HYRR0GENAT1ON PRODUCTS FROM BI0l0GlCALLY4>ERfV£D

AKSOXYiJ ^" C~ACii> ESTERS

PRIORITY CLAIM

The preseai Application claims benefit of priority f om U.S. Provisional Application o. 61 739,78 , filed December 20, 2012, the contents of which are herein incorporated.

FIELD OF INVENTION

The present invention relates to a process for the prodactioa of certain chemicals, fa particular, the invention pertains to a method for r d c n aydrogeuation products f om esters of carboxyik acids.

BACKGROUND

As valuable and important chemical compounds, 1,4-batanedioi (EDO) and y~b»fyro actone « _* ^' SL> are employed ia many industrial and commercial uses. For ins ance, EDO is an

intermediate that is used la common industrial sad commercial products, such as poiyether diois, nrethane polymers, and polyester polymers, or as a piastkker, a carrier solvent in printing inks, and a cleaning agent A significant nse of GBL is as a chemical intermediate In the aaufactnre of pyrrolidones. Other uses of G L. because of ts strong solvency properties, ioelnde being a slain remover, paint stripper, super-glue ren¾over, or a cleaner for circuit hoards ia electronics and high technology industry. Other applications Include the production of herbicides and as a processing aid in the production of pharmaceuticals,

fa conventional Industrial synthesis of BOO, as originally developed by Walter Reppe for IG Farben in the 1930s, acetylene reacts w h two equivalents of formaldehyde to o m 1,4- butyoediol, also known as bat--2-yne~l,4-dioi. Mydrogenation of ~b«ty«edkd coverts to 1,4- butaaediol. The requirements of handling acetylene meant that tor many years ordy a select few manufacturers could perform the production of BOO. The vslae of BDO and its derivatives (tetrauydrofnran (THF), GBL, etc.). however, sparred substantial efforts ia new process development thai resulted its a number of additional processes, including butadiene scetoxySatiou and ally! alcohol (from propylene oxide) aydroformylation, together with various routes from a- btstaae via muieie anlrydride/makk acid.

Industrial synthesis of BOO according to the process developed by Paw eKee Ltd., involves conversion of butane-derived inaieic acid anhydride via an intem»ediate methyl ester to BOO. Is particular, the Davy process converts mak-ic anhydride (MAH) to l,4- h«tauedlo! (BDO), tetrahydrofuran (THF) and gamma bntyroiaeioae (GBL) in three process stages. First, molten MAE is mixed with methanol and reacts exotheradeaily to form mono-methyl maieate and using a proprietary acidic resin catalyst, this is converted from mono to dimethyl maieate (BM ). This is feydrogenated to dimethyl succinate 0 ⁾ MS}, and then a series »f reaction's converts DMS to gamma hutyrolactone (CSL) and then to BIX) and TMF. inall crude product is refined to marke quali y Bl>G a.ad THF by distillation; methanol is recovered for recycle to the MM! esterifieation stage, i h DMS and GBL recovered tor recycle to hydrogeaatioa.

In recent years, as interest has rows in m ving away from natural gas or petrochemical- derived hydrocarbon sources, manufacturers have concentrated on finding renewable and

sustainable greea* material resources. Many have tried to develop a process that marries a biologically-derived hydrocarbon feed source with a system for synt sizing BOO and its associated derivatives, but none have succeeded in doing so. At present, the principal way of making

biologically-derived carbon resources has been by means of fermentation to convert sugar s and other plant-based carbohydrates into earboxylk acids. The earboxyik acids are more readily transformed into other chemicals. Currently, the earboxyik acids are recovered from fermentation broths as salts instead of as free acids. Several different steps is post-fenneatafioa, downstream processing are required to isolate the free acids, to prepare the earboxylie acids for chemical transformation and to convert the raw acids to usefai compounds. These steps have demonstrated various disadvantages, including high cost, generation of significant am unts of byproduct-waste, and limits on economy of scale for easy high-volume production.

Hence, a need exists for a better, more direct method of recovering a variety of earboxyik acids, such as malic or succinic acid, and which can provide a successful route to combine a biologically-derived hydrocarbon source with the production of various products, sneh as BOO and its derivatives, by means of hydrogeaatioa.

SUMMARY OF THE INVENTION

The present invention concerns. In part, a process for producing a hydrogeaatioa product. The process involves: a) obtaining a fermentation broth containing at least one free organic acid or a mixture of organic acids, or at least one free organic acid and an associated alkali or alkaline earth metal salts of the organic acids; b) drying the fermentation broth containing free organic acids into a powder; and c) reacting said organic acid in said powder with an alcohol solvent under a€€>> atmosphere in the substantial absence of any other extrinsic catalyst at a reaction temperature and pressure that corresponds to supercritical, critical or near critical conditions for at least the alcohol, including a mixture or combination of different alcohols, or€0> to synthesize esters from said organic acids; d) Irydrogeoating at least oue of said esters to form a hy rogeaatioa product therefr m. The hydrogenatkm products that can be made by this ethod from the corresponding free organic acids may include, for example, any one or more of the following: 1,4- hutaaediol (BDQ), tetraaydrolaran (THF), γ-bufyro!actene (GBL), N ^v -niet yl«2-pyrreiide.8e

{ MP), 2-pyrroUdoae. The esters used to provide hese hydrogenation products caa be ixioaoesiers, dlesiers, or trtesters. Preferably, the ester feed to a hydrogenatien step is comprised of mostly d ^j esters or triesters of the rg nise acids in the fermentation r th.

From not er perspective, the present invention provides a process for genera in a carbon feedstock stream asiag carboxyiie acid esters recovered from a fermentation system that are subjected to hydrogenation.

T e estent eation reaction temperature is between about 15 °€ and a boat 2.5b ^:': C, sod the operational r cti n pressure is between a boat 400 psi and a out 3,iHKi pss (gage), ^' Depending on the desired re abs, the esteriffcation reaction can be run for a ut 4 hoars, up to about 12 hoars.

In another aspect, the present invention pertains to a method of processing an gricultural product or biomass. The method includes obtaining carbohydrates from the agricultural product or biomass, fermenting the carbohydrates to produce a fermentation broth, dr ing the

fermestaiiosi broth to produce a fernseaiation broth powder, and transporting t¾e fermenta ion broth powder to a second processing site. The second processing site can be located ne rer to a .source of demaad for a product derivable from the fe ment ion broth powder, which eao be processed at the second site to produce a product therefrom..

