WO2015006360A1 - Acyclic alkenes via ozonolysis of multi-unsaturated cycloalkenes - Google Patents

Abstract

A method of making a compound of formula (IIa) by selective ozonolysis of a compound of formula (I) is provided, wherein A is a C₆-C₁₀ alkene chain with at least one double bond, R¹ is a C₁-C₁₀ alkyl, and R³ is an oxygen-containing functional group.

Description

ACYCLIC ALKENES VIA OZONOLYSIS

OF MULTI-UN SATURATED CYCLOALKENES

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority filing date of U.S. Provisional application serial number 61/845,067, filed July 11, 2013, the disclosures of which are specifically incorporated herein by reference in their entireties.

FIELD OF THE INVENTION

[0002] The disclosures herein relate to a method of making a compound of formula Ila:

from a compound of formula I: , wherein A is C₆-C₁₀ alkene chain with at least one double bond; R¹ is a Ci-Cio alkyl and R³ is an oxygen-containing functional group.

BACKGROUND OF THE INVENTION

[0003] It is known that 1,5,9-cyclododecatriene (CDDT) and 1,5-cyclooctadiene (COD) are co-products of the cyclotrimerization of butadiene, and that each are available on an industrial scale. The conversion of CDDT and COD to multi-functionalized acyclic compounds has immediate industrial importance as a source of additives, intermediates and monomers. Known methods for converting multi-unsaturated cyclic alkenes to acyclic alkenes by contact with ozone are known. For example, the ozonolysis of cyclic alkenes and production of acidic aldehydes is known from U.S. Patent No. 4,085,127, assigned to SNIA VISCOSA, (the Ί27 patent) according to a method comprising: subjecting a solution containing a cycloalkene having more than one unsaturation, to a selective ozonization step in the presence of a solvent mixture of at least one non-polar solvent and at least one polar solvent, whereby the mono-ozonolysis product of the said cyclo-alkene is obtained. The mono-ozonolysis product is subjected to at least one transposition step, to obtain an omega-formyl-alkenoic acid. The mono-ozonide, as soon as it forms, reacts with the polar solvent to produce a heavy phase which is insoluble and separates from solution during the ozonization step. Not more than one alkeneic unsaturation is removed by the ozonization step and the solvent mixture further includes an organic acid anhydride, with the weight ratio of said anhydride to the polar solvent being set at between 1 :2 and 2:1. The non- polar solvent is a saturated hydrocarbon. Furthermore, the method disclosed in the ' 127 patent is characterized by the fact that the selective ozonization is effected in a reactor, and includes decanting the heavy phase containing the mono-ozonolysis product from the reactor, and recycling at least part of the residue from said transposition step to the reactor.

[0004] U.S. 3,868,392 (the '392 patent) discloses a method of producing peroxide-like derivatives of ozonides by ozonization of the corresponding olefins, comprising the step of placing an olefin in the presence of ozone in solution in a solvent mixture which comprises at least a nonpolar solvent (inert with respect to the olefin concerned) and at least a polar solvent, in which the as formed ozonide is reactively dissolved, a heavy weight phase being formed which contains the peroxide-like derivative. The derivative in question is removed from the reaction environment so as to substract it from superoxidation and polymerization effects.

[0005] A disadvantage of the method disclosed in the '392 patent is that the reaction system is complicated, requiring introduction of the ozone gas only in the nonpolar solvent phase where the olefin is dissolved, and more importantly, isolation of the peroxide-like ozonide away from the reaction environment and into the second polar phase. This bi-functional, bi-phasic solvent requirement leads to a complicated reactor design having to deal with and manage immiscible solvent phases in said proportions.

[0004] The disclosed process has eliminated the step of physically isolating the ozonolysis product from the reaction environment. In the disclosed method, a starting olefin and reagent are contacted with medium comprising ozone to form an ozonolysis product that is not isolated from the medium.

[0005] GB Patent No. 903,683 to ESSO (the '683 patent) discloses a process for the preparation of unsaturated dicarboxylic acids. The '683 patent relates to a method for converting a cyclic non-conjugated polyalkene to products by the selective mono-ozonolysis of, for example, CDDT. More particularly, the '683 patent relates to a process for the selective oxidation of the selective mono-ozonolysis product to convert the latter to the corresponding unsaturated alpha, omega-dicarboxylic acid. However, one of the disadvantages of the method disclosed in the '683 patent is its low conversion. According to the '683 patent, if more than about 0.1 mol of ozone per mol equivalent of double bonds in the starting material is employed, the selectivity of the ozonolysis reaction is no longer obtainable. For example, Example I of the '683 patent discloses that 0.13 mol of ozone per mol of CDDT resulted in a conversion about 1/24 of the olefinic bonds in CDDT. In comparison, when about 0.6 mol of ozone was reacted per mol of CDDT, the ozonolysis reaction was not selective to the monoozonolysis product.

[0006] In contrast, in the disclosed process, the selectivity of monoozonolysis is preserved with much higher conversions. (E.g., see Examples 15, 18, 24, and 28 in Table 3.)

[0007] Schreiber et al, Tetrahedron Letters, 23(38): 3867 (1982) disclose that ozonolysis of a mono-unsaturated cycloalkene is carried out at a temperature of -78°C to form an aldehyde- alkoxy hydroperoxide intermediate. Schreiber et al, report "[t]he aldehyde-alkoxy hydroperoxides, 2, were often oligomeric and tended to be difficult to purify".

[0008] A disadvantage in the Schreiber method is its complex reacting system of little or no practical value, requires handling of hazardous and carcinogenic solvents and very low temperatures. The Schreiber one-pot sequence is not practical and cost-effective with respect to recovering the recyclable components from an economic standpoint.

[0009] Adlof, Journal of Labelled Compounds and Radiopharmaceuticals, Vol. XXIV, No. 6, 1987, 695-698, discloses a method to prepare methyl 8-oxooctanoate-4,5-d₂ and methyl 12- oxododecanoate-4,5,8,9-d4. In Adlof, the monoozonation of 1,5 cyclooctadiene and 1,5,9 cyclododecatriene yielded the mono- or di-unsaturated aldehydic acids, which were converted to the corresponding acetal esters. Adlof reports "[ujnlike the aldehydic ester, the acetal ester does not trimerize and can be stored for years before hydrolysis and use."

[0010] On the contrary, we have unexpectedly and surprisingly found that the prepared

aldehyde esters, e.g., a compound of formula III:

, wherein A is a C₁₀ alkene chain with at least one carbon-carbon double bond, R¹ is a C₁-C₄ alkyl, and R³ is an aldehyde, are stable in our processing conditions. The compound of formula III may be obtained from the disclosed CDDT ozonolysis method. The disclosed method is a significant improvement over the Adlof preparations of the unsaturated acetal esters in that it does not require the additional esterification step utilizing CH₃OH/trimethylorthoformate/HCl.

[0011] Dygos et al., J. Org. Chem. 1991, 56, 2549-2552, disclose an 11 -step synthesis of the antisecretory prostaglandin enisoprost starting with (Z,Z)-l,5-cyclooctadiene. Methyl 8-oxo- 4(Z)-octenoate was synthesized and purified by a rather complicated system, which involves multiple reagents, complicated reaction conditions, and multiple filtrations and extractions to obtain a crude product with about 80% purity.

|0012] Van Lier et al. , Prog. Essent. Oil Res., Proc. Int. Symp. Essent. Oils, 16^th (1986), 215- 225, disclose that after partial ozonolysis of (Z,Z)-l,5-cyclooctadiene to methoxy hydroperoxide, the crude reaction mixture, without any purification or isolation, was added to a FeCl₃-6H₂0 methanol solution at 60°C to form (Z)-7-chloro-l,l-dimethoxy-4-heptene.

[0013] In Tolstikov et al, Zh rnal Organicheskoi Khimii (1985), 21(1), 72-82, 11-formyl- 4E,-8E-undecadienoate was synthesized in two steps from E, E, E-cyclododecatriene.

[0014] The disadvantages with the above-mentioned methods are that the preparations are complex and involve stringent conditions, various reaction components, environmentally unfriendly solvents, metallic salts, etc.

[0015] Herein, the problems attendant to performing ozonolysis in solvent mixtures of non- polar and polar solvents; as well as, those of selectivity to useful products when ozone is contacted with compounds that possess unconjugated double-bonds.

[0016] Accordingly, it will be desirable to provide a process which enables, in a technically simple and economically viable manner, to make a stable compound by transforming the compound of formula I by contact with medium comprising ozone and a reagent, without isolating the ozonolysis product from the medium, and subsequently recovering the ozonolysis product. It would also be desirable to eliminate the use of hazardous solvents and/or complexities of dealing with the immiscible solvents. SUMMARY OF THE INVENTION

[0017] One aspect of the disclosed process is directed to a method of making a compound of

OR¹

R³— A <^

formula Ila: ^00H , comprising:

a) contacting a compound of formula I: , and a reagent with a medium comprising ozone, and

b) forming a reaction mixture comprising the compound of formula Ila, and without isolating the product from the ozone of a), and

c) recovering the product of b) comprising the compound of formula Ila;

wherein, A is a C₆-C₁₀ alkene group with at least one double bond; R¹ is a C^Cio alkyl; R³ is an oxygen-containing functional group.

[0018] Another aspect of the disclosed process is directed to a composition comprising a

compound of formula II:

_? wherein A is a C6-C₁₀ alkene chain with at least one double bond; R¹ is a Q-Qo alkyl; R² is H, acetyl; and R³ is an oxygen-containing functional group.

[0019] Another aspect of the disclosed process is directed to a system for the chemical

transformation of a compound of formula I: to a compound of formula Ila:

and with the preservation of the total number of carbon atoms in the compound of formula I, comprising: a. the compound of formula I and a reagent, optionally in combination with a solvent; b. a medium comprising ozone;

c. an ozonolysis product and

d. the compound of formula Ila, and

wherein, components a, b, c and d are present in a single means for carrying out the chemical transformation; and wherein A is C₆-C₁₀ alkene chain with at least one double bond; R is a Q-Cio alkyl and R is an oxygen-containing functional group.

[0020] Another aspect of the disclosed process is directed to a method of making R⁴-A-R⁴ comprising:

i. contacting a compound of formula I:

and an agent with a medium comprising ozone;

ii. forming an ozonolysis product, wherein the resulting ozonolysis product is not isolated; and

iii. allowing the ozonolysis product to transform to R⁴-A-R⁴;

wherein A is a C6-C₁₀ alkene chain with at least one double bond and R⁴ is an aldehyde group.

BRIEF DESCRIPTION OF THE FIGURES

[0021] Figure 1 shows the heat flow characteristics of the compounds according to Example 56, measured by single-cell, Differential Scanning Calorimetry (DSC).

[0022] Figure 2 shows the heat flow characteristics of the compounds according to Examples 56 and 57, measured by single-cell DSC.

DETAILED DESCRIPTION OF THE INVENTION

[0023] Embodiments of the invention described and claimed herein are not to be limited in scope by the specific embodiments herein disclosed, since these embodiments are intended as illustration of several aspects of the disclosure. Any equivalent embodiments are intended to be within the scope of this disclosure. Indeed, various modifications of the embodiments in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

[0024] The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0025] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural reference unless the context clearly dictates otherwise. Thus, for example, a reference to "a reactor" includes a plurality of reactors, such as in a series of reactors. In this document, the term "or" is used to refer to a nonexclusive or, such that "A or B" includes "A but not B," "B but not A," and "A and B," unless otherwise indicated.

