WO2016191682A1 - Preparation of acid chlorides from 5-(chloromethyl) furfural - Google Patents

Abstract

Acid chloride derivatives of 5-(chloromethyl)furan-2-carboxylic acid and furan-2,5-dicarboxylic acid (FDCA) can be produced in high yield by treatment of the precursor aldehydes 5-(chloromethyl)furfural (CMF) and 2,5-diformylfuran (DFF) with tert-butyl hypochlorite, which is inexpensively prepared from commercial bleach and tert-butanol. 5-(Chloromethyl)furan-2-carbonyl chloride (CMFCC) and furan-2,5-dicarbonyl chloride (FDCC) are highly useful intermediates for the production of furoate ester biofuels and polymers of FDCA.

Description

PREPARATION OF ACID CHLORIDES FROM 5-(CHLOROMETHYL) FURFURAL CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application No. 62/167,651, filed May 28, 2015, which is incorporated herein by reference in its entirety. BACKGROUND

[0002] Few renewable polymers have made as forceful an impact on the landscape of petroleum alternatives as polyethylene furanoate (PEF). Serving both as a novel replacement for the high-volume polymer polyethylene terephthalate (PET) and a good alternative to bio-based PET, PEF is poised to make strong inroads into the PET market, due mainly to its outstanding performance (gas-barrier and mechanical properties), recyclability, and biodegradability

(Furandicarboxylic Acid (FDCA), A Versatile Building Block for a Very Interesting Class of Polyesters. In Biobased Monomers, Polymers, and Materials; ACS Symposuim Series 1105; American Chemical Society: Washington, DC, 2012; pp 1í13; Macromolecules, 2014, 47, 1383). Much of the present interest in PEF has been fueled by advances in the availability of the furan-2,5-dicarboxylic acid (FDCA) monomer 1. Currently, the most efficient routes to FDCA are exclusively based on the oxidation of 5-(hydroxymethyl)furfural (HMF) 2 (Catal. Surv. Asia, 2012, 16, 164; Appl. Catal. A: Gen., 2010, 385, 1). Uncertainties however regarding the economics of HMF production on a commercial scale have been a source of continuing speculation as to whether it can live up to its promise as a renewable platform molecule (Chem. Rev., 2013, 113, 1499). Difficulties specifically with its production from any feedstock other than fructose, and its isolation from the media in which it is produced, have no industrially practical resolutions to date. [0003] Furans presenting a single carboxylic acid function have also been singled out as precursors to high-performance furoate ester biofuels (U.S. Application Publication No.

2015/0047251), polymers (J. Polym. Sci., Polym. Chem. Ed., 1984, 22, 863), and fragments of cytokine interleukin-2 inhibitors (J. Am. Chem. Soc., 2003, 125, 3714) and anti-leukemia agents (Bioorg. Med. Chem., 2007, 15, 1732). Substituted furoic acids are, in general, also approached synthetically via HMF by selective oxidation of the aldehyde group (Green Chem., 2014, 16, 2762). [0004] 5-(Chloromethyl)furfural (CMF) 3 has been advanced as a functionally equivalent alternative to HMF that can be produced in high yield directly from raw biomass and, due to its hydrophobic character, presents no problems in its isolation (Angew. Chem. Int. Ed., 2008, 47, 7924; ChemSusChem, 2009, 2, 859). Here, we demonstrate that CMF can be oxidized simply and directly to its corresponding acid chloride 5-(chloromethyl)furan-2-carbonyl chloride (CMFCC) 4 and that CMF-derived 2,5-diformylfuran (DFF) 10 can likewise be oxidized to the diacid chloride furan-2,5-dicarbonyl chloride (FDCC) 11, both of which are highly versatile synthetic intermediates for a range of green chemical derivatives. [0005] The synthetically versatile acid chlorides CMFCC 4 and FDCC 11 are two and three simple, efficient steps removed from raw biomass, respectively, being derived from the HMF- equivalent platform chemical CMF 3. Although furan-2-carboxylates and furan-2,5- dicarboxylates have been produced from HMF, the process is burdened by the poor accessibility of HMF from biomass. The opportunity to access these acids, which are platform chemicals in their own right, in the form of soluble, conveniently derivatizable acid chlorides, will serve to broaden the scope of commercially relevant biorefinery products that can be derived from carbohydrates. BRIEF SUMMARY OF THE INVENTION