Additional features and advantages of the present methods will be disclosed in the following detailed description, i t Is understood that both the foregoing sum and the following detailed description asd examples are merely representative of the snveotio , and are Intended to provide an overview for understanding the invention as claimed.

BRIEF DESCRIPTION OF FIGURES

F!G. 1 Is a schematic diagram illustrating aa iteration of the present process for esteriiybsg an organic carbosyiic acid derived from fermentation broth, asd farther downstream processes that can isolate the resulting esters and/or generate other compounds from such esters,

FIG, 2 Is a schematic diagram showing an example of ester production using succinic acid derived from fermentation, and a downstream process in which a and Mg salts are recycled back into the fermentation reactor, in accordance with a part of aa embodiment of the present process.

FLO, 3 is a diagram that illustrates CG -assisted esterifieatlon of free succinic add In various akohois that are converted to corresponding dimethyl, diethyl, or dibntyl esters, according to the present invention. F t¾ ^, 4 is a diagram thai illustrates€O assisied esterifkatioB of other polyearboxyik adds,

Fi€. 5 shows a series of reaction agr ms t ai summarize variations in temperature for CO assisted esterifieation of free succinic acid derived from fermentation broth.

¥\G. 6 shows a series of reaction diagrams t ai summarize ariation in initial operational pressure for COrassisted esterifieation of free organic acid according to the invention.

F1G~ 7 shows a series of reaction diagrams thai summarize variations in temperature, and reaction times for CO> assisted esterifjcatioo of free organic acid according to the invention.

FIG. shows a series of reaction diagrams that sominar&e the results of reaction saccinic acids and their Mg aad Ca" salts.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

Section i ~ Description

A.

The present disclosure describes, in part, a process for ma ng various hydrogenation products such as 1,4 hutaaedioi (BOO), γ-hatyrolactone (O L ^' tetrahydrofuraa (THF), and their derivatives, from a biologically-derived carbon source, such as sugar or other p!aat-based carbohydrates. The process joins ao ability to recover an organic acid from a fermentation broth, with as ability to use the acid as a feedstock for hydrogenation reactions in a streamlined procedure. The present process inc!ades a method of c n ertin the earboxylic acid to its corresponding ester (e.g., mono-ester, di-esler, or tri-ester) in a relatively efficient aad cost effective manner.

in particular, the present process involves obtaining a fermentation broth, from which cell mass and insoluble compounds have been either removed or not, containing a mixture of free organic acid of interest, optioaally with associated alkali or alkaline earth metal salts (e.g.,, sodium, potassium, or magnesium salts); drying the raw or clarified fermentation broth eontaiaing free organic acid into a powder; reacting the organic acid in the powder with an alcohol under a CO* atmosphere in substantial absence of any other acid catalyst at a reaction temperature aad pressure correspoadiag to supercritical, critical or »ear critical conditions for the alcohol and/or CO? to synthesize a.a ester; aad subjecting the ester to hydrogeaation to form a hydrogenation product. As «sed herein the term "free carboxyiic acid" refers to a ewbcn ik acid compound that is at least 50% in its protoaated state when in solution, at or below its pKa value. The present invention involves the discovery of a simple, but effective way of producing esters from organic acids thai are otherwise costly and difficult to isolate. As used herein, the term "substantial absence" refers to a condition in which another acid catalyst is either largely or completely absent, or is present in d minimis or race amount of less than catalytic efficacy, in other word , no o er acid catalyst is reset or is present at a level less than 1.0%, 5%, 3%, or 1% weight/weight relat ve to the earhoxybe acid ias the reaction,

tgare 1 Is a schematic representation showing a ene al process of extracting organic acids from fermentation br t that includes a version of the present esterificatson reaction integrated with farther processes that can alibze the resulting esters. As shows?, fermentation broth from a reactor is filtered (ultra) J to remove biomaleriais such as cell mass, and yield organic acids including their salts, by products assd other compounds. All of these materials are then dried 3a to make at? unrefined mi tu e .1 This dried mi ture of materials is then reacted 7 in a l quid system with an alcohol (R-OH; R - aikyl C _r C _i: <) and C0 ₂ a at? elevated operational reaction temperature and pressure to yield either monoesters or diesters, or a mixture of both. Ouly the organic acids react in solution. The resulting mixture 9 is filtered ./ to separate the esters 13 ami other byproducts IS. The esters are soluble while other by-product compounds are insoluble, The by products include carbonate salts of calcium, magnesium, or sodium, which can be recovered and recycled 7 back into the fermentation reactor ⁽ K This recycling can lead to significant cost savings and improves the efficiency of the overall fermentation and extraction process. The esters can be processed subsequently either by distillation 21, hydrogenation 23, or hydrogenotysis treatment , respectively, to separate the different esters, produce Q platform compounds such as the hydrogenation products fe<g„ BIXX GBL, MF, etc) discussed herein, and bioftseis Ce,g„ ethane, etkanoi, butane, hotanoi, propane, propanol, etc).

As used herein the ferns ⁴ *bio.faels" refers to a gaseous, liquid, or solid substance that is used as a fuel, which is produced from renewable biological resources such as plant, eelluiosk, or agricultural biomass or derivatives thereof. In particular, a biofuei refers to a material tha ears be used in or as a transportation fuel in internal eosnbnstioo engines, to power certain machinery, or energy generation applications. For instance, propanol and bufanoi can be a gasoline additive much the same as ethaool. Butane -and propane in U nefied petroleum gas (LF ) and ethane in natural gas can be adapted as fuels in certain transportation systems. Other biologkaliy>denved hydrocarbons, like octanoi octaoe, or alkanes heavier than C _s or C« may also be biofuels.

