US 2017.0015614A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0015614 A1 ORAZOV et al. (43) Pub. Date: Jan. 19, 2017

(54) PRODUCTION OF ALPHA-HYDROXY Publication Classification CARBOXYLIC AIDS AND ESTERS FROM (51) Int. Cl. HIGHER USING TANDEMI C07C 67/00 (2006.01) CATALYST SYSTEMS C07C 51/00 (2006.01) (71) Applicant: CALIFORNLA INSTITUTE OF (52) U.S. Cl. TECHNOLOGY, PASADENA, CA CPC ...... C07C 67/00 (2013.01); C07C 51/00 (US) (2013.01) (72) Inventors: MARAT ORAZOV, PASADENA, CA (57) ABSTRACT (US); MARK E. DAVIS, PASADENA, The present disclosure is directed to methods and compo CA (US) sition used in the preparation of alpha-hydroxy carboxylic acids and esters from higher Sugars using a tandem catalyst (21) Appl. No.: 15/207,822 system comprising retro-aldol catalysts and Lewis acid catalysts. In some embodiments, these alpha-hydroxy car (22) Filed: Jul. 12, 2016 boxylic acids may be prepared from and . The retro-aldol and Lewis catalysts may be characterized by Related U.S. Application Data their respective ability to catalyze a 12-carbon shift reaction (60) Provisional application No. 62/194,069, filed on Jul. and a 1.2-hydride shift reaction on an or 17, 2015. substrate. Patent Application Publication Jan. 19, 2017. Sheet 1 of 13 US 2017/0015614 A1

FIG. 1 O O O- OH OH, -N-O -A GA

O l OH O ...A FIG. 2

QH 2 r OH O s --s. O ro 2-hydroxy-3-biterrois acid OH Aidotetrose t - ". -- { f ^ gas Ho-2 O Obi Sycolaideyde 2,3-dihysioxytsiataxic acic 3- Q { Giyoxa KY, w Y. O gy{{ i &is Patent Application Publication Jan. 19, 2017. Sheet 2 of 13 US 2017/0015614 A1

FIG. 3

{- O io us -- e {} - Aicisexisse

-----OH OH Ho r r > QH-OH Otis a OH OH s {SA Keithexose

FIG. 4 in Qi; r . (3 exege.: r (3: 3-M-r35 ^2-'-- \ i Yol --s its O. : s 5-Hydroxymethylf rural Aitchexose Kettslexese Ns: . s s os -' s &

fig a r -Nso -Ns' Oilw lu e't 2-C-(hydroxymetiyl)-aidepentose Gycelaidehyde Eihydroxyacetose i {s ig Y. m . -as-a- sity 1. x Y s f SYl "Y-2 wwry sevey R Pyruvaldehycie Aliyi sciate Adetetrose theniacets A Ny C stadi Cs products | by-products Patent Application Publication Jan. 19, 2017. Sheet 3 of 13 US 2017/0015614 A1

FIG. 5

HO O O O O OH

sm wner R R2 R. R. R R2

FIG. 6

C - '' h s' \ i C s t se Y. O Y s h {i : 'chiot t

:-3-

D- D-arameiose

A/YA \\ s \/\/ / 2Yay.' W s' \ y x \\ C 2. s -: ^ s vy is a C-C- - i is ''/ s *- HCHC s HHC C}-l. at 0:8 - D- agatose Patent Application Publication Jan. 19, 2017. Sheet 4 of 13 US 2017/0015614 A1

FIG. 8

fictose

N kill. . Ju scies: Starticiaci

&xavaMaxxxxxaasaxxxxsar Patent Application Publication Jan. 19, 2017. Sheet 5 of 13 US 2017/0015614 A1

FIG. 9

Scase &actics: Fractity

J - UU U.

was www.swax'Yaa'ss M U VAwo- U

FIG. 10 Secse Reacts Factioi

Soisse Stasia: Patent Application Publication Jan. 19, 2017. Sheet 6 of 13 US 2017/0015614 A1

FIG. 11 Psicosef Bia; 3-O-hydroxytet:y-atticestesse Raascist assics:

OA 2-C-hydroxymethy airiopertos:

Psilasa Statixia.

5.4 5.2 ssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssss-xxx-xxxxx'sssssssssss-Xxxxx-x-xx-xx-xx-xxxx5.0 4.8 4.6 44 42 4.0 3.8 3.6 3.4

FIG. 12 agakose eactics Fascist

-l -u. ------& S& Stadiatri

www.wyww. xxxxxww.xxxxwww.xxwww.www.www --M.------M.--a-M' xywww. agatase Stacia:

9.65 9.55 4.95 4.is 4,0s. 3.95 3.85 3.75 3.65 3.5s 3.45 (ppt) Patent Application Publication Jan. 19, 2017. Sheet 7 of 13 US 2017/0015614 A1

FIG. 13 Siara: seiose

See actii A.

S. --- ra MW-ta.-- 3 x3- V Safe: sease Stassistic

FIG. p : 3,5 N N waaaaaaaaaaaaaa. XXXAXWAXXXWWAXX'. a.k. Aaasa y Y-w ask-WkamskWsksaaxas-XaXmasa Aax&XMXaa-XXX-X p: s ,S

sassssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssss Patent Application Publication Jan. 19, 2017. Sheet 8 of 13 US 2017/0015614 A1

FIG. 15

--- wo--~ to

SO,

%

SO,

SO%. A. AO: i 30% is 2% 10%

% : - O O 3C 4. St. Patent Application Publication Jan. 19, 2017. Sheet 9 of 13 US 2017/0015614 A1

FIG. 17 3% 70% 60% 50% 40% 30%

20% i --5 mg Mod, 0% : --20 mg Moo, --80 mg Moo, %, ...... arr war rrrr r < r n x < r n > Y r n w w arr warr w w arr r s rar r s a rrrr rrrr "...... { i 2O 3. &O S Time, h

70% 60% :

s 40%

is 0% --50 mg Sn-MF O% - N -100 mg Sr-MF -r-200 Big Sr-MF % ------O 3. s Time, h Patent Application Publication Jan. 19, 2017. Sheet 10 of 13 US 2017/0015614 A1

FIG. 19 8% - 70% 80%

St: .

4% 30% 20% : 10% - see a yi , P. r war as yt & F O% ------s

FIG. 20 O. : 80% 70% 60%

-0-80 mg Mo03, iOO ng Sn-MF, F --80 mg MoQs, Ong Si-viri, F 40% - -- 0 mg MoOs, OO ng Sn-viFi, 3. % -- 80 mg Moos, O mg Sn-viri, GAfi A % - texx 0 mg Mo.Os, OO ring Sn-viri, GAfDA O%. , Patent Application Publication Jan. 19, 2017. Sheet 11 of 13 US 2017/0015614 A1

FIG. 21

re s s e s and s * ii. o alth a MOO2

O% her -3PMos2O4.

% 2 30 4: O Time, h FIG. 22 88. --80 mg Moos & - -20 mg Ni(N,N,N',N'-Meen, Cl, 70% --2 mg NiN,N,N',N'-Meen),c, so to 200mg Torp. m e Six six w s 3: ar 23 & Patent Application Publication Jan. 19, 2017. Sheet 12 of 13 US 2017/0015614 A1

FIG. 23 93% ...;

: . . . 80% : -0-80 mg MoC3, 50 mg Sn-Beta, F p 8. wn 80 mg Mo.O.s, 50 mg Sn-MF, F 60% : ---80 mg MoOs, 50 mg Sn-Beta, G - ), 50 mg Sn-Beta, DHA

30%

10% %

FIG. 24 9% - 80% 70% A- w w a a a we w a a as a w w a i. 60% 50%

30% worritose 20% ow Psicose or rainaeiose 10% K. Sorose ---agatose % ye. ------:------Patent Application Publication Jan. 19, 2017. Sheet 13 of 13 US 2017/0015614 A1

FIG. 25 80%,

70%

is 60% --Ethanoi SO% --Methano 540% ----90 wt.% Ethanol, 10 wit% Water - ) . Water 30% O O...... ''''''''' 20% ---- as in a r er r * 1 stA 10% - O% ------O O 30 40 SO Time, h FIG. 26 16

14 12 10

8

2 --Batch 50 mg at t = Oh) --Semibatch (50 mg at t = Oh and 50 mg atts: 20 h.

O 18) 2O 3O 40 SO Time, h US 2017/0015614 A1 Jan. 19, 2017

PRODUCTION OF ALPHA-HYDROXY 0009. The feedstock includes any cellulosic CARBOXYLIC AIDS AND ESTERS FROM and hemicellulosic biomass material, either as-provided or HIGHER SUGARS USING TANDEMI partially or completely hydrolyzed to its constituent oligo-, CATALYST SYSTEMS di-, or . In preferred embodiments, the feedstock is characterized as comprising at least one CROSS REFERENCE TO RELATED or . In other embodiments, the car APPLICATIONS bohydrate feedstock is characterized as comprising at least one aldose or ketose monosaccharide. , , 0001. This application claims the benefit of priority from fructose, and are only some of the materials useful in U.S. Patent Application No. 62/194,069, filed Jul. 17, 2015, these disclosed methods. the contents of which are incorporated by reference herein 0010. These first and second catalysts may be described for all purposes. either functionally or chemically, or in both functional and chemical terms, and all of Such descriptions are considered GOVERNMENT RIGHTS within the scope of the present disclosure. 0002 This invention was made with government support 0011. In some embodiments, the retro-aldol catalyst is under Grant No. DE-SC000 1004/T-108118 awarded by the described as a material capable of performing the 12-carbon Department of Energy. The government has certain rights in shift reaction on an aldose or ketose Substrate, i.e.: the invention.

TECHNICAL FIELD HO O V OH 0003. This application is related to the formation of alpha-hydroxy carboxylic acids and esters and intermediates R R R. R. from higher Sugars. 0012 where R is a carbohydrate chain, and R is H or BACKGROUND CHOH. Such a capability may be independently observed 0004 Chemocatalytic routes for the production of C-hy in the absence of the second Lewis acid catalyst. In other droxy carboxylic acids (e.g. lactic acid, 2-hydroxy-3- embodiments, the first retro-aldol catalyst may also be butenoic acid, 2,4-dihydroxybutanoic acid, and glycolic described as capable of converting a pentose or hexose acid) from biomass-derived Sugars have been extensively monosaccharide to a diose, , or intermediate, studied in the recent years, as these acids, their esters, and with the elimination of or glyceraldehyde lactones have been recognized to hold large potential as (see, e.g., FIGS. 1-4). In still other embodiments, the first renewable, green platform chemicals for a number of indus retro-aldol catalyst is capable of effecting the 12-intramo tries (e.g. polymers, solvents, and fine chemicals). lecular carbon shift reaction of the pentose/hexose and is 0005 Considerable progress has been made on the pro also capable of effecting retro-aldol reactions to as to form duction of lactic acid and alkyl-lactates from (glyc a dioseftriose?tetrose intermediate. eraldehyde (GLA) and (DHA)), with 0013 The first retro-aldol catalyst may also be described nearly quantitative yields achievable with the state-of the art by its chemical nature. In various embodiments, this catalyst catalysts (e.g. tin containing Zeotypes Sn-Beta and Sn-MFI. comprises an optionally substituted oxO(hydroxy)molyb which catalyze 1.2 intramolecular hydride shift (1.2-HS) date, sulfomolybdate, or oxy(hydroxy)tungstate; a Ni(II) reactions) at moderate temperatures (ca. 100° C.) (FIG. 1). diamine complex; an alkali-exchanged hafno-, stanno-, Similarly, the C- and C-products, 2-hydroxy-3-butenoic titano-, or Zirconosilicate; an optionally Substituted amor acid, 2,4-dihydroxybutanoic acid, and glycolic acid or their phous Hf() , SnO. , TiO, , or ZrO. SiO, co-precipi esters and/or lactones can be obtained in good yields when tate; or a combination thereof. (, , and ), glycolalde 0014. The Lewis acid catalyst is a material capable of hyde, or glyoxal are used as substrates (FIG. 2). However, performing the 1.2-hydride shift reaction on an aldose the Substrates required for these reactions are not easily Substrate, i.e.: obtained or isolated from biomass, as majority of terrestrial biomass comprises and (polymers of hexoses and pentoses).

