

[0062] In some embodiments, RD is selected from the group consisting of -H, -F, C1–C10 alkoxy, C1–C10 alkyl, -CN, -CF3, -NO2, and -CH=C(CN)2.

[0063] In some embodiments, RD is selected from the group consisting of -H, -F, C1–C5 alkoxy, C1–C5 alkyl, -NO2, -CN, -CF3, and -CH=C(CN)2.

[0064] In some embodiments, A1 has a chemical structure selected from the group consisting of 22POLA.P2010WO (00642386)23POLA.P2010WO (00642386)

[0068] In some embodiments, B is selected from the group consisting of

[0070] In some embodiments, the FNLC compound has a chemical structure of A1-L1-A2-L2-B, wherein A1 is selected from the group consisting of 24POLA.P2010WO (00642386) [ ,

[0072] L1is selected from the group consisting

[0073] L2 is selected from the group consisting

[0074] A2 is selected from the group consisting of25POLA.P2010WO (00642386)

[0076] B is selected from the group consisting of

[0078] In some embodiments, the FNLC compound has a chemical structure of A1-L1-A2-L2-A3- L3-B, wherein A1is selected from the group consisting of 26POLA.P2010WO (00642386)and ;

[0081] L2and L3each is independently selected from the group consisting of, ,

[0082] A2 and A3 each is independently selected from the group consisting of, 27POLA.P2010WO (00642386)

[0084] B is selected from the group consisting of

[0086] In some embodiments, the FNLC compound has a chemical structure of A1-L1-A2-L2-A3-L3- A4-L4-B, wherein A1is selected from the group consisting of 28POLA.P2010WO (00642386)

[0088] L1 is selected from the group consisting of, , , , ,and ;

[0089] L2through L4each is independently selected from the group consisting of ,

[0090] A2 through A4 each is independently selected from the group consisting of, 29POLA.P2010WO (00642386)

[0092] B is selected from the group consisting of

[0094] In some embodiments, the FNLC compound has a chemical structure of A1-L1-A2-L2-A3-L3- A4-L4-A5-L5-B, wherein A1is selected from the group consisting of, 30POLA.P2010WO (00642386)

[0097] L2through L5each is independently selected from the group consisting of,

[0098] A2 through A5 each is independently selected from the group consisting of, 31POLA.P2010WO (00642386)

[0100] B is selected from the group consisting of , , ,

[0102] In some embodiments, the FNLC compound or composition forms a glass after heating and cooling. In some embodiments, the glass phase may be formed following deposition from a solution containing a solvent. Upon removal of the solvent, the material transitions into a ferroelectric nematic glass film. Alternatively, in other embodiments, the material may initially be crystalline upon preparation and subsequently undergo a phase transition into an FNLC upon reaching its melting point. Upon cooling, rather than recrystallizing, the material instead transitions into a glassy state, thereby forming a ferroelectric nematic glass.

[0103] Table 1 is a non-limiting example showing compounds with a ferroelectric nematic phase and large calculated hyperpolarizabilities (B3LYP, SVPD, CHCl3), where I means isotropic phase, N means 32POLA.P2010WO (00642386) nematic phase, and NFmeans nematic phase with ferroelectric features. The number between each two letters means the temperature at which the compound was treated. For example, I-182-N-170-NFmeans Isotropic (above 182 °C) → Nematic (182–170 °C) → NF(below 170 °C).

[0104] Table 1.*Decomposes before clearing point

[0105] Table 2 demonstrates some embodiments with their respective λmax and r33 values, where λmax values of 425 nm and greater is illustrated, and r3 values of 30 pm / V and greater is observed. The λmax of 425 nm or greater indicates extended π-conjugation and optical transparency in the visible spectrum, which is advantageous for minimizing optical loss in photonic and display applications. The r3 value of 30 pm / V or higher reflects a strong linear electro-optic response, enabling efficient modulation of the refractive index under low applied voltages. The ferroelectric nature of the nematic phase further enhances the electro-optic performance by enabling spontaneous polarization and fast, reversible switching behavior. This combination of high optical transparency, strong electro-optic activity, and ferroelectric switching dynamics makes the disclosed FNLC compounds suitable for, e.g., high-speed, low-power electro-optic devices, including modulators, switches, and tunable photonic components. Table 2.33POLA.P2010WO (00642386)

[0106] The present application also relates to a nonlinear optic element comprising the FNLC composition. A nonlinear optic element can be a material or structure that exhibits a nonlinear response to incidental electromagnetic radiation in the optical frequency range. When exposed to high-intensity light, the nonlinear optic elements generate optical effects that are not linearly proportional to the applied field. This enables phenomena such as second-harmonic generation, sum- and difference- frequency generation, and optical parametric amplification.

[0107] Table 3 is a non-limiting example showing an FNLC composition having equal weight percentages of three different FNLC compounds (approx. 33.33 wt% each) that has a measured r33 of 30 pm / V. This high r₃₃ value indicates a strong linear electro-optic response, enabling efficient modulation of the refractive index under low applied voltages. The use of a ternary FNLC mixture allows for the fine-tuning of key material properties, including spontaneous polarization, viscosity, dielectric anisotropy, and phase stability, while preserving or enhancing ferroelectric switching behavior. The synergistic combination of these FNLC components contributes to improved electro-optic performance and broader operational flexibility.

[0109] The present application also relates to a nonlinear optical element integrated within an optical system configured to manipulate incident light through intensity-dependent refractive or absorptive properties. Upon exposure to an optical signal, the nonlinear element induces a change in the optical characteristics of the transmitted or reflected light, enabling functionalities such as frequency 34POLA.P2010WO (00642386) conversion, phase modulation, or optical switching. The device may include waveguides, resonant cavities, or layered structures to enhance the nonlinear interaction, and can be adapted for use in applications such as laser systems, optical communication networks, or photonic signal processors.

[0110] The following section provides illustrative examples of FNLC compounds, which incorporate a variety of linkers and linker combinations. These examples are intended to aid understanding and are not intended to limit the scope of the invention. For convenience, these illustrative compounds are collectively referred to herein as Group A, which includes the specific compounds listed below. Unless otherwise stated, Group A refers only to the compounds explicitly disclosed in this section.35POLA.P2010WO (00642386)36POLA.P2010WO (00642386)37POLA.P2010WO (00642386)38POLA.P2010WO (00642386)39POLA.P2010WO (00642386)40POLA.P2010WO (00642386)41POLA.P2010WO (00642386)42POLA.P2010WO (00642386)43POLA.P2010WO (00642386)44POLA.P2010WO (00642386)45POLA.P2010WO (00642386)46POLA.P2010WO (00642386)47POLA.P2010WO (00642386)48POLA.P2010WO (00642386)49POLA.P2010WO (00642386)50POLA.P2010WO (00642386)51POLA.P2010WO (00642386)52POLA.P2010WO (00642386)53POLA.P2010WO (00642386). 54POLA.P2010WO (00642386) EXAMPLES

[0111] The following examples are provided to illustrate certain aspects of the disclosure and should not be construed as limiting in any way. Variations in chemical structure, formulation, or processing conditions may be employed, provided they fall within the scope of the disclosure as defined by the claims. Compounds having related structural features may be prepared using the synthetic methods and procedures described herein, with appropriate modifications as would be understood by a person skilled in the art.