The recovery process and estesifieatkus method can be applied to producing chemical feedstock molecules Ce.g„ BOO, GBL, IMF etc) from free organic acids derived frost? a

fermentation broth. As advantage, of the present invention is that one can use free organic acids directly from a fermentation broth and generate corresponding esters therefrom without the need to isolate or purify the acids from the fermentation broth, as is necessary is? conventional extractions from broth. In comparison to ce tain fermentation r ces es that nesstrafee or convert the organic add to their salts, the resent process provides an easier way to isolate and extract organic acids f m a fermentation bro . The present process eliminates a need for i ation and neu ralisation of the fermentation broth thai can precipitate metal unite, and certain purification steps to produce a stea platform ehentksi. The free organic acids are converted into esters, ic are simpler to process and extract by distillatkm or other purification techniques without the use of expensive and complic ted chromatographic separation columns or resins. For instance i» a co»ve«tloaai process, one would seed to use son exchange chromatography to isolate the acids, A small amount of sal s a? ay unavoidably carry-over after the ion exchange. Hence, one assy require multiple noils of operation to purify the acid to an acceptable quality level. With each added e ati nal unit the costs of the overall process increases. In contrast i the present process ia s nt esis tig the ester of the acid, one can recover the salt as a carbonate or hydroxide, which can he used to regenerate the fermentation broth, and minimis waste. Rather, an advantage of the present proces is that onft may farther recycle the synthesis by-products directly back into the fermentation broth. By converting the organic acids to their corresponding esters, we can avoid such issues,

S.

Conventionally, esters are produced when carhoxyisc acids are heated with alcohols in the presence of an acid catalyst The mechanism for the formation of an ester from an acid and an alcohol a re the reverse of the steps for the acid-catalyzed hydrolysis of an ester. The reaction can go in either direction depending on the conditions used, lis a typical esierifkation process, a earbo.xylk acid does not react with an alcohol unless a strong acid is nsed as a catalyst. The ca alyst is usually concentrated snifark acid or hydrogen chloride. Protona ion makes the earbosy! group more eieetrophilie and enables it to react with the alcohol, which is a weak aodeophik.

In general terms, the present esterificattoa method involves a reaction of fermentation- derived, free organic earboxyik acid with an alcohol in a CO> atmosphere in substantial absence of any other acid catalyst to produce esters. The esterifkation reaction is perforated in solution under conditions that are either at supercritical, critical or near critical temperatures and/or pressures for either the alcohol and/or€<¾. Under such conditions, we believe that CO? self-genera es or factions in situ as an acid catalyst, and regenerates back after the esteriilcation reaction is completed, it is believed that a reactive intermediate (monoalKykarbonte acid) is being made i» situ in large enough quantities to drive esters fiesikm and affect ester production, This

intermediate, having a similar p&a <e.g,,~4~5> as the free organic acid, functions as a carbonic acid. which is m h weaker than t e usual strong acids. The observed trend of gr ater ester conversion at higher temperatures addu es a relatively large energy of activation for this process.

Ass advantageous feature of the inventive process is that activation of the free carboxylic acid s an ae l haiide (e.g., fluoride, chloride, bromide) or by using strong mineral acids is unnecessary unlike th some other techniques. Aeyl haiides are inconvenient to ose because these species are inherently reactive, a e ssues with stability, waste treatment, and can he cumbersome and costly to make.

la the present process, carbon dioxide functioning as a catalyst instead of the oswal strong acids removes the need to introduce a strong acid into the esterifieation reaction. This feature can circumvent the usual need to adjust pM values in order to remove the c tal sin acid, enabling a simpler and cleaner synthesis. One can simply proceed to .filter the resultant product to remove alkali or alkaline earth metal carbonate or other salts. A cleaner product will save costs in purification and downstream processing for conversion to other chemical feedstock.

The process described herein is a more environmentally benign way of producing esters. As it is believed that the carbon dioxide can self -generate an acid catalyst in situ in the presence of the alcohol daring the esterifieation reaction, the present method does not require the use or addition of another acid catalyst specie*. In other words, the reaction kinetics with COj alone can drive the esterifkatksn in the substantia! absence of any other acid catalyst. To reiterate, the present process does not require activation of free acids as, fo example, an acyl chloride or by strong acids (i.e., Fisco er e ter if Ί ca ti o ).

In general, the esterifieation is conducted at an operational or reaction tetnperatare between about ISiPC to about 250°C, at a reaction pressure of between abont 450 psi or 500 psi and 2,500 psi or 3,000 psi (gage), for an extended period, sstch as abont 4 hours, op to abont 12 hoars. Typically, the temperature can he in a range between about 170°€ or iWC to about 230°C or 24S°€ (e.g.. I75°€, 18?°€. J9S°C or 215°€), and the operational pressure is between ahoaf 900 psi or 950 psi and about 2,200 psi or 2,400 psi (e.g., 960 psi, 9M psi, 1020 psi or 1050 psi).

Alternatively, the temperature can be in a range between about 180°C to about 245°€ (e.g., abont I85°C or 2(HP€ or 210-C to about 220°C or 235°€ or 240°€), and the operational pressure is between abont a 00 psi and 2350 psi (e.g., 1,100 psi, 1 ,200 psi, 1,550 psi, :l,750 psi, psi, or 1,900 psi). Other temperatures may be within a range, for example, irons about ίόΟ'- ^' C or ISS€ to about 2 MFC or 22S°€, and other operational pressures may he ithin a range, for example, irons abont 1, 150 psi or 1,500 psi to about 1,800 psi or 2,000 psi

These reaction temperatures and pressures correspond to supercritical, critical or near critical conditions for the aieohoks) or CO> Table 1. lists, for purpose of illustration, critical parameters for some common solvents ( \, methanol, ethan L l~pro anot I~hutanoh ater, and CCVi, j Tabie 1. Critical Data for Select Substances ¥aws, C L. Chemical Pro er ies Handbook. In McCtaw-HIH: J993; pp J.-29.) Substance !¾3rrsg i fttoiectiSar Weight jjMiicalTerno. {K)/X ! Critical Pre$$w& (barj/ si I Critical Density {g cm*}

; l-^rorsarnoi i S0.0S5 I S37.4 / 2S4.2S 1 S1.02 / 39.9839 i 0.27S4

i I-Botanoi i 7 .122 ! .56.3.0 i 03/ 2SS.85 j 45.0 ± 4. / 6S2.S71 ! 0.3710

1 Water ! 18,01.5 1 S47.I3 / .973.98 i 220.55 / SiSS.SQTt i 0.-3220

! Carbon dioxide i 44.010 i 304.19 / 31.04 i 73.82 / 1070.SSS5 j 0.46S2

At conditions above the critics! point (i.e., critical temperature and/or pressure), the fluid exis s in. a supercritical phase where it exhibits properties that a e in betw en those of a li uid and a gas. More specifically, supercritical fluids (SC s) have a iiq aid-like density and gas-like transport properties (i.e., diffusivity ^ζ ηύ viscosity}-. This caa he seen in Table 2 _« wherein the typical values of these properties are compared between the three fluid types - conventional liquids, supercritical Ouids, and gases.