[0006] In one embodiment, the present invention provides a method of preparing a compound of Formula I:

(I)

the method comprising forming a reaction mixture of tert-butyl hypochlorite and a compound of Formula II:

(II) under conditions sufficient to form the compound of Formula I, wherein R is selected from the group consisting of–CH₂Cl and–C(O)H.

[0007] In a second embodiment, the present invention provides a method of preparing a compound of Formula II having the structure:

the method comprising forming a reaction mixture comprising Bi(NO₃)₃Ɣ5H₂O and a compound having the structure:

under conditions sufficient to form the compound of Formula II.

[0008] In a third embodiment, the present invention provides a method of preparing a compound of having the structure:

the method comprising forming a reaction mixture comprising ethanol and a compound having the structure:

wherein the reaction mixture is heated at a temperature of at least about 100 °C in a closed vessel, thereby forming the compound.

[0009] In a fourth embodiment, the present invention provides a compound selected from the group consisting of:

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 shows [M1]the structures of furan-2,5-dicarboxylic acid (FDCA) 1, 5- (hydroxymethyl)furfural (HMF) (2), and 5-(chloromethyl)furfural (CMF) (3). [0011] Figure 2 shows preparation of compound 5 from compound 3 where the reagents and conditions include a) t-BuOCl, 24 h; b) EtOH, 50 °C, 6 h, 82% over 2 steps. [0012] Figure 3 shows preparation of compounds 6, 7, 8 and 9 from compound 5 where the reagents and conditions include a) EtOH, 150 °C, 7 h, 96%; b) H₂, Pd/C, 2.5 h, 86%; c) BnNH₂, 50 °C, 24 h, 82%; d) 1,3,5-Me₃Ph, AlCl₃, 24 h, 95%. [0013] Figure 4 shows preparation of compounds 11, 12 and 13 from compound 3 where the reagents and conditions: a) DMSO, 150 °C, 18 h, 81%; b) t-BuOCl, 24 h; c) EtOH, 50 °C, 6 h; 76% over 2 steps; d) PhH, AlCl₃, 20 h, 66% over 2 steps. [0014] Figure 5 shows preparation of compound 10 from compound 3 using Bi(NO₃)₃Ɣ5H₂O catalyst. DETAILED DESCRIPTION OF THE INVENTION I. GENERAL [0015] The present invention is drawn to a method of preparing furan acid chlorides from furfurals using tert-butyl hypochlorite. The present invention also includes a method for preparing 2,5-diformylfuran from 5-(chloromethyl)furfural using Bi(NO₃)₃Ɣ5H₂O. Several ethyl furan-2-carboxylates are also provided. II. DEFINITIONS [0016] “Forming a reaction mixture” refers to the process of bringing into contact at least two distinct species such that they mix together and can react, either modifying one of the initial reactants or forming a third, distinct, species, a product. It should be appreciated, however, the resulting reaction product can be produced directly from a reaction between the added reagents or from an intermediate from one or more of the added reagents which can be produced in the reaction mixture. [0017] “Bismuth catalyst” refers to a bismuth containing compound capable of increasing the rate of a particular chemical reaction. The bismuth catalyst is regenerated following each chemical transformation, so a less than equimolar amount is required in the chemical reaction. The bismuth can have any suitable oxidation state, including I, II, III, IV and V. [0018] “A closed vessel” refers to a reaction vessel that is sealed such that the pressure within the closed vessel can be greater than atmospheric pressure. [0019] “Without exposure to visible light” refers to the absence of light having wavelength(s) between about 400 nm and about 750 nm. III. METHODS OF PREPARING ACID CHLORIDE COMPOUNDS [0020] The direct conversion of aldehydes to acid chlorides can be conveniently achieved using tert-butyl hypochlorite (t-BuOCl) (Handbook of Reagents for Organic Synthesis: Catalytic Oxidation Reagents, P. L. Fuchs, Ed., 2013, pp.126-132). Although not frequently used in synthesis, the transformation involves the solvent-free reaction between the reagent and