[0112] Example (I) 4'-cyano-2,3',5',6-tetrafluoro-[1,1'-biphenyl]-4-yl (E)-4-(2-(5- (dimethylamino)thiophen-2-yl)vinyl)-2-methoxybenzoate

[0113]

[0114] A mixture of methyl 4-(bromomethyl)-2-methoxybenzoate (2000 mg, 1 Eq, 7.719 mmol) and triethyl phosphite (1.347 g, 1.39 ml, 1.05 Eq, 8.105 mmol) was set stirred at 80 °C for 16h under argon, then heated to 120 °C for 1h. Solution was dry loaded onto silica gel and eluted with 2% MeOH in DCM to isolate methyl 4-((diethoxyphosphoryl)methyl)-2-methoxybenzoate.

[0116] A stirred solution of methyl 4-((diethoxyphosphoryl)methyl)-2-methoxybenzoate (700 mg, 1 Eq, 2.21 mmol), 5-(dimethylamino)thiophene-2-carbaldehyde (344 mg, 1 Eq, 2.21 mmol) and 1,4,7, 10, 13-pentaoxa-cyclopentadecane (24.4 mg, 22.3 μL, 0.05 Eq, 111 μmol) in tetrahydrofuran (160 mg, 11.1 mL, 0.2 molar, 1 Eq, 2.21 mmol) was cooled on ice bath under Argon atmosphere, and then sodium hydride (133 mg, 60% wt, 1.5 Eq, 3.32 mmol) was added at once the solution was stirred at 25 °C for 8h. The reaction mixture was carefully divided between ethyl acetate (50 mL) and water (20 mL). The organic phase was washed with brine, dried over Na2CO3 and evaporated in vacuo.

[0117] The organics were dry loaded on silica gel and extracted 20% ethyl acetate / hexane to yield 235 mg of methyl-(E)-4-(2-(5-(dimethylamino)thiophen-2-yl)vinyl)-2-methoxybenzoate as orange crystalline solid. 55POLA.P2010WO (00642386)

[0119] A stirred mixture of methyl (E)-4-(2-(5-(dimethylamino)thiophen-2-yl)vinyl)-2 methoxybenzoate (235 mg, 1 Eq, 740 μmol), lithium hydroxide (53.2 mg, 1.11 mL, 2 molar, 3 Eq, 2.22 mmol) and tetrahydrofuran (53.4 mg, 3.70 mL, 0.2 molar, 1 Eq, 740 μmol) was heated to 60 °C for 16h. The reaction mixture was cooled to 25 °C and acidified with acetic acid and divided between water (10 mL) and ethyl acetate (30 mL). The aqueous phase was extracted with ethyl acetate (2*10 mL), the combined organic phases were washed with water and brine (5 mL each), dried over Na2SO4and evaporated in vacuo to afford an orange microcrystalline solid in nearly quantitative yield.

[0121] To a stirred suspension of (E)-4-(2-(5-(dimethylamino)thiophen-2-yl)vinyl)-2-methoxybenzoic acid (50 mg, 1 Eq, 0.16 mmol) and N,N-dimethylpyridin-4-amine (40 mg, 1 % Wt, 0.02 Eq, 3.3 μmol) in acetonitrile (6.8 mg, 0.82 ml, 0.2 molar, 1 Eq, 0.16 mmol), 3-(((ethylimino)methylene)amino)-N,N- dimethylpropan-1-amine hydrochloride (38 mg, 1.2 Eq, 0.20 mmol) was added at once. Then 2',3,5,6'- tetrafluoro-4'-hydroxy-[1, 1 '-biphenyl]-4-carbonitrile (44 mg, 1 Eq, 0.16 mmol) was added at once to form an orange red, almost clear solution and was left to stir at room temperature for 16h. The reaction mixture was diluted with acetonitrile 5ml and filtered. The precipitate was dissolved with DCM and crystallized from DCM- acetonitrile (1 :1) to yield 4'-cyano-2,3',5',6-tetrafluoro-[1,1'-biphenyl]-4-yl- (E)-4-(2-(5-(dimethylamino)thiophen-2-yl)vinyl)-2-methoxybenzoate as large red crystals (34 mg).

[0122] Example (II) (E)-3,5-dimethoxy-4-(4-nitrostyryl)phenyl 4-hydroxy-2-methoxybenzoate 56POLA.P2010WO (00642386)

[0123]

[0124] A stirred solution of 4-hydroxy-2,6-dimethoxybenzaldehyde (2.00 g, 11.0 mmol, 1.0 equiv) was prepared in N,N-dimethylformamide (5.49 mL, 2.0 M, 11.0 mmol, 1.0 equiv). To the reaction mixture, tert-butyldimethylsilyl chloride (2.48 g, 16.5 mmol, 1.5 equiv) and 1H-imidazole (2.24 g, 32.9 mmol, 3.0 equiv) were added sequentially. The reaction mixture was stirred at ambient temperature overnight.

[0125] The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated, dried over sodium sulfate, and evaporated in vacuo. The crude residue was purified by column chromatography (RediSep Gold 40 g, gradient elution from 0 to 40% ethyl acetate in hexanes) to afford 4-((tert-butyldimethylsilyl)oxy)-2,6-dimethoxybenzaldehyde as a pale solid (2.7841 g, 9.3918 mmol, 85.5%).

[0126]

[0127] A stirred solution of diethyl (4-nitrobenzyl)phosphonate (2.5660 g, 2.07 mL, 9.3918 mmol, 1.0 equiv) and 4-((tert-butyldimethylsilyl)oxy)-2,6-dimethoxybenzaldehyde (2.7841 g, 9.3918 mmol, 1.0 equiv) in tetrahydrofuran (46.959 mL, 0.2 M, 9.3918 mmol, 1.0 equiv) was cooled in an ice bath under an argon atmosphere. Lithium diisopropylamide (LDA, 1.5092 g, 7.0438 mL, 2.0 M in THF / heptane / ethylbenzene, 14.088 mmol, 1.5 equiv) was added at once. The mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate, filtered, and evaporated in vacuo. The crude material was purified by column chromatography (RediSep Gold 80 g, gradient elution from 0 to 30% ethyl acetate in hexanes) to afford (E)-tert-butyl(3,5-dimethoxy-4-(4- nitrostyryl)phenoxy)dimethylsilane as a solid (736.46 mg, 1.7722 mmol, 18.87% yield). 57POLA.P2010WO (00642386)

[0129] A stirred solution of (E)-tert-butyl(3,5-dimethoxy-4-(4-nitrostyryl)phenoxy)dimethylsilane (736.46 mg, 1.7722 mmol, 1.0 equiv) in tetrahydrofuran (8.8611 mL, 0.2 M, 1.7722 mmol, 1.0 equiv) was cooled in an ice bath under an argon atmosphere. Tetrabutylammonium fluoride (TBAF, 1.3901 g, 5.3166 mL of a 1.0 M solution, 5.3166 mmol, 3.0 equiv) was added at once. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium carbonate, filtered, and evaporated in vacuo. The crude residue was purified by column chromatography (RediSep Gold 40 g, eluting with 5% ethyl acetate in dichloromethane) to afford (E)-3,5-dimethoxy-4- (4-nitrostyryl)phenol as a solid (446.12 mg, 1.4807 mmol, 83.55% yield).

[0130]

[0131] A 500 mL round-bottom flask was charged with 2,4-dihydroxybenzaldehyde (5.00 g, 36.2 mmol, 1.0 equiv) and dichloromethane (48.9 mL, 760 mmol, 21.0 equiv). The resulting solution was cooled to 0 °C. Dihydropyran (3.05 g, 3.30 mL, 36.2 mmol, 1.0 equiv) and pyridinium 4- methylbenzenesulfonate (910 mg, 3.62 mmol, 0.1 equiv) were added sequentially. The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The reaction mixture was diluted with dichloromethane (100 mL), then washed sequentially with saturated sodium bicarbonate (2 × 50 mL), water (2 × 40 mL), and brine (40 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (RediSep Gold 80 g cartridge, gradient elution from 0 to 2% methanol in dichloromethane) to afford 2-hydroxy-4-((tetrahydro-2H-pyran-2-yl)oxy)benzaldehyde as a solid (1.39445 g, 6.2745 mmol, 17.3% yield). 58POLA.P2010WO (00642386)

[0132]

[0133] A 20 mL scintillation vial was charged with 2-hydroxy-4-((tetrahydro-2H-pyran-2- yl)oxy)benzaldehyde (1.57388 g, 7.0819 mmol, 1.0 equiv) and N,N-dimethylformamide (7.62 mL, 98.438 mmol, 13.9 equiv). The solution was cooled to 0 °C. Potassium carbonate (1.9574 g, 14.164 mmol, 2.0 equiv) was added, and the reaction mixture was stirred for 15 minutes at 0 °C. Methyl iodide (1.0052 g, 442.8 μL, 7.0819 mmol, 1.0 equiv) was added to the reaction mixture (addition time: February 24, 2025, 11:34:33). The mixture was allowed to warm to ambient temperature and stirred overnight. The reaction was quenched with saturated sodium bicarbonate solution and diluted with dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure.

[0134] The crude material was purified by flash column chromatography (RediSep Gold 80 g cartridge, gradient elution from 0 to 0.25% methanol in dichloromethane) to afford 2-methoxy-4-((tetrahydro-2H- pyran-2-yl)oxy)benzaldehyde as a solid (1.1343 g, 4.8009 mmol, 67.79% yield).

[0135]

[0136] A solution of 2-methoxy-4-((tetrahydro-2H-pyran-2-yl)oxy)benzaldehyde (1.6732 g, 7.0817 mmol, 1.0 equiv) was prepared in a mixture of dimethyl sulfoxide (DMSO, 35.409 mL, 0.2 M, 7.0817 mmol, 1.0 equiv), tetrahydrofuran (THF, 35.409 mL, 0.2 M, 7.0817 mmol, 1.0 equiv), and water (17.704 mL, 0.4 M, 7.0817 mmol, 1.0 equiv), and the solution was cooled to 0 °C. Sodium dihydrogen phosphate monohydrate (3.4202 g, 24.786 mmol, 3.5 equiv) was added, followed by sodium chlorite (2.402 g, 80 wt%, 21.245 mmol, 3.0 equiv). The reaction mixture was allowed to warm to ambient temperature and stirred overnight. The reaction was diluted with ethyl acetate and deionized water. The aqueous layer was acidified with concentrated hydrochloric acid and extracted twice with ethyl acetate. The combined organic extracts were washed five times with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography (RediSep Gold 40 g, gradient elution from 0 to 50% ethyl acetate in hexanes) to afford 2-methoxy-4- ((tetrahydro-2H-pyran-2-yl)oxy)benzoic acid as a solid (0.8764 g, 3.474 mmol, 49.06% yield). 59POLA.P2010WO (00642386)

[0137]

[0138] A 50 mL recovery flask equipped with a magnetic stir bar was charged with (E)-3,5-dimethoxy- 4-(4-nitrostyryl)phenol (143.3 mg, 475.7 μmol, 1.0 equiv), 2-methoxy-4-((tetrahydro-2H-pyran-2- yl)oxy)benzoic acid (120.0 mg, 475.7 μmol, 1.0 equiv), tetrahydrofuran (849.4 μL, 0.56 M, 475.7 μmol, 1.0 equiv), DMAP (18.60 mg, 152.2 μmol, 0.32 equiv), and dicyclohexylcarbodiimide (DCC, 105.0 mg, 509.0 μmol, 1.07 equiv). The reaction mixture was stirred at room temperature overnight. The crude reaction mixture was dry loaded onto silica gel and purified by column chromatography (RediSep Gold 40 g, gradient elution from 0 to 50% ethyl acetate in hexanes). The desired product co-eluted with residual phenol. A second purification was performed by isocratic column chromatography (RediSep Gold 80 g, 5% ethyl acetate in dichloromethane) to afford (E)-3,5-dimethoxy-4-(4-nitrostyryl)phenyl 2-methoxy-4-((tetrahydro-2H-pyran-2-yl)oxy)benzoate as a solid (153.17 mg, 286.01 μmol, 60.13% yield).

[0139]

[0140] (E)-3,5-Dimethoxy-4-(4-nitrostyryl)phenyl-2-methoxy-4-((tetrahydro-2H-pyran-2- yl)oxy)benzoate (153.17 mg, 286.01 μmol, 1.0 equiv) was dissolved in ethanol (572.01 μL, 0.5 M, 286.01 μmol, 1.0 equiv) and tetrahydrofuran (572.01 μL, 0.5 M, 286.01 μmol, 1.0 equiv). The solution was stirred and cooled to 0 °C. Pyridinium p-toluenesulfonate (PPTS, 143.75 mg, 572.01 μmol, 2.0 equiv) was added. The ice bath was removed, and the reaction mixture was heated to 60 °C and stirred for 2 hours. The reaction was diluted with ethyl acetate and water. The aqueous layer was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was identified as (E)-3,5-dimethoxy-4-(4- nitrostyryl)phenyl 4-hydroxy-2-methoxybenzoate (142.13 mg, 314.84 μmol, 110.08% yield).

[0141] Example (III) 4-((3,5-dimethoxy-4-((E)-4-nitrostyryl)phenoxy)carbonyl)-3-methoxyphenyl 4-((E)-(4-((E)-(4-(dimethylamino)-2-isopropoxyphenyl)diazenyl)-2-fluoro-6- methoxyphenyl)diazenyl)-2-isopropoxybenzoate 60POLA.P2010WO (00642386)

[0142]

[0143] The above reaction mixture was stirred overnight and then cooled to room temperature. The mixture was divided between MTBE (40 mL) and water (20 mL). The organic layer was washed sequentially with water, 1 M NaOH, water, and brine (10 mL each). The organic phase was dried over Na₂CO₃, filtered, and concentrated in vacuo. The crude residue was purified by silica gel chromatography (RG120g + 15g sample) using 10–30% EtOAc / hexanes as eluent to afford methyl 4- amino-2-isopropoxybenzoate as a yellowish crystalline solid (1155 mg, 5.520 mmol, 37.33% yield).