[0026] Values expressed in a range format should be interpreted in a flexible manner 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. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not just about 0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement "about X to Y" has the same meaning as "about X to about Y," unless indicated otherwise. Likewise, the statement "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z," unless indicated otherwise.

[0027] In the methods described herein, the steps can be carried out in any order without departing from the principles of the invention, except when a temporal or operational sequence is explicitly recited. Furthermore, specified steps can be carried out concurrently unless explicit claim language recites that they be carried out separately. For example, a claimed step of doing X and a claimed step of doing Y can be conducted simultaneously within a single operation, and the resulting process will fall within the literal scope of the claimed process.

[0028] The term "about" as used herein can allow for a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of a range.

[0029] The term "substantially" as used herein refers to a majority of, or mostly, as in at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more.

[0030] The term "alkene" as used herein refers to a linear or branched hydrocarbon olefin that has at least one carbon-carbon double bond.

[0031] The term "alkyl" or "alkylene" as used herein refers to a saturated hydrocarbon group which can be an acyclic or a cyclic group, and/or can be linear or branched unless otherwise specified.

[0032] The term "reagent" as used herein means a consumable material that provides the suitable R¹ functionality in the compound of formula Ila. In some embodiments, the reagent is polar. In other embodiments, the reagent provides a single continuous phase of the reaction. In yet another embodiment, the reagent improves the flowability characteristics of the reaction medium. In some embodiments, the reagent improves the heat transfer properties of the reaction medium.

[0033] The term "agent" as used herein means a consumable material that allows the ozonolysis product to transform to R⁴-A-R⁴. In some embodiments, the agent is polar. In other embodiments, the agent provides a single continuous phase of the reaction. In another embodiment, the agent may provide a multi-phase reaction medium. In yet another embodiment, the agent improves the flowability characteristics of the reaction medium. In some embodiments, the agent improves the heat transfer properties of the reaction medium. [0034] All publications, including non-patent literature (e.g., scientific journal articles), patent application publications, and patents mentioned in this specification are incorporated by reference as if each were specifically and individually indicated to be incorporated by reference.

[0035] It is understood that the descriptions herein are intended to be illustrative, and not restrictive. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. In the appended claims, the terms "including" and "in which" are used as the plain- English equivalents of the respective terms "comprising" and "wherein," respectively. Moreover, the terms "first," "second," "third," and the like are used merely as labels, and are not intended to impose numerical requirements on their objects.

[0036] One aspect of the disclosed process is directed to a method of making a compound of

formula Ila:

, comprising:

a) contacting a compound of formula I:o , and a reagent with a medium comprising ozone;

b) forming a reaction mixture comprising the compound of formula Ila, and without isolating the product from the ozone of a); and

c) recovering the product of b) comprising the compound of formula Ila;

wherein, A is a C₆-C₁₀ alkene group with at least one double bond; R¹ is a Ci-Cio alkyl; R³ is an oxygen-containing functional group.

[00371 In some embodiments, R¹ is a Q-Q alkyl. In another embodiment, R¹ is a C₂-C₄ alkyl. In a further embodiment, R¹ is propyl or butyl.

[0038] In some embodiments, A is a Q, or C₁₀ alkene chain with at least one double bond. In one embodiment, A is a C₁₀ alkene with two double bonds. In another embodiment, A is a C₆ alkene with one double bond. [0039] In some embodiments, R³ is an aldehyde, an acid, or an ester group. In a further embodiment, R is an aldehyde or an acid group. In another further embodiment, R is an aldehyde group.

[0040] The compound of formula I may include cyclic trienes and cyclic dienes. Examples of the compound of formula I include, but are not limited to, cyclohexadiene, cycloheptadiene, cyclooctadiene, cyclooctatetraene, cyclododecadiene, cyclododectriene, cyclododecapentaene including isomers and mixtures thereof. In some embodiments, the compound of formula I is cyclododecatriene or cyclooctadiene. In a further embodiment, the compound of formula I is 1,5,9-cyclododectriene (CDDT) or 1,5-cyclooctadiene (COD). In another further embodiment, the compound of formula I is CDDT.

[0041] In some embodiments, the compound of formula I has a purity of at least 90%. In other embodiments, the compound of formula I has a purity of at least 95%. In a further embodiment, the compound of formula I has a purity of at least 98%. In another further embodiment, the compound of formula I has a purity of at least 99%.

[0042] In some embodiments, the reagent is a C Qo alcohol. Examples of the suitable alcohol include, but are not limited to, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2- butanol, iso-butanol, t-butanol, and mixtures thereof. In some embodiments, the alcohol is 1- propanol, 2-propanol, 1-butanol, 2-butanol, iso-butanol, t-butanol, and mixtures thereof. In other embodiments, the reagent is a C₄-C₁₀ alcohol. Higher alcohols such as butanols, etc., are preferred.

[0043] In some embodiments, the reagent is anhydrous, preferably contains less than 0.5 wt.% water, or more preferably less than 0.1 wt.% water. In other embodiments, the water content may be no more than 0.08 wt.%, preferably no more than 0.04 wt.%.

[00441 In some embodiments, the amount of the reagent may vary and generally excess reagent may be used. For purposes of the disclosed process, the molar ratio of the compound of formula I to the reagent may be about 100:1 to about 1:100, preferably about 25:1 to about 1 :25, and more preferably about 10:1 to about 1:10. In one embodiment, the molar ratio of the compound of formula I to the reagent is about 4:1 to about 1 :10. In another embodiment, the molar ratio of the compound of formula I to the reagent is about 6:1 to about 1 :6. In yet another embodiment, the molar ratio of the compound of formula I to the reagent is about 3:1 to about 1 :3.

[0045] In one embodiment, the reagent is provided in excess. In this context, the term "excess" is defined as the molar amount of the reagent that is more than the reacted compound of formula I. In some embodiments, the method further comprises at least partially removing the excess reagent in c). In a further embodiment, majority of the excess reagent is removed in c). In some embodiments, the excess reagent is removed via flash distillation. In some embodiments, the removed reagent from c) is partially or totally recycled back to a). In another embodiment, the removed reagent of c) is refined and purified.

[0046] In some embodiments, steps a) through c) are performed in a single continuous phase. In other embodiments, the reagent is provided in the quantity at least sufficient to react to a desired conversion at the conditions of a). In an embodiment, the reagent is provided to improve flowability characteristics of the reaction medium. In another embodiment, the reagent is provided to improve the heat transfer properties of the reaction medium.

[0047] In some embodiments, steps a) through c) may be conducted in the presence of an optional inert solvent. In other embodiments, the inert solvent is a polar solvent. Examples of the suitable polar solvent include, but are not limited to, Ci-C₆ alkyl acetates, ethers, dimethyl formamide (DMF), dimethyl acetamide (DMAc), dimethyl sulfoxide (DMSO), n-methyl pyrrolidinone (NMP), tetrahydrofuran (THF), and mixtures thereof.

[0048] In some embodiments, the concentration of the compound of formula I in the reaction zone, by weight, may be about 0.1% to 99.9% range. In one embodiment, the compound of formula I is present in the about 0.5%-25% concentration range. In other embodiments, the compound of formula I is present in the about 25%-35%, in the about 35%-45%, in the about 45%-55%, in the about 55%-65%, in the about 65%-75%, in the about 75%-85%, in the about 85%-95%, or in the about 95-99.9% concentration range. In some embodiments, the compound of formula I concentration range may be from about 1% to about 99%. In a further embodiment, the compound of formula I concentration range may be from about 10% to about 90%. In another further embodiment, the compound of formula I concentration range may be from about 25% to about 85%, preferably from about 30% to about 75%, and more preferably from about 30% to about 65%. In one embodiment, the compound of formula I is from about 35% to about 60% by weight.

[0049] The ozone-containing gas may comprise a mixture of ozone and at least one carrier gas. The amount of ozone may vary. In some embodiments, ozone may be from about 0.01 mol.% to about 100 mol.%. In a further embodiment, ozone may be from about 0.1 mol.% to about 10 mol.%, from about 10 mol.% to about 30 mol.%, from about 30 mol.% to about 50 mol.%, from about 50 mol.% to about 70 mol.%, from about 70 mol.% to about 90 mol.%, or from about 90 mol.% to about 100 mol.%. In other embodiments, ozone may be from about 0.1 mol.% to about 25 mol.%. In a further embodiment, ozone may be from about 1 mol.% to about 20 mol.%. In another further embodiment, ozone may be from about 1 mol.% to about 15 mol.%.

[0050] In some embodiments, the carrier gas may be selected from the group consisting of nitrogen, argon, carbon dioxide, oxygen, air, and mixtures thereof. In one aspect, the ozone- containing gas may comprise ozone, oxygen, and argon. In one embodiment, the ozone- containing gas may comprise ozone, oxygen, and nitrogen. In another embodiment, the ozone- containing gas may comprise ozone and carbon dioxide. There is no restriction on which carrier is to be used so long as it is chemically compatible with ozone and the carrier itself does not lead to undesirable reactions with the hydrocarbon substrate.

[0051] In some embodiments, the ozone may be introduced in the dissolved state using an appropriate solvent. In other embodiments, the concentration of ozone may be enriched by injecting ozone into a pressurized circulation loop.

[0052] In some embodiments, the medium comprising ozone may be further enriched to obtain a concentrated ozone feed. Suitable forms of ozone enrichment may include the use of materials having the ozone affinity, such as the packed beds, solvents. In other embodiments, the ozone may be selectively separated and concentrated from the medium comprising dilute concentrations of ozone. [0053] In some embodiments, the concentration of ozone in the ozone-containing medium, by weight, may be from about 0.01% to about 100%. In other embodiments, the ozone concentration may be from about 0.5% to about 5%, from about 5% to about 25%, from about 25% to about 50%, from about 50% to about 75%, from about 75% to about 100%.

[0054] In some embodiments, the total addition of ozone is at least partially influenced by the desired conversion and efficiency of ozone take-up. The ozone-containing gas is passed through the reaction solution for a period of time sufficient to permit selective cleavage of only one double bond. In some embodiments, the period of time may range from about 10 minutes to about 300 minutes. In a further embodiment, the period of time may range from about 30 minutes to about 200 minutes. The total ozone fed to the process can be sub-stoichiometric, stoichiometric or excess with respect to the one double bond in the compound of formula I that is converted. In one example, the total moles of ozone fed to the process are in the stoichiometric ratio with respect to the moles of one double bond in the compound of formula I that is converted.

i_i

[0055] The contacting step can be carried out for a suitable time determined by a reasonable amount of trial and error. For example, an embodiment includes introducing a flow of gas during a time period that is from about 40 minutes to about 240 minutes. In another embodiment, a flow of gas is introduced during a time period that is from about 5 minutes to about 500 minutes or more. In a batch configuration the ozone addition time is at least partially influenced by the flow rate of ozone (moles per mole of multi-unsaturated cyclic alkene per minute), the desired conversion and the efficiency of ozone uptake.

[0056] The flow rate of ozone fed may depend on the scale of operation and the desired conversion within the reaction time chosen. In some embodiments, the ozone flow rate is in the range from about 0.001 g/min to about 1 g/min. In a further embodiment, the ozone flow rate is in the about 0.005 g/min to about 0.8 g/min range. In another further embodiment, the ozone flow rate is in the about 0.01 g/min to about 0.2 g/min range. In yet another further embodiment, the ozone flow rate is in the about 0.02 g/min to about 0.1 g/min range.