the aldehyde by stirring at room temperature. The tert-Butyl hypochlorite reagent can be produced in high yield in the course of a few minutes by mixing household bleach, acetic acid, and tert- butanol (Org. Synth., 1969, 49, 9). The reagent is isolated in a pure state by simply separating phases. In effect, the t-butanol becomes a carrier of the bleach and enables it to work in a hydrophobic environment. [0021] The reaction between CMF and t-BuOCl to give CMFCC 4 is shown in Scheme 1. Quantitative analysis by NMR using an internal standard indicated a CMFCC yield of 85%. Although 4 can be isolated, in practice, there is no real advantage in doing this, since acid chlorides are only ever intermediates en route other carboxylic acid derivatives. Thus, for the purposes of demonstration, the product was quenched into ethanol to give the ethyl ester 5 and the isolated yield over both steps is reported which, in this case, is 82%. [0022] One thing that immediately stood out was the enhanced stability of the chloromethyl group in 5 compared to that of CMF 3. Whereas dissolution of CMF in ethanol leads to 5- (ethoxymethyl)furfural, no analogous substitution was observed in CMFCC 4, even after heating at 50 °C over the course of several hours. The substitution could however be forced by heating 5 in a closed vessel at 150 °C for 7 h (Scheme 2). The ethyl 5-(ethoxymethyl)furan-2-carboxylate product 6 is a previously unreported molecule among a class of 5-(alkoxymethyl)furan-2- carboxylate esters that are little known in the chemical literature. The high stability of 6 compared to 5-(ethoxymethyl)furfural, itself a proposed biofuel (Fuel, 2015, 150, 236; J. Mat. Chem. A, 2015, 3, 4992; RSC Advances, 2014, 4, 5689), suggests the potential of a similar application for 6 and its congeners. [0023] We have also derivatized ester 5 by hydrogenolysis of the C-Cl bond to give ethyl 5- methylfuroate 7. This and related "408" (http://xftechnologies.com) esters are currently being commercialized as motor fuel oxygenates. In addition to being hydrophobic, high energy, non- toxic liquids, they also reduce particulate emissions, enhance lubricity, and improve cold-flow properties when blended with biodiesel. Substitution of 5 on the other hand with the nitrogen and carbon nucleophiles benzylamine and mesitylene leads respectively to derivatives 8 and 9 in high yields. [0024] An extension of the oxidation of CMF to CMFCC would be the analogous oxidation of 2,5-diformyl furan (DFF) 10 to access the bis(acid chloride) of FDCA, namely furan-2,5- dicarbonyl chloride (FDCC) 11. Conveniently, Laugel and co-workers have reported the preparation of DFF by the simple heating of CMF in DMSO (Kornblum oxidation), providing 10 in >80% yield (ChemCatChem, 2014, 6, 1195). Treatment of DFF with t-BuOCl at room temperature cleanly provided FDCC 11 (Scheme 3), as demonstrated by ¹H NMR of the reaction mixture, which indicated a yield of 80% based on peak integration against an internal standard. As was the case for CMFCC 4, the FDCC was not isolated but quenched into ethanol, giving a yield of 76% of the corresponding diethyl ester 12 over the two steps. A particular advantage of FDCC 11 is that it is freely soluble in common organic solvents, compared to FDCA 1 which is soluble only in polar aprotic solvents such as DMSO. Derivatization by Friedel-Crafts acylation of benzene with 11 provided the bis(aryl) ketone 13. [0025] The present invention describes a method of preparing acid chlorides from furfurals using tert-butyl hypochlorite. In some embodiments, the present invention provides a method of preparing a compound of Formula I:

the method comprising forming a reaction mixture of tert-butyl hypochlorite and a compound of Formula II:

under conditions sufficient to form the compound of Formula I, wherein R is selected from the group consisting of–CH₂Cl and–C(O)H. In some embodiments, compound of Formula I has the structure selected from the group consisting of:

[0026] In some embodiments, the method comprises forming the reaction mixture of tert-butyl hypochlorite and the compound of Formula II having the structure:

under conditions sufficient to form the compound of Formula I having the structure:

.

[0027] In some embodiments, the method comprises forming the reaction mixture of tert-butyl hypochlorite and the compound of Formula II having the structure:

under conditions sufficient to form the compound of Formula I having the structure:

.

[0028] The reaction mixtures of the method for preparation of Formula I can be at any suitable temperature. For example, the temperature of the reaction mixture can be of from about 0 ºC to about 200 ºC, such as at about 0, 5, 10, 15, 20, 22 (room temperature), 25, 30, 35, 40, 45 or about 50 ºC. In some embodiments, the temperature of the reaction mixture can be from about 0 ºC to about 30 ºC, or of from about 10 ºC to about 30 ºC, or of from about 15 ºC to about 25 ºC. In some embodiments, the temperature of the reaction mixture can be about room temperature. [0029] In some embodiments, the method also includes, prior to the step of forming the reaction mixture, forming a second reaction mixture comprising a bismuth (III) catalyst and the compound of Formula II having the structure:

under conditions sufficient to form the compound of Formula II having the structure:

.

[0030] The present invention also provides methods of preparing diformyl compounds. In some embodiments, the present invention provides a method of preparing a compound of Formula II having the structure:

the method comprising forming a reaction mixture comprising Bi(NO₃)₃Ɣ5H₂O and a compound having the structure:

under conditions sufficient to form the compound of Formula II.

[0031] Representative bismuth (III) catalysts useful in the method of the present invention include, but are not limited to, Bi(NO₃)₃, Bi(NO₃)₃Ɣ5H₂O, BiCl₃, BiBr₃, Bi(OTf)₃, Bi(OAc)₃, Bu₃Bi, Ph₃Bi, and others. In some embodiments, the bismuth (III) catalyst can be Bi(NO₃)₃, Bi(NO₃)₃Ɣ5H₂O, BiCl₃, BiBr₃, Bi(OTf)₃, or Bi(OAc)₃,. In some embodiments, the bismuth (III) catalyst can be Bi(NO₃)₃Ɣ5H₂O. [0032] The method of forming the compound of formula II can be performed at any suitable temperature. For example, the temperature of the reaction mixture can be of from about 0 ºC to about 200 ºC, such as at about 0, 5, 10, 15, 20, 22 (room temperature), 25, 30, 35, 40, 45 or about 50 ºC. In some embodiments, the temperature of the reaction mixture can be from about 20 ºC to about 60 ºC, or of from about 30 ºC to about 60 ºC. In some embodiments, the temperature of the reaction mixture can be about 45 ºC. [0033] In some embodiments, the reaction mixture is formed without exposure to visible light. [0034] The present invention also provides methods of making ethyl ethers from chloromethyl groups. In some embodiments, the present invention provides a method of preparing a compound of having the structure:

the method comprising forming a reaction mixture comprising ethanol and a compound having the structure:

wherein the reaction mixture is heated at a temperature of at least about 100 °C in a closed vessel, thereby forming the compound.