\ Viscosity {Pa-s} j !ø ^' * io ^"4 ] lb ^'5

likewise, "n ar critical ⁵ * refers to the conditions at which either the tempera tare or the pressure of at least the alcohol species or CO gas is below but within 15QK (e.g., within 5ίΚ10ΘΚ}, or 220 psi {e.g. _> within -15 psi) of their respective critical points. It is believed that as temperatures and pressures reach near critical, critical or supercritical conditions, the solubility of the reagents are enhanced, which promotes the esterificatiea reaction, la other words, the CO> gas. alcohol, aad acid or salt species are heifer able to interact under near eritieal, critical or supercritical conditions than under less rigorous conditions, T he reaction docs not require that both the alcohol species aad COj gas be at .near-eriikal, critical or sapercriticai conditions; rather., the reaction is operative as long as either one of the species satisfies such a condition.

If the present esterifieatioo reactions are operated at higher temperatures and greater pressures, op to about 250°€ and 3,000 psi, respectively, for reaction times of up to about 0 or 12 hoars, one coo produce significant amounts of ester product at relatively greater selectivity and level of purity within a shorter reaction time than before, which was about 18-20 hours. At lower operational temperatures (< I98°C), formation of moaoester molecules of polyearhoxy!ic acids Is more prevalent, while reactions at temperatures > I90 ^¾ C or 195*0, will convert preferentially the polycarboxylic acids to diesters. By selecting a temperature in a higher range fr m ab ut 190°€ or 195°C or 2 0°C to about 245°€ or 25<f°C, one can preferentially drive the reaction to a higher rate of diester conversion. Toe esterification can yield a minimum of about 50%, desirably at least 65% or 70%, of a diester of the organic add, Reactions that are performed at or near supercritical o a ing condition* tend to produce better results. When operated at or near critical conditions of a boat 2M°€ or about 240 ^i' € for methanol and a boot 3PC/10Ofi psi for C ¾, one is able to achieve conversions- rates of about 90% or better, typically about 93% or 95%. One can achieve high yields by adjusting the perma tatioKS of different combinations of tempe atu e and reaction times (e.g., higher temperatures and shorter reaction times (e.g., less than 1 or 12 hours, b t e n 4 and § boars) or vice versa), which can be ass advantage over current approaches. With o t misa ion, esterification conducted at 2S0*C under either the sam or greater€(>> pressure, the yield would be nearly quantitative (i,e„, > 95% yield), for example, up to about 98%, 99%, or 99.9% conversion;.

As the accompanying Examples will show-, variation in reaction conditions suggests that one can generate snore diester product with higher temperatures and/or protracted reaction limes. As stated before, however, different permutations In temperature can Influence the duration of the esteriiie ion reactions to produce the same amount of ester product The reactions according to the present method arc not conducive to a significant degree of side product formation; hence one eaa avoid ey ization of the earhoxyik, acids and other starling reagents. Potential dangers of decarboxylation at high temperatures (ie,, >I45°€ or >J50 ^& C) are not observed in the present method.

Using ass amount of the alcohol solvent in excess of the carboxylk acid, one can prod ace a very dean esteriik tion. The present synthesis process produces very clean ester products at about 7 %-?2% initial purity, w ithout generation of significant amounts of side products such as low molecular weight acids - acetic or formic acid ~ molecular rearrangements or cyclic products, which one eoakl normally find in standard acid catalysed esterification at high iensperaiares. The esters ears be refined to achieve about 90-98% purity. The purification can he accomplished, fornstance, by means of crystallisation, chromatography, or distillation.

Typically, the resulting ester products can he either monoesters or diesters, or form a mixt re of both. One can control the. reaction to drive the esterification toward either one ester form or another. For instance, one may select an operational temperature and pressure that preferentially drives the esterification reaction towards formation of diester nsolecnles ^, L ikewise, one can control whether esters are formed from either a single organic acid species <e,g., succinic acid) or a mixture of multiple different kinds organic acids (e.g., acetic, citric, lactic, malic, maieic, succinic acids) that may foe present and derivable from fermentation broth. In other words, one can use a variety of different Minis of earhoxyik acids in accord with e present esterification re tion to produce a variety of di ferent esters. These esters, in tur , can be isolated, farther modified in downstream chemical process s and converted, so certain embodiments, into useful compounds saeh as for pharmaceutical, cosmetic, food, feed, polymer materials, For instaaee, succinic esters can he converted into a polymer, saeh as poi butylene succinate (PBS).

In the pres nt esterifkatioo process, both the catalyst {€(¾) aod the esterifkation reageat iaicohoi) are present in large excess relative to the amosat of tree organic acid. CO _? should he in the gas phase during the reaction phase, regardless of its origin (e.g., gas tank or dry see), as the reaction is conducted at high temperatures. Addition of solid CO> is strategic its the ease where sealed pressure reactors are used, in that it allows for slow sublimation of gaseous COj .formation as the reaction apparatus is bein assembled. Th s cm minimize CO _? , loss. In a CO; (i.e., CO _:

containing) atmosphere, the coaeesvtraiioo of C0 ₂ in the reaction atmosphere can be at least 30% or 15% by volume, favorably about 25% or 30%, preferably greater than 50%. For better reaction results, the concentration of CO; should be maximized. Desirable concentrations of COj are from about 75% or 80% to about 99.9% by olume, typically between about 85% and about 98%.

Nitrogen (N ₂ ) gas or air is permissible in the reactor, bid preferably the concentration of gases other lhan C0 ₂ is kept at either a minor percentage ( 50%) or de minimis amount.

Any liquid alcohol with an R-gronp of€ C _M can serve as the solvent reagent in certain embodiments, the R~group of the alcohol can be either saturated, unsaturated, or aromatic species. A mixture of different kinds of alcohols (e.g., C C _n ) can also be «sed ia the reaction, bat will produce a corresponding mixture of different esters depending OH the particular R-gronp. Alcohols s«eh as methanol, ethanoi, propaaoi, or hotanol are preferred as the reagent in view of their common availability, isexpensiveness, and mechanistic simplicity in the esierificatioa reaction, Alternatively, in some embodiments, the alcohol can also be a€ C<.-diol Esterifkatioo with a dio! can generate monomers or low molecular weight oligomers that can be readily polymerized.