[0057] The readers may appreciate that there is no limit as such on either the ozone feed rate, ozone concentration or the contact time. The described ranges are non-limiting and those skilled in the art may appreciate the even broader ranges that may be required to achieve the desired conversion, product yields and reaction heat management at various production scales.

[0058] In some embodiments, a sufficient quantity of ozone may be generated from a chemical conversion device such as Ultraviolet (UV) converter, Corona Discharge converter, etc. The source of elemental oxygen for ozone generation may be selected from diatomic oxygen, carbon monoxide, carbon dioxide, nitrogen oxides, water, oxygenated chemicals, air and like. In one embodiment, pure oxygen may be used for the ozone generation. In another embodiment, carbon dioxide may be used for the ozone generation. In yet another embodiment, oxygen generated from a water electrolysis device may be fed to the ozone generator. In one embodiment, an oxygen-rich offgas from a chemical process may be used for the ozone generation. Examples of such chemical processes may include, but are not limited to, oxidation, combustion, aerobic, fuel-cells, absorption, fermentation, etc.

[0059] The term "percent conversion" means: [(Number of grams of the compound of formula I present prior to step a) - (Number of grams of the compound of formula I present after step c)] / (Number of grams of the compound of formula I present prior to step a) x 100.

[0060] In some embodiments, the conversion of the compound of formula I is from about 0% to about 100%. In a further embodiment, the conversion of the compound of formula I is from about 10% to about 95%. In other further embodiments, the conversion of the compound of formula I is from about 20% to about 90%, from about 30% to about 70%, or from about 30%o to about 60%. In other embodiments, the conversion of the compound of formula I is at least 20%. In a further embodiment, the conversion is at least 25%. In another further embodiment, the conversion is at least 30%, 35%, 40%, 45% or 50%.

[0061] In one embodiment, the conversion may be performed sequentially, i.e., the compound of formula I, and an optional inert solvent, is contacted first with medium comprising ozone to produce an ozonolysis product. The ozonolysis product may be further contacted with a medium comprising a reagent to obtain the desired product. In another embodiment, the conversion may be performed concurrently. In yet another embodiment, the conversion may be performed partially or completely. [0062] The term "selectivity" for a compound defined as a percent means: [Number of moles of the compound formed during steps a-c)] / [Number of moles of the compound of formula I converted during steps a-c)] x 100. For reaction mixtures comprising more than one formed compound during steps a-c), the selectivity is normalized.

[0063] The term "carbon preservation selectivity" means: [Number of moles of compounds present after step c) that are formed from cleaved molecules from the ozone attack on first double bond in the compound of formula I] x 100 / [Number of moles of the compound of formula I present prior to step a)].

[0064] The term "non-selective product" means a compound that is formed from a cleaved molecule from the ozone attack on additional double bond(s) in the A chain after the first double bond in the compound of formula I is cleaved.

[0065] In some embodiments, the disclosed method includes carbon preservation selectivity from about 0.1% to about 10%, 10% to 20%, 20% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 69.99%, and combinations of the listed upper and lower percent conversions.

[0066] In some embodiments, the carbon preservation selectivity is at least 50%. In other embodiments, the carbon preservation selectivity is at least 60%. In a further embodiment, the carbon preservation selectivity is at least 70%. In yet other further embodiments, the carbon preservation selectivity is at least 75%, 80%, 85%, 90%, or 95%.

[0067] In some embodiments, the ozonolysis reaction can be conducted under conditions to selectively ozonize only one carbon-carbon double bond in the compound of formula I to form the compound of formula Ila. In a non-selective ozonolysis, more than one carbon-carbon double bonds are converted and non-selective products are formed. In some embodiments, the ozonolysis conditions favor the compound of formula Ila with the preservation of "A" as in the compound of formula I. For example, in the compound of formula Ila from the ozonolysis of CDDT, "A" should be a C₁₀ alkene chain with two carbon-carbon double bonds. Due to the cleaving of more than one double bond, in some embodiments, the non-selective products contain the compound of formula Ila with fewer carbon numbers in "A" than the compound of formula I. [0068] In some embodiments, the mixture in b) may comprise from about Owt.% to about 50wt.% the compound of formula I, from about 0 wt.% to about 80 wt.% reagent, from about 0 wt.% to about 50 wt.% the compound of formula Ila, and up to about 15 wt.% non-selective products. The non-selective products may include compounds having two terminal oxygenated groups, which include dialdhydes, diacids, diesters, acid-esters, aldehyde-acids. In some embodiments, at least some of the non-selective products are saturated, for example, linear C₄ species, e.g., succinic acid. In a preferred embodiment, the mixture in b) comprises from about 0 wt.%) to 50 wt.% of the compound of formula I, from about 0 wt.% to about 80 wt.% reagent, from about 0 wt.% to about 50 wt.% the compound of formula Ila, and up to about 10 wt.% nonselective products. In some embodiments, the ozonolysis effluent is a stable, flowable liquid at ambient conditions.

[0069] In some embodiments, the compound of formula Ila is formed with a selectivity of at least 50%. In other embodiments, the compound of formula Ila is formed with a selectivity of at least 60%. In another embodiment, the compound of formula Ila is formed with a selectivity of at least 70%). In other embodiments, the selectivity for the compound of formula Ila is at least 80%. In another embodiment, the selectivity for the compound of formula Ila is at least 85%). In a further embodiment, the selectivity for the compound of formula Ila is at least 90%. In another further embodiment, the selectivity for the compound of formula Ila is at least 95%. In some embodiments, the selectivity for the non-selective products is less than 10%>. In a further embodiment, the selectivity for the non-selective products is less than 5%.

[0070] In some embodiments, the ozonolysis reaction may be conducted at a temperature of less than 50°C, preferably from about -25°C to about 50°C, from about -25°C to about 50°C, from about -20°C to about 50°C, from about -15°C to about 50°C, from about -10°C to about 50°C, from about -10°C to about 45°C, preferably from about -10°C to about 40°C, and more preferably from about -10°C to about 35°C. The ozonolysis reaction is exothermic and, in some embodiments, the temperature of the reactor is maintained by a cooling system, such as an active jacketed cooler.

[0071] Pressures can be above or below atmospheric, and are selected to maintain the cyclic alkene feed in the liquid phase and the ozone-containing gas in the gaseous phase. In some embodiments, the ozonolysis reaction may be conducted at a pressure from about 100 torr to about 200 Psig. In other embodiments, the ozonolysis reaction may be conducted at a pressure from about 100 torr to about 100 Psig. In a further embodiment, the ozonolysis reaction may be conducted at a pressure from about 0 Psig to about 50 Psig, preferably from about 0 Psig to about 25 Psig, more preferably from about 0 Psig to about 20 Psig, and most preferably from about 0 Psig to about 10 Psig.

[0072] In some embodiments, the sub-atmospheric pressure may be used when the reaction heat is removed by above-surface solvent evaporation, commonly referred to as evaporative cooling. In other embodiments, the reaction off-gas vent may be scrubbed by the suitable means and the entrained organics recovered for re-use. In one embodiment, the incoming feeds, indigenous to the process, may be appropriately contacted with the reactor offgas in a manner sufficient to perform the scrubbing of the condensables away from the non-condensables. In another embodiment, a new medium that is non-reactive but effective at scrubbing may be introduced as an agent.

[0073] Schreiber discloses that "[t]he aldehyde-alkoxy hydroperoxides, 2, were often oligomeric and tended to be difficult to purify." Surprisingly and unexpectedly, in the disclosed process, it has been found that the compound of formula Ila is appreciably stable at the processing conditions, as further illustrated in Thermal Stability sub-section, Examples 56 and 57, and Figures 1 and 2. Advantageously, the unexpected stability allows for the effective removal of the excess reagent. Removal of the reagent avoids the formation of reagent azeotropes in the downstream sections.

[0074] In one embodiment, the compound of formula Ila is formed from ozonolysis of CDDT, wherein A is -CH₂-CH₂-CH=CH-CH₂-CH₂-CH=CH-CH₂-CH₂-. This compound of formula Ila is thermally stable at our processing conditions.

[0075] The term "ozonolysis product" includes those structures, transient or otherwise susceptible to isolation if desired, resulting from the reaction of one ozone molecule with a single double bond of a multi-unsaturated cyclic molecule. However, the applicants do not wish to be limited by or subject to any particular mechanistic interpretation as to the formation of an ozonolysis product. [0076] In some embodiments, the compound of formula Ila may be further transformed into

a compound of formula III:

. The transformation may be performed catalytically or non-catalytically, and, optionally, in the presence of an inert solvent. In one embodiment, an anhydride and amine mixture is used for this transformation. In another embodiment, an anhydride and a mixture of acid and amine are used for this transformation. In yet another embodiment, a mixture of acetic anhydride, acetic acid and triethylamine is used for this transformation. In one embodiment, a mixture comprising of acetic anhydride, and a reclaimed stream comprising acetic acid and triethylamine is used.

[0077] In some embodiments, the anhydride and amine mixture may be freshly prepared or obtained as a recycle stream from the process. In other embodiment, a homogeneous recycle mixture of triethylamine and acetic acid is used for the transformation reaction in combination with the fresh anhydride. In another embodiment, a mixture of triethylamine and acetic acid may be obtained from a distillation process.

[0078] In some embodiments, the anhydride and amine-acid complex are added to a mixture containing the compound of formula Ila that is substantially free of the reagent. In another embodiment, the reagent in the mixture is less than 1 wt%. In yet another embodiment, the reagent in the mixture is less than 0.5 wt%.

[0079] The choice of anhydride is not limited to acid anhydride and may include maleic anhydride, succinic anhydride, boron anhydride, inorganic anhydrides and other commercially available reagents in the anhydride family. Acetic anhydride is preferred.

[0080] Similarly, the choice of amine is not limited to triethylamine and may include other linear and branched components from the amines family. Triethylamine is preferred.

[0081] The choice of reagent depends on the downstream separation conditions and flammability considerations. Reagents containing less than 2 carbon atoms have too low a boiling point to be of practical use from a flammability standpoint. On the other hand, reagents having more than 10 carbon atoms have too high a boiling point which makes the downstream separation and recovery difficult. In one embodiment, the reagent used may be from the Ci- o alcohol class. In another embodiment, the reagent used may be from the C₃-C₁₀ alcohol class. In yet another embodiment, the reagent used may be from the C₃-C₆ alcohol class. The C₃-C₄ alcohols, e.g., propanols, butanols, are preferred.

[0082] In some embodiments, the reagent may be fresh, recycled, reclaimed or compatible mixtures thereof.

[0083] In some embodiments, the reagent and the optional inert solvent used in any of the steps a) through c) may be produced either from a conventional hydrocarbon feedstock or from a sustainable feedstock via cellulosic, bio-refinery routes. In one embodiment, the butanol used may be obtained as bio-butanol. In another embodiment, tetrahydrofuran used may be obtained from a bio-refinery produced butanediol. In yet another embodiment, the ethanol used may be obtained as bio-ethanol from the cellulosic feedstock.

[0084] In some embodiments, the water level in the reagent used may be appropriately regulated by the methods known in the chemicals manufacturing industry. The method examples are distillation, extraction, membrane purification, decantation, ion exchange, cryogenic separation, and combinations thereof. In one embodiment, a reagent may be dried over the commercial molecular sieves. In another embodiment, the reagent used may be slightly wet, especially if an azeotropic distillate is reclaimed from the purification step. In yet another embodiment, the desired amount of water may be intentionally metered in to effectively achieve the target product distribution that would be of commercial value.

[0085] In some embodiments, the contact between the compound of formula I and the reaction medium may be established using multi-phase contacting devices that are commonly known in the chemicals manufacturing industry. Examples are tower column, horizontal contactor, packed column, trickle-bed column, CSTR, tube reactor, bubble column, static mixer, jet reactor, micro-structure reactor, and variations thereof. The devices may be used alone, in sequence, in parallel or as combination of two or more. The described examples are non-limiting and those skilled in the art may appreciate all arrangement variations of such multi-phase contacting devices to achieve an efficient exchange of materials and heat which may result in acceptable product yields and quality. Whichever the arrangement may be, readers may also recognize that achieving a safe operation is the primary objective from a commercial standpoint.

[0086] In some embodiments, the contact between the compound of formula I and ozone medium may be carried out in a counter-current flow mode. The counter-current flow mode means the two or more reacting phases are traveling in the opposite direction of each other. In other embodiments, the contact may occur in a co-current flow mode. The co-current flow mode means the two or more reacting phases are travelling in the same direction of each other. Other flow modes for the contact may include, but not limited to, sparged-flow, cross-flow, up-flow, down-flow, laminar-flow, turbulent-flow, thin film-flow, dispersion-flow, circulatory-flow, and combinations thereof.

[0087] In some embodiments, the contacting device may be equipped with an external or internal loop-around for efficient mixing and heat exchange. In one embodiment, the ozone medium may be introduced in the high-turbulence, loop-around section of the contacting device. In another embodiment, the ozone medium may be introduced through a distribution system across the reaction zone. In yet another embodiment, the ozone medium may be staged across the reaction zone to develop the desired spatial concentration profiles.

[0088] In one embodiment, the medium comprising ozone may be appropriately introduced to minimize the ozone entrainment in the gas-phase and to minimize aerosol formation. In another embodiment, the liquid droplets (or aerosol) from the offgas vent may be trapped and removed from the gas space. Most commonly used trapping devices include mist eliminator, aerosol coalescing section, spray section, cyclone separator, baffled serpentine flow section, and combinations thereof. The trapping section may or may not be temperature controlled. The trapped material may be returned back to the reaction zone or diverted for recovery.

[0089] In some embodiments, the reactor off-gas comprising the entrained hydrocarbons, ozone, oxygen may be adequately treated with the use of non-catalytic or catalytic thermal oxidation [TO], physical or chemical scrubbing, bio-ponds, and other known industrial abatement techniques. In another embodiment, the offgas may be fed to a co-gen facility for the fuel value recovery. In yet another embodiment, the offgas may be a useful organic food for a biological cell culture. In a further embodiment, the off gas may be an effective oxygen-rich feed for the solid-oxide fuel cell power generation system.

10090] Recovered products include components with terminal oxygenated functional groups such as aldehydes. For example, when the terminal oxygenated functional groups comprise aldehyde, the concentration of the multi-unsaturated cyclic alkene can be about 2 weight percent to about 30 weight percent. When the terminal oxygenated functional groups comprise aldehyde, and the solvent comprises water, in a concentration of about 5 weight percent to about 80 weight percent. The presence of water in the reaction mixture enhances the formation of an acyclic alkene having aldehyde functional groups.

[0091] In some embodiments, the compound of formula III may be non-catalytically or catalytically hydrolyzed into its corresponding acid, wherein R¹ is hydrogen. Hydrolysis may be performed in the hot water, boiling water, organic solvent, and/or in the absence or presence of a catalyst. Suitable catalysts may include mineral acids and bases. In other embodiments, an acid equivalent of the compound of formula III may be transformed into its corresponding amine derivative, which may serve as another monomer of some commercial value.

[0092] Another aspect of the disclosed process is directed to a composition comprising a

compound of formula (II):

_; wherein A is a C₆-C₁₀ alkene chain with at least one double bond; R¹ is a Ci- o alkyl; R² is H or acetyl; and R³ is an oxygen-containing functional group.

[0093] In some embodiments, R¹ is a C₁-C₄ alkyl. In a further embodiment, R¹ is a C₂-C₄ alkyl. In a further embodiment, R¹ is a C₂-C₄ alkyl. In another further embodiment, R¹ is a C₃- C₄ alkyl. In yet another further embodiment, R¹ is a C₄ alkyl.

[0094] In some embodiments, A is a C₆ or C₁₀ alkene chain. In a further embodiment, A is - CH₂-CH₂-CH=CH-CH₂-CH₂-CH=CH-CH₂-CH₂-.

[0095] In one embodiment, R² is H. In another embodiment, R² is acetyl. [0096] In some embodiments, R is an aldehyde, an acid, or an ester group. In a further embodiment, R³ is an aldehyde or an acid group. In another further embodiment, R³ is an aldehyde group.

[0097] Another aspect of the disclosed process is directed to a system for the chemical

transformation of a compound of formula

to a compound of formula Ila:

and with the preservation of the total number of carbon atoms in the compound of formula I, comprising: a. the compound of formula I and a reagent, optionally in combination with a solvent;

b. a medium comprising ozone;

c. an ozonolysis product; and

d. the compound of formula Ila;

wherein, components a, b, c and d are present in a single means for carrying out the chemical transformation; and wherein A is C₆-C₁₀ alkene chain with at least one double bond; R¹ is a C Cio alkyl and R³ is an oxygen-containing functional group.

[0098] In some embodiments, the compound of formula I is cyclododecatriene or cyclooctadiene.

[0099] Another aspect of the disclosed process is directed to a method of making R⁴-A-R⁴ comprising:

i. contacting a compound of formula I:

and an agent with a medium comprising ozone;

ii. forming an ozonolysis product, wherein the resulting ozonolysis product is not isolated; and

iii. allowing the ozonolysis product to transform to R⁴-A-R⁴; wherein A is a C₆-Ci₀ alkene chain with at least one double bond and R⁴ is an aldehyde group.

[00100] Examples of the suitable agent include, but are not limited to water, carboxylic acid, dimethyl sulfoxide (DMSO), water/manganese diacetate, 4.1-9.6 pH buffer solutions (Table 2). Examples of the carboxylic acid include, but are not limited to, acetic acid, succinic acid, maleic acid. In some embodiments, the agent is water or carboxylic acid. In a further embodiment, the agent is water. In yet another embodiment, the agent is acetic acid.

[00101] In some embodiments, the agent in the reaction mixture is about 0.1% to about 99% by weight. In a further embodiment, the agent in the reaction mixture is about 5% to about 80% by weight.

[00102] In some embodiments, the amount of the agent may vary and generally excess agent may be used. For purposes of the disclosed process, the molar ratio of the agent to the compound of formula I may be about 500:1 to about 1 :100, preferably about 400:1 to about 1:75, and more preferably about 300:1 to about 1 :50. In one embodiment, the molar ratio of the agent to the compound of formula I is about 250:1 to about 1 :30. In another embodiment, the molar ratio of the agent to the compound of formula I is about 225:1 to about 1 :25. In yet another embodiment, the molar ratio of the agent to the compound of formula I is about 200:1 to about 1 :20.

[00103] The phrase "allowing the ozonolysis product to transform" includes any changes to the reaction parameters (for example temperature) or addition of further reagents (for example a nucleophile) such that the ozonolysis product transforms to an acyclic alkene having terminal oxygenated functional groups and one fewer unsaturation. The word "transform" may include isomerization, reaction with one or more other molecules or both.

[00104] In some embodiments, the obtained dialdehyde from the compound of formula I may be transformed into a saturated dialdehyde. In other embodiments, the dialdehyde may be further transformed into a diamine. The diamine functionality is of some commercial value and may be used as a monomer to polymerize into a polyamide of commercial importance. [00105] In some embodiments, the dialdehyde from the compound of formula I may be transformed into an unsaturated diamine. In other embodiments, the unsaturated diamine may be further polymerized into different polyamides of some commercial value.

[00106] In some embodiments, the dialdehyde obtained from the compound of formula I may serve as a useful raw material for making products comprising: diacids, diols, diesters, aldehyde acids, hydroxyl acids, ester acids, hydroxyl esters, and mixtures thereof. In one embodiment, the dialdehyde may be partially or completely oxygenated into an aldehyde acid, diacid, and mixtures thereof. In another embodiment, the dialdehyde may be partially or completely hydrogenated to hydroxyl aldehyde, diol, and mixtures thereof. In yet another embodiment, the diacid, obtained from the dialdehyde, may be partially or completely esterified to an acid ester, diester and mixtures thereof. In other embodiments, the unsaturated dialdehyde may be transformed into other useful products of varying unsaturations.

Thermal Stability

[00107] Schreiber discloses that "[t]he aldehyde-alkoxy hydroperoxides, 2, were often oligomeric and tended to be difficult to purify." The disclosed process has unexpectedly found that the compound of formula Ila has thermal stability at commercially useful processing conditions. Advantageously, the step b) product stability allows for the effective removal of the excess reagent in step c) without compromising the product. Removal of the remaining reagent in step c) eliminates the downstream process complexity and thus making it an economically viable process. Additional cost benefit comes from the fact that the removed reagent may be partially or totally recycled back in the process, or in some cases, recovered and purified for other uses.

[00108] In some embodiments, when the concentrated compound of formula Ila obtained from CDDT ozonolysis is exposed to heat at 10°C/minute temperature ramp from 20°C to 220°C the material exhibits sufficient thermal stability up to about 60°C above which the single-cell, Differential Scanning Calorimetry (DSC) data indicates measurable heat flow. The thermal stability data are represented in Examples 56 and 57, and Figures 1 and 2. [00109] Due to its appreciable thermal stability at commercially useful processing conditions, the excess reagent may be distilled off at about 50°C under reduced pressure without any measurable product decomposition and thus no measurable yield loss. In an embodiment, the excess reagent may be removed at about 15°C to about 60°C temperature range and the pressure range of about 0 torr to about 100 torr. In another embodiment, the excess reagent may be removed at about 25°C to about 55°C temperature range and the pressure range of about 0.05 to about 30 torr. The net impact is an improved overall cost-effective process with a surprisingly simple back-end separations scheme not having to deal with the reagent azeotropes.

Analytical Methods

[00110] Analysis is conducted using an Agilent 7890A GC with an FID. The GC column is an Agilent DB-1 column, 60 meter long with a diameter of 0.32 micron and a film thickness of 1.00 micron. NMP is used as the internal standard. Typically, the injection volume is 1 microliter. The injection port temperature is 250°C with an inlet pressure of 10.0 psi. The total Helium flow is 11 ml/min with a split ration of 10:1. The GC oven ramp program is typically: 40°C initial temp, (no hold time); 10°C/min ramp rate; 200°C (15 min. hold time); 10°C/min ramp rate; 275°C final temp. (15 min. hold time). The detector is set at 275°C with a Hydrogen flow of 40 ml/min, 400 ml/min air, 24 ml/min Helium make up. The reaction product is analyzed for various organic compounds. In addition, samples are derivatized using Ν,Ο- bis(trimethylsilyl)trifluoroacetamide (BSTFA) in order to detect and quantify carboxylic acid type products. The GC data is used to determine the weight percent of starting material and products. The weight percent data is used to calculate conversion of starting material and the molar selectivity for various products.

[00111] The DSC characterization of the compounds disclosed in the disclosed process: Examples are performed using a Q200 Series™ standard-cell Differential Scanning Calorimeter, manufactured by TA Instruments. The Q200 DSC instrument provides the temperature measurement accuracy of ± 0.1 °C and the temperature precision of ± 0.05°C. The calorimetric reproducibility (Indium metal) is ± 0.1% with the calorimetric precision (Indium metal) of ± 0.1%. The Q200 DSC instrument sensitivity for heat flow measurements is 0.2 μψ. [00112] The Nuclear Magnetic Resonance [NMR] characterization of the compounds disclosed in the disclosed process, is performed using a Bruker AV400 NMR spectrometer with a QNP CryoProbe. The NMR sample tubes used for these measurements are 5-mm in diameter. A total of 16 scans are co-added for 1H experiments, while 1024 scans are collected for ¹³C experiments. In 1H experiments using the magic angle spin, 30 degree tipping angle is used with a relaxation delay of 1.5 seconds. For ¹³C experiment, standard proton decoupling is applied throughout the relaxation delay and data acquisition period.

[00113] The following Examples further demonstrate the disclosed process and its capability for use. The invention is capable of other and different embodiments, and its several details are capable of modifications in various apparent respects, without departing from the scope and spirit of the disclosed process. Accordingly, the Examples are to be regarded as illustrative in nature and not as restrictive. All percentages are by weight unless otherwise indicated.

[00114] Example 1: A 500ml jacketed round-bottom flask is fitted with a dry ice condenser, mechanical stirrer, stainless steel feed tube for sub-surface ozone gas addition and a fourth port for addition of reagents, sampling and thermocouple connection. Cylinder air is dried and made contaminant-free by feeding through a Zero Air Generator (Balston) and then fed to an ozone generator (Pacific Ozone). The exit gas from the ozone generator is flowed through an ozone monitor (Teledyne Instruments) for 30min to observe stable ozone concentration in the feed gas. The reaction temperature is maintained at a desired target via jacketed cooling. The exit gas containing residual oxygen and nitrogen is passed through an ice water cold trap to recover any volatile solvent. Upon reaction time completion, dry nitrogen is passed into the reactor for 30min to displace any residual ozone and oxygen and the vessel warmed to room temperature. 1,5,9-cyclododecatriene (CDDT) is used as received from INVISTA™ Specialty Intermediates, Table 1 depicts a typical composition. Table 1: Typical 1,5,9-cyclododecatriene composition

Typical Composition, wt%

1,5,9-Cyclododecatriene >99

Tert-butyl catechol 30-50 ppm

Isomers

cls, trans, trans 98

trans, trans, trans 1.5

cis, cis, trans 0.3

cis, cis, cis 0.1

[00115] A steady concentration of 25. lg ozone/m³ in 3 liter/min air flow (0.063g ozone/min) is sparged into the reaction vessel for 47 minutes containing a liquid mixture of lO.Og (0.062 moles) of CDDT, 30.0g deionized water and 120.0g methyl acetate. Total of 2.96g of ozone is fed to the reaction, equivalent to a CDDT/ozone molar ratio of about one. The reaction is carried out at 2.3°C bulk temperature. The final product, recovered from the reaction vessel, is a mixture of organic (93.9g) and aqueous (16.9g) phases. GC analysis indicates 92.5% CDDT conversion upon run completion. The GC-analyzed, solvent-free, product distribution is 8.1g dodeca-4,8-diene-l,12-dialdehyde (4,8-dodecadienedial or C₁₂ dialdehyde), 0.5g 12-oxo-dodeca- 4,8-dieneoic acid (12-oxo-4,8-dodecadienoic acid or C₁₂ oxo acid), 0.4g doceca-4,8-diene-l,12- dioic acid (4,8-dodecadiendioic acid or C₁₂ diacid), 0.7g unreacted CDDT, and 3.3g of not identified by-products. This represents normalized CDDT molar selectivity of 68% to C₁₂ dialdehyde, 2.4% to C₁₂ oxo acid, 2.8% to C₁₂ diacid, 73.2% to C₁₂ products.

[00116] Examples 2-14 are conducted analogous to Example 1 with parameter variations as identified in Table 2.

Table 2

* balance consisted of C8 & C4 species

** consisted of 24.1% methyl ester of 12-oxo-dodeca-4,8-dieneoic acid

# 4.1 pH buffer solution is prepared by mixing 2.04g Potassium hydrogen phthalate [KHP], 96.6ml Dl water with 1.3ml O.IM sodium hydroxide solution.

§ 5.0 pH buffer solution is prepared by mixing 100ml O.IM sodium dihydrogen phosphate solution [NaH2P04.2H20] with 2.47ml O.IM sodium hydroxide solution. D 9.6 pH buffer solution is prepared by mixing 100ml 0.05M sodium bicarbonate solution with 10ml O.IM sodium hydroxide solution.

[00117] Example 15: Employing the reactor and procedure described in Example 1, a steady concentration of 26.2g ozone/m³ in 2 liter/min argon flow (0.044g ozone/min) is sparged into the reaction vessel for 85 minutes containing 15.0g (0.092 moles) of CDDT, 7.0g dry methanol and 90. Og methyl acetate. Total of 4.44g of ozone is fed to the reaction to achieve a CDDT/ozone molar ratio of about one. The reaction is carried out at 5.5°C bulk temperature. Upon completion of ozonolysis reaction, a liquid mixture containing 30.0g acetic anhydride (ACAN) and 8.0g of triethylamine (Et₃N) is added to the reaction mixture in seven 5cc increments with 650 RPM stirring of the reaction mixture. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature never exceeds 15°C. The reaction mixture is allowed to warm to room temperature and stirred for an additional one hour. Reaction product is recovered as a single phase (107g). The final GC analysis indicates 83% CDDT conversion. The GC-analyzed, solvent-free, product distribution is 14.8g 12-oxo- dodeca-4,8-dieneoic acid-methyl ester (Methyl 12-oxo-4,8-dodecadienoate or C₁₂ oxo ester), 0.7g C₁₂ dialdehyde, 0.3g C₁₂ oxo acid, O.Og C₁₂ diacid and 1.6g not identified by-products. 2.5g of CDDT fed is unconverted in this example. The normalized molar selectivity of the reacted CDDT is 84% for C₁₂ oxo ester and 4.3% for C₁₂ dialdehyde.

[00118] Examples 16-30 are conducted analogous to Example 15 with parameter variations as identified in Table 3.

Table 3

*balance consisted of C8 & C4 species

** consisted of 61.4% trans/trans and 34.9% trans/cis

100119] 12-Oxo-dodeca-4,8-dienoic acid, n-butyl ester, major product in Example 30):

1H NMR (CDC1₃, 400ΜΗζ):δ_Η 9.75 (1H, s, H , 5.32 (1H, t, H₄), 5.32 (1H, t, H₅), 5.32 (1H, t, He), 5.32 (1H, t, ¾), 4.15 (2H, t, ¾), 2.36 (2H, m, ¾), 2.36 (2H, m, H₁₀), 2.36 (2H, m, H_n), 2.15 (2H, m, H₃), 2.07 (2H, m, ¾), 2.07 (2H, m, H₇), 21.58 (2H, m, Hi₄), 1.35 (2H, m, H₁₅), 0.96 (3H, t, Hi₆). ¹³C NMR (CDC1₃, 125MHz): 5_C 202.5 (s, C₁₂), 173.4 (s, Ci), 129.8 (s, C₄), 129.8 (s, C₅), 128.4 (s, C₈), 128.4 (s, C₉), 64.2 (s, C₁₃), 44.9 (s, C₂), 31.8 (s, C₆), 31.8 (s ,C₇), 31.8 (s, Cn), 30.6 (s, Cio), 28.4 (s, C₃), 30.6 (s, C₁₄), 19.3 (s, C₁₅), 13.9 (s, C₁₆).

[00120] Example 31: A 125ml jacketed reactor vessel is fitted with a dry ice condenser, mechanical stirrer, stainless steel feed tube for sub-surface ozone gas addition and a fourth port for addition of reagents, sampling and thermocouple connection. A premixed oxygen-in-argon gas is fed to an ozone generator (Pacific Ozone). The exit gas from the ozone generator is flowed through an ozone monitor (Teledyne Instruments) for 30min to observe stable ozone concentration in the feed gas. The reaction temperature is maintained at a desired target via jacketed cooling. The exit gas containing residual oxygen and nitrogen is passed through an ice water cold trap to recover any volatile solvent. Upon reaction time completion, dry nitrogen is passed into the reactor for 30min to displace any residual ozone and oxygen and the vessel warmed to room temperature. 1,5-cyclooctadiene (COD) is obtained from a commercial lab chemicals supplier in it's pure form.

[00121] A steady concentration of 34.9g ozone/m³ in 1 liter/min argon flow (0.037g ozone/min) is sparged into the reaction vessel for 85 minutes containing 7.0g (0.065 moles) of COD, and 59. Og methyl acetate. Total of 3.1 lg of ozone is fed to the reaction to achieve a COD/ozone molar ratio of about one. The reaction is carried out at 5°C bulk temperature. Upon completion of ozonolysis reaction, the reaction mixture is warmed to 10°C and 10. Og of dimethyl sulfoxide (DMSO) is slowly added to the reaction mixture while stirring to maintain below 15°C. The reaction mixture is allowed to warm to room temperature and stirred for 30 minutes. Reaction product is recovered as a single phase (66. Og). The final GC analysis indicates 54% COD conversion. The GC-analyzed, solvent-free, product distribution is 1.8g Cg dialdehyde, 3.3g unconverted COD and 3.0g of not identified by-products. The normalized molar selectivity of the reacted COD is 51% for Cg dialdehyde.

[00122] Example 32: Employing the reactor, procedure and CDDT described in Example 1, a 2 liter/min total gas flow, containing a steady concentration of 26.3g ozone/m³ is sparged subsurface into the reaction vessel for 60 minutes containing a liquid mixture of 35. Og (0.216 moles) of CDDT and 20.0g of n-butyl alcohol that is dried over the molecular sieves. The total ozone fed is 3.15g at the 0.053 g/min feed rate, which is equivalent to the molar feed ratio of 0.3 ozone/CDDT. The reaction is carried out at 5°C bulk temperature. When the reaction is complete, a cooled liquid mixture of 20.0g ACAN and 2.5g Et₃N is added to the reaction intermediate via pump at an average feed rate of 2.81 g/min with 650 RPM stirring of the reaction mixture. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature is maintained at or below 10°C. The reaction mixture is allowed to reach room temperature and stirred for additional 30 minutes for completion.

[00123] 73g of one-phase liquid reaction product is recovered. The final GC analysis indicates 39.5% CDDT conversion. The GC-analyzed, solvent-free, product weight distribution of the C₁₂ components is: 12.2g n-butyl ester of 12-oxo-dodeca-4,8-dieneoic acid, 0.5g dodeca- 4,8-diene-l,12-dialdehyde and 0.05g 12-oxo-dodeca-4,8-dieneoic acid. The non-selective products are: O.lg unsaturated C₈ dialdehyde, 0.3 g other unsaturated C₈ components and O.lg of combined C₄ impurities. 21.2g of CDDT fed remaines unconverted in this example. The normalized molar selectivity of the reacted CDDT is 90.5% for n-butyl ester of 12-oxo-dodeca- 4,8-dieneoic acid, 5.1% for dodeca-4,8-diene-l,12-dialdehyde, 0.5% for 12-oxo-dodeca-4,8- dieneoic acid, 0.85% for unsaturated Cg dialdehyde and 2.5% for the combined other unsaturated C₈ and saturated C₄ impurities. The overall preservation of the C₁₂ species is calculated to be 96% on a normalized basis with the remaining 4% non-selectively cleaved molecules from the ozone attack on second double bond, i.e., C₈'s and the corresponding C₄'s.

[00124] Examples 33-35 are conducted analogous to Example 32 with parameter variations as identified in Table 4. The achieved CDDT conversion in these examples is in the 40% to 76% range.

Table 4

*21% in Argon gas used for ozone generation [00125] Example 36: Employing the reactor and procedure of Example 31 and the CDDT described in Example 1, a 1 liter/min total gas flow, containing a steady concentration of 26.2g ozone/m³ is sparged sub-surface into the reaction vessel for 120 minutes containing a liquid mixture of 45.0g (0.277 moles) of CDDT and 8.0g of n-butyl alcohol that is dried over the molecular sieves. The total ozone fed is 3.14g at the 0.026 g/min feed rate, which is equivalent to the molar feed ratio of 0.24 ozone/CDDT. The reaction is carried out at 5°C bulk temperature. When the reaction is complete, a cooled liquid mixture of 18.6g ACAN and 5.0g Et₃N is added to the well-agitated reaction intermediate. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature is maintained at or below 10°C. The reaction mixture is allowed to reach room temperature and stirred for additional 30 minutes for completion.

[00126] 74.9g of one-phase liquid reaction product is recovered. The final GC analysis indicates 21.1% CDDT conversion. The GC-analyzed, solvent-free, product weight distribution of the C₁₂ components is: 14.3g n-butyl ester of 12-oxo-dodeca-4,8-dieneoic acid, O.lg dodeca- 4,8-diene-l,12-dialdehyde and 0.3g 12-oxo-dodeca-4,8-dieneoic acid. The non-selective products are: O.lg unsaturated n-butyl ester of C₈ aldehyde acid, O.lg unsaturated n-butyl diester of C₈ diacid, 0.2g of combined C₄'s and 0.3 unidentified impurities. 35.5g of CDDT fed is unconverted in this example. The normalized molar selectivity of the reacted CDDT is 93.4% for n-butyl ester of 12-oxo-dodeca-4,8-dieneoic acid, 0.6% for Dodeca-4,8-diene-l,12- dialdehyde, 2.4% for 12-oxo-dodeca-4,8-dieneoic acid, 1.4% for unsaturated C₈ dialdehyde and 3.0%) for the combined other unsaturated C₈ and saturated C₄ impurities. The overall preservation of the C₁₂ species is calculated to be 96% on a normalized basis with the remaining 4% non-selectively cleaved molecules from the ozone attack on second double bond, i.e., Cg's and the corresponding C₄'s.

[00127] Example 37: Employing the reactor and procedure described in Example 36, a 1 liter/min total gas flow, containing a steady concentration of 26.3 g ozone/m³ is sparged subsurface into the reaction vessel for 202 minutes containing a liquid mixture of 35.0g (0.216 moles) of CDDT and 14.0g of n-butyl alcohol. The total ozone fed is 5.32g at the 0.026 g/min feed rate, which is equivalent to the molar feed ratio of 0.514 ozone/CDDT. The reaction is carried out at 15°C bulk temperature. Upon completion, the reactor content is cooled to 5°C and a cooled liquid mixture of 28. Og ACAN and 12. Og Et₃N is added while agitated. The reaction

exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature is maintained at or below 10°C. The reaction mixture is allowed to reach room temperature and stirred for additional 30 minutes for completion. Some moisture in the surrounding air condensed on the overhead cold surfaces, trickled down the glassware and some water condensate fugitively leaks in the reaction vessel during this run. The amount of water intrusion is not measured but qualitatively estimated to be less than 5.0g total.

[00128] 88.9g of one-phase liquid reaction product is recovered. The final GC analysis indicates 38.2% CDDT conversion. The GC-analyzed, solvent-free, product weight distribution of the C₁₂ components is: 16g n-butyl ester of 12-oxo-dodeca-4,8-dieneoic acid, 2.8g Dodeca- 4,8-diene-l,12-dialdehyde and 0.4g 12-oxo-dodeca-4,8-dieneoic acid. The non-selective products are: 0.2g unsaturated n-butyl ester of C8 aldehyde acid, 0.2g unsaturated n-butyl diester of C₈ diacid, 0.2g of combined C₄'s and 0.3g unidentified impurities. 21.6g of CDDT fed is unconverted in this example. The normalized molar selectivity of the reacted CDDT is 75% for n-butyl ester of 12-oxo-dodeca-4,8-dieneoic acid, 17.8% for Dodeca-4,8-diene-l,12-dialdehyde,

2.1% for 12-oxo-dodeca-4,8-dieneoic acid, 0.93% for unsaturated C8 dialdehyde and 5.1% for the combined other unsaturated C₈ and saturated C impurities. The overall preservation of the

C species is calculated to be 95% on a normalized basis with the remaining 5% non-selectively cleaved molecules from the ozone attack on second double bond, i.e., C₈'s and the corresponding

C₄'s.

[00129] Examples 38 and 39 are conducted analogous to Example 37 with parameter variations as shown in Table 5.

Table 5: 45.0g CDDT, 16.0g n-BuOH, 0.026 g/min ozone feed, 210 min reaction time, 5°C,

36.0g ACAN / lO.Og triethylamine

Molar Selectivity (Normalized)

Total Ci2

Ex. Gas used for ozone generation CDDT Conversion, C]₂ Oxo Ester Co dialdehyde Ci2 oxo acid Ci2 diacid Cs Species Other Preservation

% (normalized)

38 21% 0₂ in Argon 41.6 94.4 1.2 2.3 0.0 0.8 1.2 97.9

39 21% 0₂ in Nitrogen 39.0 86.9 5.2 2.4 0.0 1.1 4.4 94.5 [00130] Examples 40-44 in Table 6 are conducted analogous to Example 32 but with fresh anhydride and a recycle stream of triethylamine and acetic acid (~30wt% contained amine).

Table 6: 20.0g CDDT, 0.078 g/min ozone feed, 142 min reaction time, 5°C

[00131] Examples 45-49 are conducted analogous to Example 32 with the reaction temperature variation in the 5°C to 40°C range as shown in Table 7.

Table 7: 60.0g CDDT, 27.4g n-BuOH, 0.078 g/min ozone feed, 114 min reaction time, 35.2g

ACAN / 7.5g amine (Examples 45-48)

*60.0g CDDT, 42.4g n-BuOH, 0.028 g/min ozone feed, 265 min reaction time, 35.2g ACAN / 7.5g amine

[00132] Example 50: A 125cc Hastelloy C metal autoclave, equipped with an agitator, heat exchange jacket, bulk liquid thermocouple and inert nitrogen purge, is used for catalytic hydrogenation and reductive amination chemistries.

[00133] Preparation of 1,12-dodecadial: Fifty grams of a mixture consisting of 13.5g Dodeca- 4,8-dienedial, 11.4g methyl acetate, 4.4g CDDT and the balance water, washed initially 2x with 10% Na₂S₂0₃ to remove H₂0₂, is charged to the autoclave at 15°C. 5% Pd on carbon (1.25g Evonik PI 092) is next added and the autoclave sealed. The autoclave is pressure tested at 500psig with slow stirring. The residual nitrogen is removed with two purges of 200psig hydrogen without stirring at 15°C. The autoclave is warmed to 25°C and 900 RPM stirring commences at 200psig. The hydrogenation is run for 5.5hrs followed by depressurization to the ambient pressure and nitrogen purging. The product is filtered through Celite filter aid under vacuum to recover 34g solution. GC analysis shows 100% conversion of the Dodeca-4,8- dienedial resulting in 8.98g of 1,12-dodecanedial and 1.09g 12-oxo-dodecanol in 77.6% overall yield from dodeca-4,8-dienedial.

[00134] Preparation of 1,12-dodecadiamine: A solution of 5.0g 1,12-dodecadial in 50.0g isopropanol is charged to the autoclave described in Example 50 at 10°C. To the feed in the autoclave is slowly added 15. Og of 28% aqueous NH₄OH (temperature rise is noted). Raney^® Ni (1.3g, Raney^® 3111) is next added. The autoclave is sealed and pressure tested at 200psig. After the pressure test, the temperature is raised to 60°C and run at 600psig with 900 RPM stirring. The run time is determined by hydrogen uptake and/or disappearance of starting oxo or imine as measured by LC. The reaction mixture is sampled with time to determine the extent of conversion. After the run, the autoclave is depressurized slowly at 20°C to remove most of the ammonia and the product and catalyst are removed under N₂ into a tared bottle. The catalyst is filtered from the product under N₂ and stored in refrigerator. GC analysis shows complete conversion of the 1,12-dodecdial to the 1,12-dodecanediamine.

[00135] Example 51: A solution of 15.0g 1,12-dodecanedial in 20.0g toluene is charged into a 125cc jacketed glass vessel. Mn(OAc)₂ catalyst (O.lg) is also added to the solution. Air is sparged into the vessel at 500ml/min for 6 hrs at 50°C. GC analysis of the product shows 50% conversion of the 1,12-dodecandial to both insoluble 12-oxo-dodecanoic acid and 1,12- dodecandioic acid products.

[00136] Example 52: A 48.0g solution consisting of 2.53g 1,12-dodecadial, 1.43g 12-oxo- dodecanol, 2.34g cyclododecane, 4.8g methyl acetate with the balance isopropanol is charged to the autoclave described in Example 50 at 15°C. The autoclave is pressure tested at 500psig with slow stirring. The residual nitrogen is removed with two purges of 200psig hydrogen without stirring at 15°C. The autoclave is warmed to 45°C and 900 RPM and stirring commences at 400psig. The hydrogenation is run for 3hrs followed by depressurization to the ambient pressure and nitrogen purging. The product is filtered through Celite filter aid under vacuum to recover approximately 41.7g solution and 8.9g rinse. GC analysis shows complete conversion of 1,12- dodecadial and 12-oxo-dodecanol to 3.56g 1,12-dodecanediol in 89% yield.

[00137] Example 53: Employing the reactor and procedure of Example 31 and the CDDT described in Example 1, 15.0g (0.094 mole) CDDT and 40.0g THF are charged to the reactor. The reactor contains a Dry Ice condenser, mechanical stirrer running at 650 RPM, tube for ozone addition and a port for sampling, addition of secondary reagents and a 1/8" thermocouple. Coolant from a 13 liter chiller bath is circulated through the reactor at 15 liter per min. A total gas flow of 1 liter/min, containing a steady state ozone concentration of 26g ozone/m³, is sparged into the vessel for 150 minutes at 5°C. An ozone monitor continually records the ozone concentration with time. Upon completion, the ozone is stopped and nitrogen is then passed into reactor for 5 minutes to remove any residual ozone.

[00138] To the solution is added 5.0g methanol at 5°C and run for 15 minutes. This is followed by addition of a transformation solution consisting of 18.0g AC AN and 8.0g Et₃N while maintaining the temperature below 10°C. This is then followed by additional 5.0g methanol. After 1 hour the reaction mixture is analyzed by Gas Chromatography on a HP 1 capillary column. Conversion of CDDT is 61.3% and the normalized selectivity to dodeca-4,8- dienedial (C₁₂ dialdehyde), 12-oxo-dodeca-4,8-dienoic acid (C₁₂ aldehyde acid) and 12-oxo- dodeca-4,8-dienoic acid methyl ester (C₁₂ aldehyde ester) is 69.1%>, 18.5%) and 13. Irrespectively. A repeat run similarly shows the normalized selectivities for the same products in the previous order as 66.5%, 21.8% and 11.8% at 55% CDDT conversion.

[00139] Example 54: Employing the reactor and procedure of Example 53 and the CDDT described in Example 1, 45.0g (0.277 mole) CDDT, 21.0g methanol and 50.0g methyl acetate solvent are charged to the reactor. The jacketed reactor contains a Dry Ice condenser, mechanical stirrer running at 600 RPM, tube for ozone addition and a port for sampling, addition of secondary reagents and a 1/8" thermocouple. Coolant from a 13 liter chiller bath is circulated through the reactor at 15 liter per min. A total gas flow of 2 liter/min, containing a steady state ozone concentration of 26. Og ozone/m³, is sparged into the vessel for 175 minutes at 5°C. Because of the reaction time and methyl acetate volatility, additional methyl acetate is slowly added by a pump to replace the methyl acetate lost by volatilization. An ozone monitor continually records the ozone concentration with time. Upon completion, the ozone is stopped and nitrogen is then passed into reactor for 5 minutes to remove any residual ozone.

[00140] To the solution is added a transformation solution consisting of 60.0g ACAN and 24.0g Et₃N while maintaining the temperature below 10°C. After 1 hour, the reaction mixture is analyzed by Gas Chromatography on a HP 1 capillary column. Conversion of CDDT is 57% and the normalized selectivity to dodeca-4,8-dienedial (C₁₂ dialdehyde), 12-oxo-dodeca-4,8-dienoic acid (C₁₂ aldehyde acid) and 12-oxo-dodeca-4,8-dienoic acid methyl ester (C ₂ aldehyde ester) is 2.2%, 2.4% and 89%, respectively.

[00141] Example 55: Employing the reactor and procedure described in Example 1, a steady concentration of 26.2g ozone/m³ in 1 liter/min argon flow is sparged into the reaction vessel for 225 minutes containing 35.0g (0.22 moles) of 1,5,9-cyclododecatriene (CDDT) and 15.0g acetic acid. The reaction is carried out at 5.0°C bulk temperature. When the reaction is complete, the top layer is removed and 2.0g of sodium acetate dissolved in 9.0g of acetic acid is added to the bottom reaction mixture in small increments with 650 RPM stirring of the reaction mixture. The reaction exotherms, observed during these additions, are managed by active jacketed cooling to ensure the temperature never exceeds 10°C. The reaction mixture is allowed to warm to room temperature and stirred for an additional two hours. The final GC analysis indicates 64.7% CDDT conversion and normalized product selectivity distribution of 96.7% to the C₁₂ dialdehyde, 1.4% to the C₁₂ oxo acid, 0.8% to the diacid and 1.1% to the C₈ dialdehyde is obtained.

[00142] Example 56: The thermal stabilities of three different intermediates generated from the ozonolysis of CDDT are investigated using the standard-cell DSC experiments. The three different ozonolysis intermediates used are:

is obtained from the ozonolysis of the presence of methanol at conditions analogous to Example 15 but in the absence of

B)

, is obtained from the ozonolysis of

CDDT in the presence of 1-propanol at conditions analogous to Example 15 but in the absence of solvent; and

C)

is obtained from the ozonolysis of

CDDT in the presence of n-butanol at conditions analogous to Example 15 but in the absence of solvent.

[00143] In the DSC experiment, each sample is first equilibrated at 20°C for 1.0 min. The equilibrated sample temperature is then ramped at the 10.0°C/min rate to the target temperature of 220.0°C. The sample is maintained at the target temperature for 1.0 min before completing the first cycle via cool-down to 20°C. Figure 1 shows the DSC-measured heat flow activity on the Y-axis with respect to the sample temperature on the X-axis for the three intermediates tested in this example. The onset of heat flow (in watts/gram) from each of the three samples is at least after 80°C, more like at the 90°C mark on the X-axis. The DSC data provides sufficient confirmation of the thermal stability of the three intermediates disclosed herein.

[00144] Ozonolysis intermediate B (12-propoxy-12-hvdroperoxy-dodeca-4,8-dienal):

1H NMR (CDC1₃, 400ΜΗζ):δ_Η 9.75 (1H, s, ¾), 5.32 (1H, t, ¾), 5.32 (1H, t, H₅), 5.32 (1H, t, ¾), 5.32 (1H, t, H₉), 5.37 (1H, t, H₁₂), 4.14 (2H, t, H₁₃), 2.36 (2H, m, H₂), 2.15 (2H, m, H₃), 2.07 (2H, m, H₆), 2.07 (2H, m, H₇), 2.05 (2H, m, H₁₀), 1.62 (2H, m, Hn), 1.65 (2H, m, H₁₄), 0.99 (3H, t, His). ¹³C NMR (CDC1₃, 125MHz): 8₀ 202.5 (s, C_t), 129.8 (s, C₄), 129.8 (s, C₅), 128.4 (s, C₈), 128.4 (s, C₉), 107.3 (s, C₁₂), 68.2 (s, C₁₃), 43.7 (s, C₂), 35.6 (s, C₁₄), 31.8 (s, C₆), 31.8 (s, C₇), 30.8 (s, Cn), 28.4 (s, C₃), 28.4 (s, C₁₀), 28.4 (s, C₁₄), 10.3 (s, C₁₅).

[00145] Ozonolysis intermediate C (12-butoxy-12-hvdroperoxy-dodeca-4,8-dienal):

H NMR (CDC1₃, 400MHz): δ_Η 9.75 (1H, s, H , 5.37 (2H, 1H, t, H_!2), 5.32 (1H, t, H₄), 5.32

(1H, t, H₅), 5.32 (1H, t, ¾), 5.32 (1H, t, H₉), 4.15 (2H, t, H₁₃), 2.36 (2H, m, H₂), 2.15 (2H, m, ¾), 2.07 (2H, m, H₆), 2.07 (2H, m, H₇), 2.05 (2H, m, H₁₀), 1.62 (2H, m, Hn), 1.42 (2H, m, H₁₄), 1.42 (2h, m, H₁₅), 0.96 (3H, t, H₁₆). ¹³C NMR (CDC1₃, 125MHz): 5_C 202.5 (s, d), 129.8 (s, C₄), 129.8 (s, C₅), 128.4 (s, C₈), 128.4 (s, C₉), 107.3 (s, C₁₂), 64.2 (s, Ci₃), 44.9 (s, C₂), 31.8 (s, C₆), 31.8 (s ,C₇), 31.8 (s, Cn), 30.6 (s, C₁₀), 30.6 (s, C₁₄), 28.4 (s, C₃), 19.3 (s, C₁₅), 13.9 (s, C₁₆).

[00146] Example 57: The DSC conditions of Example 56 are re-run for an additional

intermediate D: The intermediate D is obtained from the intermediate C) of Example 56 at conditions analogous to Example 15 but in the absence of solvent. In Figure 2, the solid-lined data refers to the intermediate C) of Example 56, and the dash-lined data refers to the intermediate D.

[00147] Example 56 provides sufficient evidence of the thermal stability of the intermediates A) through C) as obtained according to the disclosed process. The significant DSC heat flow activity for all three analogs is recorded after the sample temperature of 80°C in Figure 1. The Example 56 intermediate A) shows the largest peak for heat flow activity [measure of exothermicity] in comparison with the other two intermediates B) and C) that show a similar heat flow activity level.

[00148] Example 57 further shows the thermal stability of the intermediate D for temperatures below 60°C and compares with its pre-cursor, intermediate C) of Example 56. The DSC data therefore obtains the operating conditions for the process before compromising the reaction products which may otherwise thermally degrade.

[00149] Intermediate D (12-butoxy-12-acetylperoxy-dodeca-4,8-dienal):

1H NMR (CDCfe, 400MHz): δ_Η 9.75 (IH, s, H , 5.3? (2H, IH, t, H₁₂), 5.32 (IH, t, ¾), 5.32 (IH, t, ¾), 5.32 (IH, t, H₈), 5.32 (IH, t, H₉), 4.15 (2H, t, ¾), 2.36 (2H, m, ¾), 2.20 (3H, s, acetylperoxy-CHj), 2.15 (2H, m, H₃), 2.07 (2H, m, H₆), 2.07 (2H, m, H₇), 2.05 (2H, m, H₁₀), 1.62 (2H, m, H„), 1.42 (2H, m, H₁₄), 1.42 (2H, m, His), 0.96 (3H, t, H₁₆). ¹³C NMR (CDC1₃, 125MHz): 5_C 202.5 (s, d), 169.4 (s, acetylperoxy-C=0), 129.8 (s, C₄), 129.8 (s, C₅), 128.4 (s, C₉), 128.4 (s, Cio), 107.3 (s, C₁₂), 64.2 (s, C₁₃), 44.9 (s, C₂), 31.8 (s, C₆), 31.8 (s ,C₇), 31.8 (s, C₈), 30.6 (s, Cn), 30.6 (s, C₁₄), 28.4 (s, C₃), 22.0 (s, acetylperoxy-CH₃), 19.3 (s, C₁₅), 13.7 (s, Cie).

[00150] 12-Propoxy- 12-acetylperoxy-dodeca-4, 8 -dienal :

1H NMR (CDCI3, 400ΜΗζ):δ_Η 9.75 (1H, s, H , 5.37 (2H, 1H, t, H₁₂), 5.32 (1H, t, ¾), 5.32 (1H, t, H₉), 5.32 (1H, t, H₄), 5.32 (1H, t, H₅), ), 4.15 (2H, t, H₁₃), 2.36 (2H_S m, ¾), 2.15 (2H, m, ¾), 2.07 (2H, m, H₆), 2.07 (2H, m, H₇), 2.05 (2H, m, H₁₀), 2.20(s, 3H, acetylperoxy-CH₃), 1.62 (2H, m, Hnl.65 (2h, m, Hi₄), 0.99 (3H, t, H₁₅). ¹³C NMR (CDC1₃, 125MHz): 6_C 202.5 (s, d), 169.5 (s, acetylperoxy-C=0), 129.8 (s, C₄), 129.8 (s, C₅)₅ 128.4 (s, C₈), 128.4 (s, C₉), 107.3 (s, C12), 68.2 (s, C13), 43.7 (s, C₂), 35.6 (s, C₁₄), 31.8 (s, C₆), 31.8 (s, C₇), 30.8 (s, Cn), 28.4 (s, C₃), 28.4 (s, Cio), 28.4 (s, C₁₄), 22.0 (s, acetylperoxy-CH₃), 10.3 (s, C₁₅).

[00151] Example 58: Fifty grams of a mixture consisting of 13.5g octa-3-enedial, 11.4g methyl acetate, 4.4g 1,5-cyclooctadiene and the balance water, washed initially 2x with 10% Na₂S₂0₃ to remove H₂0₂, is charge to the autoclave described in Example 50 at 15°C. 5% Pd on carbon (1.25g Evonik P1092) is next added and the autoclave sealed. The autoclave is pressure tested at 500psig with slow stirring. The residual nitrogen is removed with two purges of 200psig hydrogen without stirring at 15°C. The autoclave is warmed to 25°C and 900 RPM stirring commences at 200psig. The hydrogenation is run for 5.5hrs followed by depressurization to the ambient pressure and nitrogen purging. The product is filtered through Celite filter aid under vacuum to recover 34.0g solution. GC analysis shows 100% conversion of octa-3-enedial resulting in 10.6 g of 1,8-octanedial in 78% yield from the octa-3-enedial.