[0035] The reaction mixture can be at any suitable temperature. For example, the temperature of the reaction mixture can be of from about 0 ºC to about 200 ºC, such as at about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190 or about 200 ºC. In some embodiments, the temperature of the reaction mixture can be from about 100 ºC to about 200 ºC, or of from about 125 ºC to about 175 ºC. In some embodiments, the temperature can be at least about 100 ºC. In some embodiments, the temperature can be about 150 ºC. [0036] The reaction mixture can be present in a closed vessel, such that when the vessel is heated, the pressure inside the closed vessel increases. The closed vessel can be of any suitable material, including glass, metal or plastic. [0037] The reaction mixtures of the present methods can be at any suitable temperature. For example, the temperature of the reaction mixture can be of from about 0 ºC to about 200 ºC, such as at about 0, 5, 10, 15, 20, 22 (room temperature), 25, 30, 35, 40, 45 or about 50 ºC. In some embodiments, the temperature of the reaction mixture can be from about 0 ºC to about 30 ºC, or of from about 10 ºC to about 30 ºC, or of from about 15 ºC to about 25 ºC. In some

embodiments, the temperature of the reaction mixture can be about room temperature. [0038] The reaction mixtures of the method can be at any suitable pressure. For example, the reaction mixture can be at atmospheric pressure or above atmospheric pressure. Pressures greater than atmospheric pressure can be achieved by using a pressure vessel and pressurizing with a suitable gas, or using a closed vessel that is then heated. The reaction mixtures can be also be exposed to any suitable environment, such as atmospheric gases, or inert gases such as nitrogen or argon. [0039] The reaction mixtures of the method can also be agitated by any suitable means. For example, the reaction mixtures can be stirred, shaken, vortexed, or others. [0040] Each reaction mixture of the method can be mixed for any suitable period of time from minutes to hours. For example, the reaction mixture can be mixed for about 5 minutes, or 10, 15, 20, 30, 45 or 60 minutes, or for about 1, 2, 3, 4, 6, 12, 16, 24, 36 or 48 hours. [0041] The reaction mixtures of the method can include a variety of other components. For example, the reaction mixtures can include salts, buffers, stabilizers, solvents, etc. Useful salts include, but are not limited to, sodium chloride, potassium chloride, and others. [0042] The present invention also provides compounds prepared by the methods of the invention. In some embodiments, the present invention provides a compound selected from the group consisting of:

In some embodiments, the present invention provides a compound having the structure:

.

In some embodiments, the present invention provides a compound having the structure:

.

In some embodiments, the present invention provides a compound having the structure:

.

IV. EXPERIMENTAL SECTION [0043] Tert-butyl hypochlorite was prepared using a published procedure (Org. Synth.1969, 49, 9).5-(Chloromethyl)furfural (CMF) is most conveniently produced on a large scale from fructose using a method based on the work of Szmant and Chundury (J. Chem. Technol.