SUMMARY 0006. The present invention disclosure is directed to methods of preparing alpha-hydroxy carboxylic acids and where R is a carbohydrate chain. The second Lewis acid esters, such as lactic acid and its esters, from higher Sugars catalyst may also be described functionally as a catalyst using coupled tandem catalysts. In certain of these embodi capable of converting a diose, triose, or tetrose intermediate ments, the methods comprise contacting a carbohydrate (e.g., as provided by the reaction of the retro-aldol catalyst feedstock with Such tandem catalyst system, the contacting with the appropriate feedstock) to an O-hydroxy carboxylic resulting in the formation of an O-hydroxy carboxylic acid acid or C-hydroxy carboxylic acid ester. Again, Such a or C-hydroxy carboxylic acid ester, wherein the tandem capability may be independently observed in the absence of catalyst system comprises: the first retro-aldol catalyst. 0007 (a) a first retro-aldol catalyst; and 0015 The second Lewis acid catalyst may also be 0008 (b) a second Lewis acid catalyst. described by its chemical nature. In its broadest context, the US 2017/0015614 A1 Jan. 19, 2017

Lewis acid catalyst comprises any Lewis acid capable of 0026 FIG. 8 shows "H NMR spectra of D-fructose effecting the transformation of functions attributed to it. In standard solution and of the fructose-containing fraction other various embodiments, this catalyst comprises one or isolated after reaction of D-fructose with MoO in water at more of a hafnium-, tin-, titanium-, or Zirconium-substituted 100° C. for 4 h. Sorbose is present in the collected fraction. crystalline microporous silicate or Zeolite, or an amorphous 0027 FIG. 9 shows "H NMR spectra of L-sorbose stan hafnium-, tin-, titanium-, or Zirconium-silicate co-precipi dard solution and of the Sorbose-containing fraction isolated tate. In certain of these embodiments, crystalline micropo after reaction of D-fructose with MoO in water at 100° C. rous materials having pores equal to 10-MR or 12-MR (or for 4 h. larger) may be useful. While larger pore sized materials are (0028 FIG. 10 shows 'C NMR spectra of L-sorbose within the scope of the present disclosure, 10-MR systems standard Solution and of the Sorbose-containing fraction may have the potential to confer size selectivity for isolated after reaction of D-fructose with MoO, in water at improved yields. 100° C. for 4 h. 0016. The reaction solvents of the disclosed methods do 0029 FIG. 11 shows "H NMR spectra of D-psicose not appear to be particularly restricting, though polar sol standard solution and of the psicose-containing fraction vents (either protic or aprotic) appear to be useful. Protic isolated after reaction of D-fructose with MoO in water at alcoholic solvents appear to work better than aqueous sol 100° C. for 4 h. DHA and a 2-C-(hydroxymethyl)-aldopen vents, perhaps due to solubility and passivation consider tose are present in the collected fraction. HDO peak ca. 4.8 ations. ppm is digitally Suppressed for clarity. 0017. In addition to the methods described, the disclosure 0030 FIG. 12 shows "H NMR spectra of D- and also considers those compositions used or derived from the GLA standard Solutions and of the tagatose-containing frac methods as specific embodiments. tion isolated after reaction of D-fructose with MoO in water at 100° C. for 4 h. Glyceraldehyde is present in the collected BRIEF DESCRIPTION OF THE DRAWINGS fraction. 0031 FIG. 13 shows "H NMR spectra of D-Hamamelose 0018. The present application is further understood when and of the hamamelose-containing fraction isolated after read in conjunction with the appended drawings. For the reaction of D-fructose with MoO in water at 100° C. for 4 purpose of illustrating the Subject matter, there are shown in h. DHA and an unknown are present in the collected the drawings exemplary embodiments of the Subject matter; fraction. however, the presently disclosed subject matter is not lim 0032 FIG. 14 shows "H NMR spectra of methyl group in ited to the specific methods, processes, devices, and systems molybdate-lactate complex formed in the reaction of D-fruc disclosed. In addition, the drawings are not necessarily tose with MoC), and Sn-MFI in water at 100° C. for 16 h. drawn to scale. In the drawings: Top spectrum (pH=2.5) is of a reaction aliquot prior to pH 0019 FIG. 1 schematically illustrates the formation of C. adjustment to 7.5 (bottom spectrum) by addition of sodium C-hydroxy carboxylic acids from trioses. bicarbonate. 0020 FIG. 2 schematically illustrates the formation of C4 0033 FIG. 15 shows "H NMR spectra of reaction solu and C2 C-hydroxy carboxylic acids from tetroses, glycola tion of D-fructose with MoO, and Sn-MFI in MeOH at 100° ldehyde, and glyoxal. C. for 30 h (ca. 68% methyl lactate yield) showing the three 0021 FIG. 3 schematically illustrates representative intense resonances of methyl lactate (ca. 1.25, 3.60, and 4.25 retro-aldol reactions of aldo- and keto-hexoses. ppm) and small peaks associated with by-products. MeOH 0022 FIG. 4 schematically illustrates representative peak ca. 3.19 ppm is digitally Suppressed for clarity. reaction network in which ketohexoses can isomerize to 0034 FIG. 16 provides data for ethyl lactate yield as a aldohexoses via 1.2-HS (r1) and to 2-C-(hydroxymethyl)- function of time at different temperatures (indicated in aldopentoses via 1.2-intramolecular carbon shift (1.2-CS) legend). Reaction conditions: 80 mg Mo.O.; 100 mg Sn (r11) reactions. Retro-aldol reactions of hexose species (r2. MFI; 50 mg D-fructose; 4.9 g EtOH: 50 mg naphthalene as r3, and r12) lead to the formation of C2, C3, and C4 internal standard. carbohydrate fragments. Lewis acids can then catalyze the 0035 FIG. 17 provides data for ethyl lactate yield as a formation of O-hydroxy carboxylic acids from these smaller function of time for varying MoC) catalyst amounts (indi fragments (e.g., r7, r8, and r9 in the formation of alkyl cated in legend). Reaction conditions: 100° C.; 100 mg lactate from trioses). Side reactions, involving dehydration Sn-MFI; 50 mg D-fructose; 4.9 g EtOH: 50 mg naphthalene reactions of fructose to 5-HMF (rS), redox and fragmenta as internal standard. tion reactions of unstable intermediates, and various humin 0036 FIG. 18 provides data for ethyl lactate yield as a forming condensation reactions, lead to loss of yield of function of time for varying Sn-MFI catalyst amounts (indi desired products. cated in legend). Reaction conditions: 100° C.; 80 mg 0023 FIG. 5 is a schematic representation of a 1.2-CS MoO; 50 mg D-fructose; 4.9 g EtOH: 50 mg naphthalene (R—H for or R=CH-OH for , and R. as internal standard. represents the remainder of the saccharide) that involves 0037 FIG. 19 provides data for ethyl lactate yield as a simultaneous breaking and forming of C-C bonds. function of time for varying concentrations of fructose 0024 FIG. 6 illustrates a schematic representation of the (indicated in legend). Reaction conditions: 100° C.; 80 mg stereospecific molybdate-catalyzed isomerization of D-fruc MoO; 100 mg Sn-MFI; 4.9 g EtOH: 50 mg naphthalene as tose to D-hamamelose. internal standard. 0025 FIG. 7 illustrates structures of Sorbose, tagatose, 0038 FIG. 20 provides data for ethyl lactate yield as a and psicose structural analogues of tetradentate molybdate function of time for control runs illustrating the necessity of complex of fructose hypothesized to be involved in isomer catalyst. Reaction conditions: 100° C.: catalyst amounts ization to hamamelose. specified in legend: 50 mg of D-fructose (F) or mixture of 25 US 2017/0015614 A1 Jan. 19, 2017

mg of GLA and 25 mg DHA (GLA/DHA) 4.9 g EtOH: 50 a feature or embodiment associated with a composition, it is mg naphthalene as internal standard. appreciated that such a description or claim is intended to 0039 FIG. 21 provides data for ethyl lactate yield as a extend these features or embodiment to embodiments to the function of time for varying Mo-containing retro-aldol cata method of making or using the composition, and vice lysts (indicated in legend). Reaction conditions: 100° C.; versa—i.e., a feature described in one context is also appli 100 mg Sn-MFI; 50 mg D-fructose; 4.9 g EtOH: 50 mg cable in all of these contexts (i.e., compositions, methods of naphthalene as internal standard. making, and methods of using). 0040 FIG. 22 provides data for methyl lactate yield as a 0046. The present disclosure is based on the recognition function of time for MoO and Ni(N.N.N',N'-Meen), IC1 of the need to use retro-aldol reactions to fragment the larger catalysts (amounts indicated in legend). Reaction condi sugars' carbon backbones (FIG.3 and FIG. 4) to form these tions: 100° C.; 100 mg Sn-MFI; 50 mg D-fructose; 4.9 g, C-C C-hydroxy carboxylic acids from hexoses and pen MeOH: 50 mg naphthalene as internal standard. toses (e.g., r2 and r3 in FIG. 4). For the common aldo- and 0041 FIG. 23 provides data for ethyl lactate yield as a keto-hexoses and pentoses, these C-C bond-splitting reac function of time for Sn-Beta/Sn-MFI comparison. Reaction tions have large activation energies and unfavorable ther conditions: 100° C.; 80 mg MoOs: Sn-Beta or Sn-MFI modynamics at low-to-moderate temperatures. As a result, amount specified in legend: 50 mg of D-fructose (F), D-Glu most attempts at the catalytic production of C-C C.-hy cose (G), or DHA; 4.9 g EtOH: 50 mg naphthalene as droxy carboxylic acids from hexoses and pentoses have internal standard. involved high temperature conditions (>160° C.). Carbon 0042 FIG. 24 provides data for ethyl lactate yield as a basis yields ca. 64-68% of methyl lactate at full conversion function of time for different ketohexoses and a 2-C-(hy were reported for reactions of catalyzed by Sn-Beta droxymethyl)-aldopentoses (hamamelose) as Substrates. at 160° C. for 20 h. Lower yields ca. 40-44% were reported Reaction conditions: 100° C.; 80 mg MoO; 100 mg Sn for monosaccharide Substrates in the same study. Similarly, MFI; 50 mg of D-fructose, D-psicose, D-hamamelose, lower yields of lactate products were reported for the reac L-sorbose, or D-tagatose; 4.9 g EtOH: 50 mg naphthalene as tion of sucrose in different solvents (39%, <30%, 25% for internal standard. ethanol, water, and isopropanol, respectively). The Sn-Beta 0043 FIG. 25 provides data for alkyl lactate yield as a catalyst was shown to be reusable, but needed to be calcined function of time for different solvents (specified in legend): between runs due to deposition of carbon that happens at 100° C.; 80 mg MoO: 100 mg Sn-MFI, 50 mg of D-fructose high temperatures. Recently, methyl lactate yields upwards (F); 4.9 g solvent: 50 mg naphthalene as internal standard. of 75% from sucrose with Sn-Beta at 170° C., when specific In case of water, external standard (DSS) was used for H amounts of alkali carbonates were added to the reaction NMR quantification instead of naphthalene. system. Again, the yields from monosaccharides were sig 0044 FIG. 26 provides data for ethyl lactate weight nificantly lower. fraction as a function of time for batch and semi-batch 0047 Among the potential reasons for the carbon depo reactions. Reaction conditions: 100° C.; 80 mg MoO: 100 sition on the catalyst and low selectivities in some solvents mg Sn-MFI; 4.9 g EtOH: 50 mg naphthalene as internal are the poor thermal stability of sugars beyond 100° C. and standard. For batch operation, 50 mg of D-fructose was the lack of substrate and reaction specificity of the catalytic added at t=0 h. For semi-batch operation, 50 mg of D-fruc sites investigated in the aforementioned systems. Dehydra tose was added at t=0 h. After 20 h of reaction, the reactor tion reactions of ketohexoses to 5-hydroxymethyl furfural was rapidly quenched with ice and opened. At this point, the (5-HMF) become prevalent at high temperatures (rS in FIG. first aliquot was taken and another 50 mg of D-fructose was 4). The Subsequent fragmentation and coupling reactions of added to the reactor. After re-sealing the reactor, regular 5-HMF can lead to the formation of insoluble humins that operation and sampling procedure was resumed. deposit on the catalyst, thereby leading to catalyst deacti Vation. Furthermore, large-pore catalysts like Sn-Beta can DETAILED DESCRIPTION OF ILLUSTRATIVE promote aldose-ketose isomerization reactions (rl in FIG. 4) EMBODIMENTS of Substrates as large as because the Lewis 0045. The present invention may be understood more acid sites that are active for 1.2-HS reactions are accessible readily by reference to the following description taken in to Such species. The same Lewis acid sites have been connection with the accompanying Figures and Examples, previously proposed as the active sites in retro-aldol reac all of which form a part of this disclosure. It is to be tions. As a result, Sn-Beta (and other 12-MR materials) does understood that this invention is not limited to the specific not readily allow for size-dependent discrimination among products, methods, processes, conditions or parameters the Substrates, and results in retro-aldol reaction happening described or shown herein, and that the terminology used on both aldo- and keto-hexoses, resulting in the concomitant herein is for the purpose of describing particular embodi formation of C and C products, in addition to the more ments by way of example only and is not intended to be desired C products. That is, even when ketohexose sub limiting of any claimed invention. Similarly, unless specifi strates are used, C and C products derived from aldoses cally otherwise stated, any description as to a possible concomitantly form with the more desired C products mechanism or mode of action or reason for improvement is derived from ketoses (ra and r7-r10 in FIG. 4, respectively). meant to be illustrative only, and the invention herein is not Because of these features, catalytic strategies that allow for to be constrained by the correctness or incorrectness of any retro-aldol reactions of hexoses to proceed in the absence of Such suggested mechanism or mode of action or reason for aldose-ketose isomerization would be highly useful, as they improvement. Throughout this specification, claims, and would have the potential to significantly affect the distribu drawings, it is recognized that the descriptions refer to tion of C, C, and C products compositions and processes of making and using said com 0048 For these reasons, catalysts and catalytic strategies positions. That is, where the disclosure describes or claims that allow for lower temperature retro-aldol reactions and US 2017/0015614 A1 Jan. 19, 2017