[00152] Example 59: A 500mL jacketed reactor is charged with 35.0g 1,5-cyclcooctadiene (0.324mole) and 65.0g (0.878mole) 1-butanol. A flow of 21% 0₂ in Argon is fed to the ozone generator followed by flowing to an ozone monitor. A flow of 2 1pm is set on the ozone generator that flows to the ozone monitor. A steady state (20-3 Omin) concentration of 33.0g ozone/m³ in Argon is measured continuously on the monitor. After ~ 15min at steady state, the feed ozone in Argon is diverted to the reactor. The jacketed reactor containing, a mechanical stirrer, a tube for the ozone addition, an exit gas fitting and a fourth port for addition of reagents and sampling with a thermocouple is maintained at minus 5°C. The coolant from the circulating bath (13 liters, 15 liter/min) is circulated through the vessel. The gas is flowed through the reactor followed by passing through a Dry Ice cold trap followed by a scrubber containing 66. Og tetradecane. The ozone monitor continually measures the ozone concentration fed during the run. The run time is 141min. The ozone generator is then turned off and nitrogen is then passed into the reactor for 5 min to remove any residual ozone. [00153] When the reaction is complete, un-reacted 1-butanol is removed under high vacuum at < 50°C (max) and ~ 462-472 mtorr. The reactor is warmed to 25°C followed by the addition of 32. Og acetic anhydride (0.313 mole) and run for 15min. Triethylamine (12. Og, 0.118mole) is next added while keeping the temperature below 25°C. After the complete addition the reaction is run for 120min. The conversion of 1,5-cyclooctadiene is 81% (92% accounted for with the remaining lost in the off gas). Selectivity to 8-oxo-octa-4-eneoic acid butyl ester is 84.1% along with selectivities of 7.5%, 6.1% and 3.1% to 4-oxo-succinic acid butyl ester, dibutyl succinate and 1,8-octadial, respectively.

[00154] Example 60: A 500 mL jacketed reactor is charged with 15. Og 1,5-cyclooctadiene (0.139 mole), 80.0g methyl acetate and 48.0g (2.66 moles) DI water. A flow of 21% 0₂ in Argon is fed to the ozone generator followed by flowing to an ozone monitor. A flow of 2 1pm is set on the ozone generator that flows to the ozone monitor. A steady state (20-3 Omin) concentration of 33. Og ozone/m³ in Argon is measured continuously on the monitor prior. After ~ 15min at steady state, the feed ozone in Argon is fed to the reactor. The jacketed reactor containing, a mechanical stirrer, a tube for the ozone addition, an exit gas fitting and a fourth port for addition of reagents and sampling and TC is maintained at 5°C. The coolant from the circulating bath (13 liters, 151iter/min) is circulated through the vessel. The gas is flowed through the reactor followed by passing through a Dry Ice cold trap, a scrubber containing 66. Og tetradecane followed by a KI scrubbing solution. The ozone monitor continually measures the ozone concentration during the run. Run time is 202min. The ozone generator is then turned off and nitrogen is then passed into the reactor for 5 min to remove any residual ozone.

[00155] The reaction produces two layers with the bottom layer containing a majority of the C₈ and C₄ dialdehyde products. Some C₈ (0.30g) and C₄ (0.36g) dialdehyde products are observed in the top aqueous/methyl acetate layer. The bottom layer contains 16.7g and 2.1g 1,8- octa-4-enedial and 1 ,8-succindial, respectively. Both layers contain H₂0₂, a co-product from dialdehyde production. The H₂0₂ is destroyed with 10% aqueous Na₂S₂0₃. The conversion of cyclooctadiene is 100%) (some lost in the off gas). The selectivity to 1,8-octadial is 81.8% along with 18.9%» selectivity to 1,2-succindial. [00156] Example 61: A solution of 35. Og 1,8-octanedial in 20. Og isopropanol is charged into the autoclave described in Example 50 at 25°C. The autoclave is pressure tested at 500psig with slow stirring. The residual nitrogen is removed with two purges of 200psig hydrogen without stirring at 15°C. The autoclave is warmed to 50°C and 900 RPM stirring commences at 500psig. The hydrogenation is run for 6hrs followed by depressurization to the ambient pressure and nitrogen purging. The product is filtered through Celite^® filter aid under vacuum to recover the 1,8-octanediol. GC analysis shows > 90% conversion of 1,8-octanedial to 1,8-octanediol.

[00157] Example 62: A solution of 15.0g 1,8-octanedial in 20.0g toluene is charged into a lOOcc jacketed glass vessel. Mn(OAc)₂ catalyst (O.lg) is also added to the solution. Air is sparged into the vessel at 500ml/min for 6 hrs at 50°C. GC analysis of the product shows 50% conversion of the 1,8-octanedial to insoluble 1,8-octanedioic acid and 8-oxo-octanoic acid products.

[00158] Example 63: A solution of 5.0g 1,8-octanedial in 50.0g isopropanol is charged to the autoclave described in Example 50 at 10 C. To the feed in the vessel is slowly added 15.0g of 28%o aqueous NH OH (temperature rise is noted). Raney^® Ni (1.3g, Raney® 3111) is next added. The autoclave is sealed and pressure tested at 200psig. After the pressure test, the temperature is raised to 60°C and run at 600psig with 900 RPM stirring. The run time is determined by hydrogen uptake and/or disappearance of starting oxo or imine as measured by LC. The reactor content is sampled with time to determine the extent of conversion. After the run, the autoclave is depressurized slowly at 20°C to remove most of the ammonia and the product and catalyst are removed under N₂ into a tared bottle. The catalyst is filtered from the product under N₂ and stored in refrigerator. GC analysis shows complete conversion of the 1,8- octanedial to the 1,8-octanediamine.

[00159] Example 64: This Example illustrates scaled-up production of a stream comprising a compound of formula III starting from CDDT, n-butanol and ozone gas. An industrial-scale, continuous gas-liquid contactor is used which provides uniform gas dispersion in the liquid phase and efficient heat exchange. A pure oxygen stream is used to generate ozone at the rate of about 200 lb/hr and about 10% 0₂ to O3 conversion in the ozone generator. A dry, nitrogen gas is added to the 0₃/0₂ mix as an inert at the N₂/0₂ feed ratio of 3.8:1. The CDDT is fed to the contactor at the rate of about 2,100 lb/hr and fresh n-butanol at the rate of about 390 lb/hr. This maintains the ozone: CDDT molar ratio of about 0.32:1 and the CDDT (reacted) : butanol molar ratio of about 1 :1.4. The CDDT ozonolysis is carried out at 10 Psig pressure and 5°C bulk liquid temperature to obtain about 29% molar conversion of CDDT. The off-gas is separated from the contactor effluent which comprises the compound of formula Ila, unconverted CDDT, excess butanol and other non-selective products. The excess butanol is stripped in a flash distillation unit at conditions of about 50°C and 30 mmHg vacuum. The butanol-stripped ozonolysis effluent containing the compound of formula Ila is pumped to a liquid-liquid reaction vessel where a fresh mixture of acetic anhydride and triethylamine is gradually added while maintaining the temperature to about 5-10°C. The feed mixture is catalytically transformed into a mixture comprising the compound of formula III. The molar ratios of acetic anhydride: CDDT (reacted) and triethylamine: CDDT (reacted) are maintained at 1.5:1 and 0.3:1, respectively. The product is a homogeneous, flowable liquid mixture comprising the n-butyl ester of ca-formyl-4,8- dodecadienoic acid, i.e., the compound of formula III. The excess butanol, stripped before the transformation step, is collected and refined into dry butanol for recycle.

Claims

What is claimed is:

1. A method of making a compound of formula I , comprising:

a) contacting a compound of formula I:

, and a reagent with a medium comprising ozone;

b) forming a reaction mixture comprising the compound of formula Ila, and without isolating the product from the ozone of a); and

c) recovering the product of b) comprising the compound of formula Ila;

wherein, A is a C₆-C₁₀ alkene group with at least one double bond; R is a Ci-C₁₀ alkyl; R is an oxygen-containing functional group.

2. The method of claim 1, wherein the reaction mixture is a single continuous phase.

3. The method of claim 1, wherein the reagent is provided in excess.

4. The method of claim 3, wherein the reagent is at least partially removed in c).

5. The method of claim 4, wherein the reagent is removed via flash distillation.

6. The method of claim 1 , wherein the reagent is a Q -C₁₀ alcohol.

7. The method of claim 1, wherein the reagent is a C₃-C₆ alcohol.

8. The method of claim 1, wherein the reagent is propanol or butanol.

9. The method of claim 1, wherein the reagent is anhydrous.

10. The method of claim 1, wherein the compound of formula Ila is formed with high selectivity.

11. The method of claim 1, wherein the compound of formula I is cyclododecatriene or cyclooctadiene.

12. The method of claim 1, wherein R³ is an aldehyde group.

13. The method of claim 1, wherein the conversion of the compound of formula I is at least 20%.

14. The method of claim 1, wherein the carbon preservation selectivity is at least 50%.

15. The method of claim 1, wherein the selectivity is greater than 70%.

16. The method of claim 1 wherein the concentration of the compound of formula I is about 1 weight percent to about 90 weight percent.

17. The method of claim 1, wherein a) is in the presence of an inert solvent.

18. The method of claim 17, wherein the solvent is polar.

19. The method of claim 1, wherein the reagent is in a concentration of about 5 weight

percent to about 75 weight percent.

20. The method of claim 1, wherein a)-c) are conducted at a temperature range of about - 25°C to about 50°C.

21. The method of claim 1, wherein a) further comprises introducing a flow of gas during a time period of about 10 minutes to about 300 minutes.

22. A method of making R⁴-A-R⁴ comprising:

i. contacting a compound of formula I:o and an agent with a medium comprising ozone;

ii. forming an ozonolysis product, wherein the resulting ozonolysis product is not isolated; and

iii. allowing the ozonolysis product to transform to R⁴-A-R⁴;

wherein A is a C6-C₁₀ alkene chain with at least one double bond and R⁴ is an aldehyde group.

23. The method of claim 22, wherein the agent is water or a carboxylic acid.

24. A composition comprising a compound of formula (II):

_; wherein A is

* 1 * 2 * a C -C₁₀ alkene chain with at least one double bond; R is a Ci-Cw alkyl; R is H, acetyl; and R is an oxygen-containing functional group.

25. The composition of claim 24, wherein R¹ is a C C₄ alkyl.

26. The composition of claim 25, wherein A is a C₆ alkene chain.

27. The composition of claim 26, wherein R is H.

28. The composition of claim 27, wherein R¹ is a C₂-C₄ alkyl.

29. The composition of claim 24, wherein A is -CH₂-CH₂-CH=CH-CH₂-CH₂-CH=CH-CH₂- C¾-.

30. A system for the chemical transformation of a compound of formula

to a

compound of formula Ila:

and with the preservation of the total number of carbon atoms in the compound of formula I, comprising:

a. the compound of formula I and a reagent, optionally in combination with a

solvent;

b. a medium comprising ozone;

c. an ozonolysis product; and

d. the compound of formula Ila;

wherein, components a, b, c and d are present in a single means for carrying out the chemical transformation; and wherein A is C₆-C₁₀ alkene chain with at least one double bond; R¹ is a Q-Cio alkyl and R³ is an oxygen-containing functional group.

31. The system of claim 30, wherein the compound of formula I is cyclododecatriene or cyclooctadiene.