Biotechnol.1981, 31, 205.). 2,5-Diformylfuran (DFF) can be prepared from CMF using the method of Laugel, et al. (ChemCatChem 2014, 6, 1195). Nitromethane and mesitylene were purchased from Sigma-Aldrich and dried over 4 Å molecular sieves. Anhydrous ethanol, anhydrous benzene, and aluminum chloride were purchased from Sigma-Aldrich and used as received. All chromatographic separations were carried out on silica gel (40-63 ^m particle size) purchased from Dynamic Adsorbents. Example 1. 5-(Chloromethyl)furan-2-carbonyl chloride (CMFCC) 4 and ethyl 5- (chloromethyl)furan-2-carboxylate 5 [0044] 5-(Chloromethyl)furfural 3 (2.226 g, 15.40 mmol) and tert-butyl hypochlorite (10.5 mL, 10.1 g, 92.7 mmol) were introduced into a 50 mL round-bottomed flask wrapped with aluminum foil. The mixture was stirred rapidly at room temperature under air. After 24 h, a measured amount of 1,4-dioxane was added as an internal standard and the yield of CMFCC 4 was determined to be 85%. [0045] The volatiles were evaporated at room temperature and the crude CMFCC 4 (2.90 g) was dissolved in anhydrous ethanol (20 mL). The clear yellow solution was stirred at 50 °C for 6 h. The solvent was evaporated and the residue was chromatographed using CH₂Cl₂/hexane (1:1 to 3:1 gradient) to give ethyl 5-(chloromethyl)furan-2-carboxylate 5 as a colorless oil (2.390 g, 82%).¹H NMR (300 MHz, CDCl₃) į 7.06 (d, J = 3.5 Hz, 1H), 6.44 (d, J = 3.5 Hz, 1H), 4.55 (s, 2H), 4.31 (q, J = 7.1 Hz, 2H), 1.32 (t, J = 7.1 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) į 158.35, 153.96, 145.02, 118.54, 111.37, 61.10, 36.68, 14.26. Example 2. Ethyl 5-(ethoxymethyl)furan-2-carboxylate 6 [0046] A solution of ethyl 5-(chloromethyl)furan-2-carboxylate 5 (1.486 g, 7.879 mmol) in ethanol (25 mL) was heated in a closed vessel at 150 °C for 7 h. The solvent was evaporated to give ethyl 5-(ethoxymethyl)furan-2-carboxylate 6 as a yellow oil (1.500 g, 96%).¹H NMR (300 MHz, CDCl₃) į 7.04 (d, J = 3.4 Hz, 1H), 6.34 (d, J = 3.4 Hz, 1H), 4.40 (s, 2H), 4.26 (q, J = 7.1 Hz, 2H), 3.47 (q, J = 7.0 Hz, 2H), 1.27 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.0 Hz, 3H).¹³C NMR (75 MHz, CDCl₃) į 158.59, 156.38, 144.36, 118.43, 110.37, 66.14, 64.55, 60.76, 14.96, 14.22. ESI- HRMS calcd. for C₁₀H₁₅O₄: m/z 199.0965 (M+H)⁺, found: 199.0961. Example 3. Ethyl 5-methylfuran-2-carboxylate 7 [0047] To a solution of ethyl 5-(chloromethyl)furan-2-carboxylate 5 (1.416 g, 7.508 mmol) in ethanol (50 mL) was added 10% palladium on activated carbon (145 mg) and the mixture was carefully evacuated and then backfilled with hydrogen three times. The reaction flask was pressurized to 2.5 atm hydrogen and shaken for 160 min. The mixture was filtered through a short plug of Celite, which was further rinsed with ethanol (30 mL). The solvent was evaporated to give ethyl 5-methylfuran-2-carboxylate 7 as a pale yellow oil (994 mg, 86%).¹H NMR (600 MHz, CDCl₃) į 7.05 (d, J = 3.2 Hz, 1H), 6.08 (d, J = 3.2 Hz, 1H), 4.32 (q, J = 7.1 Hz, 2H), 2.35 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H); ¹³C NMR (151 MHz, CDCl₃) į158.84, 157.01, 143.22, 119.18, 108.34, 60.68, 14.36, 13.99. Example 4. Ethyl 5-[(benzylamino)methyl]furan-2-carboxylate 8 [0048] A solution of ethyl 5-(chloromethyl)furan-2-carboxylate 5 (446 mg, 2.36 mmol) and benzylamine (1.30 mL, 1.27 g, 11.9 mmol) in ethanol (30 mL) was heated in a closed vessel at 50 °C for 24 h. The reaction was cooled to room temperature and the volatiles were evaporated under vacuum. The residue was taken up in NaOH (0.2 M, 50 mL) and the mixture was extracted with dichloromethane (3 x 50 mL). The combined organic layer was washed with water and brine and then dried over Na₂SO₄. The solvent was evaporated and the residue was