One ca n use a variety of different organic acids, for example, selected front; a)

moaocarboxylfc acids: formic acid, acetic acid, propionic acid , lactic acid, butyric acid, isoboryric acid, valeric acid, feexanoic acid, heptaook acid, decanoie acid, laarie acid, myristk acid, and C» ₅ - C _iS fatty acids; b) dicarboxyltc acids: famarie acid, itaconic acid, malic acid, succinic acid, omfek acid, m&fcmic acid, gtuiaric acid, glncaric acid, oxalic acid, adipic acid, pimelic acid, suberic acid, axelasc acid, sebsek acid, dodeeanedioic acid, glotaeonic acid, ortho-phthalie acid, isophthaik acid, terephthaiic acid; or c) tric boxylic acids: citric acid, ssoeiirie acid, aeooitie acid, trlearbaiiv.be acid, and trimesk acid. The organic acids can include alkali or alkaline earth metal (e.g„ sodium, pot ssium, or magnesias*) salts of these organic acids. Desirably, the organic acid is a dicarboyxlk or tricarboxylic acid.

The process can red ce the amonat of waste by means of recycling of by-products back into the fermentation broth, either in a eontinnoas or batch process. We have also found that in the present esterirl cation process, when free organic acid is reacted with an akolsol and CO _? . absent aay other cid catalyst, the free prorogated form of the organic acids has greater solubility in the alcohol solvent Hum their corresponding salts. Performed nnder simila r reaction co.aditio.os, the esteriflcatioa reaction using iae free orgaaic acid as reagent will yield abou 2-3 braes greater suuouot of ds-esier product than the reaction thai uses the salt species as reagent. This result can be seen when one compares site reaction of accompanying Figure 3.8 (free add) with that of Figure $A (acid salt), and ia Table 4, Examples 2 and 3 (acid salt), with Examples 5 and 6 (free acid), respectively, is believed that solubility is a factor for t e difference. For instance* since the soi ability of ma nesium salts in Methanol and eihaso! are significantly better than that of calcium salts, product yield from a reaction of a calcium sail is much lower than that produced from a starting reagent of a corresponding maguesinn? salt.

The preseat invention includes a method for esterifying a polycarboxyile acid. The esterificaiioa method involves: providing and reacting a solution of one or more free organic acids wit h an alcohol in€(¾ a (Biosphere without the presence of any other acid catalyst; and selecting an operational reaction temperatnre or reaction pressure corresponding to supercritical, critical or near critical conditions for the alcohol and/or CO; to yield an ester. The reaction temperature and pressure conditions preferentially drive the reaction towards the formation of at least diester molecules over monoester otoleeales whea the organic acid is a pol carhosy lie acid. As with the recovery process, the operational reaction temperature is between aboa I SiPC aad about 250°€, and the operational reaction pressure is between about 400 psi and about 2,S00 psi. Depending on the desired results, the reaction can be ran for ap to aboai 12 hoars.

€.

The esterlfkatlon process described above can be integrated into fertneoiatioo- based production of carbon chain feedstocks and to provide a more convenient method of generating esters from carboxylic acids derived from a renewable source. The presen invention provides a direct roate by which biologically-derived carboxylic acids can be recovered in a simple, cost- efficient process from a fernseatation broth, converted into esters, and then subjected to hyd ogeoation process to produce EDO, GBL, THF aad their derivatives,

] i hrough the distillation process one can concentrate the esters driving off the alcohol, ami then filter the by-products resultant from ester synthesis. Further distillation of a mixed-acid ester product mixtu e according to the boiling points of the different ester species, permits one to separate the various individual esters. For ins anc . Table 3 provides boiling points for a sample of common esters that may be present in an ester product mixture according to the present invention.

After recovering the esters in the remaining solution, the materials are in a readily osabie form and one can either distill Che ester mixture to separate the different ester species and any remaining alcohol. Oaee the esters are recovered, one can use the monoesters as precursors for conversion into chelating agents, and the diesters as solvents.

An advantage of recovering the organic acids from fermentation m the form of their corresponding esters is that downstream processing of the esters is less energy intensive than the hydregenation of the free acids. Another advantage of the present estenfication process is that, one will find the present process simpler and easier, as compared to other approaches, to refine organic acids for chemical platforms from fermentation, it simplifies efforts to separate esters from the other insoluble materials, as well as minimises the amount of salt that one needs to separate, in an integrated process enables one to directly esferi y a combination of free acid and sails that is produced in a knv-o.lf fermentation, in whic the fermentation is operated at a pli of less than t e pKa of the organic acids. The process can be less energy intensive than current recovery

approaches.

Figure 2 shows a schematic diagram of a downstream processing that incorporates an iteration of the present esterification process, la particular, Figure 2 depicts an example of using succinic acid or say other kind of organic acid derived from a fermentation broth is extracted and reacted with an alcohol in the presence of excess CO?, to generate esters. According to this iteration of the process, glucose, corn steep liquor, or other sugars, and MgiOHfc / aOM are introduced into a fermentation reactor 1 and fermented 2 to produce carboxyh ^' e acids. A fermentation broth liquid 4 containing a mixture of organic acids, salts (e.g., succinic acid and its sodium or magnesium salts), and other by-prod acts is .filtered 6 to remove cell mass 8 and other insoluble matter. The

fermentation is performed at a pH value, in which one starts at a higher pH (e.g., pH ~7 or 8) and during the oarse of the fermentation, the pM value- drops to about 2-3. One will r du e a iBKtore of salts and free acid present, for exampl , in a ratio range of about 9: 1 w/w to 7:3 w/w of salt to acid. The fermentation broth is retrieved from a fermentation reactor at a p i value of ^' less than the p a of the organic acids, {e. ., H 5>> Typically, the fermentation broth is at a pff value m a range between about 1.5 and about 4.5.

The broth extract is then dried 10 to a powder. When drying the mixed acid filtrate should remove as much water as possible.. The drying step east be accomplished, for instance, by means of .spray dryiag, drum dryiag, or eryodesieeatkm. As with este ifieation in general, relatively low water content is desired, otherwise the reversible reaction will tend to hydrolyste back so tin;

diearhoxyiic acid. Its the present process, a maximu residual moisture content of about 5% by weight should be maintained. One would expect m increase in ester y ield of up to about 98 or 99% with samples that contain less than 3% wt. of water.

The dried powder (average moisture content between about Iwi.% and 5wt.%, desirably < 3 wt.%) is then reacted 12 with as alcohol 14 which serves as no alkylating agent, in excess C0 ₂ at a temperature between about 18I C to about 25CPC for a duration of about 4 hours or o e to esierlfy the organic acids. In this example, succinic acid is reacted ia methanol and€C½ to generate dimethyl succinate. Along with the free organic acid, any remaining free amino acids which were ia the fermentation broth are also esteriiied,

Ouee the carboxyiie acid esters are generated and collected, one is then able to feed the esters into a hydrogenation process. The hydrogenation can be conducted according to varioas different methods, systems aud their permutations, such as described in U.S.. Patent N«s»

7,49S,4S0B2 (relating to homogenous hydrogenation of dlearboeilic acids and/or anhydrides), tS.433.i93E, or 3,969,164, (relating to a process for production of tetrahydrofarau aud γ~ butyroiaeione by hydrogenation of maleic anhydride); U.S. Patent . 4,584,419 A (relating to process for the production of bnfuue~L4~diol involving the hydrogenation of a di(C _s to C> alkyf) ester of a C ₄ diaeid); UK .Patent Application No. GB2207914A (relating to a process for production of a mixtu re of butane -d.iol, y bufyroiaetoue, aud tetrahydrof ^' uran from maieate and fuaserate); oternaiioaal Patent Application os. WO880O937A (relating to a process for the eo-produetlon of butane- -dio! and γ ^» butyroiaeione by means of hydrogenation of dialkyl maleatc) or WO

82/03854 (relating to a process for hydrogeaolysis of a carboxyiic acid ester), or an article by S.

Varadarajan "Catalytic Upgrading of ^mentation d ived Organic Acids," BiOTOCHNOL. PROG, 1999, 15, 845-854, the content of each of the preceding disclosures is incorporated herein in its entirety by reference. As the example illustrates in Fig re 2, wises reacted with methanol in accord watts the reaction temperatures and pressure parameters defined above, succinic acid esterified to produce dime hyl succinate (as predominant product), aHCO* Mg€0. _> / Mg(MCOj) ₂ and excess methanol 16, I be dimethyl succinate and methanol IS are separated from aBCOj and MgCOj 20, Use carbonates, unlike CaSO* can be recycled 22 back o the reactor /, either for a continuous r cess or i» a fresh batch process. The dimethyl succinate and methanol are farther separated 24 i on* each other with the methan l 14 beiag recycled 26. Subsequently, the dimethyl succinate 28 can h hydrogenated 30 Mo a variety of different chemical products 32, including for instance, 1,4- batane-ldsol (EDO), tetrahydrofarao (THF), γ-buiyrolactone (GBLj, or N-metbyl-2-pyrrolidoae C MPs.

A nother advantage of the present process is that it can simplify the transport ami processing of crops for fermentation products. For instance, with a dried fermentation b oth powder one is freed from issues associated with working with wet or liquid stock A dried

fermentation broth powder can he more economically shipped to a location different, from where f fee fermentation broth is de or sosrreed. This will enable the reaction for ester synthesis to be performed at a remote location different from where the fermentation broth is sourced, and expand the geography of where the final processing facilities can. be sitssated.

Hence, we also envision that the esterification process described herein, can be in tegrated Mo a method for processing an agricultural product or bionsass. The method involves obtaining carbohydrates from the agricultural product or biomass, fermenting the carbohydrates to produce a fermentation broth, drying the fe mentati n broth to produce a fermentation broth powder, and transporting the fermentation broth powder to a second processing site. This second site can be located closer to a sonree of demand for a product derivable from the bro h powder, which can IK? ester s ^' fied and/or otherwise processed at she second site to produce a product therefrom.

Section .11 - Examples

A,

Examples prepared according to the present esteritkation method are integrated into a process for isolating free carboxyiie acid from a .fermentation broth- The method involves genes-ally the following steps; a) filtering a ernde fermentation broth to remove ceil mass and other biological debris from a fermentation broth; b) desiccating he fermentation broth; c) reacting the dried fermentation broth with an excess of methanol (€R ₃ Oli) or eihanoi {€ >M<.OH} and carbon dioxide (CO;) at a temperature about 350°€ ss.p to the near critical or critical temperature and under near critical or critical pressure of the alcohol and/or CO reagents, to produce a mixture of tnoaoesters asd diesters aad carbonate ( aMCO.V MgCO»); d) filtering Use reaction product to remove by-products; and e) purifying by distilling e esters.

The fermenta ion broth filtrate was dried to remove all or nea ly ail of the 'o ier to produce a powder of mixed organic*. Using a spray dryer or drum dryer, o»e aerosolizes the raw soiutioa containing m xed organic acids to desiccate into a powder. The desiccated powder is suspended in &» alcohol solvent, The powder resets wi h the alcohol according to the conditions described herein to esters fy into either monasters or diesters.

Each of the following examples was performed accordiag to the following genera! protocol, except for variations in reaction temperature, pressure, time, aad/or acid species as indicated, m ates mutandis. Ten grams of freexe-dried succinic add fermentation broth (off-white powder) and 3Θ0 g of methanol were charged to a !L stainless steel vessel, jacketed, and fixed to a Parr reactor. While stirring mechanically at .1.100 rpm, the internal head pace of the reactor vessel was purged with j and then pressurized initially to 400 psi with€0> &nd heated to 180 C for 5 hours. The interna! pressure was observed to he -165 psi at 180 ^* C. After the reaction time, the reactor body was cooled is a water hath until reaching room temperature and pressure released. The heterogeneous mixture was then filtered and solids were dried overnight under vacuum. Samples of the solid material and the solution were analysis quantitatively using gas-chromatography/mass spectrometry (GC/M.S). The yield of dimethyl succinate was determined to be 31.9% with more than 95% of the available osagnesiuus succinate consumed in the r action. The remaining haian.ee of product included the corresponding mouoesters as the greater past, and was in a range of about 60% to about 65%.

As the reactions depicted in the accompanying figures and tables show, modification and selection of certain temperature and pressure parameters causes reactions to y ield preferentially more of the diester eoiapoaads. In certain examples of the present process, the esterifieation reactions yielded more than 50%, typically snore than 70% or 80% ds~aky! succinate or ntaiate. As stated before, the unreacted materials and the uadesired products are recycled into the

fermentation reactor. Subsequent separation of the mono-esters and di-esters was achieved by crystallisation.

Figure 3 shows a series of esterifieation reactions which summarize C O assisted

esterifieation of free succinic acid in various alcohols. Figure 3.4 shows saeeinie acid reacted with asethaaol in 400 psi CO _> gas, at i5 °C for 5 hours, w hich achieved a yield of about 37% dimethyl succinate. When the operational temperature was increased to 180°€ is the reaction of Figure 3B and ail other parameters kepi the same as in Figure 3 A, the amount of dimethyl succinate yield increases more than two-fold to about SI .2%,

IS F ^j gnsre 3C represents free succinic acid reaction at 18 °€ under present operational conditions in ethanol, which generates diethyl succinate in good yield of abou 60.8%, rs Figure 31X free succinic acid was reacted at J.80°C under operational conditions in »~hatanol, which generates dibatyi succinate at about 52.2% yield. These examples demonstrate the versatility of the present esterifkation reaction ia view of different kinds of alcohols.

Figure 4 shows examples of COrussisted esterifkatioo of other kinds of earboxylk

poiyacids, in Figure 4A and 4 , succinic acid was substituted respectively with citric acid, a tricarboxylic acid, and malic acid. The yield of t imethyicitrate was reasonable at about 20,1 %, demonstrating that the C Vassisted protocol can be applied to tricarboxylic acids. The yield of the dimethyl analogue of malic acid was good at a boat 84.3%, Hence, the new method of esterifkation is feasible for general use with other acids.

Table 4 summames results of several reactions that were performed according to the esterifieation method of the present disclosure as depicted in Figures 5, 6, and 7. Each set of examples is arranged in terms of a variation of an operational condition unde which the reaction was performed: A) temperature, B) pressure, and C) reaction time. In each of the examples, succinic acid irons a fermentation broth is used as the substrate. The filtered clarified broth containing free acid and salts are dried and later reacted with methanol and C > ia solution. (As the reactions are heated, the actual operational temperatures and pressures within the reactor vessel will exceed the initial temperatures and pressures provided herein.)

In the three examples of Set A, we carried out the reaction for 5 hours at an initial€<>> pressure of 400 psi, under different temperatures: Ex. A-i at 18 °C, Ex. A-2 at 210°€, and Ex. A~3 at 230°€ The percent conversion of acid to its corresponding diester increased with higher operational temperature. Figure 6 shows the effect of varying temperature in a series of

esterifieation reactions of succinic aeid and its salt, ia Figure 5A, the esterifseation of succinic acid is per formed at a temperature of about I >WC. over a period of 5 hoars. The reaction produced ahoatO.9% yield of dimethy l succinate. Figure SB shows the ame reaction as in Figure SA, when the reaction time held constant, bus with Use temperature raised to about 2IiP€, which yields about 42,9%. Figure SC shows a reaction at 230*C and yields about 72.4%. This suggests that as the temperature Increases, the reaction kinetics drives toward a snore complete reaction of the acid and alkylating agent, and a greater yield of the dialkyl-ester. Reactions performed at or near critical temperature and/or pressure conditions can produce at least 95%, likely > 97% or 98%, conversion.

in Set and Figure 6, we performed the esferillcation reaction for 5 hours at an initial temperature of 180°€, and varied the initial C0 ₂ gas pressures: Ex. B- at 400 psi, Ex. 8-2 at 500 psi. and Ex. B-3 at 60 psi. The percent cos version of acid to its corresponding diester was moderate, and he amount yield did not show significant difference statistically. The initial CO gas ressure in the reactor did not exe maefe effect in conversion of the acid to its diester, but the operational pressures in the reactor darin the reaction suggest an effect 55 yields.

in Set C aod Figure 7, we performed the estenfleation reaction at a constant pressare and temperature bnt varied the duration of the reaction. Ex,€-1 at 5 hours, Ex. C-2 at 2 hours, aod Ex. C-3 at 0,5 hours. The examples shows m Figure 8 suggest thai a grea ter amount of diester was converted from the acid with increas d reaction time.

Figure 8 shows a first set of C<¾~assisted estenfleation reactions using a concentration of succinate salts of about 4% w, , which arc presented as Examples ί-3 in Table 5. la Examples 1 and 2, succinic acid aod its magnesium (Mg ^{" '} ) sail was reacted its methanol and ethanol at 2 H C and I8Q°C, respectively, for a reaction time of 5 hours. The reactions produced about 33% dimethyl succinate and ahont 1% diethyl succinate, respectively. Methanol exhibits a greater capacity to dissolve the succinate salt than eth-anoi. Magnesium succinate exhibits a reasonable level of solubility in methanol, while it exhibits limited solubility in eihanoi, even at high

temperatures, Hence, the yield of dietnyisuceinate was negligible. Example 3 shows a reaction asiag caleinm (Ca* ^" ) sacciaaie, at ISCC, over 5 hoars. The reaction yields only about 1.33% of the corresponding dlmethylsuccinate. Relatively low conversion rates in Examples 2 and 3, also highlights the solubility difference between corresponding alkali earth salts. The calcium succinate salt is !nsoinb!e in methanol, even at high temperatures. The methanol to salt molar ratio used in the CO; experiments was approximately 11β;ί for methanol to magnesium succinate. Likewise, the ratio was about 100; i for .methanol to the other earboxylsc acids.

present method. Examples 1, 2 aad 3 demonstrate the importance of substrate solnhility of succinic acid as compared to the salts of succinate. Exam les 4-7 is a second set of reactions lis which free succinic acid was reacted in methanol, ethauoi, sad l~huta.ooi in similar fashion, Examples 8 and 9 show tltat reactions with other organic acids, such as citric acid ami malic add can achieve relatively good yields of a bo at 20% and 86%, respectively.

Free succinic acid reacts readily with the alcohols, since it is completely solable is me han l, ethanol, hntanel, and other alcohols up to aad including octaaoi (Q alcohol), In Examples 6 and 7, succinic add reacted in eihanol aad i~batanol, yields 60, aad 52,2% conversion, respectively.

The solubility of carboxyHc salts so a particular solvent can have a» influence o» the esterifieation process. The greater solubility of free-acid permits a greater reactivity than the carboxyUtte salt, which lacks as add functionality. Accordingly, the yields of the corresponding esters tend to he significantly greater than the control samples when comparing the t o sets of reactions. The reactions of Examples 4-7 yielded signilkaoily greater amounts of

corresponding d festers than that of Examples 1-3. The earboxylk acid itself may be sufficient to catalyze the esterilicatiou reaction under the present operational temperature and pressure conditions. One can adjust the substrate solubility for successful esters fieation according to the present method.

B,

Example; Hydrogenatioa

Usin a process like one of those described in the references cited above, one can perform direct hydrogeoaiion of the earboxyiie add esters collected from the esteriiieaiion process described above. For examples, one can use metallic copper catalysts for the hydrogenatioa of dialkyl succinate esters to BBO, GBL, and THF. The following describes an illustration of the hydrogenation process,

I ^' he copper catalysts were prepared hy wet impregnation of copper salts onto the following supports (all - 16+30 mesh): silica-alumina (93% silica, 7% alumina Sigma

Chemicals) and two chromatographic silicas (Phase Separations, Inc.) XOA-400 and X B-030.

Ten milliliters of solution containing copper mtrM- to produce the desired loading was added to

10 g of support The slurry was stirred at room temperat ure for 2 hrs. and then dried for 2 hrs. under vacuum at 60 *C - 70 °C. The d ried solid was then calcined its air in a furnace a t 500 °C for 1 1-12 h to give copper oxides. The catalyst material was then loaded Into the reactor and reduced in-sita in pure hydrogen at 200 °C aad 200 psig for 3 hrs. Catalyst supports were characterized before aad after reaction hy nitrogen SE surface area aad mercury hensse.oe wUh lh«etliyla««na¾ohe¾2.ene (p& ^" _s ~ 3.9) as the indicator.

A cone closure reactor {Autoclave n ineers, lac.) made of 326 Stainless Steel, 167 mm long x 5 mm inner diameter (id,), was charged with one gram of catalyst supported on a quart?, frit The reactor was surrounded by a clamshell furnace controlled by as Omega series CN-2010 programmable tetnperature controller. Dimethyl succinate was fed to the op of the reactor as 30 wt % solution in methanol using a Biorad HPLC pump. Hydrogen gas was also fed to the top of the reactor from a standard tank and bigh-pressare regulator; a rotameter was used to monitor gas flow rate at the reactor outlet. The liquid feed rate was fixed at 0.05 nA/udu, and the hydrogen rate was set at 400 mh of STP/min to give a weight hourly space velocity {WHSV) of 0 ^, 9 g of DMS g of c&t/h and a Hj/sue nafe ratio of 260:1.

Condensable products were collected in single-ended 10 mL Whitey sample cylinders immersed in ice baths. Three-way valves were used to divert reaction products to either of two sample cylinders: daring reaction, condensable prod acts were collected in the traps f a timed period, after which the trap was removed and weighed and the contents were removed for analysis. Gas exiting the collection cylinders passed through a rupture disk assembly and was stepped d w n to atmospheric pressure using a hack-pressure regulator. Gas products were collected in gas bags for analysis using gas chromatography to quantify non-condensable product formation.

Condensable products were weighed following collection and analyzed in a Varian 3300 gas chro atog.raps qui ed with a Same ionization detector and a Sa eleo SFB-1 wkie-hore (0,5 mm) capillary column (50 -200 °C @ 12 °€/min» hold @ 200 °C). Methyl lactate was used as ass internal standard to facilitate the calculation of product concentrations.

Example: Mydrogenolysis

The esters, resulting from the fermeatation extraction described above is then hydrogesoiyxed over a catalyst (e.g., reduced CnO/ZnO), which should obtain high conversions (>98%) and sekeiicities (e.g., International Patent Application No. WO 82/03854).

Alternatively, one can proceed according to a process such as described in U.S. Patent No. 4,584,419. A stainless steel with an oil jacket maintained at 231 °€ was used for this reaction. Hydrogen was introduced by w ay of a pressure regulator and Oow controller (not shown) through line to the bottom end of a vaporiser containing a number of steel bails. Ester w as metered as a liquid to vaporiser through a line. The resulting vaporous mixture of ester and hydrogen w as passed through preheating coil to reactor. This contained a layer of glass balls, on which rested the catalyst bed. The remainder of the reactor was filled with glass balls and the upper end of the reactor was fitted with as exit tube which led to a condenser (not downstream from the condenser usin a wet gas m er.

A charge of 30 ml of a granulated copper chromlte catalyst: was placet! in the reactor hich as then purged with nitrogen at 42 bar. The oil bath was raised to a temperature of 231. degree. C. A 2% M.sul>,2 I» N- ufcJ aseous mi ture at 42 bar was then passed over the catalyst for 8 hours* followed by 10% H.suh.2 in .sah.2 (stiU at 42 bar) for a further 16 h urs, and then by pn e H,s«fe,2 (also at 42 har) for an additional 12 hours.

Diethyl succinate was then introduced into the vaporizer corresponding to a liquid ho rly space velocity of 0.2/hr. The hydrogen gastester molar ratio in the vaporous mixture was 313 ^; !. The temperature of the sand bat was maintained at 23i°C The condensate was analyzed by gas chromatography using a 1.82 meter long stainless steel column with an interna! diameter of 3.18 mm containing 10% dielhylene glycol succinate on Chromusorfe F ^' W, a helium gas f ow rate of 3 ml/minute and a liaise iouisation detector. The n trumen was fitted with a chart recorder having a peak integrator and was calibrated asing a mixture of diethyl inaleafe, dialkyl succinate, bntyrelactsne, butane- 1, 4-dioi, teirahydrofuran and water of known composition. The exit gas was also sampled and analyzed by gas chromatography using the same tech usque. The identity of the peaks was confirmed by comparison of the retention times observed with those of authentic specimens of the materials in question and fey .mass

spectroscopy. The following compounds were detected in the reaction mixture: diethyl succinate, hutyroiactone, butane- i,4~dkd, teirahydrofuran and water. Trace amounts of minor byproducts, including 2-eihoxytetrahydrofyran and 2~ethoxybutane-l ,4-dio! were also detected n the reaction mixture, From the results obtained it appeared that diethyl succinate had been smoothly converted to products with a selectivity to teirahydrofuran of 52.2mol %, a selectivity to o-butanol of l l.6 moi , a selectivity to gamma-butyrolactene of 2o.i snol %, and a selectivity to fe«ta.ne-l,4~d5ol of 10.1 snol %, the balance being minor byproducts.

The present invention has been described in general and in detail by way of examples, Persons of skill in th art understand that the Invention is not limited necessarily to the embodiments specifically disclosed, but that modifications and variations may be made without departing from the scope of the invention as defined by the following claims or their

equivalents, including other equivalent components presently know n, or to he developed, which may be used within the scope of the present invention. Therefore, unless changes otherwise depart from the scope of the invention, the changes should he construed as being included herein.