tunability of accessible active site ratios for the retro-aldol these methods. Glucose, mannose, fructose, and Xylose are and isomerization reactions are desired. especially attractive substrates for these methods. 0049. The present invention is directed to the preparation 0055. The methods are described in terms of a “tandem of alpha-hydroxy carboxylic acids and esters using catalytic catalyst system,” which refers to the use of both first and systems comprising moderate-temperature (around 100° C.) second catalysts on a common feedstock and/or reaction retro-aldol reactions of various hexoses in aqueous and mixture. In some embodiments, this refers to a comingled alcoholic media with catalysts traditionally known for their mixture of the first and second catalysts, both in a common capacity to catalyze 1.2-intramolecular carbon shift (1.2-CS) vessel in a common reaction mixture and common solvent reactions of aldoses. Because these catalysts do not readily system. But in other embodiments, these catalysts may be catalyZealdose-ketose interconversion through 1.2-HS, they applied separately/sequentially to a given feedstock, for are candidate co-catalysts for reaction pathways that benefit example, in a recycle situation. from aldose- or ketose-specific, retro-aldol fragmentation. 0056. The first retro-aldol and second Lewis acid cata Here, these retro-aldol catalysts are combined with Lewis lysts may be described either functionally or chemically, or acid catalysts to enable the moderate-temperature conver in both functional and chemical terms, and all of Such sion of hexoses into C-hydroxy carboxylic acids. descriptions are considered within the scope of the present 0050. In this disclosure, various embodiments provide disclosure. Unless otherwise specified, the first and second methods for the preparation of certain C.-hydroxy carboxylic catalysts perform comprise different discrete materials, the acid or C-hydroxy carboxylic acid esters, for example lactic first acting as the retro-aldol catalyst and the second as the acid or esters of 2-hydroxy-3-butenoic acid, 2,4-dihy Lewis acid catalyst. However, when explicitly specified, a droxybutanoic acid, glycolic acid, or esters thereof from the first and second catalysts may be combined to provide a carbohydrate feedstocks. In certain embodiments, the meth composite catalyst, wherein a single integrated composition ods comprise contacting a carbohydrate feedstock with a comprises both types of materials. For example, a partially tandem catalyst system, the contacting resulting in the Substituted a stannosilicate that is partially ion-exchanged formation of an O-hydroxy carboxylic acid or C-hydroxy may be seen as having both 1.2-HS and 1.2-CS/retro-aldol carboxylic acid ester, wherein the tandem catalyst system sites. Similarly, a stannosilicate (or other 1.2-HS catalyst) comprises: that is impregnated with a 1,2-CS catalyst (such as a MoOx 0051 (a) a first retro-aldol catalyst; and species or Ni (II) diamine complexes) may provide Such 0052 (b) a second Lewis acid catalyst. multifunctional, composite activity. 0053. In the present case, the methods are operable at 0057. In some embodiments, the retro-aldol catalyst is temperatures of 200° C. or less, preferably 160° C. or less, described as a material capable of performing the 12-carbon more preferably about 100° C., to effect conversions to the extent as described in the Examples. In certain embodi shift reaction on an aldose or ketose Substrate, i.e.: ments, the methods can be effected at temperatures defined by one or more ranges from 60° C. to 80° C., from 80° C. HO O O OH to 100° C., from 100° C. to 120° C., from 120° C. to 140° C., from 140° C. to 160° C., from 160 to 180° C., from 180° C. to 200°C., or higher. In order to maintain these tempera R R2 Y R7( R2 tures with some of the contemplated solvents or solvent systems, the methods are typically done in sealed vessels, in which the pressures are those autogenous pressures associ where R is a carbohydrate chain, and R is H or CH-OH. ated with the systems. Such a capability may be independently observed in the 0054 The carbohydrate feedstock includes any cellulosic absence of the second Lewis acid catalyst. For example and hemicellulosic biomass material, either as-provided or (referring to FIG. 3), for an exemplary aldose: partially or completely hydrolyzed to its constituent oligo-, di-, or monosaccharides. In some related embodiments, these methods further comprise hydrolyzing or otherwise OH O treating (e.g., by alcoholysis) biomass so as to provide the O O constituent oligo-, di-, or monosaccharides or glycoside, - rx NH glycophosphate, acetal, or hemiacetal derivatives thereof. In R2 R. R. preferred of these, the treatment results in the formation of O the monosaccharides. Alternatively, the methods use these OH OH HO O constituent materials as provided from other sources. In O NH preferred embodiments, the feedstock is characterized as HO r H comprising at least one pentose or hexose monosaccharide. OH OH H HO OH The carbohydrate feedstock may also be characterized as OH comprising at least one aldose or ketose monosaccharide. As OH intended herein, aldose monosaccharides include one or more of , , Xylose, (pentoses) and R2 = H; R1 = ~% , , glucose, mannose, , , , and OH, OH (hexoses). Similarly, the ketose monosaccharides include one or more of , (pentoses), fruc tose, psicose, Sorbose, and tagatose (hexoses). Similarly, While not intending to be bound by the correctness of any branched chain monomers, such as hamamelose, its stereoi particular theory, it is possible that this mechanism may act Somers, and/or pentose analogues, may be suitably used in as a pre-step to the second retro-aldol reaction: US 2017/0015614 A1 Jan. 19, 2017

pentose/hexose and is also capable of effecting retro-aldol reactions to as to form a diose?triose?tetrose intermediate. HO H |O HO 0058. In some embodiments, the first retro-aldol catalyst comprises an optionally substituted oxO(hydroxy)molyb N/CH -- date, sulfomolybdate, or oxy(hydroxy)tungstate; a Ni(II) HO y ( HO \, diamine complex; an alkali-exchanged crystalline micropo OH ON OH rous hafno-, stanno-, titano-, or Zirconosilicate; an optionally Substituted amorphous hafnium-, tin-, titanium-, or Zirco HO HO nium-silicate co-precipitate; or a combination thereof. The active catalyst may be added to the reaction mixture as such, H >s -E HO 4 + HO 1.4.” or as a precursor that is effective for the described purpose. These catalysts are known to be effective for the epimeriza tion of the aldoses and for the rearrangement of ketoses to 2-C-hydroxymethyl aldoses, as described herein. Similarly, for an exemplary ketose: 0059. As used herein, the terms “oxo(hydroxy) molyb date' and sulfomolybdate' include those complexes of molybdenum having oxo and optional hydroxy ligands and OH O Sulfide ligands, respectively; these are often complex poly O O anions in use, which may or may not be substituted with -- H n H other elements, for example, LiNbMoO and HNbMoO). In R2 R R2 other specific embodiments, the first retro-aldol catalyst is OH either present as or derived from an oxomolybdate or sulfomolybdate precursor of MoC), MoC), MoS MoS, MoSs. MoO(OH), MoC), Mos0, Mo.O., Mo.O. R2 = -CH2OH; R = ry HPMo.Oao (or other Keggin structures containing Mo). OH Mo.O.", or a combination thereof. Again, the term OH O "derived from reflects the use of these materials, as added OH to the reaction mixture, which convert to active catalytic HO s species during the course of the reaction. In many cases, the OH OH active materials have complex structures which may not be O fully characterized. Where the materials are anions or poly anions, the materials may be added as ammonium, alkali HO O metal, alkaline earth metal, or transition metal (e.g., Zinc) n H salts. The catalysts may be soluble or insoluble salts or may HO CH2OH be immobilized onto an anion exchange Support, or on an OH inert Surface. Such as a Solid oxide (e.g., silica). OH 0060. In other embodiments, the first retro-aldol catalyst H comprises a diamine complex of Ni(II), typically a bidentate HO HC d HO diamine complex, and preferably an ethylenediamine com plex of Ni(II). In some embodiments, the ethylenediamine al -- complexes of Ni(II) include mono-, di-, tri-, or tetraalkyl HO O (OI in \ ethylenediamine complexes of Ni(II), including nickel n H halides, for example Ni(II) (N.N.N',N'-tetramethylethylene OH diamine)Cl. OH OH 0061 The Lewis acid catalyst is a material capable of HC performing the 1.2-hydride shift reaction on an aldose or \pH E resul- -- ketose Substrate, i.e.: H1 O O

Alternatively, it is possible that the retro-aldol catalysts where R is a carbohydrate chain. Again, such a capability operates to enable the 12-carbon shift reaction in parallel may be independently observed in the absence of the first with or through a common intermediate of the retro-aldol retro-aldol catalyst. The second Lewis acid catalyst may also reaction. In some embodiments, the first retro-aldol catalyst be described functionally as a catalyst capable of converting may also be described as capable of converting a pentose or a diose, triose, or tetrose intermediate (e.g., as provided by hexose monosaccharide to a diose, triose, or tetrose inter the reaction of the retro-aldol catalyst with the appropriate mediate, for example with the elimination of glycolaldehyde feedstock) to an O-hydroxy carboxylic acid (such as lactic or glyceraldehyde (see, e.g., FIGS. 1-4). In still other acid) or C-hydroxy carboxylic acid ester (such as a lactic embodiments, the first retro-aldol catalyst is capable of acid ester). In addition to lactic acid from trioses, 2-hydroxy effecting the 1.2-intramolecular carbon shift reaction of the 3-butenoic acid, 2,4-dihydroxybutanoic acid, and glycolic US 2017/0015614 A1 Jan. 19, 2017

acid and their esters have been observed with diose and A), PAR (3.5x6.9 A), PON (5.0x5.3 A), RRO (4.0x6.5 A), tetrose Substrates reacting with 1.2-HS catalysts. See, e.g., SFF (5.4x5.7A), SFG (5.2x5.7 A, 4.8x5.7A), STF (5.4x5.7 M. Dusselier, et al., ChemCatChem 2013, 5 (2), 569-575 and A), STI (4.7x5.0 A), STW (5.9x5.9 A), SZR (4.1x5.2 A), P. Y. Dapsens, et al., Green Chem. 2014, 16 (3), 1176. TER (5.0x5.0 A, 4.1 x7.0 A), TON (4.6x5.7 A), TUN 0062) Again, without intending to be bound by the cor (5.6x5.5 A, 5.4x5.5 A), WEI (3.1x5.4 A), and WEN (2.5x rectness of any particular theory, it is believed that the 4.8 A). Parenthetical pore sizes attributable to the topology 1.2-HS is implicated in the formation of lactates as shown in come from the Ch. Baerlocher, Atlas of Zeolite Framework the added schematic (R is H or alkyl group from alcohol Types, Sixth Revised Edition, 2007, Structure Commission solvent). See, e.g., P. P. Pescarmona, P. P. et al., Green of the International Zeolite Association. In preferred Chem. 2010, 12 (6), 1083. embodiments, the crystalline microporous materials com prising 10-membered rings include those having MFI, MWW, MEI, and FER topologies. HO O O OH 0065 Crystalline microporous materials comprising 1-membered rings believed to be useful in this capacity ) / 12-HS ) / include those having topologies of AFI (7.3x7.3 A), AFR HO HO (6.7x6.9 A), AFS (7.0x7.0 A), AFY (6.1x6.1 A), ASV (4.1x4.1 A), ATO (5.4x5.4 A), ATS (6.5x7.5 A), *BEA /to (6.6x6.7 A, 5.6x5.6 A), BEC (6.3x7.5 A, 6.0x6.9 A), BOG O O HO O (7.0x7.0 A), BPH (6.3x6.3 A), CAN (5.9x5.9 A), CON He (6.4x7.0 A, 7.0x5.9 A), CZP (3.8x7.2 A), DFO (7.3x7.3 A, ) / ROH , ( 6.2x6.2 A), EMT (7.3x7.3 A, 6.5x7.5A), EON (6.7x6.8A), O -R EZT (6.5x7.4A), FAU (7.4x7.4A), GME (7.0x7.0 A), GON (5.4x6.8 A), IFR (6.2x7.2 A), ISV (6.1 x6.5 A, 5.9x6.6 A), RoN 4.2-HS IWR (5.8x6.8A), IWV (6.2x6.9A, 6.2x6 A), IWW (6.0x6.7 O OH A), LTL (7.1 x7.1 A), MAZ (7.4x7.4 A), MEI (6.9x6.9 A), MOR (6.5x7.0 A), MOZ (6.8x7.0 A, 6.8x6.8 A), MSE (6.4x6.8 A), MTW (5.6x6.0 A), NPO (3.3x44 A), OFF O-R (6.7x6.8 A), OSI (5.2x6.0 A), RON (4.3x4.3 A), RWY (6.9x6.9A), SAO (6.5x7.2 A, 7.0x7.0 A), SBE (7.2x7.4 A), 0063. The second Lewis acid catalyst may also be SBS (6.8x6.8 A, 6.9x7.0 A), SBT (6.4x7.4 A, 7.3x7.8 A), described by its chemical nature. In its broadest context, in SFE (5.4x7.6 A), SFO (6.9x7.1 A), SOS (3.9x9.1 A), SSY Some embodiments, the Lewis acid catalyst comprises any (5.0x7.6 A), USI (6.1x6.2 A), and VET (5.9x5.9 A). In Lewis acid capable of effecting the transformation of func preferred embodiments, the crystalline microporous mate tions attributed to it. In certain embodiments, these Lewis rials comprising 12-membered rings include those having acid catalysts are specifically devoid of Brønsted acidity. In BEA, FAU, CON, AFI, and MOR topologies other embodiments, the Lewis acid catalyst may exhibit 0066. In the context of these frameworks, in some some Bronsted acidity. The Lewis acid catalyst may be a embodiments, the second Solid Lewis acid catalyst com heterogeneous catalyst or a soluble homogeneous catalyst, prises a crystalline microporous hafno-, stanno-, titano-, for example a Lewis acid salt. Lewis acid salts have been Zirconosilicate, or mixed metal silicate. In other embodi reported to enable the isomerization of trioses into lactates, ments, the crystalline microporous hafno-, stanno-, titano-, so it is to be expected that such salts, which include but are or Zirconosilicate is a hafno-, Stanno-, titano-, or ZirconoZeo not limited to aluminum, chromium, tin, or Zinc salts such as lite. Again, in preferred embodiments, these crystalline AlCl, Al(SO). CrCl CrSO. CrC1, SnCl, ZnSO, may microporous silicates or Zeolites are alkali-free forms of also be operable in the present tandem catalytic system; see, these materials. In specific independent embodiments, as e.g., C. B. Rasrendra, et al., ChemSusChem 2011, 4 (6), shown in the Examples, the crystalline microporous solid is 768-777, which is incorporated by reference herein at least a tin-substituted Zeolite of MFI topology or a tin-substituted for its teaching of the salts and reaction conditions. In other Zeolite beta. Extra-framework aluminum Lewis acid sites various embodiments, the second Lewis acid catalyst com have also been reported for the 1.2-HS, and are considered prises a Substituted crystalline microporous solid containing within the scope of the present invention. pores equal to or greater than 10-MR. In independent embodiments, the crystalline microporous solid contains 0067. In other embodiments, the Lewis Acid catalyst may 10-MR pores, 12-MR pores, or larger pores. In preferred also comprise a tin-, titanium-, Zirconium-, and/or hafnium embodiments, these crystalline microporous Solids are containing amorphous silicate co-precipitates. alkali-free forms of these materials. 0068. In the method reactions, the feedstocks, or their 0064 Crystalline microporous materials comprising Substrate components, are typically distributed within a 10-membered rings believed to be useful in this capacity Solvent, preferably a polar solvent. In some embodiments, include those having topologies of AEL (4.0x6.5 A), AFO the solvent is protic, such as an alcohol or water. In other (4.3x7.0 A), AHT (3.3x6.8 A), CGF (2.5x9.2 A), CGS embodiment, the solvent is a polar aprotic Solvent, such as (3.5x8.1 A), DAC (3.4x5.3 A), EUO (4.1x5.4 A), FER acetonitrile, dimethylsulfoxide (DMSO), dimethylforma (4.2x5.4 A), HEU (3.1x7.5 A), IMF (5.5x5.6 A, 5.3x5.4 A, mide (DMF), dimethylacetamide (DMA), hexamethylphos 5.3x5.9 A, 4.8x5.4 A5.1x5.3 A), ITH (4.8x5.3 A, 4.8x5.1 phoramide (HMPA), N-methyl pyrrolidone (NMP), a diox A), LAU (4.0x5.3 A), MEL (5.3x5.4 A), MFI (5.1x5.5 A, ane, a Substituted furan, or an optionally tetrahydrofuran 5.3x5.6 A), MFS (5.1x5.4 A), MTT (4.5x5.2 A), MWW (e.g., 2-methyl furan or 2-methyl tetrahydrofuran). Ionic (4.0x5.5 A, 4.1x5.1 A), NES (4.8x5.7 A), OBW (5.0x5.0 liquids may also be used in this capacity. US 2017/0015614 A1 Jan. 19, 2017

0069. In some embodiments where the solvent comprises value, unless the context clearly indicates otherwise. Thus, a protic solvent, that solvent is aqueous, containing water in for example, a reference to “a material' is a reference to at a range of from 10 wt % to 100 wt % with respect to the total least one of such materials and equivalents thereof known to weight of the solvent. In other embodiments, the solvent is those skilled in the art, and so forth. or comprises an alcohol, for example, one or more of a C I0082. When a value is expressed as an approximation by alcohol. The solvent may comprise a saturated, unsaturated, use of the descriptor “about' or “circa” (ca.), it will be or aromatic alcohol. In certain preferred embodiments, the understood that the particular value forms another embodi alcohol is at least one C alcohol, for example a methyl, ment. In general, use of the term “about indicates approxi ethyl, propyl, butyl, pentyl, hexyl alcohol, or a mixture mations that can vary depending on the desired properties thereof. More preferably the alcohol is C alcohol, i.e., sought to be obtained by the disclosed subject matter and is methanol, ethanol, n-propanol, isopropanol, or a mixture to be interpreted in the specific context in which it is used, thereof. In some embodiments, the solvent comprises an based on its function. The person skilled in the art will be aqueous alcohol mixture. In other embodiments, the solvent able to interpret this as a matter of routine. In some cases, the comprising the one or more alcohols is anhydrous or Sub number of significant figures used for a particular value may stantially anhydrous, the term “substantially anhydrous’ be one non-limiting method of determining the extent of the meanings that no water is deliberately added. Where speci word “about.” In other cases, the gradations used in a series fied, the term “substantially anhydrous may also mean that of values may be used to determine the intended range deliberate steps are taken to remove adventitious water. available to the term “about for each value. Where present, Alcohol solvents appear to be preferred over aqueous sol all ranges are inclusive and combinable. That is, references vents possible because of the poorer solubility of the retro to values stated in ranges include every value within that aldol catalysts, therein, relative to water. Alcohols may also range. be preferred due to reduction of passivation by coordination I0083. It is to be appreciated that certain features of the with alpha-hydroxy acids (because esters are formed invention which are, for clarity, described herein in the instead. context of separate embodiments, may also be provided in 0070 While any and all of the various permutations of combination in a single embodiment. That is, unless obvi feedstocks, Substrates, first and second catalysts, solvents ously incompatible or specifically excluded, each individual and conditions are considered within the scope of the present embodiment is deemed to be combinable with any other invention, in certain specific embodiments, the methods embodiment(s) and Such a combination is considered to be comprise contacting the catalysts and Substrates where: another embodiment. Conversely, various features of the 0071 (a) the carbohydrate feedstock comprises a C5 or invention that are, for brevity, described in the context of a C6 aldose or ketose monosaccharide; single embodiment, may also be provided separately or in 0072 (b) the first retro-aldol catalyst comprises an oxo any sub-combination. Finally, while an embodiment may be (hydroxy)molybdate: described as part of a series of steps or part of a more general 0073 (c) the second Lewis acid catalyst comprises a structure, each said step may also be considered an inde Sn-beta or Sn-MFI Zeolite; and pendent embodiment in itself, combinable with others. 0074 (d) the tandem catalyst system further comprises an I0084. The transitional terms “comprising,” “consisting alcohol solvent; essentially of and “consisting are intended to connote their wherein the method is operated under conditions so as to generally in accepted meanings in the patent Vernacular; that produce an O-hydroxy carboxylic acid or C-hydroxy car is, (i) “comprising,” which is synonymous with “including.” boxylic acid ester. “containing,” or “characterized by, is inclusive or open 0075 To this point, the present invention has been ended and does not exclude additional, unrecited elements described in terms of the methods for preparing the C-hy or method or process steps; (ii) “consisting of excludes any droxy carboxylic acid or C-hydroxy carboxylic acid ester, element, step, or ingredient not specified in the claim; and the present disclosure also encompasses the associated com (iii) “consisting essentially of limits the scope of a claim to positions used or generated by these methods. For example, the specified materials or steps “and those that do not certain embodiments comprise: materially affect the basic and novel characteristic(s) of the 0076 (a) a carbohydrate feedstock as described in the claimed invention. Embodiments described in terms of the context of any one of the preceding embodiments; phrase “comprising (or its equivalents), also provide, as 0077 (b) a first retro-aldol catalyst as described in the embodiments, those which are independently described in context of any one of the preceding embodiments; terms of “consisting of and “consisting essentially of For 0078 (c) a second Lewis acid catalyst as described in the those embodiments provided in terms of "consisting essen context of any one of the preceding embodiments; and tially of the basic and novel characteristic(s) is the facile 0079 (d) optionally at least one O-hydroxy carboxylic operability of the methods (or the systems used in such acid or C-hydroxy carboxylic acid ester; and methods or the compositions derived therefrom) to convert 0080 (e) optionally at least one aqueous or alcoholic a higher to an O-hydroxy carboxylic acid, or ester or solvent. other derivative thereof Representative embodiments of these compositions also I0085. When a list is presented, unless stated otherwise, it include those described or evident from the Examples is to be understood that each individual element of that list, recited herein. and every combination of that list, is a separate embodiment. For example, a list of embodiments presented as "A, B, or TERMS C is to be interpreted as including the embodiments, “A.” 0081. In the present disclosure the singular forms “a, “B,” “C.” “A or B,” “A or C.” “B or C.” or “A, B, or C. “an, and “the' include the plural reference, and reference to 0086. Unless defined otherwise, all technical and scien a particular numerical value includes at least that particular tific terms used herein have the same meaning as commonly US 2017/0015614 A1 Jan. 19, 2017

understood by one of ordinary skill in the art to which this artisan, insofar as it connotes separating or isolating the invention belongs. Although any methods and materials material (e.g., terephthalic acid or ester) from other starting similar or equivalent to those described herein can also be materials or co-products or side-products (impurities) asso used in the practice or testing of the present invention, ciated with the reaction conditions yielding the material. As representative illustrative methods and materials are Such, it infers that the skilled artisan at least recognizes the described herein. existence of the product and takes specific action to separate 0087. Throughout this specification, words are to be or isolate it. Absolute purity is not required, though pre afforded their normal meaning, as would be understood by ferred, as the material may contain minor amounts of those skilled in the relevant art. However, so as to avoid impurities and the separated or isolated material may contain misunderstanding, the meanings of certain terms will be residual solvent or be dissolved within a solvent used in the specifically defined or clarified. reaction or Subsequent purification of the material. 0088. The term “aldose' carries its conventional meaning of a monosaccharide (a simple Sugar) that contains only one 0094. As used herein, the term "crystalline microporous aldehyde ( CH=O) group per molecule. The chemical solids' or “crystalline microporous silicates' are crystalline formula takes the form C(H2O). The simplest possible structures having very regular pore structures of molecular aldose is the diose glycolaldehyde, which only contains two dimensions, i.e., under 2 nm. The maximum size of the carbon atoms. Examples of aldose include glycolaldehyde (a species that can enter the pores of a crystalline microporous diose), glyceraldehyde (a triose), erythrose, threose (tet solid is controlled by the dimensions of the channels. roses), ribose, arabinose, Xylose, lyxose (pentoses), allose, altrose, glucose, mannose, gulose, idose, talose, and galac (0095. The term “silicate” refers to any composition tose (hexoses). Similarly, the term “ketose' is also a mono including silicate (or silicon oxide) within its framework. It saccharide containing a single ketone group. Examples of is a general term encompassing, for example, pure-silica ketose include dihydroxyacetone (a triose), erythrulose (a (i.e., absent other detectable metal oxides within the silicate tetrose), ribulose, Xylulose (pentoses), fructose, psicose, framework), aluminosilicate, borosilicate, ferrosilicate, Sorbose, tagatose (hexoses), and (a ). Stannosilicate, titanosilicate, or Zincosilicate structures. The term "Zeolite” refers to an aluminosilicate composition that 0089. Unless otherwise indicated, the term “isolated is a member of this family. The term “aluminosilicate” refers means physically separated from the other components so as to any composition including silicon and aluminum oxides to be free of solvents or other impurities; additional embodi within its framework. In some cases, either of these oxides ments include those where the compound is substantially the may be substituted with other oxides. When described as only solute in a solvent or solvent fraction, such a analyti “optionally substituted, the respective framework may con cally separated in a liquid or gas chromatography phase. tain aluminum, boron, gallium, germanium, hafnium, iron, 0090. As used herein, the terms “methods” or “pro tin, titanium, indium, Vanadium, Zinc, Zirconium, or other cesses' may be used interchangeably. atoms substituted for one or more of the atoms not already 0091. The term “microporous,” according to IUPAC contained in the parent framework. Typically, the aluminum notation refers to a material having pore diameters of less and other metals are tetrahedrally located within the frame than 2 nm. Similarly, the term “macroporous” refers to work, providing Lewis acidity to the framework. Where an materials having pore diameters of greater than 50 nm. And oxide is described as being “extra-framework' (as in extra the term “mesoporous” refers to materials whose pore sizes framework aluminum Lewis acid sites), those oxides are are intermediate between microporous and macroporous. positioned within the framework but not part of the crystal Within the context of the present disclosure, the material line framework structure. properties and applications depend on the properties of the framework Such as pore size and dimensionality, cage 0096. The term “substantially anhydrous” in the context dimensions and material composition. Due to this there is of solvents means that no water has been deliberately added. often only a single framework and composition that gives Where specified, the term “substantially anhydrous may optimal performance in a desired application. also mean that deliberate steps are taken to remove adven 0092 “Optional” or “optionally” means that the subse titious water. quently described circumstance may or may not occur, so 0097. The following listing of embodiments is intended that the description includes instances where the circum to complement, rather than displace or Supersede, the pre stance occurs and instances where it does not. For example, vious descriptions. the phrase “optionally substituted” means that a non-hydro gen Substituent may or may not be present on a given atom, and, thus, the description includes structures wherein a Embodiment 1 non-hydrogen Substituent is present and structures wherein a non-hydrogen Substituent is not present. Similarly, the 0098. A method comprising contacting a carbohydrate phrase "optionally isolated” means that the target molecule feedstock with a tandem catalyst system, the contacting or other material may or may not be separated from other resulting in the formation of an O-hydroxy carboxylic acid materials used or generated in the method, and, thus, the or C-hydroxy carboxylic acid ester, wherein the tandem description includes separate embodiments where the target catalyst system comprises: molecule or other material is separated and where the target 0099 (a) a first retro-aldol catalyst; and molecule or other material is not separated, such that Sub sequence steps are conducted on isolated or in situ generated 01.00 (b) a second Lewis acid catalyst. product. In certain Aspects of this Embodiment, the retro-aldol cata 0093. The terms “separating” or “separated carries their lyst is capable of performing the 1.2-carbon shift reaction on ordinary meaning as would be understood by the skilled an aldose or ketose Substrate, i.e.: US 2017/0015614 A1 Jan. 19, 2017

oxomolybdate or sulfomolybdate precursor of MoC) HO O V OH MoO, MoS MoS MoSs. MoO(OH), MoO, MosO4, Mo.O., , Mo.O.47, HPMo.Oao, IMO,OI, or a combination thereof. In certain Aspects of this Embodi R R2 R R2 ment, the catalysts are either soluble or insoluble salts or may be immobilized onto an anion exchange Support. where R is a carbohydrate chain, and R is H or CHOH. In other Aspects of this Embodiment, the Lewis acid catalyst is Embodiment 8 capable of performing the 1.2-hydride shift reaction on an 0107 The method of any one of Embodiments 1 to 6, aldose Substrate, i.e.: wherein the first retro-aldol catalyst comprises an ethylene diamine complex of Ni(II). HO / O OH Embodiment 9 0108. The method of any one of Embodiments 1 to 8, R R wherein the second Lewis acid catalyst comprises a catalyst capable of converting a diose, triose, or tetrose intermediate where R is a carbohydrate chain. to an O-hydroxy carboxylic acid or C-hydroxy carboxylic acid ester. Embodiment 2 0101 The method of Embodiment 1, wherein the carbo Embodiment 10 hydrate feedstock comprises a pentose or hexose monosac 0109. The method of any one of Embodiments 1 to 9, charide. wherein the second Lewis acid catalyst comprises a crys talline microporous solid containing pores equal to or Embodiment 3 greater than 10-MR. In certain Aspects of this Embodiment, 0102 The method of Embodiment 1 or 2, wherein car the crystalline microporous solid containing 10-MR pores. bohydrate feedstock comprises an aldose or ketose mono In other Aspects of this Embodiment, the crystalline saccharide. In certain independent Aspects of this Embodi microporous solid containing 12-MR pores. Other Aspects ment, the aldose monosaccharides includes ribose, of this Embodiment include those crystalline microporous arabinose, Xylose, lyxose (pentoses) and allose, altrose, materials comprising 10- and 12-membered rings described glucose, mannose, gulose, idose, talose, and galactose (hex elsewhere herein. oses). In other independent Aspects of this Embodiments, the ketose monosaccharides includes one or more of ribu Embodiment 11 lose, Xylulose (pentoses), fructose, psicose, Sorbose, and 0110. The method of any one of Embodiments 1 to 10, tagatose (hexoses) wherein the second Lewis acid catalyst comprises a crys Embodiment 4 talline microporous hafno-, stanno-, titano-, or Zirconosili cate. In certain Aspects of this Embodiment, the crystalline 0103) The method of any one of Embodiments 1 to 3, microporous hafno-, stanno-, titano-, or Zirconosilicate is a wherein carbohydrate feedstock comprises glucose, man hafno-, stanno-, titano-, or ZirconoZeolite. In other Aspects nose, fructose, psicose, Sorbose, tagatose, or a combination of this Embodiment, the crystalline microporous solid is a thereof. tin-substituted Zeolite of MFI topology. In other Aspects of this Embodiment, the crystalline microporous solid is a Embodiment 5 tin-substituted zeolite beta. 0104. The method of any one of Embodiments 1 to 4, wherein the first retro-aldol catalyst comprises a catalyst Embodiment 12 capable of converting a pentose or hexose monosaccharide 0111. The method of any one of Embodiments 1 to 11, to a diose, triose, or tetrose intermediate. where in the tandem catalyst system is or comprises a composite catalyst, the composite catalyst comprising hav Embodiment 6 ing both the first retro-aldol catalyst and the second Lewis 0105. The method of any one of Embodiments 1 to 5, acid catalyst. In some Aspects of this Embodiment, the wherein the first retro-aldol catalyst comprises an optionally composite catalyst comprises the chemicals associated with substituted oxo (hydroxy)molybdate, sulfomolybdate, or oxy the first and second catalysts. (hydroxy)tungstate; a Ni(II) diamine complex; an alkali exchanged hafno-, Stanno-, titano-, or Zirconosilicate; an Embodiment 13 optionally Substituted amorphous hafnium-, tin-, titanium-, or Zirconium-silicate co-precipitate; or a combination 0112 The method of any one of Embodiments 1 to 12, thereof wherein the tandem catalyst system comprises polar solvent. In certain Aspects of this Embodiment, the solvent is protic, Such as an alcohol; in other Aspects, the solvent is aprotic, Embodiment 7 such as DMSO, dimethylsulfoxide (DMSO), dimethylfor 0106 The method of any one of Embodiments 1 to 6, mamide (DMF), dimethylacetamide (DMA), a dioxane, or wherein the first retro-aldol catalyst is derived from an an optionally Substituted furan. US 2017/0015614 A1 Jan. 19, 2017 10

Embodiment 14 Example 1 0113. The method of any one of Embodiments 1 to 13, Materials and Methods wherein the tandem catalyst System comprises an alcohol solvent. In some Aspects of this Embodiment, the solvent Example 1.1 comprises a C-2 alcohol, preferably a C alcohol, more preferably a C- alcohol. Sources of Materials Embodiment 15 0129. MoO (Alfa Aesar, 99.95%), MoO, (Sigma-Al drich, 99%), HPMo.OXHO (Alfa Aesar), MoS (Alfa 0114. The method of Embodiment 14, wherein the alco Aesar, 99%), NaMoO (Sigma-Aldrich, 98%), (NH) holic solvent is Substantially anhydrous. Mo.O.4H2O (Alfa Aesar, 99%), NiCl2.6H2O (Sigma Aldrich, c.98%), N.N.N',N'-tetramethylethylenediamine, Embodiment 16 (Alfa Aesar, 99%), D-fructose (Sigma-Aldrich, -99%), L-Sorbose (Sigma-Aldrich, a 98%), D-tagatose (Sigma-Al 0115 The method of any one of Embodiments 1 to 14, drich, -98.5%), D-psicose (Sigma-Aldrich, -95%), D-ha wherein the tandem catalyst system comprises an aqueous mamelose (Sigma-Aldrich, -99.5%), D-Glucose (Sigma solvent. Aldrich, -98%), D/L-glyceraldehyde (Sigma-Aldrich, >90%), dihydroxyacetone dimer (Alfa Aesar, a 70%), lactic Embodiment 17 acid (Sigma-Aldrich, -98%), methyl lactate (Sigma-Al drich, c.98%), ethyl lactate (Sigma-Aldrich, 99%), ethanol 0116. The method of any one of Embodiments 1 to 16, (Koptec, anhydrous 200-proof), methanol (Sigma-Aldrich, wherein 99.8%), naphthalene (Sigma-Aldrich, 99%), tetraethylam 0117 (a) the carbohydrate feedstock comprises a C5 or monium hydroxide solution (Sigma-Aldrich, 35% in water), C6 aldose or ketose monosaccharide; tetraethylorthosilicate (Sigma-Aldrich, 98% (w/w)), tin (IV) 0118 (b) the first retro-aldol catalyst comprises an oxo chloride pentahydrate (Sigma-Aldrich, 98%), hydrofluoric (hydroxy)molybdate: acid (Sigma Aldrich, 54% (w/w) in water), tetraethylammo 0119 (c) the second Lewis acid catalyst comprises a nium fluoride dihydrate (Sigma-Aldrich, 97%), NaNO3 Sn-beta or Sn-MFI Zeolite; and (Sigma Aldrich, 99.0%), NaOH (Alfa Aesar 97%) were 0120 (d) the tandem catalyst system further comprises an purchased and used as received. Chloride form of Amberlite alcohol solvent; IRA-400 (Sigma-Aldrich) resin was used for immobilization wherein the method is operated under conditions so as to of molybdate salts. TiO, SiO, co-precipitate (type III, No. produce an O-hydroxy carboxylic acid or C-hydroxy car 2) was obtained from W. R. Grace (Si/Ti-56) and was calcined in flowing air (100 mL min-1, Air Liquide, breath boxylic acid ester. ing grade) at 580°C. (ramped up at 1° C. min-1) for 6 hprior Embodiment 18 tO use. 0121 A composition comprising: Example 1.2 0122) (a) a carbohydrate feedstock as described in the context of any one of the preceding Embodiments; Syntheses of Materials 0123 (b) a first retro-aldol catalyst as described in the 0.130 Sn-MFI and Sn-Beta were synthesized according context of any one of the preceding Embodiments; to previously reported procedures. The as-synthesized solids 0.124 (c) a second Lewis acid catalyst as described in the were centrifuged, washed extensively with water, and dried context of any one of the preceding Embodiments; and at 100° C. overnight. The dried solids were calcined in 0.125 (d) optionally at least one O-hydroxy carboxylic flowing air (100 mL min'), Air Liquide, breathing grade) at acid or C-hydroxy carboxylic acid ester derived from any 580° C. (ramped up at 1° C. min') for 6 h. one of the reactions described herein; and Example 1.2.1 0126 (e) optionally at least one aqueous or alcoholic solvent. Synthesis of Sn-Beta EXAMPLES I0131 Sn-Beta was synthesized as follows: 15.25 g of tetraethylammonium hydroxide solution (35% (w/w) in 0127. The following Examples are provided to illustrate water) were added to 14.02 g of tetraethylorthosilicate, some of the concepts described within this disclosure. While followed by the addition of 0.172 g of tin (IV) chloride each Example is considered to provide specific individual pentahydrate. The mixture was stirred until tetraethylortho embodiments of composition, methods of preparation and silicate was completely hydrolyzed and then allowed to use, none of the Examples should be considered to limit the reach the targeted H2O: SiO2 ratio by complete evaporation more general embodiments described herein. of ethanol and partial evaporation of water. Next, 1.53 g of 0128. In the following examples, efforts have been made hydrofluoric acid (54% (w/w) in water) were added, result to ensure accuracy with respect to numbers used (e.g. ing in the formation of a thick gel. The final molar compo amounts, temperature, etc.) but some experimental error and sition of the gel was 1 SiO/0.0077 SnCl/0.55 TEAOH/0.54 deviation should be accounted for. Unless indicated other HF/7.52 H2O. As-synthesized Si-Beta (vide infra) was wise, temperature is in degrees C., pressure is at or near added as seed material (5 wt % of SiO in gel) to this gel and atmospheric. mixed. The final gel was transferred to a Teflon-lined US 2017/0015614 A1 Jan. 19, 2017

stainless steel autoclave and heated at 140° C. in a static In each procedure, n med of ion capacity worth of resin was oven for 25 days. The recovered solids were centrifuged, used per 1 med of anion to be immobilized, where n is the washed extensively with water, and dried at 100° C. over charge of the anion. The resin was Suspended in an aqueous night. The dried solids were calcined in flowing air (100 mL solution of anion for 24 h, filtered, washed extensively with min', Air Liquide, breathing grade) at 580°C. (ramped up at water, and dried at ambient temperature overnight by an 1° C. min') for 6 h. impinging flow of air. Example 1.2.2 Example 1.3 Synthesis of Si-Beta Reaction Analyses 0132 Si-Beta was synthesized as follows: 4.95 g of 0.136 Carbohydrate analysis and fractionation were per tetraethylammonium fluoride dihydrate was added to 10.00 formed via high performance liquid chromatography on an g of water and 10.01 g of tetraethylorthosilicate. The mixture Agilent 1200 system equipped with refractive index and was stirred until tetraethylorthosilicate was completely evaporative light scattering detectors. An Agilent Hi-Plex Ca hydrolyzed and then allowed to reach the targeted H2O: column held at 80°C. was used with ultrapure water as the SiO ratio by complete evaporation of ethanol and partial mobile phase (flow rate of 0.6 mL min'). evaporation of water. The final molar composition of the gel 0.137 Quantitative GC/FID analysis of alkyl lactates was was 1 SiO/0.55 TEAF/7.25 H.O.The gel was transferred to performed on an Agilent 7890BGC system equipped with a a Teflon-lined stainless steel autoclave and heated at 140°C. flame ionization detector and an Agilent HP-5 column. in a rotation oven (60 rpm) for 7 days. The solids were Qualitative GC/MS analysis of side-products was performed recovered by filtration, washed extensively with water, and on an Agilent 5890 GC system with an Agilent 5970 mass dried at 100° C. overnight. The dried solids were calcined in spectrometer and an Agilent DB-5 column. flowing air (100 mL min', Air Liquide, breathing grade) at I0138 Liquid H and 'C NMR spectra were recorded 580° C. (ramped up at 1° C. min') for 6 h. with a Varian INOVA 500 MHz spectrometer equipped with an auto-X pfg broad band probe. All liquid NMR analysis Example 1.2.3 was performed in DO solvent, with 4,4-dimethyl-4-silapen Synthesis of Sn-MFI tane-1-sulfonic acid (DSS) as an internal standard. 0133) Sn-MFI was synthesized as follows: 0.92 g of tin 1.6 (IV) chloride pentahydrate in 6.08g of water added to 28.00 g of tetraethylorthosilicate and stirred (uncovered) for 30 0.139 Reactions were performed in 10 mL thick-walled min. Next, 48.21 g of tetrapropylammonium hydroxide crimp-sealed glass reactors (VWR) that were heated in a solution (25% (w/w) in water) was added to the mixture temperature-controlled oil bath. A typical reaction procedure under stirring. After 1 h of additional stirring (uncovered), involved: addition of desired amount of catalysts (i.e. MoO, the remaining water was added, to achieve the final molar Sn-MFI, etc.), carbohydrate substrate (i.e. D-fructose, DHA. composition of the gel of 1 SiO/0.02 SnCl/0.45 TPAOH/ etc.), and solvent (i.e. EtOH, MeOH, etc. with pre-dissolved 35H2O. The gel was stirred for an additional 30 min naphthalene as internal standard) to reactor, sealing of (covered), evenly split among three Teflon-lined stainless reactor with crimp-top, agitation of reactor at ambient tem steel autoclaves, and heated at 160° C. in a static oven for 48 perature until dissolution of Substrate, and placement of h. The solids were recovered by filtration, washed exten reactor in the oil bath at desired temperature. Aliquots (~100 sively with water, and dried at 100° C. overnight. The dried uL) were extracted at indicated times, filtered with a 0.2 um solids were calcined in flowing air (100 mL min', Air PTFE syringe filter, and analyzed by GC/FID. For reactions Liquide, breathing grade) at 580° C. (ramped up at 1° C. with Ni(N.N.N',N'-Meen)C1, aliquots were agitated with 20 mg of DoweX 50WX2 (hydrogen form) resin to min') for 6 h. remove nickel (II) species prior to filtration. For product Example 1.2.4 identification by HPLC, liquid NMR, or GC/MS, internal standard was excluded and the entire reactor content was Na-Exchange of Sn-Beta used. Rotary evaporation was used to remove solvent when 0134. Three successive sodium ion exchanges were per needed. formed according to previously described procedure (3) as Example 2 follows: calcined Sn-Beta was stirred in a solution of 1 M NaNO, and 10-4 M NaOH in distilled water. Each ion exchange step was carried out for 24 hours at ambient Results and Discussions temperature, using 45 mL of exchange or wash Solution per 0140. Retro-aldol reactions of hexoses and pentoses were 300 mg of starting solids. The material was recovered by observed to proceed in alcoholic and aqueous media at centrifugation, and washed three times with 1 MNaNO in moderate temperatures (ca. 100° C.) with catalysts tradi distilled water. The final material was dried at ambient tionally known for their capacity to catalyze 1.2-intramo temperature overnight by an impinging flow of air. lecular carbon shift reactions of aldoses (e.g. various molyb denum and tungsten oxide and molybdate and tungstate Example 1.2.4 species, nickel (II) diamine complexes, alkali-exchanged Stannosilicate molecular sieves, and amorphous TiO, SiO, HPWO and (NH4)Mo.O. Exchanged Resins co-precipitates). Products consistent with aldol recombina 0135 HPWO and (NH4)Mo.O. were immobilized tion reactions were observed, and were attributed to unfa by ion exchanging the chloride form of Amberlite IRA-400. vorable thermodynamics for retro-aldol reactions at tem US 2017/0015614 A1 Jan. 19, 2017

peratures and concentrations considered in this study. matograms and NMR spectra, however, fructose and Sor Co-catalysts (e.g. Lewis-acidic Zeotypes and Lewis acids on bose were eventually observed in Substantially greater quan amorphous Supports) that are known to catalyze the forma tities than tagatose, psicose, and hamamelose. Fractionation tion of C-hydroxy carboxylic acids (e.g. lactic acid, 2-hy of product solutions and NMR were used to confirm the droxy-3-butenoic acid, 2,4-dihydroxybutanoic acid, and gly presence of DHA, GLA, fructose, Sorbose, tagatose, psicose, colic acid) and their esters and lactones from tetroses, and 2-C-(hydroxymethyl)-aldopentoses (FIGS. 8-13). These trioses, and glycolaldehyde, but cannot readily catalyze results suggested that Some of the ketose isomers may form retro-aldol reactions of hexoses and pentoses at these mod as aldol condensation products of DHA and GLA, rather erate temperatures, were shown to be compatible with the than directly from fructose through hydride shift reactions, aforementioned retro-aldol catalysts. as previously hypothesized. The unfavorable equilibrium of 0141. The reported strategy of using a combination of retro-aldol reactions at these moderate temperatures may be distinct retro-aldol catalysts (e.g. MoO) and 1.2-intramo responsible for the low concentrations of DHA and GLA. lecular hydride shift catalysts (e.g. Sn-MFI) is a novel The reverse reaction, aldol coupling, was a logical second approach to lactic acid and alkyl lactate formation from ary reaction that can form the more stable ketohexose ketohexoses. This method allows for lactate species forma side-products. The possibility of aldol coupling was con tion at considerably lower temperatures (ca. 100° C.) and firmed by reacting a mixture of DHA and GLA under the consequently pressures (autogenous) than previously same conditions, resulting in the formation of ketohexoses reported methods, with yields comparable to the best-re and 2-C-(hydroxymethyl)-aldopentoses. Again, fructose and ported examples. Additionally, the Sn-MFI catalyst used in Sorbose appeared as major detectable hexose products. this study was synthesized in the absence of fluoride (a 0144. While the low production of 2-C-(hydroxymethyl)- frequently raised concern for large scale synthesis of cata aldopentoses may be due to thermodynamic limitations (e.g. lysts used in the previous studies of alkyl lactate formation hamamelose-fructose equilibrium K-14), tagatose and from hexoses e.g. Sn-Beta). In principle, even more eco psicose may have formed in Small quantities due to kinetic nomically accessible catalysts that can catalyze lactate for reasons. The Sorbose, tagatose, and psicose tetradentate mation from trioses may be paired with the retro-aldol structural analogues of the fructose-molybdate complex that catalysts reported in this study. was previously hypothesized to be the key species in the 0142. During recent investigation of epimerization reac fructose-hamamelose rearrangement are shown in FIG. 7 tions of aldohexoses on alkali-exchanged Sn-Beta materials, (along with analogs for other ketohexoses). H and 'C a change in the reaction pathway from a 12-intramolecular NMR studies of the molybdate complexes of ketohexoses hydride shift (1.2-HS) to a 1.2-intramolecular carbon shift Suggested that only fructose and Sorbose formed detectable (1,2) upon alkali exchange was observed. This 1,2-CS amounts of tetradentate molybdate complexes, while psicose pathway in aldohexoses (e.g., for the formation of mannose and tagatose tended to form tridentate complexes. These from glucose) is analogous to those previously reported for results suggested that aldol coupling reactions that would molybdate- and nickel(II) diamine-catalyzed reactions of result in the formation of tagatose and psicose would pro these aldoses (also known as Bilik reaction), where simul ceed through a more energetic transition state, resulting in taneous C-C bond-breaking and -forming steps were pro slow formation kinetics. Additionally, the same study pro posed to occur (FIG. 5). This reaction mechanism is analo vided estimates of the fraction of a given ketohexose that gous to the previously reported molybdate and nickel (II) existed in a molybdate complex, indicating that the psicose diamine catalyzed reactions. Ketoses were observed to react and tagatose complexes were more favorable, with 80-95% through analogous pathways to form branched Sugars (2-C- of the sugars bound to Mo, whereas the value for Sorbose (hydroxymethyl)-aldoses) (FIG. 6 and r11 in FIG. 4). In and fructose was only 15-20%. If the retro-aldol reactions of addition to the branched Sugars, Small amounts of ketose ketohexoses proceeded through tetradentate molybdate isomers were observed (e.g. when D-fructose was reacted complexes, these results suggested that the formation of with molybdate, the branched sugar D-hamamelose formed, tagatose and psicose, through the course of the reaction, may as well as Small quantities of ketose isomers: Sorbose, have reduced the fraction of catalytically active molybdate psicose, and tagatose). The formation of ketose isomers was species through competitive binding and formation of tri attributed to competing hydride shift side reactions. dentate complexes. A similar NMR study of molybdate and 0143 Here, the same branched sugar (D-hamamelose) tungstate complexes of fructose and Sorbose provided con and ketose isomers were observed when fructose was used flicting interpretations of complex structures. The multi as a substrate at temperatures ca. 100° C., with alkali nuclear NMR data from this study suggested that both exchanged Sn-Beta as catalysts. In addition, Small quantities Sugars form O-1.2.2.4 acyclic complexes, which do not of retro-aldol products, DHA and GLA, were observed in the involve O-3 coordination, in high proportions. It is impor HPLC chromatograms and NMR spectra of unseparated tant to note that these results were obtained at pH ca. 7.5, reaction solutions. The presence of DHA and GLA raised while, at lower pH, additional minor complexes were questions about the mechanism of ketose isomer formation, observed with proposed O-3,4,5,6 coordination. Molybdate as it was possible to form all of the ketohexoses through catalyzed epimerization of aldohexoses have been reported non-stereospecific aldol condensation of DHA and racemic to be ~20-fold faster at pH 1.5-3.5 than at pH 5.9, and a lack GLA. When water-dissolved MoO, was tested for similar of reaction was observed at pH higher than 6.0. Furthermore, products, when fructose was reacted at 100° C., initial 3-deoxy-aldohexoses do not undergo epimerization reac formation of hamamelose, DHA, and GLA was observed. tions, further Supporting the requirement of binding through Subsequently, Sorbose, tagatose, and psicose began to form, the hydroxyl group adjacent to the carbonyl. The combina without a significant change in the DHA and GLA concen tion of these results illustrated the complexity of molybdate tration. Quantification of products was not performed due to Sugar equilibria, and implicated tetradentate complexes of a multitude of partially overlapping peaks in HPLC chro fructose and Sorbose in the retro-aldol reactions. US 2017/0015614 A1 Jan. 19, 2017

0145 Although binuclear molybdate species were impli of glycolaldehyde (including aldol condensation) was esti cated in epimerization reactions catalyzed by water-dis mated to be 52.7 kJ/mol (23). These results illustrate the Solved MoC), higher structures containing molybdate ions high barriers of retro-aldol reactions. were later shown to also catalyze epimerization reactions, 0147 Nickel(II) diamine complexes in methanolic solu e.g., Keggin structure molybdenum-based polyoxometa tions were previously shown to catalyze the 1,2-CS in lates, and heptamolybdate species immobilized on anion aldoses and 2-C-(hydroxymethyl)-aldopentose formation exchange Supports. Similarly, the promotion of retro-aldol from ketohexoses at temperatures around 60° C. Ni(N.N. reactions of fructose were observed using the HPMoOo. N',N'-Meen), IC1 in methanol was also seen to accelerate Keggin ion, and by (NH), Mo.O., both as homogeneous the retro-aldol part of the methyl lactate-producing reaction catalysts and when immobilized onto an anion exchange cascade at temperatures around 100° C. support, e.g., Amberlite IRA-400, chloride form. Soluble and insoluble molybdate salts, e.g., Na-Moa and ZnMoC) 0148 Because materials that can catalyze the 1.2-intra respectively, as well as insoluble solids containing Mo(IV), molecular carbon shifts in aldoses were reported to be poor e.g., MoC), and MoS also are catalytically active in 1.2-intramolecular hydride shift catalysts for the same sub retro-aldol reactions of fructose in these studies. At this time, strates, they did not enable a route to the more thermody it is not clear whether the nominal form of each starting namically stable lactate products. As a result, retro-aldol compound was the catalytically active one, or whether intermediates, trioses, were observed. Addition of a 12 unknown catalytic species are generated in situ at reaction intramolecular hydride shift co-catalyst (Sn-WI with conditions. Due to the aforementioned complications in Si/Sn=70+6, synthesized to be fluoride free) to a 1 wt % quantification, we could not directly assess the performance fructose, 0.2 wt % MoO, aqueous solution enabled rapid of each catalyst in retro-aldol reactions. However, we did formation of lactate at 100° C. However, "H NMR data observe differences in kinetics (see below) of the lactate Suggested that at reaction conditions, lactate formed a strong forming reaction cascade when different Mo-containing complex with molybdate species, consistent with a previous species were used for the retro-aldol component of the study of pH-dependent molybdate-lactate interactions (Data pathway, i.e., r3 of cascade consisting of r3, and r7-r9 in in FIG. 14 show the shift in "H NMR resonance of the FIG. 4. methyl group of lactate when the pH of the reaction product 0146 TungState analogs of molybdate-monosaccharide was adjusted from 2.5 to 7.5 by addition of sodium bicar complexes have been reported to have formation constants bonate). Quantitative "H NMR indicated that lactate pro that are 2-3 orders of magnitude higher than molybdates. duction stopped once stoichiometric amount of 2 mole Such strong binding may be responsible for the apparent lactate per mole molybdate was produced, suggesting inhi lack of catalytic activity of H.WO and HPWO in the bition of catalysis by product coordination. epimerization of glucose to mannose at mild conditions. 0149. When the reactions of fructose with MoO, and Similarly, in these experiments, tungstate species performed Sn-MFI were performed in alcoholic media, the bulk of poorly but did produce species consistent with retro-aldol MoC) did not dissolve and the corresponding alkyl lactates reactions of hexoses at long reaction times. Interestingly, at were produced in good yield (upwards of 75% at full high temperatures (>150° C.), H.WO was recently reported fructose conversion). Turnover numbers (TONs) in excess to catalyze retro-aldol reactions of glucose and fructose, of unity indicate that alkyl lactate production was truly when coupled with a Ru/C-promoted H2-reductive step to catalytic in Such reactions, e.g., for reaction 6 in Table 1, the produce glycols. An apparent activation energy of 141.3 TONe5.5 based on Mo atoms for the retro-aldol reaction of kJ/mol for the retro-aldol reaction of glucose was reported, fructose, and TON 16.1 based on Sn atoms for lactate whereas the apparent activation energy for further reactions formation from the resulting trioses. TABLE 1. Maximum observed yields of lactic acid or alkyl lactates obtained under various reaction conditions. Mass, 1,2-HS Mass, Yield, Reaction 1,2-CS catalyst mg catalys mg Substrate Wt 96 0.6 MoO. 80 S-MF 00 Fructose 67.4 MoO. 80 S-MF 00 Fructose 65.7 MoO. 80 S-MF 00 Fructose 61.9 MoO. 80 S-MF 00 Fructose 63.2 MoO. 20 S-MF 00 Fructose 67.7 MoO. S S-MF 00 Fructose 69.2 MoO. 80 S-MF 200 Fructose 68.6 MoO. 80 S-MF SO Fructose 46.7 MoO. 80 S-MF 00 Fructose 5 21. MoO. 80 S-MF 00 Fructose O.2 74.6 Ole O Sn-MF 00 Fructose 3.9 Ole O Sn-MF OO DHAGLA O.S.O.S. 86.5 MoO. 80 none O Fructose 13.0 MoO. 80 none O DHAGLA O.S.O.S 14.6 MoO. 80 S-MF 00 Fructose S8.1 MoO. 80 S-MF 00 Fructose 48.3 HPMo12Oo 10 Sn-MF 00 Fructose S1.6 Ni(Meen)2Cl2 2 Sn-MF 00 Fructose 14.6* US 2017/0015614 A1 Jan. 19, 2017 14

TABLE 1-continued Maximum observed yields of lactic acid or alkyl lactates obtained under various reaction conditions. Mass, 1,2-HS Mass, Yield, Reaction 1,2-CS catalyst mg catalyst mg Substrate Wt 96 0.6 19 a Ni(Meen)2Cl2 2O Sn-MFI 100 Fructose 1 45.1% 20 a TiO2—SiO2 2OO Sn-MFI 100 Fructose 1 7.7 21 MoO. 80 Sn-Beta SO Fructose 1 51.0 22 MoO. 80 Sn-Beta 50 Glucose 1 40.2 23 Ole O Sn-Beta SO DEHA 1 88.4 24 MoO. 80 Sn-MFI 100 Hamamelose 1 70.2 25 MoO. 80 Sn-MFI 100 Sorbose 1 67.6 26 MoO. 80 Sn-MFI 100 Psicose 1 57.6 27 MoO. 80 Sn-MFI 100 Tagatose 1 46.1 28 a MoO. 80 Sn-MFI 100 Fructose 1 68.2 29 e MoO. 80 Sn-MFI 100 Fructose 1 22.7 30 f MoO. 10 Sn-MFI 100 Fructose 1 26.7i. Reactions were performed in 10-mL thick-walled crimp-sealed glass reactors that were heated in a temperature-controlled oil bath. Aliquots (-100 uL) were extracted and filtered with a 0.2-lim polytetra fluoroethylene syringe filter before analysis, Reaction conditions: for each reaction, the catalyst amounts, substrate concentrations, solvents, and temperature used are indicated in the table. Each reaction involving alcoholic solvents was performed with 4.9 g of solvent and 50 mg of naphthalene as internal standard for GC-FD quantification. Unless otherwise indicated, reactions done in ethanol at 100° C. Maximum yield, carbon basis, Reaction at 90° C.; reaction at 110° C.; reaction at 120° C.; In methanol; In 90% ethanol.10% water; In water *For reactions with Ni(N.N.N.N'-Me4en)2Cl2, aliquots were agitated with 20 mg of Dowex 50WX2 (hydrogen form) resin to remove nickel(II) species before filtration. For the reaction performed in water, no naphthalene was added, and 44-dimethyl-4-silapentane-1-sulfonic acid, sodium salt (DSS) was used as an external standard for quantitative H-NMR.

0150. For reactions performed in alcoholic media, MoC) amounts of both catalysts, lower initial Substrate concentra particles remained undissolved and progressively turned a tions resulted in higher ethyl lactate yields (reactions 2, 9, dark-blue color, Suggesting the possibility of partial reduc and 10 in Table 1, and FIG. 19). These data suggest that high tion of the oxide or coverage with alcohol-insoluble molyb concentrations of Substrate and intermediates are conducive date-lactate complex. Both possibilities could contribute to to side-product formation and that rapid conversion to stable lowering of lactate yield. Reversible ketalization of ketoses alkyl lactate products can reduce the extent of irreversible by the solvent was observed, and may be responsible for a side reactions. retardation of alkyl lactate production. 0152 Results from control experiments that illustrate the 0151. A number of parameters were varied in order to importance of the combination of the two catalysts are maximize the yield of lactate products and gain further shown in FIG. 20. In the absence of MoC) co-catalyst, insight into the limiting factors of this reaction network. Sn-MFI was unable to convert fructose to ethyl lactate in Unless otherwise stated, the reactions were run in EtOH as significant yields, even though high yields of ethyl lactate solvent (see Table 1). Data in FIG. 16 (Table 1, reactions were rapidly achieved by Sn-MFI alone when an equimolar 1-4) showed that increase in temperature led to increase in mixture of DHA and GLA were used as substrates. Con rate of ethyl lactate formation, but did not significantly versely, without Sn-MFI, MoO slowly catalyzed the for impact ultimate ethyl lactate yield, Suggesting that side mation of ethyl lactate from fructose, with an ultimate ethyl reactions may have comparable activation energies to the lactate yield being considerably lower than in the mixed limiting steps in lactate production. Data in FIG. 17 (Table catalyst system. Additionally, the use of equimolar DHA and 1, reactions 2, 5, and 6) showed that, at 100° C., with GLA mixture as starting Substrate did not result in signifi constant Sn-MFI amount, increase of MoC) catalyst amount cantly higher yields of ethyl lactate when MoC) was used by leads to a faster approach to ultimate lactate yield, but the itself, further illustrating the rapidity of side reactions of increase in rate is not proportional to catalyst amount, and a trioses. The MoC) and Sn-MFI combination was not the potential induction time was observed for the reaction with only one capable of catalyzing the conversion of fructose to lowest MoC) content. Conversely, fixing the amount of lactates. FIG. 21 show that other Mo-containing catalysts MoO, and varying the amount of Sn-MFI suggested that such as MoC), HPMo.O., and MoS were also able to two regimes were possible: one where the ethyl lactate accelerate the retro-aldol part of the reaction cascade. Addi production was limited by retro-aldol reactions, i.e., excess tionally, salts of molybdate (e.g. NaMoC) and (NH) Sn-MFI catalyst had the potential to deplete trioses at a rate Mo.O.4H2O) also catalyzed the retro-aldol reaction of higher than their rate of generation by retro-aldol reactions, fructose, both as homogeneous catalysts and when immo and the other where the ethyl lactate production from trioses bilized onto an anion-exchange Support (e.g. Amberlite was kinetically relevant, i.e., insufficient Sn-MFI led to IRA-400, chloride form). While the conditions for these accumulation of trioses (reactions 2, 7, and 8 in Table 1, and catalysts have not been optimized, all alternative Mo-con FIG. 18). In the former scenario, the ultimate yield of ethyl taining catalysts resulted in lower ethyl lactate yields than lactate was higher than in the latter. Similarly, at fixed were achieved with MoO. US 2017/0015614 A1 Jan. 19, 2017

0153. Nickel (II) diamine complexes in methanolic solu interactions between the various molybdate and hexose tions were previously shown to catalyze the 12-intramo species may impact the rate of retro-aldol reactions. To test lecular carbon shifts in aldoses and 2-C-(hydroxymethyl)- for this possibility, psicose, Sorbose, tagatose, and hama aldopentose formation from ketohexoses ca. 60° C. Data in melose were reacted under the same conditions as fructose. FIG. 22 show that the tetramethylethylenediamine complex Data in FIG. 24 (and Table 1, reactions 2 and 24-27) show with NiC1.6HO (Ni(N.N.N',N'-Meen), IC1,) in methanol that the initial rate of ethyl lactate formation from hama also accelerated the retro-aldol part of the reaction cascade melose was nearly identical to that from fructose. The initial ca. 100° C. The investigators of 1.2-intramolecular carbon rates of ethyl lactate formation from Sorbose and psicose shift catalysis in aldoses by nickel (II) diamine complexes were lower than from fructose, but comparable ultimate used stoichiometric amounts of nickel complexes and yields of ethyl lactate were observed. Tagatose appeared to aldoses, noting that the nickel complexes can also be used in be the slowest to react. These results indicate that the catalytic amounts, but deactivate after a few turnovers. formation of ketohexose side-products can impact the ulti Similarly, deactivation could be responsible for the early mate kinetics of ethyl lactate production. decrease in the methyl lactate production rate apparent in the data in FIG. 22. (O157 At 160° C. Sn-Beta was reported to perform much better for lactate production from sucrose in methanol than 0154 Data in FIG. 23 (Table 1, reactions 21-23) show in ethanol, isopropanol, or water. Here, for the case of that Sn-Beta (Si/Sn=95+14, synthesized using fluoride MoO/Sn-MFI, no significant differences in kinetics or sources) can be used in place of Sn-MFI for the second part ultimate yields of alkyl lactates were observed between of the reaction cascade. Furthermore, under conditions methanol and ethanol solvents, at 100° C. (reactions 2 and where the lactate formation from trioses was kinetically 28 in Table 1, and FIG. 24). However, when 10% (w/w) relevant, Sn-Beta performed better than Sn-MFI. This result water?ethanol was used as a solvent, the ultimate yield of was consistent with the reported faster kinetics of alkyl ethyl lactate was significantly lower than for neat ethanol lactate synthesis from trioses by Sn-Beta than Sn-MFI. (FIG. 25). This difference may be attributed to increased Because Sn-Beta can also catalyze glucose-fructose-man solubility of molybdate species in the mixed solvent system. nose isomerization reactions and, to some degree, retro-aldol Since lactic acid forms strong complexes with molybdate reactions of hexoses, Sn-Beta was not used as the catalyst of ions, this fraction of lactate species is missing from the yield. choice in the current study, in order to avoid additional complicating factors in the reaction network. To illustrate 0158. In addition to the main alkyl lactate products this point, data in FIG. 23 show the production of ethyl quantified in this study, species consistent with retro-aldol lactate from glucose when Sn-Beta is used in combination reactions on aldohexoses and partially oxidized products with MoC), indicating that aldose-ketose isomerization were identified in the GC-MS chromatograms (e.g. ethyl reactions occur on kinetically relevant timescales. Another acetals and ethyl esters of glycolaldehyde, glycolic acid, noted benefit of using Sn-MFI as the 1.2-HS catalyst is that pyruvic acid, 2-hydroxy-3-butenoic acid, and 2,4-dihy it can be easily synthesized in the absence of fluoride (a droxybutanoic acid were observed for reactions in ethanol). frequently raised concern for large-scale syntheses of cata Catalyst combinations that did not rapidly convert ketoses lysts to be used for biomass processing, e.g., Sn-Beta). In into alkyl lactates and generated Bronsted acidity also principle, even more economically accessible materials that resulted in minor formation of 5-HMF and its partially can catalyze lactate formation from trioses, e.g., post-Syn oxidized variants, e.g., aqueous reactions of HPMo.Oao thetically treated Al Zeolites or homogeneous Lewis acids, and Sn-MFI or HMoC) and Sn-MFI, after complete inhibi may be paired with the retro-aldol catalysts reported in this tive complexation of lactic acid with molybdate. The aldo study to produce alkyl lactates from hexoses at mild condi hexoses that are required for C2 and C4 products are tions. possibly formed in small amounts from ketohexoses by Sn 0155 Sn-Beta (and other Lewis acid-containing Zeo sites on the external surface of Sn-MFI crystallites. The types, e.g., Ti-Beta) has also been shown to catalyze the partially oxidized products may be formed by the reduction 1.2-CS reactions of aldoses in aqueous solutions when either of Mo(VI) to Mo(V) and/or Mo(IV), since particles of MoO, borate or alkali salts are present. The recently reported appear to progressively turn dark blue over the course of the increase in methyl lactate production by Sn-Beta from reaction. fructose in methanol at 170° C. (from 16% to 57%) upon 0159. The use of moderate temperatures (-100° C.) alkali carbonate addition is consistent with formation of enabled numerous desirable features for the production of 1.2-CS sites upon alkali exchange of open sites in Sn-Beta. lactic acid and alkyl lactate from hexoses such as lower Sn-Beta systems with added borate and alkali salts were process pressure and reduced catalyst deactivation due to reported to be pH sensitive and are not efficient 1,2-CS product deposition on the catalysts. The minimal operating catalysts in acidic conditions. Furthermore, if Sn-MFI is pressure for Such reactions was autogenous, and was largely used as a size-dependent 1.2-HS catalyst in conjunction with determined by the vapor pressure (P) of the solvent. For borate- or alkali-modified Sn-Beta, borate or alkali ions have instance, for methanol, P-3.5 bar at 100° C. and Psat=21.9 the capacity to enter the Sn-MFI pores and influence the bar at 170° C. Notably, in the case of reactions in ethanol at efficiency of lactate production from trioses. Thus, coupling 100° C., after ethyl lactate production from the initially of lactic acid or alkyl lactate production with retro-aldol added fructose stopped, e.g., see data in FIG. 26, -20h, the reactions in mixed Sn-based Zeotype systems may also be MoO/Sn-MFI catalyst combination was still active without useful in affecting the distribution of C, C, and C products regeneration by calcination or washing, as indicated by by limitation of aldose-ketose interconversion. further production of ethyl lactate upon introduction of 0156. As noted earlier, formation of other 2-ketohexoses additional fructose to the reaction Solution. This was con and 2-C-(hydroxymethyl)-aldopentoses is known to occur in trary to the coked state of Sn-Beta catalysts that required MoO-catalyzed reactions of fructose. The differences in catalyst calcination after high-temperature reactions. US 2017/0015614 A1 Jan. 19, 2017

0160. As those skilled in the art will appreciate, numer in the formation of an O-hydroxy carboxylic acid or C-hy ous modifications and variations of the present invention are droxy carboxylic acid ester, wherein the tandem catalyst possible in light of these teachings, and all such are con system comprises: templated hereby. All references cited within this disclosure (a) a first retro-aldol catalyst; and are incorporated by reference herein, at least for their (b) a second Lewis acid catalyst. teachings in the context presented. 2. The method of claim 1, wherein the carbohydrate 0161 The following reference may be helpful in under feedstock comprises a pentose or hexose monosaccharide. standing certain aspects of the present disclosure. 3. The method of claim 1, wherein carbohydrate feedstock (0162 (1) Werpy, T.; Petersen, G. Top Value Added comprises an aldose or ketose monosaccharide. Chemicals from Biomass: Volume I—Results of Screen 4. The method of claim 1, wherein carbohydrate feedstock ing for Potential Candidates from Sugars and Synthesis comprises glucose, mannose, fructose, psicose, Sorbose, Gas; Golden, Colo., 2004; Vol. 1. tagatose, or a combination thereof. (0163 (2) Dusselier, M.; Van Wouwe, P.; Dewaele, A.; 5. The method of claim 1, wherein the first retro-aldol Makshina, E.; Sels, B. F. Energy Environ. Sci. 2013, 6 (5), catalyst comprises a catalyst capable of converting a pentose 1415. or hexose monosaccharide to a diose, triose, or tetrose 0164 (3) Holm, M. S.; Saravanamurugan, S.; Taarning, intermediate. E. Science 2010, 328 (5978), 602. 6. The method of claim 1, wherein the first retro-aldol (0165 (4) Dusselier, M.; Van Wouwe, P.; de Clippel, F: catalyst comprises an optionally Substituted oXo(hydroxy) Dijkmans, J.: Gammon, D. W.; Sels, B. F. Chem Cat molybdate, Sulfomolybdate, or oxy (hydroxy)tungstate; a Chem 2013, 5 (2), 569. Ni(II) diamine complex; an alkali-exchanged hafno-, (0166 (5) Huber, G. W.; Iborra, S.; Corma, A. Chem. Rev. Stanno-, titano-, or Zirconosilicate; an optionally Substituted 2006, 106 (9), 4044. amorphous hafnium-, tin-, titanium-, or Zirconium-silicate (0167 (6) Dapsens, P. Y.; Mondelli, C. Kusema, B. T.; co-precipitate; or a combination thereof. Verel, R.; Perez-Ramirez, J. Green Chem. 2014, 16 (3), 7. The method of claim 1, wherein the first retro-aldol 1176. catalyst is derived from an oxomolybdate or sulfomolybdate precursor of MoC), MoC), MoS MoS MoSs. MoO(OH) 0168 (7) Taarning, E.; Saravanamurugan, S.; Spangsberg 2, MoO, MO.O, MO.O., MO, O, HPMo.O., Holm, M.: Xiong, J.; West, R. M.: Christensen, C. H. MO,OI, or a combination thereof. ChemSusChem 2009, 2 (7), 625. 8. The method of claim 1, wherein the first retro-aldol (0169 (8) Osmundsen, C. M.; Holm, M. S.; Dahl, S.; catalyst comprises an ethylenediamine complex of Ni(II). Taarning, E. Proc. Royal. Soc. A 2012, 468 (2143), 2000. 9. The method of claim 1, wherein the second Lewis acid (0170 (9) Tolborg, S.; Sádaba, I. Osmundsen, C. M.: catalyst comprises a catalyst capable of converting a diose, Fristrup, P.; Holm, M. S.; Taarning, E. ChemSusChem triose, or tetrose intermediate to an O-hydroxy carboxylic 2015, 8 (4), 613. acid or C-hydroxy carboxylic acid ester. 0171 (10) Wang, Y.; Deng, W.; Wang, B.; Zhang, Q.: 10. The method of claim 1, wherein the second Lewis acid Wan, X.; Tang, Z.; Wang, Y.; Zhu, C.: Cao, Z.; Wang, G.; catalyst comprises a crystalline microporous solid contain Wan, H. Nat. Commun. 2013, 4 (Ii), 2141. ing pores equal to or greater than 10-MR. (0172 (11) Bermejo-Deval, R.; Orazov, M. Gounder, R.; 11. The method of claim 6, wherein the second Lewis acid Hwang, S.-J.: Davis, M. E. ACS Catal. 2014, 4 (7), 2288. catalyst comprises a crystalline microporous hafno-, (0173 (12) Bilik, V.; Petrus, L.; Farkas, V. Chem. Zvesti Stanno-, titano-, or Zirconosilicate. 1975, 29 (5), 690. 12. The method of claim 11, wherein the second Lewis 0.174 (13) Tanase, T.; Shimizu, F. Kuse, M.; Yano, S.; acid catalyst comprises a tin-substituted silicate of beta or Hidai, M.: Yoshikawa, S. Inorg. Chem. 1988, 27 (23), MFI topology. 4085. 13. The method of claim 1, where in the tandem catalyst (0175 (14) Hricoviniova, Z.: Hricovini, M.; Petrus, L. system comprises a composite catalyst, comprising both the Chem. Pap. 1998, 52 (5), 692. first retro-aldol catalyst and the second Lewis acid catalyst. (0176 (15) Hricoviniova, Z.; Lamba, D.; Hricovini, M. 14. The method of claim 1, wherein the tandem catalyst Carbohydr. Res. 2005, 340 (3), 455. system comprises polar aprotic solvent. 0177 (16) Yanagihara, R.; Osanai, S.; Yoshikawa, S. 15. The method of claim 1, wherein the tandem catalyst Chem. Lett. 1992, No. 1, 89. system comprises an aqueous solvent. (0178 (17) Stankovic, E.; Bilik, V.; Fedoronko, M.: 16. The method of claim 1, wherein the tandem catalyst Königstein, J. Chem. Zvesti 1975, 29 (5), 685. system comprises a solvent comprising at least one C. (0179 (18) Petrus, L.; Petrusová, M.: Hricoviniová, Z. alcohol. 2001: pp 15-41. 17. The method of claim 16, wherein the alcoholic solvent 0180 (19) Matulova, M.; Bilik, V. 1990, 44 (1), 97. is substantially anhydrous. 0181 (20) Sauvage, J.-P. Verchere, J.-Fi: Chapelle, S. 18. The method of claim 1, wherein Carbohydr. Res. 1996, 286 (6), 67. (a) the carbohydrate feedstock comprises a C5 or C6 0182 (21) Hayes, M. L.; Pennings, N.J.; Serianni, A. S.; aldose or ketose monosaccharide; Barker, R. J. Am. Chem. Soc. 1982, 104 (24), 6764. (b) the first retro-aldol catalyst comprises an OXo(hy 0183 (22) Caldeira, M. M.: Gil, V. M. S. Polyhedron droxy)molybdate; and 1986, 5 (1-2), 381. (c) the second Lewis acid catalyst comprises a Sn-beta or What is claimed: Sn-MFI Zeolite; and 1. A method comprising contacting a carbohydrate feed (d) the tandem catalyst System further comprises an stock with a tandem catalyst system, the contacting resulting alcoholic solvent; US 2017/0015614 A1 Jan. 19, 2017 17 wherein the method is operated under conditions so as to produce an O-hydroxy carboxylic acid or C-hydroxy car boxylic acid ester. 19. A composition comprising: (a) a carbohydrate feedstock comprising at least one aldose or ketose monosaccharide; (b) a first retro-aldol catalyst; (c) a second Lewis acid catalyst, and (d) optionally at least one O-hydroxy carboxylic acid or C-hydroxy carboxylic acid ester, and (e) optionally at least one aqueous or alcoholic solvent. k k k k k