chromatographed using DCM/EtOAc (1:0 to 0:1 gradient) to give ethyl 5- [(benzylamino)methyl]furan-2-carboxylate 8 as a yellow oil (505 mg, 82%).¹H NMR (600 MHz, CDCl₃) į 7.30 (m, 4H), 7.23 (m, 1H), 7.36– 7.18 (m, 5H), 7.10 (d, J = 3.5 Hz, 1H), 6.30 (d, J = 3.5 Hz, 1H), 4.33 (q, J = 7.1 Hz, 2H), 3.82 (s, 2H), 3.77 (s, 2H), 1.34 (t, J = 7.0 Hz, 3H); ¹³C NMR (151 MHz, CDCl₃) 158.78, 158.52, 143.94, 139.47, 128.43, 128.23, 127.13, 118.69, 109.21, 60.82, 52.82, 45.41, 14.36. ESI-HRMS calcd. for C₁₅H₁₈NO₃: m/z 260.1281 (M+H)⁺, found: 260.1278. Example 5. Ethyl 5-(2,4,6-trimethylbenzyl)furan-2-carboxylate 9 [0049] To a mixture of ethyl 5-(chloromethyl)furan-2-carboxylate 5 (1.05 g, 5.57 mmol), mesitylene (15 mL) and nitromethane (10 mL) was added aluminum chloride (1.41 g, 10.6 mmol) and the mixture was stirred for 24 h. The volatiles were evaporated under vacuum and the residue was chromatographed using hexane/EtOAc (10:1 to 5:1 gradient) to give ethyl 5- (2,4,6-trimethylbenzyl)furan-2-carboxylate 9 as a yellow oil (1.436 g, 95%).¹H NMR (600 MHz, CDCl₃) į 7.01 (d, J = 3.3 Hz, 1H), 6.87 (s, 2H), 5.73 (d, J = 3.4, 1H), 4.33 (q, J = 7.1 Hz, 2H), 4.00 (s, 2H), 2.26 (s, 3H), 2.24 (s, 6H), 1.36 (t, J = 7.1 Hz, 3H); ¹³C NMR (151 MHz, CDCl₃) į159.20, 158.88, 143.48, 136.82, 136.37, 130.12, 129.00, 118.95, 107.97, 60.70, 28.57, 20.87, 19.85, 14.37. ESI-HRMS calcd. for C₁₇H₂₁O₃: m/z 273.1485 (M+H)⁺, found: 273.1486. Example 6. Conversion of 5-(chloromethyl)furfural to 2,5-diformylfuran 10 [0050] A mixture of 5-(chloromethyl)furfural (1.00 g, 6.92 mmol) and powdered

Bi(NO₃)₃Ɣ5H₂O (2.70 g, 5.57 mmol) was stirred at 45 °C. After a latent period of 5-8 min, there was vigorous reaction with evolution of NO₂ gas. The flask was immediately transferred into a water bath to control the exotherm. Once NO₂ evolution had subsided (5-10 min), the flask was transferred back into the oil-bath and stirred for an additional for 30 min. Note that effective stirring throughout the process is essential to the outcome of the reaction. The resulting beige paste was triturated with dichloromethane (5 x 10 mL). The combined triturate was dried over Na₂SO₄ and evaporated to give 2,5-diformylfuran as a yellow crystalline solid (0.560 g, 65% based on CMF).¹H NMR (CDCl₃, 300 MHz) į 9.87 (2H, s), 7.35 (2H, s); ¹³C NMR (CDCl₃, 75 MHz) į 179.5, 154.1, 119.7. Example 7. Furan-2,5-dicarbonyl chloride (FDCC) 11 and diethyl furan-2,5-dicarboxylate 12 [0051] 2,5-Diformylfuran 10 (1.315 g, 10.60 mmol) and tert-butyl hypochlorite (14.4 mL, 13.8 g, 127 mmol) were introduced into a 50 mL round-bottomed flask wrapped with aluminum foil. The suspension was stirred rapidly at room temperature under air for 24 h, resulting in a clear yellow solution. A measured amount of 1,4-dioxane was added as an internal standard and the yield of FDCC 11 was determined to be 80%. [0052] The volatiles were evaporated at room temperature and the crude FDCC 11 (1.840 g) was dissolved in anhydrous ethanol (20 mL). The mixture was stirred at room temperature for 5 h. The solvent was evaporated and the residue was chromatographed using CH₂Cl₂/hexane (1:1 to 1:0 gradient) to give diethyl furan-2,5-dicarboxylate 12 as a yellow oil (1.700 g, 76%).¹H NMR (600 MHz, CDCl₃) į 7.19 (s, 2H), 4.39 (q, J = 7.1 Hz, 4H), 1.38 (t, J = 7.1 Hz, 6H); ¹³C NMR (151 MHz, CDCl₃) į 158.06, 146.89, 118.22, 61.58, 14.24.

