Method for the synthesis of acrylate derivatives

Abstract

The disclosure relates to the synthesis of quaternary salts of various acrylates in high yield and high purity.

Description

METHOD FOR THE SYNTHESIS OF ACRYLATE DERIVATIVESCROSS-REFERENCE TO RELATED APPLICATIONS[1] This application claims priority to U.S. provisional patent application No. 63 / 605,837, which was filed on December 4, 2023, and U.S. provisional patent application No. 63 / 652,236, which was filed on May 28, 2024, the disclosures of each of which are hereby incorporated by reference in their entireties.FIELD OF THE INVENTION[2] The present invention relates to an efficient high yield synthesis of acrylate derivatives. The synthesis generally includes a coupling reaction between an activated carbonyl-containing compound and an alcohol, followed by salt formation.BACKGROUND TO THE INVENTION[3] The monomer of 12-methacryloyloxy dodecylpyridinium bromide (MDPB) has been widely used in the field of dentistry due to its antibacterial activity. The known synthesis of MDPB generally involves the formation of a pyridinium salt, which is then coupled with an acid chloride to provide the target compound. The yield and purity of the product vary depending on the specific rea cti on con d i ti ons .[4] A need exists for an improved method which is suitable for the synthesis of various acrylates and derivatives. In particular, the method should be amenable to large scale production.SUMMARY OF THE INVENTION[5] The disclosure relates to the synthesis of quaternary salts of various acrylates in high yield and high purity. The method can be employed in large scale synthesis.[6] Hence, the disclosure relates to a method for synthesizing the compound of Formula (I ),comprising(a) reacting a compound with anhydride (III) "PA in the presence of a base to provide a compound of formula (IV)(b) reacting the compound of formula (IV) with M to provide the compound of Formula (I), whereinR is H or a Cj-6 alkyl;X i s a leaving group n is an integer between 1 and 16, inclusive; andM is a tertiary amine, a triaryl phosphine or a heteroaryl.DETAILED DESCRIPTION OF THE INVENTION[7] The disclosure relates to a method of synthesizing acrylate derivatives, and specifically 12-methacryloyl oxydodecyl pyridinium bromide (MDPB)[8] The disclosure relates to a method of making a compound of formula (I):whereinR is H or a Cur, alkyl,X is a leaving group; n is an integer 1 to 16, inclusive; andM is a tertiary amine, a tri aryl phosphine or a heteroaryl.[9] In some embodiments, R is H. In some embodiments, R is Cnf, alkyl. In some embodiments, R is Ciu alkyl. In some embodiments, R is methyl.

[0010] In some embodiments, M is a tertiary amine, which can be a cyclic or n on- cyclic amine. Non-limiting examples include N-methylmorpholine, trimethylamine, diethylamine, N-alkylpiperidine, and N-alkylmorpholine. Insome embodiment, M is heteroaryl which contains a nitrogen having a lone electron pair capable of being protonated. In some embodiments, the heteroaryl is optionally substituted pyridine, or imidazole. The heteroaryl can have one, two or three substituents such as Cvralkyl, halogen, hydroxyl, (foualkynyl, (CH2)nCF3OCHF2, OCF3, C3-6 cycloalkyl, O(CH2)nC3-6 cycloalkyl, amide, reverse amide, ester, ketone, NO2, CN, amino, sulfonate, sulfonamide, ether, Cwo heterocyclyl, C6-10 aryl, OC6-10 aiyl, and OC5-10 heterocyclyl. Heterocyclyl includes heteroaryl and non-aromatic rings containing one or more heteroatoms. Non-limiting examples of substituted pyridines include para-dimethyl amino pyridine, 2- fluoropyridine, 3 -fluoropyridine, 4-11 uoropyri dine, 4-(trifluoromethyl)pyridine, 3-(trifluoromethyr)pyridine, 2-(trifluoromethyl)pyridine, 4-methylpyridine, 3- m ethylpyridine, 2-m ethylpyridine, 3 ,4-dimethy 1 py ridi ne, 2,4-dimethylpyri dine, 2,3-dimethylpyridine, 2,5-dimethylpyridine, 2,6-dimethylpyridine, perfluoropyridine, 2-methoxypyridine, 3-meihoxypyridine, and 4- methoxy pyridine. In some embodiments, M is a triaryl phosphine. Examples of aryl groups include but are not limited to phenyl, tolyl, and naphthyl.

[0011] X is a leaving group which includes for example trifluoromethanesulfonate (OTf), p-toluenesulfonate (OTS), methanesulfonate (MsO) and a halogen which can be chlorine, bromine, or Iodine. In embodiments, X is chlorine. In embodiments, X is bromine.

[0012] The integer n is any number between 1 and 16 such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. 11, 12, 13. 14, 15, and 16. In embodiments, n is anv number between I and 5. In embodiments, n is any number between 6 and 12. In embodiments, n is any number between 8 and 12. In embodiments, n is any number between 10 and 12. In embodiments, n is any number between 6 and 14. In embodiments, n is any number between 8 and 14. In embodiments, n is any number between 6 and 16. In embodiments, n is any number between 8 and 16. In embodiments, 11 is 11, R is methyl, M is pyridine, and X is bromine.

[0013] The synthesis of compound of Formula (I) comprises reacting a compound of formula (II) with an anhydride (III) to provide a compound of formula (IV) (Scheme 1).Scheme 1

[0014] The reaction is conducted in the presence of a base. Suitable bases include, but are not limited to trimethylamine, diisopropyl ethylamine, 4- dimethylaminopyridine and pyridine. In some embodiments, the base is trimethylamine. The reaction can be conducted in the presence of triethylamine amine (TEA) and 4-dimethyla.minopyridine (DM AP). The reaction can be carried out in the presence of a solvent. Solvents can be for example toluene, tetrahydrofuran, alcohols or chlorinated hydrocarbons such as methylene chloride. The solvent can be dichloromethane (DCM). The reaction can be carried out at room temperature. The reaction can be carried below room temperature. In some embodiments, the reaction mixture is quenched with a solution of NaHCCh, for example 20% NaHCO3, 50% NaHCO3In some embodiments, the reaction mixture can be further washed with NaHCO3, for example 20% NaHCO3, 50% Na2CO?,. The resulting reaction mixture can be further dried. In some embodiments, the reaction mixture can further be treated with Na^SCA and / or MgSOv In some embodiments, the reaction mixture can be further washed with a solution of NaCI for example 20% NaCI, 100% NaCI. In some embodiments, the reaction mixture can further be filtered through a pad of silica gel. The reaction can be conducted at. room temperature. The reaction can be conducted for 10 to 30 hours. In embodiments, the compound of formula (III) is methacrylate anhydride. In embodiments, X is Br. In embodiments n is 1 1. In embodiments, n is 11, R is methyl, and X is bromine

[0015] The preparation of a compound of formula (I) can also comprise reaction a compound of formula (II) with an acid (V) in the presence of an acid (Scheme 2).Scheme 2

[0016] The reaction can be conducted in the presence of a solvent. The solvent can be dichloromethane. In some embodiments, the acid is concentrated sulfuric acid. In some embodiments the reaction is conducted at about 50 °C. In some embodiments, a compound of formula (II) is treated with an acid of formula (V) at room temperature and then concentrated sulfuric acid is added without presence of solvent.

[0017] The reaction can be conducted in the presence of a solvent. The solvent can be dichloromethane. In some embodiments, the acid is concentrated sulfuric acid. In some embodiments the reaction is conducted in the presence of an acid at about 40-80 °C. In some embodiments the reaction is conducted in the presence of an acid at about 40 °C. In some embodiments the reaction is conducted in the presence of an acid at about 45 °C. In some embodiments the reaction is conducted in the presence of an acid at about 50 °C. In some embodiments the reaction is conducted in die presence of an acid at about 55 °C. In some embodiments the reaction is conducted in the presence of an acid at about 60 °C. In some embodiments the reaction is conducted in the presence of an acid at about 70 °C. In some embodiments the reaction is conducted in the presence of an acid at about 80 °C.

[0018] The synthesis of compound of formula (I) can further comprise reacting a compound of formula (IV) with VI (Scheme 3).Scheme 3

[0019] The reaction can be conducted in the presence of a solvent. The solvent can be M. M can be pyridine. In some embodiments, where no additional solvent is present, pyridine serves as a reactant as well as a solvent. In embodiments, n is 11 , R is methyl, VI is pyridine, and X is bromine

[0020] The reaction can be conducted at room temperature. The reaction can be heated. The temperature of the reaction can be from about 30-60 °C. The temperature of die reaction can be from about 45-50 °C. The temperature can be about 45 °C.

[0021] After completion of the reaction, removal of M can be done by concentration under reduced pressure. For example, pyridine can be removed by rotary evaporation. The temperature for pyridine removal is controlled at about 10-35 °C. In some embodiments, the temperature for pyridine removal is controlled at about 30 ° C. Purification of the compound of formula (I) can further comprise addition of a solvent, sonication, stirring and decanting of the solvent. The solvent can be methyl tertiary-butyl ether (M I BE). Purification of the compound of formula (I) can further comprise seeding. Purification of the compound of formula (I) can further comprise recrystallization. Recrystallization can comprise seeding. Recrystallization can be done at room temperature or can be cooled. The recrystallization can be done at about -20° C.Certain Definitions

[0022] As used in the description and the appended claims, the singular forms “a” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a composition” includes mixtures of two or more such compositions, reference to “an agent” includes mixtures of two or more such agents, reference to “the component” includes mixtures of two or more such components, and the like.

[0023] The term “about” when immediately preceding a numerical value means a range (e.g., plus or minus 10% of that value). For example, “about 50” can mean 45 to 55, “about 25,000” can mean 22,500 to 27,500, etc., unless the context of the disclosure indicates otherwise, or is inconsistent with such an interpretation. For example, in a list of numerical values such as “about 49, about 50, about 55, ...”, “about 50” means a range extending to less than half the interval(s) between the preceding and subsequent values, e.g., more than 49.5 to less than 52.5. Furthermore, the phrases “less than about” a value or “greater than about” a value should be understood in view of the definition of the term “about” provided herein. Similarly, the term “about” when preceding a series of numerical values or a range of values (e.g., “about 10, 20, 30” or “about 10-30”) refers, respectively to all values in the series, or the endpoints of the range.

[0024] As used herein “aromatic” refers to an unsaturated cyclic molecule having 4n + 2 n electrons, wherein n is any integer. The term “non-aromatic” refers toany unsaturated cyclic molecule which does not fall within the definition of aromatic.

[0025] “Alkyl”, “alkyl chain” or “alkyl group” refer to a fully saturated, straight or branched hydrocarbon chain radical having from one to forty carbon atoms, and which is attached to the rest of the molecule by a single bond. Alkyls comprising any number of carbon atoms from 1 to 40 are included. An alkyl comprising up to 40 carbon atoms is a C1-C40 alkyl, an alkyl comprising up to 10 carbon atoms is a C1-C10 alkyl, an alkyl comprising up to 6 carbon atoms is a C1-C6 alkyl and an alkyl comprising up to 5 carbon atoms is a C1-C5 alkyl. A C1-C5 alkyl includes C5 alkyls, C4 alkyls, C3 alkyls, C2 alkyls and Ci alkyl (i.e., methyl). A C1-C6 alkyl includes all moieties described above for C1-C5 alkyls but also includes C6 alkyls. A C1-C10 alkyl includes all moieties described above for C1-C5 alkyls and Ci-C6 alkyls, but also includes C7, C8, C9 and C10 alkyls. Similarly, a C1-C12 alkyl includes all the foregoing moieties, but also includes C11 and C12 alkyls. Non- limiting examples of C1-C12 alkyl include methyl, ethyl, n -propyl, i-propyl, sec- propyl, n -butyl, i-butyl, sec-butyl, t-butyl, n -pentyl, t-amyl, n -hexyl, n -heptyl, n- octyl, n -nonyl, n -decyl, n -undecyl, and n -dodecyl. Unless stated otherwise specifically in the specification, an alkyl group can be optionally substituted.

[0026] “Aryl” refers to a hydrocarbon ring system radical comprising hydrogen, 6 to 18 carbon atoms and at least one aromatic ring. For purposes of this invention, the aryl radical can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include fused or bridged ring systems. Aryl radicals include, but are not limited to, aryl radicals derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. Unless stated otherwise specifically in the specification, the term “aryl” is meant to include aryl radicals that are optionally substituted.

[0027] “Heteroaryl” refers to a 5 to 20 membered ring system radical comprising hydrogen atoms, one to thirteen carbon atoms, one to six heteroatoms selected from nitrogen, oxygen and sulfur, and at least one aromatic ring. For purposes of this invention, the heteroaryl radical can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include fused or bridged ring systems; and thenitrogen, carbon or sulfur atoms in the heteroaryl radical can be optionally oxidized; the nitrogen atom can be optionally quatemized. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodi oxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[Z>][l,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodi oxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotri azolyl, benzo[4,6]imidazo[l,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2- oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1- oxidopyrazinyl, 1-oxidopyridazinyl, 1 -phenyl - 1 H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e. thienyl). Unless stated otherwise specifically in the specification, a heteroaryl group can be optionally substituted.

[0028] The term “substituted” used herein means any of the above groups (i.e., alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclyl, aryl, heteroaryl, alkoxy, aryloxy, acyl, alkylcarbamoyl, alkylcarboxamidyl, alkoxycarbonyl, alkylthio, or arylthio) wherein at least one atom is replaced by a non-hydrogen atoms such as, but not limited to: a halogen atom such as F, Cl, Br, and I; an oxygen atom in groups such as hydroxyl groups, alkoxy groups, and ester groups; a sulfur atom in groups such as thiol groups, thioalkyl groups, sulfone groups, sulfonyl groups, and sulfoxide groups; a nitrogen atom in groups such as amines, amides, alkylamines, dialkylamines, arylamines, alkylarylamines, diarylamines, N-oxides, imides, and enamines; a silicon atom in groups such as trialkylsilyl groups, dialkylarylsilyl groups, alkyldiarylsilyl groups, and triarylsilyl groups; and other heteroatoms in various other groups. “Substituted” also means any of the above groups in which one or more atoms are replaced by a higher-order bond (e.g., a double- or triple-bond) to a heteroatom such as oxygenin oxo, carbonyl, carboxyl, and ester groups; and nitrogen in groups such as imines, oximes, hydrazones, and nitriles. For example, “substituted” includes any of the above groups in which one or more atoms are replaced with -NRgRh, -NRgC(=0)Rh, -NRgC(=0)NRgRh, -NRgC(=0)0Rh, -NRgSO2Rh, - 0C(=0)NRgRh, -0Rg, -SRg, -SORg, -SO2Rg, -OSO2Rg, -SO2ORg, =NSO2Rg, and -SO2NRgRh. “Substituted also means any of the above groups in which one or more hydrogen atoms are replaced with -C(=0)Rg, -C(=0)0Rg, -C(=0)NRgRh, -CH2SO2Rg, -CH2SO2NRgRh. In the foregoing, Rgand Rh are the same or different and independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, thioalkyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclyl, N -heterocyclyl, heterocyclylalkyl, heteroaryl, / f-heteroaryl and / or heteroarylalkyl. “Substituted” further means any of the above groups in which one or more atoms are replaced by an amino, cyano, hydroxyl, imino, nitro, oxo, thioxo, halo, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, thioalkyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclyl, N-heterocyclyl, heterocyclylalkyl, heteroaryl, N- heteroaryl and / or heteroarylalkyl group. “Substituted” can also mean an amino acid in which one or more atoms on the side chain are replaced by alkyl, alkenyl, alkynyl, acyl, alkylcarboxamidyl, alkoxycarbonyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl. In addition, each of the foregoing substituents can also be optionally substituted with one or more of the above substituents.EXAMPLES

[0029] Summary of synthesis of MDPB:Stepl : Synthesis of Compound 3

[0030] To an oven-dried 500 mL single neck round bottom flask was added 12- bromododecanol 1 (30 g, 113.1 mmol) and anhydrous dichloromethane (210 mL) while under argon. This solution was treated with methacrylic anhydride (1.1 eq., 18.5 mL, 124.4 mmol) via dropwise, followed by dropwise addition of triethylamine (1.3 eq., 20.5 mL, 147 mmol) and DMAP (3 mol%, 0.42 g, 3.4 mmol) at room temperature under argon. The light brown reaction solution was stirred for 25h at room temperature under argon. An aliquot (50 μL) from the reaction mixture was concentrated under reduced pressure and dried in vacuo for 30 min. 1H NMR (CDCl3showed that the reaction was complete and contained less than 5% of 12-bromodocanol. The resulting solution was diluted with dichloromethane (180 mL) and quenched with 50% NaHCO3solution (180 mL). The organic layer was separated, washed with 50% NaHCO3solution (180 mL) followed by 50% Na2CO3solution (180 mL, x2), 80% NaHCO3(180 mL, x1), H2O (180 mL, x1) and brine solution (180 mL, x1). The resulting organic layer was dried on anhydrous sodium sulfate, which was filtered through a pad of silica gel (2-inch in 600 mL sintered flask, F Frit) using anhydrous dichloromethane. The solution was concentrated in vacuo to afford 32.4 g (86%) of compound 3 as a pale brown oil, which was used in the next step without further purification.1H NMR (300 MHz, CDCh) d 1.25-1.42 (m, 16H), 1.60-1.67 (m, 2H), 1.78-1.87 (m, 2H), 1.92 (s, 3H), 3.36-3.41 (t, J= 6.9 Hz, 2H), 4.08-4.13 (t, J= 7.2 Hz, 2H), 5.52- 5.53 (m, 1H), 6.08 (m, 1H).Step 2: Synthesis of MDPB, Compound 4

[0031] In a 500 mL single neck round bottom flask, the above compound 3 (27.3 g, 81.9 mmol) was dissolved in anhydrous pyridine (6.0 eq, 39.8 mL, 491.5 mmol), and stirred for 10 mins at room temperature under argon. The reaction mixture was heated overnight at 45°C using a heating block while under argon. The progress of the reaction was monitored by LC / MS and the reaction was complete after 25h based on the complete disappearance of compound 3. The reaction mixture was cooled at ambient temperature and concentrated to remove excess pyridine at 30°C water bath under reduced pressure. The crude viscous oil was treated with distilled anhydrous MTBE* (335 mL), then sonicated for 30 seconds, followed by stirring at room temperature for 30-60 min under argon. Themixture was settled without stirring to allow for two layers to form (approx. 10 minutes). Most of the MTBE layer (top) was decanted and discarded. This process of MTBE addition, sonication, stirring and decanting was repeated three times using 335 mL of distilled anhydrous MTBE* each time. The bottom layer, which was almost filter cake, was diluted with 50 mL of anhydrous MTBE*. The resulting mixture was stirred at room temperature for 15 min and stabilized under argon to give a clear MTBE layer and white filter cake. Then, pure MDPB (0.3 g) was seeded to the mixture and kept in the refrigerator (-20°C) overnight. The following day, the slurry was collected by filtration using a 600 mL sintered funnel (Fine Frit) under a nitrogen flush and washed with MTBE. The collected solid was dried in vacuo to afford 30.9g (91%) of MDPB 4 as a white solid (purity >99%). Calcd for C2iH34BrNO2(FW = 412.40 g / mol): C2iH34NO2+(Br salt) 332.26 g / mol (M+H)+; 333.26, Found: 332.35, 1H NMR (300 MHz, CDC13) d 1.26-1.36 (m, 16H), 1.64 -1.70 (m, 2H), 1.95 (s, 3H), 1.96-2.09 (m, 2H), 4.12-4.17 (t, J = 6.3 Hz, 2H), 5.04-5.09 (t, J= 7.5 Hz, 2H), 5.56-5.57 (m, 1H), 6.11 (m, 1H), 8.10-8.15 (t, J= 7.2 Hz, 2H), 8.48-8.53 (t, J= 7.8 Hz, 1H), 9.49-9.50 (d, J= 5.1 Hz, 2H). *MTBE solvent purification: The benzophenone / ketyl still was used to produce moisture, oxygen, and peroxide free tert-methyl butyl ether (MTBE). The glassware and stir bar used were oven-dried and purged with inert gas (N2). The MTBE used was either purchased as an anhydrous grade or was pre-dried overnight over molecular sieves (3 or 4 Å). All joints were sealed using polytetrafluoroethylene (PTFE) sleeves.

[0032] While under the hood, a block of sodium metal was extracted from the container using forceps and placed on a dry area. The sodium block was rinsed with a minimum amount of hexanes to remove the oil / kerosene. A clean and dry razor blade was used to slice the sodium block into thin slices such that they fit in the neck of the round bottom flask (3L, 3-neck round bottom flask). The sodium pieces (approximately 5 g) were added to the flask and the flask was sealed while under N2; any sodium shavings, the forceps, and the area used to slice the sodium were rinsed with isopropyl alcohol, followed by methanol, and then H2O. Approximately 30 g of benzophenone and 2 L of MTBE, as well as a stir bar, were added to the round bottom flask. The flask was properly sealed into position of thestill setup and the heating mantle was slowly ramped up until the MTBE began to simmer. The mixture was refluxed for several hours until the deep blue color of benzophenone ketyl forms (Na[Ph2O]). The distilled solution was then collected in the distillation head and transferred to an oven-dried 2 neck round bottom flask that has been purged with N2.

Claims

CLAIMSWe claim:

1. A method of synthesizing the compound of formula (I),O comprising(c) reacting a compoundwith an anhydride of formula (III in the presence of a base to provide a compound of formula ; and(d) reacting the compound of formula (IV) with M to provide the compound of formula (I), whereinR is H or a C 1 -C6 alkyl;X is a Cl, Br, I, OTf. OMs or OTs;R’ is hydrogen, Ci-6 alkyl or aryl n is an integer between 1 and 16, inclusive, andM is a tertiary amine or is selected from the group consisting of pyridine, para-dim ethylamino pyridine, 2-fluoropyridine, 3-fluoropyridine, 4- fluoropyridine, 4-(trifluoromethyl)pyridine, 3-(trifluoromethyl)pyridine, 2- (trifluoromeihyl)pyridine, 4~methyl pyridine, 3 -methylpyridine, 2- methylpyridine, 3,4-dimethylpyridine, 2,4-dimethylpyridine, 2,3- dimethylpyridine, 2,5-dimethylpyridine, 2,6-dimethylpyridine, perfluoropyridine, 2 --methoxypyridine, 3-methoxypyridine, 4-methoxypyridine, and N -methyImorpholine .

2. The method of claim 1, wherein R is methyl.

3. The method of any one of claims 1-2, wherein n is 11.

4. The method of any one of claim 1-3, wherein X is Br.

5. The method of any of claims 1-4, wherein M is pyridine.

6. The method of claim 1, wherein R is methyl, n is 11, X is Br, and M is pyridine.

7. The method of any one of claims 1-6, wherein step (a) further comprises a solvent.

8. The method of claim 7, wherein the solvent is dichloromethane.

9. The method of any one of claims 1-8, wherein the base is tri ethylamine and DMAP.

10. The method of any one of claims 1-9, wherein step (a) is performed at room temperature.

11. The method of any one of claims 1-10, wherein step (b) is performed at about 45° C.

12. The method of any one of claims 1-11, wherein step (b) further comprises removing excess pyridine under a temperature of about 30° C.

13. The method any one of claims 1-12, wherein step (b) further comprises purifying the compound of Formula I by recrystallization in methyl tertiary butyl ether.

14. A method of synthesizing 12-methacryloyl oxy dodecylpyridinium bromide (MDPB) comprising(a) reacting 12-bromododecanol with methacrylic anhydride in the presence of triethylamine and DM AP in the presence of dichloromethane to provide a compound of formula (3)(b) reacting the compound of formula (3) with pyridine to provideMDPB.

15. The method of claim 14, wherein step (a) is performed at room temperature.

16. The method of claim 14 or 15, wherein step (b) is performed at about 45° C.

17. The method of any one of claims 14-16, wherein step (b) further comprises removing excess pyridine under a temperature of about 30° C.

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