[00144]

[0145] To a stirred solution of methyl 4-amino-2-isopropoxybenzoate (410 mg, 1 Eq, 1.96 mmol) in AcOH (1 mL), sulfuric acid (384 mg, 3.92 mL, 1 molar, 2 Eq, 3.92 mmol) was added at once. A clear colorless solution formed. The mixture was cooled on an ice–acetone bath. A solution of sodium nitrite (162 mg, 1.2 Eq, 2.35 mmol) in water (0.5 mL) was added dropwise during 1 min. A yellow solution is observed. Urea (47.1 mg, 50% Wt, 0.2 Eq, 392 μmol) was added after 15 minutes. 3-fluoro-5- methoxyaniline (277 mg, 1 Eq, 1.96 mmol) in MeOH (1 mL) and TFA (0.1 mL) was added after 5 minutes. Slow darkening to orange suspension. Stirred for 3 minutes. Na₂CO₃ (415 mg, 3.92 mL, 1 molar, 2 Eq, 3.92 mmol) was added as a saturated solution. Vigorous foaming observed. Stirred for 5 min, then neutralized with excess Na₂CO₃ and divided between water (20 mL) and EtOAc (30 mL). The organic phase was dried over Na₂CO₃, filtered, and evaporated in vacuo. Chromatography on silica gel (RG40g), eluting with 20→40% EtOAc / hexanes, afforded methyl (E)-4-((4-amino-2-fluoro-6- methoxyphenyl)diazenyl)-2-isopropoxybenzoate (328 mg, 908 μmol, 46.3% yield) as a red crystalline solid. 61POLA.P2010WO (00642386) [0

[0147] To a cold stirred solution of sulfuric acid (1.38 g, 15 Eq, 14.1 mmol) in a cold-water bath, sodium nitrite (97.1 mg, 1.5 Eq, 1.41 mmol) was added in small portions. Significant self-heating occurred. The resulting suspension was stirred for 5 min, then allowed to warm to room temperature and stirred for 1 h until full dissolution. To a stirred suspension of methyl (E)-4-((4-amino-2-fluoro-6- methoxyphenyl)diazenyl)-2-isopropoxybenzoate (339 mg, 1 Eq, 938 μmol) in a mixture of acetic acid (56.3 mg, 4.69 mL, 0.2 M, 1 Eq, 938 μmol) and propionic acid (69.5 mg, 4.69 mL, 0.2 M, 1 Eq, 938 μmol), sulfuric acid (0.14 g, 1.5 Eq) in AcOH (0.5 mL) was added at once. The mixture was cooled on an ice bath. The NOHSO₄ solution from step 1 was added dropwise over 5 min. LCMS after 3 min showed mostly starting material with crystals observed. DCM (5 mL) was added at 5 min, resulting in fast dissolution. Urea (113 mg, 50% Wt, 1 Eq, 938 μmol) was added. The mixture was stirred for 10 min. 3-isopropoxy-N,N-dimethylaniline (202 mg, 1.2 Eq, 1.13 mmol) in AcOH (0.5 mL) was added. The mixture darkened immediately.

[0148] The reaction was transferred into a flask containing Na₂CO₃ (1.99 g, 18.8 mL, 1 M, 20 Eq, 18.8 mmol). Foaming observed. Stirred for 15 min at room temperature, then divided between water (20 mL) and EtOAc (50 mL). The organic phase was dried over Na₂CO₃, filtered, and evaporated in vacuo. Sample dissolved in DCM, loaded on ~10 g silica gel, and dried under air flow in a samplet. Chromatography on silica gel (RG120g), eluting with 40% EA / hexanes, gave clean separation. Lower polarity solvent systems (20% EA or 20% EA + 20% DCM) did not separate isomers. Product isolated as methyl 4-((E)-(4-((E)-(4-(dimethylamino)-2-isopropoxyphenyl)diazenyl)-2-fluoro-6- methoxyphenyl)diazenyl)-2-isopropoxybenzoate (0.25 g, 0.45 mmol, 48% yield).

[0149] 62POLA.P2010WO (00642386)

[0150] A stirred mixture of methyl 4-((E)-(4-((E)-(4-(dimethylamino)-2-isopropoxyphenyl)diazenyl)- 2-fluoro-6-methoxyphenyl)diazenyl)-2-isopropoxybenzoate (0.25 g, 1 Eq, 0.45 mmol), lithium hydroxide (33 mg, 0.68 mL, 2 M, 3 Eq, 1.4 mmol), and tetrahydrofuran (33 mg, 2.3 mL, 0.2 M, 1 Eq, 0.45 mmol) was stirred at 60 °C overnight. The mixture was cooled to room temperature and quenched with acetic acid (0.27 g, 10 Eq, 4.5 mmol). The mixture was divided between water (10 mL) and DCM (40 mL). The organic phase was washed with brine, dried over Na₂SO₄, filtered, and evaporated in vacuo. The resulting amorphous black solid gradually turned into microcrystalline black-golden solid under vacuum to yield 4-((E)-(4-((E)-(4-(dimethylamino)-2-isopropoxyphenyl)diazenyl)-2-fluoro-6- methoxyphenyl)diazenyl)-2-isopropoxybenzoic acid (246 mg, 458 μmol, 100% yield).

[0151]

[0152] (E)-3,5-Dimethoxy-4-(4-nitrostyryl)phenyl 4-hydroxy-2-methoxybenzoate (33.59 mg, 74.41 μmol, 1.0 equiv), tetrahydrofuran (1.00 mL, 12.3 mmol, 166 equiv), 4-((E)-(4-((E)-(4-(dimethylamino)- 2-isopropoxyphenyl)diazenyl)-2-fluoro-6-methoxyphenyl)diazenyl)-2-isopropoxybenzoic acid (40.00 mg, 74.41 μmol, 1.0 equiv), EDC·HCl (17.83 mg, 78.13 μmol, 1.05 equiv), and DMAP (2.727 mg, 22.32 μmol, 0.3 equiv) were charged to a 50 mL recovery flask equipped with a magnetic stir bar. The reaction mixture was stirred at room temperature overnight. The crude reaction mixture was diluted with dichloromethane and water. The aqueous layer was separated and extracted with dichloromethane (3 ×). The combined organic layers were dried over sodium sulfate, filtered, and evaporated under reduced pressure. The crude residue was dry-loaded onto silica gel and purified by column chromatography (Redisep Gold 40 g column) using 5% ethyl acetate in dichloromethane as eluent. The resulting material was further purified by recrystallization from minimal acetonitrile to afford 4-((3,5- dimethoxy-4-((E)-4-nitrostyryl)phenoxy)carbonyl)-3-methoxyphenyl 4-((E)-(4-((E)-(4- (dimethylamino)-2-isopropoxyphenyl)diazenyl)-2-fluoro-6-methoxyphenyl)diazenyl)-2- isopropoxybenzoate as a solid (50.3 mg, 51.8 μmol, 69.6% yield). 63POLA.P2010WO (00642386)

[0153] Example (IV) 2,6-difluoro-4'-nitro-[1,1'-biphenyl]-4-yl 4-((E)-(4-((E)-(7-ethoxy-1-methyl- 1,2,3,4-tetrahydroquinolin-6-yl)diazenyl)-2-methoxyphenyl)diazenyl)-2-methoxybenzoate

[0154]

[0155] A stirred mixture of 4-bromo-3,5-difluorophenol (1.000 g, 4.785 mmol, 1.0 equiv), (4- nitrophenyl)boronic acid (1.198 g, 7.177 mmol, 1.5 equiv), 1,4-dioxane (23.92 mL, 0.2 M, 4.785 mmol, 1.0 equiv), aqueous sodium carbonate (7.177 mL of a 2.0 M solution, 14.35 mmol, 3.0 equiv), and Pd(PPh₃)₄ (552.9 mg, 478.5 μmol, 0.10 equiv) was prepared under argon. The vial was sealed, and the mixture was stirred at 80 °C overnight. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate (50 mL) and water (30 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo. The crude residue was subjected to column chromatography on silica gel (220 g + 15 g samplet) using a gradient elution of 15–20% ethyl acetate in hexanes. A clean separation was achieved between the desired product and a less soluble forepeak impurity (presumed bis(4-nitrophenyl) species, isolated as colorless crystals). To further purify, the crude fractions were dissolved in a 1:1 mixture of methyl tert-butyl ether and hexanes, filtered to remove insoluble material, and evaporated in air. The desired product was obtained as a solid (734 mg, 2.92 mmol, 61.0% yield).

[0156]

[0157] A round-bottom flask was charged with methyl 4-amino-2-methoxybenzoate (400.0 mg, 2.208 mmol, 1.0 equiv) and hydrochloric acid (6.623 mL of a 5.0 M solution, 33.11 mmol, 15.0 equiv). The mixture was cooled to 0 °C. Sodium nitrite (143.5 mg, 2.080 mmol, 0.942 equiv) in distilled water (1.5 mL) was added dropwise over 15 minutes. The reaction was stirred at 0 °C for an additional 15 minutes. The resulting diazonium solution was transferred to a second flask containing 3-methoxyaniline (256.1 mg, 2.080 mmol, 0.942 equiv), acetic acid (4.550 mL, 79.47 mmol, 36.0 equiv), and potassium acetate 64POLA.P2010WO (00642386) (1.062 g, 10.82 mmol, 4.9 equiv), previously cooled to 0 °C. The mixture was stirred for 30 minutes at 0 °C. The reaction was quenched by adjusting the pH to 7 using saturated sodium carbonate solution. The mixture was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by column chromatography (RediSep Gold 40 g cartridge, gradient elution from 0 to 50% ethyl acetate in hexanes) to afford methyl (E)-4-((4-amino-2-methoxyphenyl)diazenyl)-2-methoxybenzoate as a solid (464.79 mg, 1.4740 mmol, 66.77% yield).

[0158]

[0159] A round-bottom flask was charged with methyl (E)-4-((4-amino-2-methoxyphenyl)diazenyl)- 2-methoxybenzoate (200.0 mg, 634.3 μmol, 1.0 equiv) and hydrochloric acid (1.903 mL of a 5.0 M solution, 9.514 mmol, 15.0 equiv). The mixture was cooled to 0 °C. Sodium nitrite (43.76 mg, 634.3 μmol, 1.0 equiv) in distilled water (1.0 mL) was added dropwise over 15 minutes. The reaction was stirred at 0 °C for an additional 15 minutes. The resulting diazonium solution was transferred to a second flask containing 7-ethoxy-1-methyl-1,2,3,4-tetrahydroquinoline (121.3 mg, 634.3 μmol, 1.0 equiv), acetic acid (1.307 mL, 22.83 mmol, 36.0 equiv), and potassium acetate (305.0 mg, 3.108 mmol, 4.9 equiv), previously cooled to 0 °C. The mixture was stirred for 30 minutes at 0 °C. The reaction was quenched by adjusting the pH to 7 using saturated sodium carbonate solution. The mixture was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by column chromatography (RediSep Gold 40 g cartridge, gradient elution from 0 to 2% methanol in dichloromethane) to afford methyl 4-((E)-(4- ((E)-(7-ethoxy-1-methyl-1,2,3,4-tetrahydroquinolin-6-yl)diazenyl)-2-methoxyphenyl)diazenyl)-2- methoxybenzoate as a solid (202.54 mg, 391.31 μmol, 61.70% yield). 65POLA.P2010WO (00642386) [0

[0161] A 20 mL scintillation vial was charged with methyl 4-((E)-(4-((E)-(7-ethoxy-1-methyl-1,2,3,4- tetrahydroquinolin-6-yl)diazenyl)-2-methoxyphenyl)diazenyl)-2-methoxybenzoate (202.54 mg, 391.31 μmol, 1.0 equiv), tetrahydrofuran (782.63 μL, 0.5 M, 391.31 μmol, 1.0 equiv), water (391.31 μL, 1.0 M, 391.31 μmol, 1.0 equiv), and lithium hydroxide monohydrate (98.52 mg, 2.3479 mmol, 6.0 equiv). The reaction mixture was stirred at 60 °C overnight. The reaction was diluted with ethyl acetate and water. The aqueous phase was acidified with glacial acetic acid (6 mL) and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was identified as 4-((E)-(4-((E)-(7-ethoxy-1-methyl-1,2,3,4-tetrahydroquinolin- 6-yl)diazenyl)-2-methoxyphenyl)diazenyl)-2-methoxybenzoic acid (49.07 mg, 97.45 μmol, 24.90% yield).

[0162]

[0163] A 10 mL scintillation vial equipped with a magnetic stir bar was charged with 2,6-difluoro-4'- nitro-[1,1'-biphenyl]-4-ol (24.48 mg, 97.45 μmol, 1.0 equiv), 4-((E)-(4-((E)-(7-ethoxy-1-methyl- 1,2,3,4-tetrahydroquinolin-6-yl)diazenyl)-2-methoxyphenyl)diazenyl)-2-methoxybenzoic acid (49.07 mg, 97.45 μmol, 1.0 equiv), tetrahydrofuran (2.00 mL, 24.7 mmol, 253 equiv), DMAP (11.91 mg, 97.45 66POLA.P2010WO (00642386) μmol, 1.0 equiv), and EDC·HCl (22.23 mg, 97.45 μmol, 1.0 equiv). The reaction mixture was stirred at room temperature overnight. The crude mixture was dry loaded onto silica gel and purified by column chromatography (RediSep Gold 24 g cartridge, gradient elution from 0 to 30% ethyl acetate in hexanes). The isolated material was triturated from methyl tert-butyl ether (MTBE) to afford 2,6-difluoro-4'-nitro- [1,1'-biphenyl]-4-yl 4-((E)-(4-((E)-(7-ethoxy-1-methyl-1,2,3,4-tetrahydroquinolin-6-yl)diazenyl)-2- methoxyphenyl)diazenyl)-2-methoxybenzoate as a solid (49.5 mg, 67.2 μmol, 68.9% yield).

[0164] Example (V) 2,6-difluoro-4'-nitro-[1,1'-biphenyl]-4-yl 4-((E)-(2-fluoro-4-((E)-(7-fluoro-1- methyl-1,2,3,4-tetrahydroquinolin-6-yl)diazenyl)-6-methoxyphenyl)diazenyl)-2-methoxybenzoate

[0165]

[0166] A 150 mL sealed pressure tube was charged with 7-fluoro-1,2,3,4-tetrahydroquinoline (150.0 mg, 992.2 μmol, 1.0 equiv), methyl iodide (154.9 mg, 68.24 μL, 1.091 mmol, 1.1 equiv), potassium carbonate (150.8 mg, 1.091 mmol, 1.1 equiv), and N,N-dimethylformamide (992.2 μL, 1.0 M, 992.2 μmol, 1.0 equiv). The reaction mixture was stirred under an argon atmosphere and heated to 80 °C overnight. The reaction was cooled and quenched by partitioning between water and ethyl acetate. The organic phase was washed five times with water to remove residual DMF, dried over sodium sulfate, decanted, and concentrated in vacuo. The residue was identified as 7-fluoro-1-methyl-1,2,3,4- tetrahydroquinoline (147.86 mg, 894.98 μmol, 90.20% yield) and used without further purification.

[0167] 67POLA.P2010WO (00642386)

[0168] A round-bottom flask was charged with methyl 4-amino-2-methoxybenzoate (500.0 mg, 2.760 mmol, 1.0 equiv). The reaction mi in distilled water (1.5 ditional 15 minutes at ng 3-fluoro- 5-methoxy mmol, 36.0 equiv), and led to 0 °C. The reacti adjusted to approximat e times with dichlorome ltered, andconcentrated in vacuo. The crude residue was purified by normal-phase column chromatography (RediSep Gold 40 g cartridge, gradient elution from 0 to 50% ethyl acetate in hexanes) to afford methyl (E)-4-((4-amino-2-fluoro-6-methoxyphenyl)diazenyl)-2-methoxybenzoate as a solid (507.29 mg, 1.5219 mmol, 55.15% yield).

[0169]

[0170] To stirred sulfuric acid (246 μL, 450.3 mg, 98 wt%, 4.500 mmol, 15.0 equiv) cooled in an ice bath, sodium nitrite (31.05 mg, 450.0 μmol, 1.5 equiv) was added all at once. The resulting suspension was stirred at room temperature for 1 hour, during which full dissolution occurred. In a separate flask, a tirr d n i n f m th l (E)-4-((4- min -2-fl r -6-m th x h n l)di z n l)-2- me m sul sol wtFluoro-1-methyl-1,2,3,4-tetrahydroquinoline (74.35 mg, 450.0 μmol, 1.5 equiv) in acetic acid (1.0 mL) was added to the reaction mixture. Sodium carbonate (4.770 g, 10 wt% solution, 4.500 mmol, 15.0 equiv) was added dropwise, resulting in intense darkening of the reaction mixture to a violet-black color. The reaction was stirred overnight. The mixture was partitioned between dichloromethane and water. The organic phase was washed with 10% sodium carbonate solution, dried over sodium carbonate, and evaporated in vacuo. The crude product was purified by column chromatography (RediSep Gold 24 g 68POLA.P2010WO (00642386) cartridge, gradient elution from 0 to 30% ethyl acetate in hexanes) to afford methyl 4-((E)-(2-fluoro-4- ((E)-(7-fluoro-1-methyl-1,2,3,4-tetrahydroquinolin-6-yl)diazenyl)-6-methoxyphenyl)diazenyl)-2- methoxybenzoate as a solid (12.38 mg, 24.30 μmol, 8.10% yield).

[0171]

[0172] A 20 -1-methyl- 1,2,3,4-tetra 30.47 mg, 59.80 μmol, μL, 1.0 M, 59.80 μmol, quiv). The reaction mix of lithium hydroxide (3 he reaction mixture was cial acetic acid (6 mL) adried over sodium sulfate, filtered, and concentrated in vacuo. The residue was identified as 4-((E)-(2-fluoro-4- ((E)-(7-fluoro-1-methyl-1,2,3,4-tetrahydroquinolin-6-yl)diazenyl)-6-methoxyphenyl)diazenyl)-2- methoxybenzoic acid (33.2 mg, 67.0 μmol, 112% yield). 69POLA.P2010WO (00642386)

[0173]

[0174] A 10 mL scintillation vial equipped with a magnetic stir bar was charged with 2,6-difluoro-4'- nitro-[1,1'-biphenyl]-4-ol (16.8 mg, 67.0 μmol, 1.0 equiv), 4-((E)-(2-fluoro-4-((E)-(7-fluoro-1-methyl- 1,2,3,4-tetrahydroquinolin-6-yl)diazenyl)-6-methoxyphenyl)diazenyl)-2-methoxybenzoic acid (33.2 mg, 67.0 μmol, 1.0 equiv), tetrahydrofuran (3.00 mL, 37.0 mmol, 552 equiv), DMAP (8.19 mg, 67.0 μmol, 1.0 equiv), and EDC·HCl (15.3 mg, 67.0 μmol, 1.0 equiv). The reaction mixture was stirred at room temperature overnight. The crude reaction mixture was dry-loaded onto silica gel and purified by column chromatography (RediSep Gold 24 g cartridge, gradient elution from 0 to 100% ethyl acetate in hexanes). Pure fractions were combined and recrystallized from a minimal amount of acetonitrile to afford 2,6-difluoro-4'-nitro-[1,1'-biphenyl]-4-yl 4-((E)-(2-fluoro-4-((E)-(7-fluoro-1-methyl-1,2,3,4- tetrahydroquinolin-6-yl)diazenyl)-6-methoxyphenyl)diazenyl)-2-methoxybenzoate as a solid (17.0 mg, 23.3 μmol, 34.8% yield).

[0175] Example (VI) 2-methoxy-4'-((E)-4-nitrostyryl)-3'-propoxy-[1,1'-biphenyl]-4-yl 4-((E)-2-(5- (dimethylamino)thiophen-2-yl)vinyl)-2-fluorobenzoate

[0176]

[0177] A suspension of 1-(bromomethyl)-4-nitrobenzene (3269 mg, 1 Eq, 15.13 mmol) in triethyl phosphite (2.640 g, 2.72 mL, 1.05 Eq, 15.89 mmol) was stirred at 80 °C. The mixture was then heated to 100 °C. The reaction was cooled to room temperature and subjected to column chromatography on silica gel (RG120g) using 2% MeOH / DCM as eluent. The desired product, diethyl (4- 70POLA.P2010WO (00642386) nitrobenzyl)phosphonate, was isolated as a yellow oil (4.259 g, 15.59 mmol, 103.0% yield).

[0178] A stirred solution of diethyl (4-nitrobenzyl)phosphonate (500 mg, 1 Eq, 1.83 mmol) in tetrahydrofuran (132 mg, 9.15 mL, 0.2 M, 1 Eq, 1.83 mmol) under argon was cooled in an ice–acetone bath. Lithium diisopropylamide (206 mg, 961 μL, 2 M in THF, 1.05 Eq, 1.92 mmol) was added dropwise over 1 minute. The mixture was stirred for 5 minutes at –10 °C. Solid 4-bromo-2-propoxybenzaldehyde (445 mg, 1 Eq, 1.83 mmol) was added in one portion. The reaction was stirred for 1 hour at 0 °C, then stored in a refrigerator overnight. The reaction mixture was divided between ethyl acetate (50 mL) and water (20 mL). The organic layer was separated, washed with brine (20 mL), dried over Na₂CO₃, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography (RG40g eluting with 2% EtOAc + 20% DCM in hexanes.) Central fractions were combined and concentrated. The residue was recrystallized from EtOH (~10 mL), filtered, washed with cold EtOH, and dried in air to yield (E)-4-bromo-1-(4-nitrostyryl)-2-propoxybenzene (276 mg, 762 μmol, 41.6% yield) as a bright yellow solid.

[0179]

[0180] To a stirred mixture of 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (276 mg, 2 Eq, 1.10 mmol), (E)-4-bromo-1-(4-nitrostyryl)-2-propoxybenzene (200 mg, 1 Eq, 552 μmol), 1,4-dioxane (48.6 mg, 2.76 mL, 0.2 molar, 1 Eq, 552 μmol), aqueous sodium carbonate (176 mg, 828 μL, 2 molar, 3 Eq, 1.66 mmol), and Pd(PPh₃)₄ (63.8 mg, 0.1 Eq, 55.2 μmol), was added to a reaction vial. The mixture was purged with argon, sealed, and stirred at 80 °C. After completion, the mixture was cooled to room temperature and divided between dichloromethane (20 mL) and water (10 mL). The organic layer was 71POLA.P2010WO (00642386) separated, dried over sodium carbonate, filtered, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (RediSep R40g + 10g samplet, eluting with 20→40% ethyl acetate in hexanes) to afford (E)-2-methoxy-4'-(4-nitrostyryl)-3'-propoxy-[1,1'-biphenyl]-4-ol (190 mg, 469 μmol, 84.9% yield).

[0181]

[0182] A suspension of methyl 4-(bromomethyl)-2-fluorobenzoate (263 mg, 1 Eq, 1.06 mmol) in triethyl phosphite (186 mg, 192 μL, 1.05 Eq, 1.12 mmol) was stirred at room temperature. The reaction mixture was heated to 80 °C and stirred overnight. The mixture was further heated to 120 °C for 1 hour. The reaction mixture was cooled to room temperature and purified by column chromatography on silica gel (Redisep Gold 12g cartridge, eluting with 2% MeOH in DCM). Chromatogram was erratic due to pump issue; all fractions were collected and combined. The combined material was concentrated in vacuo to afford methyl 4-((diethoxyphosphoryl)methyl)-2-fluorobenzoate (337 mg, 1.11 mmol, 104% yield) as a colorless heavy oil.

[0183]

[0184] A stirred solution of methyl 4-((diethoxyphosphoryl)methyl)-2-fluorobenzoate (324 mg, 1 Eq, 1.06 mmol) and 5-(dimethylamino)thiophene-2-carbaldehyde (165 mg, 1 Eq, 1.06 mmol) in tetrahydrofuran (76.8 mg, 2.13 mL, 0.5 molar, 1 Eq, 1.06 mmol) was cooled on a dry ice bath under argon atmosphere. Lithium diisopropylamide (137 mg, 639 μL, 2 molar, 1.2 Eq, 1.28 mmol) was added dropwise. The reaction mixture was stirred and allowed to warm to room temperature. After 4 hours, the reaction was deemed complete by LCMS analysis. The mixture was cooled to −20 °C and quenched with a mixture of ethyl acetate (20 mL) and water (5 mL). The resulting mixture was warmed to room temperature, and the layers were separated. The organic layer was washed with water (5 mL) and brine (5 mL), dried over sodium carbonate, filtered, and concentrated in vacuo. The crude material was purified by column chromatography on silica gel (Redisep Gold 24g cartridge, eluting with 20% ethyl 72POLA.P2010WO (00642386) acetate + 20% DCM in hexanes) to afford methyl (E)-4-(2-(5-(dimethylamino)thiophen-2-yl)vinyl)-2- fluorobenzoate (260 mg, 851 μmol, 80.0% yield) as an orange solid.

[0185]

[0186] A stirred mixture of methyl (E)-4-(2-(5-(dimethylamino)thiophen-2-yl)vinyl)-2-fluorobenzoate (260 mg, 851 μmol, 1.0 equiv), lithium hydroxide (61.2 mg, 2.55 mmol, 3.0 equiv, 1.28 mL of 2 M aqueous solution), and tetrahydrofuran (4.26 mL, 0.2 M) was heated at 60 °C and stirred overnight. The reaction mixture was neutralized with acetic acid (256 mg, 4.26 mmol, 5.0 equiv), and partitioned between water (3 mL) and ethyl acetate (30 mL). Solid remained undissolved. The ethyl acetate layer was decanted, filtered, and evaporated to give ~30 mg of crude product. The remaining solid was dissolved in excess 5% MeOH / DCM, filtered, and evaporated in vacuo. The EtOAc extract was boiled in EtOAc (5 mL), cooled to room temperature, and decanted. LCMS showed removal of impurity. The combined product was dissolved in a 1:1 mixture of THF and iPrOH (50 mL) containing 1 M NaOH, forming a yellow, soap-like phase. The suspension was stirred at room temperature over the weekend. The mixture was treated with acetic acid (3 mL) and ultrasonicated. The solid rapidly dissolved, and a red precipitate formed. The mixture was heated to boiling, cooled to room temperature with stirring, filtered, washed with 50% THF, and dried in air. The final product, (E)-4-(2-(5- (dimethylamino)thiophen-2-yl)vinyl)-2-fluorobenzoic acid, was obtained as a red solid (50 mg, 170 μmol, 20% yield).

[0187] 73POLA.P2010WO (00642386)

[0188] To a stirred mixture of (E)-4-(2-(5-(dimethylamino)thiophen-2-yl)vinyl)-2-fluorobenzoic acid (50 mg, 0.17 mmol, 1.0 equiv), N,N-dimethylpyridin-4-amine (21 mg, 0.17 mmol, 1.0 equiv), and (E)- 2-methoxy-4'-(4-nitrostyryl)-3'-propoxy-[1,1'-biphenyl]-4-ol (70 mg, 0.17 mmol, 1.0 equiv) in acetonitrile (0.86 mL, 0.2 M, 0.17 mmol, 1.0 equiv), 3-(((ethylimino)methylene)amino)-N,N- dimethylpropan-1-amine hydrochloride (36 mg, 0.19 mmol, 1.1 equiv) was added in one portion. The reaction mixture was stirred at ambient for 3 days. The mixture was then heated to 50 °C for 3 hours and subsequently cooled to room temperature. The reaction mixture was filtered, and the solid residue was washed with acetonitrile (2 mL), dispersed in dichloromethane, and washed again with dichloromethane. The crude residue was concentrated to approximately 0.5 mL and was crystallized by slow addition of acetonitrile (1 mL). The mixture was heated to boiling, then cooled slowly to room temperature with stirring. The resulting solid was filtered, washed with acetonitrile, and dried in air to provide 2-methoxy-4'-((E)-4-nitrostyryl)-3'-propoxy-[1,1'-biphenyl]-4-yl-4-((E)-2-(5- (dimethylamino)thiophen-2-yl)vinyl)-2-fluorobenzoate (40 mg, 0.06 mmol, 30% yield). EMBODIMENTS

[0189] The following examples pertain to specific embodiments and point out specific features or elements that can be used or otherwise combined in achieving such embodiments.

[0190] Embodiment 1: A liquid crystal composition exhibiting a ferroelectric nematic (NF) liquid crystal phase comprising at least one molecule having a structure A1-L1-A2-L2-(Ax-Ly)n-B (Formula (I)), where n is from 0 to 5 where A1is74POLA.P2010WO (00642386)independently -H, or –(CH2)(0-10-)-(CH3), where D, E, and J are independently -H, -F, -CN, -CF3, -NO2, or -CH=C(CN)2, Z is independently C or N, A is independently -H, -F, -O-(CH2)(0-10)-(CH3), -(CH2)(0-10)-(CH3), -NO2, CN, or CF3, and R3and R4are independently H or F.

[0191] Embodiment 2: The composition of Embodiment 1 having an electro-optic coefficient greater than 5 pm / V.

[0192] Embodiment 3: The composition of Embodiments 1-2, wherein Formula I has a structurehaving a structure selected from either Formula IA1 or Formula IA2(Formula IA1) (Formula IA2).

[0193] Embodiment 4:The composition of Embodiments 3, having the structure of Formula IA2, where A3is an aryl.

[0194] Embodiment 5: The composition of Embodiment 1, wherein Formula I has a structure wherehaving a structure selected from either Formula IA3 or Formula IA4 75POLA.P2010WO (00642386)(Formula IA3) (Formula IA4).

[0195] Embodiment 6: The composition of Embodiment 5, having the structure of Formula IA4, where A3is an aryl,.

[0196] Embodiment 7: The composition of Embodiment 1, wherein Formula I has a structure wherehaving a structure selected from either Formula IA5 or Formula IA6(Formula IA5) (Formula IA6).

[0197] Embodiment 8: The composition Embodiment 7, having a chemical structure of Formula I7A:(Formula I7A).

[0198] Embodiment 9: The composition of Embodiment 7, having the structure of Formula IA6, where A3is an aryl.

[0199] Embodiment 10: The composition Embodiment 9, having a chemical structure of Formula I8A 76POLA.P2010WO (00642386)(Formula I8A).

[0200] Embodiment 11: The composition of Embodiment 1, wherein Formula I has a structure where A1 is(Formula IA7) (Formula IA8).

[0202] Embodiment 12: The composition of Embodiment 9, having the structure of Formula IA8, where A3 is an aryl.

[0203] Embodiment 13: The composition of Embodiment 1, wherein Formula I has a structure where A1 ishaving a structure selected from either Formula IA9 orFormula IB1 77POLA.P2010WO (00642386)(Formula IA9) (Formula IB1) .

[0204] Embodiment 14: The composition of Embodiment 11, having the structure of Formula IB1, where A3 is an aryl.

[0205] Embodiment 15: The composition of Embodiment 1, wherein Formula I has a structure where A1 ishaving a structure selected from either FormulaIB2 or Formula IB3(Formula IB2) (Formula IB3).

[0207] Embodiment 16: The composition of Embodiment 13, having the structure of Formula IB3, where A3 is an aryl. 78

Claims

POLA.P2010WO (00642386) We claim:

1. A ferroelectric nematic liquid crystal (FNLC) compound having a chemical structure of A1-L1-A2-L2-(Ax-Ly)n-B, wherein n is from 0 to 3; A1 has a chemical structure of ; L1is selected from the group consisting of azo, azo oxygen complex, ethene, fluoro-substituted ethene, and acetylene; L2and Lyeach is independently selected from the group consisting of azo, azo oxygen complex, ethene, fluoro-substituted ethene, acetylene, and ester; A2and Axeach is independently selected from the group consisting of thienylene, fused thienylene, thiazolylene, phenylene, naphthalene, azabenzene, fused heterocyclic, and combinations thereof, each of which may be optionally substituted with one or more substituents RC; B is selected from the group consisting of phenylene, naphthalene, thienylene, and fused thienylene, fused heterocyclics, and combinations thereof, each of which may be optionally substituted with one or more substituents RD; and wherein the FNLC compound exhibits a ferroelectric nematic liquid crystal phase.

2. The FNLC compound of claim 1, wherein RA and RB is independently selected from the group consisting of -H and C1-C10 alkyl, either of which may optionally form fused cyclic structure with Ar.

3. The FNLC compound of claims 1 and 2, wherein Ar is selected from the group consisting of thienylene, fused thienylene, phenylene, naphthalene, fused heterocyclics, azabenzene, and combinations thereof, each of which may be optionally substituted with one or more substituents RC, wherein RC is selected from the group consisting of -H, -F, C1–C10 alkoxy, C1- C10 alkyl, -NO2, -CN, and -CF3.

4. The FNLC compound of claim 1, wherein RCis selected from the group consisting of -H, -F, C1–C10alkoxy, C1-C10alkyl, -NO2, -CN, and -CF3. 79POLA.P2010WO (00642386) 5. The FNLC compound of claim 1, wherein RC is selected from the group consisting of -H, -F, C1–C5alkoxy, C1-C5alkyl, -NO2, -CN, and -CF3.

6. The FNLC compound of claim 1, wherein RD is selected from the group consisting of -H, -F, C1–C10 alkoxy, C1-C10 alkyl, -CN, -CF3, -NO2, and -CH=C(CN)2.

7. The FNLC compound of claim 1, wherein RD is selected from the group consisting of -H, -F, C1–C5 alkoxy, C1-C5 alkyl, -NO2, -CN, and -CF3.

8. The FNLC compound of claim 1, wherein A1 is selected from the group consisting of , ,9. The FNLC compound of claim 1, wherein L1,L2and Lyeach is independently selected from the group consisting of10. The FNLC compound of claim 1, wherein A2 and Ax each is independently selected from the group consisting of 80POLA.P2010WO (00642386),81POLA.P2010WO (00642386)12. The FNLC compound of claim 1, wherein the compound demonstrates an electro-optic coefficient greater than 5 pm / V.

13. The FNLC compound of claim 1, wherein the compound demonstrates a λmaxgreater than 400 nm.

14. The FNLC compound of claim 1, wherein the compound forms a glass after heating and cooling.

15. A nonlinear optic element comprising the compound of claim 1.

16. A FNLC composition exhibiting a ferroelectric nematic liquid crystal phase comprising two or more compounds of claim 1.

17. A FNLC compound having a chemical structure of A1-L1-A2-L2-B, wherein A1 is selected from the group consisting of 82POLA.P2010WO (00642386) ,L2 is selected from the group consisting ofA2is selected from the group consisting of, 83POLA.P2010WO (00642386)wherein the FNLC compound exhibits a ferroelectric nematic liquid crystal phase.

18. A FNLC compound having a chemical structure of A1-L1-A2-L2-A3-L3-B, wherein A1is selected from the group consisting of 84POLA.P2010WO (00642386)L2and L3each is independently selected from the group consisting of, ,A2 and A3 each is independently selected from the group consisting of85POLA.P2010WO (00642386)wherein the liquid crystal compound exhibits a ferroelectric nematic liquid crystal phase.

19. A FNLC compound having a chemical structure of A1-L1-A2-L2-A3-L3-A4-L4-B, wherein A1is selected from the group consisting of 86POLA.P2010WO (00642386),A2 through A4 each is independently selected from the group consisting of87POLA.P2010WO (00642386)wherein the FNLC compound exhibits a ferroelectric nematic liquid crystal phase.

20. A FNLC compound having a chemical structure of A1-L1-A2-L2-A3-L3-A4-L4-A5-L5-B, wherein A1is selected from the group consisting of 88POLA.P2010WO (00642386),A2 through A5 each is independently selected from the group consisting of89POLA.P2010WO (00642386),wherein the FNLC compound exhibits a ferroelectric nematic liquid crystal phase.

21. A FNLC compound selected from the group consisting of compounds of Group A, wherein the FNLC compound exhibits a ferroelectric nematic liquid crystal phase. 90

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