[0053] 2,5-Diformylfuran 10 (650 mg, 5.24 mmol) and tert-butyl hypochlorite (7.20 mL, 6.90 g, 63.6 mmol) were introduced into a 20 mL vial wrapped with aluminum foil. The suspension was stirred rapidly at room temperature under air for 24 h. The volatiles were evaporated at room temperature and the crude FDCC 11 was dissolved in anhydrous benzene (15 mL). To this was added aluminum chloride (1.35g, 10.1 mmol) and the mixture was stirred for 20 h. The reaction was poured into aq HCl (1.0 M, 50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic phase was washed with brine and dried over Na₂SO₄. The solvent was evaporated and the residue was chromatographed using hexane/EtOAc (1:0 to 5:1 gradient) to give furan-2,5-diylbis(phenylmethanone) 13 as a pale yellow solid (950 mg, 66%).¹H NMR (600 MHz, CDCl₃) į 8.09 (d, J = 7.6 Hz, 4H), 7.63 (t, J = 7.5 Hz, 2H), 7.52 (t, J = 7.6 Hz, 4H), 7.38 (s, 2H) ^¹³C NMR (151 MHz, CDCl₃) į 182.38, 153.95, 136.24, 133.32, 129.66, 128.61, 120.04. ESI-HRMS calcd. for C₁₈H₁₃O₃: m/z 277.0859 (M+H)⁺, found: 277.0861. [0054] Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, one of skill in the art will appreciate that certain changes and modifications may be practiced within the scope of the appended claims. In addition, each reference provided herein is incorporated by reference in its entirety to the same extent as if each reference was individually incorporated by reference. Where a conflict exists between the instant application and a reference provided herein, the instant application shall dominate.

Claims

WHAT IS CLAIMED IS: 1. A method of preparing a compound of Formula I:

the method comprising

forming a reaction mixture of tert-butyl hypochlorite and a compound of Formula II:

under conditions sufficient to form the compound of Formula I, wherein R is selected from the group consisting of–CH₂Cl and–C(O)H.

2. The method of claim 1, wherein the compound of Formula I has the structure selected fro the group consisting of:

3. The method of claim 1, wherein the method comprises: forming the reaction mixture of tert-butyl hypochlorite and the compound of Formula II having the structure:

under conditions sufficient to form the compound of Formula I having the structure:

.

4. The method of claim 1, wherein the method comprises: forming the reaction mixture of tert-butyl hypochlorite and the compound of Formula II having the structure:

under conditions sufficient to form the compound of Formula I having the structure:

.

5. The method of claim 4, further comprising prior to the step of forming the reaction mixture:

forming a second reaction mixture comprising a bismuth (III) catalyst and the compound of Formula II having the structure:

under conditions sufficient to form the com ound of Formula II having the structure:

.

6. The method of claim 5, wherein the bismuth (III) catalyst is Bi(NO₃)₃Ɣ5H₂O.

7. A method of pre arin a com ound of Formula II having the structure:

the method comprising:

forming a reaction mixture comprising Bi(NO₃)₃●5H₂O and a compound having the structure:

under conditions sufficient to form the compound of Formula II.

8. A method of preparing a compound of having the structure:

the method comprising:

forming a reaction mixture comprising ethanol and a compound having the structure:

wherein the reaction mixture is heated at a temperature of at least about 100 °C in a closed vessel, thereby forming the compound.

9. A compound selected from the group consisting of: