WO2025034470A1

WO2025034470A1 - Continuous cross-aldol condensation of linear aldehydes using solid-supported basic catalyst and polar cosolvents

Info

Publication number: WO2025034470A1
Application number: PCT/US2024/040253
Authority: WO
Inventors: Kimberly Dinh; Rachel E. M. BROONER; Erich Molitor; Michael Gardner; Howard Duane VANCE
Original assignee: Dow Global Technologies LLC
Current assignee: Dow Global Technologies LLC
Priority date: 2023-08-04
Filing date: 2024-07-31
Publication date: 2025-02-13
Anticipated expiration: 2026-02-04

Abstract

Processes for cross-aldol condensation of alkyl aldehydes that include providing a reactant mixture including a first alkyl aldehyde, a second alkyl aldehyde, and a polar cosolvent, the first alkyl aldehyde having a lower carbon number than the second alkyl aldehyde, and the feed stock having a molar ratio of 1:1 or more of the first alkyl aldehyde to the second alkyl aldehyde; and contacting the reactant mixture with a solid-supported basic catalyst in a reactor; operating the reactor to generate a product mixture containing a cross-aldol product of the first alkyl aldehyde and the second alkyl aldehyde.

Description

CONTINUOUS CROSS-ALDOL CONDENSATION OF LINEAR ALDEHYDES USING SOLID-SUPPORTED BASIC CATALYST AND POLAR COSOLVENTS

FIELD

Embodiments relate to processes for the generating branched aldehyde products by cross-aldol condensation using solid- supported basic catalysts and polar cosolvents.

BACKGROUND

Cross-aldol condensation is a type of organic reaction that involves the formation of a carboncarbon bond between two carbonyl compounds (aldehydes or ketones). In cross-aldol condensation, carbonyl compounds combine to form a ^-hydroxy carbonyl compound product under acidic or basic conditions. For example, an unsupported basic catalyst, such as hydroxide (OH), may be used to deprotonate an a-carbon of one carbonyl compound, producing an enolate capable of subsequent nucleophilic attack. The enolate species can then combine with another carbonyl compound to generate a condensation product.

Cross-aldol condensations proceed readily under standard catalytic conditions, but traditional catalysts offer little control over selectivity for the cross-aldol product. Standard reaction conditions utilizing hydroxide catalysts also involve combination of the carbonyl reactants with an aqueous phase, which must be removed from the resulting product mixture. In addition to the target cross- aldol, product mixtures often contain significant amounts of self-aldol condensation byproducts, which lead to increased costs in terms of starting materials and time and processes to remove undesired products, catalysts, and caustic aqueous waste. Previous approaches to cross-aldol condensation include few ways to increase cross-aldol selectivity, and have focused predominantly on the use of activated substrate molecules having different rates of catalyst activation for aldol condensation. For example, selectivity may be introduced through the use of aldehydes having higher rates of reactivity in the presence of ketones, or the use of steric controls such as cross-aldol reactions between branched or functionalized aldehyde and linear aldehydes.

SUMMARY

Embodiments disclosed herein include processes for cross-aldol condensation of alkyl aldehydes, including providing a reactant mixture including a first alkyl aldehyde, a second alkyl aldehyde, and a polar cosolvent, the first alkyl aldehyde having a lower carbon number than the second alkyl aldehyde, and the feed stock having a molar ratio of 1:1 or more of the first alkyl aldehyde to the second alkyl aldehyde; and contacting the reactant mixture with a solid- supported basic catalyst in a reactor; operating the reactor to generate a product mixture containing a cross-aldol product of the first alkyl aldehyde and the second alkyl aldehyde.

In another aspect, embodiments disclosed herein include systems for cross-aldol condensation of aldehydes including: a reactor including a solid- supported basic catalyst; a reactor input for providing a reactant mixture that includes a first alkyl aldehyde, a second alkyl aldehyde, and one or more polar- cosolvents, the first alkyl aldehyde having a lower carbon number than the second alkyl aldehyde; and a reactor output for obtaining a product mixture containing 20 wt% or more of the cross-aldol product of the first alkyl aldehyde and the second alkyl aldehyde.

DETAILED DESCRIPTION

Embodiments disclosed herein relate to processes for cross-aldol condensation using solid- supported basic catalysts and one or more polar cosolvents to generate branched aldehyde products from mixed alkyl aldehydes with improved yield, selectivity, and conversion. Methods may include batch or continuous processes that include reacting a first alkyl aldehyde and a second alkyl aldehyde having a higher carbon number in the presence of a solid- supported basic catalyst and polar cosolvent. In some cases, processes may generate cross-aldol condensation products having a selectivity for the cross-aldol product of 2 or more over the concentration of the competing self-aldol products.

Cross-aldol condensations disclosed herein include supported (or heterogenous) solid- supported basic catalysts having improved selectivity and conversion compared to alternative methods utilizing unsupported basic catalysts (i.e., aqueous hydroxide). Solid-supported basic catalysts may include modified resins and substrates capable of catalyzing cross-aldol condensation between unmodified alkyl aldehydes without the requirement for aldehyde activation or functionalization to direct the reaction or increase reactivity. Moreover, the use of a heterogeneous catalyst reduces the need for introducing aqueous streams associated with unsupported basic catalysis, and minimizes or omits the need for post-reactor separation of the catalyst from the product stream.

Cross-aldol condensations disclosed herein may utilize one or more cosolvents that reduce catalyst deactivation. As cross-aldol condensations using solid- supported basic catalysts proceed, there is often a noticeable decrease in activity (e.g., reduction of reactant conversion and/or product yield) that increases as a function of time. Without being limited by any particular theory, catalyst deactivation may occur by the accumulation of water released during beta-elimination to form the alpha-beta unsaturated product. Accumulated water may then block active sites on the catalyst and reduce reactant conversion and product yield. In order to displace water and disrupt the aqueous layer, one or more polar cosolvents may be added as a component of the feed to reduce activation and, in some cases, enhance yield and cross-aldol product selectivity.

Methods disclosed herein include reacting at least two alkyl aldehydes in the presence of a solid- supported basic catalyst and polar cosolvent under cross-aldol condensation conditions to yield a product mixture containing a fraction of longer-chain, branched aldehydes. Cross-aldol reactions proceed by an addition reaction shown in Eq. 1 that is followed by a condensation reaction shown in Eq. 2. In both equations, Ri and R2 represent unique alkyl substituents attached to the carbonyl groups.

R1CH₂C(H)=O + R₂HC(H)=O + Catalyst - R₂CH(OH)CH(RI)C(H)=O (1)

R₂CH(OH)CH(RI)C(H)=O R₂CH=C(RI)C(H)=O + H₂O (2)

Eqs. 1 and 2 are shown as reactions between two aldehydes, however, one or both of the species may be ketones without departing from the scope of the disclosure.

The catalyst is a solid- supported basic catalyst containing basic functional groups capable of promoting deprotonation of carbonyl species and enolate formation. Solid- supported basic catalysts may be made from an inert matrix (e.g., polymer, silica) that is functionalized with varying levels of basic functional groups (e.g., primary, secondary, tertiary, or quaternary amines). An exemplary reaction is shown in Eq. 3, depicting the reaction of butyraldehyde with nonanal to generate a mixture of cross-aldol C13 isomers and self-aldol products.

Methods may be applied in batch and flow reactor setups, including methods in which the catalyst is regenerated for repeated use. For example, following a batch reaction, the catalyst may be regenerated using a suitable solvent and then re-used in one or more successive reactions. Similarly, in continuous methods (e.g., flow reactor), the solid- supported basic catalyst may be regenerated (continuously or intermittently) to allow for repeated catalyst use.

Cross-aldol condensations may be performed between two or more alkyl aldehydes. As used herein, alkyl aldehydes are differentiated as “first” and “second,” where the first alkyl aldehyde as a lower carbon number than the second alkyl aldehyde. The alkyl aldehydes may have the general formula of RCH2C(H)=O, where R is an alkyl group that may be linear and/or non-functionalized (i.e., include aldehydes having non-branching alkyl substituents). Tn some cases, the first alkyl aldehyde has a carbon number in the range of 2 to 6 and the second alkyl aldehyde has a carbon number in the range of 7 to 20. Suitable reactant aldehydes include acetaldehyde, propanal, n-butanal, n-pentanal, hexanal, heptanal, octanal, longer chain aldehydes, and the like. In one example, crossaldol condensations are used to generate branched C13 aldehydes or alcohols from linear C4 and C9 aldehydes as shown in Scheme II.

Cross-aldol condensations may proceed from a reactant mixture (i.e., for a batch process) or feed (i.e., for a continuous process) containing a molar ratio of first alkyl aldehyde: second alkyl aldehyde in a range of 4:1 to 1:4, 3:1 to 1:3, or 2:1 to 1:2. Alkyl aldehydes may be provided as is suitable for the particular reaction (i.e., batch or continuous). In batch methods, aldehydes may be added at the same time or in sequence, and at the total concentration or added, respectively, into a batch reactor in one or more fractions.

In batch methods, the combined aldehyde concentration in the reactant mixture as a percent by weight (wt%) ranging from 5 wt% to 99.9 wt%, 25 wt% to 95 wt%, or 40 wt% to 80 wt%. The resulting product mixture of a batch reaction may contain the cross-aldol product at a percent by weight (wt%) of 20 wt% or more, 30 wt% or more, or 40 wt% or more, or ranging from 5 wt% to 99.9 wt%, 25 wt% to 95 wt%, or 40 wt % to 80 wt%. In flow or continuous methods, the combined aldehyde concentration in the reactant mixture as a percent by weight (wt%) ranging from 5 wt% to 99.9 wt%, 25 wt% to 95 wt%, or 40 wt% to 80 wt%. The resulting product mixture of a flow reaction may be provided as an exit stream containing the cross-aldol product at a percent by weight (wt%) of 5 wt% or more, 10 wt% or more, or 20 wt% or more.

Cross-aldol condensations disclosed herein may be catalyzed by one or more solid-supported basic catalysts, including basic ion exchange resins. While not limited by a particular theory, solid- supported basic catalysts may include Bronsted bases that associated with hydroxides and other basic species capable of catalyzing aldol addition and/or condensation. For example, solid- supported basic catalysts that increase the local concentration of basic species that activate carbonyl-containing species and promote enolate formation.

Ion exchange catalysts may include a heterogeneous catalyst support that contains or is functionalized with one or more basic (or cationic) moieties, including quaternary ammonium salts or other organic or inorganic cationic species associated with strongly basic anions such as hydroxide. Cationic moieties may be anchored to the support by any suitable linker and/or anchoring chemistry, and may include linear, branched, substituted, and/or heterocyclic (e.g., piperazine) ammonium functional groups. Catalyst supports include any solid substance that is inert under the reaction conditions and can be modified with the selected basic functional group. The support material can be inert materials including various polymers (e.g., crosslinked and non-crosslinked) including vinylaromatics such as styrene divinylbenzene, and the like, or oxides such as silica, alumina, and titania. The catalyst support can be in the form of powder, granules, pellets, or the like that are dimensioned for operation in the selected reactor. Examples of solid- supported basic catalysts may include catalyst supports (e.g., resins, inorganics) functionalized with amines such as trialkyl ammonium, dialkyl 2-hydroxyethyl ammonium, ammonium, and the like.

Solid-supported basic catalysts may be stable for any suitable operation temperature, including temperatures up to 100 °C or up to 150 °C, including at temperatures of 40 °C or more, or in the range of 40 °C to 150 °C, 50 °C to 150 °C, or 60 °C to 100 °C.

Solid-supported basic catalysts disclosed herein may have an active site concentration in the range of 0.01 eq/mL to 10 eq/mL.

Solid-supported basic catalysts may be added at a molar percent of moles of base content of the catalyst to total moles aldehydes (mol%) of at least 1 mol%, at least 5 mol%, or at least 10 mol%, or in a range of 1 mol% to 20 mol%, or 1 mol% to 10 mol%.

Solid-supported basic catalysts may be stored and/or placed into a reactor with a compatible solvent that is not water and unreactive in the reaction conditions. Solvents may include one or more hydrocarbons, including alkanes and alkenes having 4 to 15 carbon atoms. Solvents may be present in the reaction mixture and/or the product mixture at a percent by weight (wt%) of 10 wt% or more, or in a range of 10 wt% to 80 wt%.

In some cases, solid-supported basic catalysts may undergo some level of deactivation during the reaction. Without being limited by theory, this may be due to the association with water or other polar species with the active sites of the catalyst that function to block active site access. Cross-aldol condensations disclosed herein may utilize one or more polar cosolvents that reduce catalyst deactivation that are fed into a reactor alone or in combination with a feed (i.e., reactant mixture or component thereof) with one or more reactants. Polar cosolvents may include relatively low molecular weight alcohols, such as C2 to C8 alcohols, polyols such as ethylene glycol, propylene glycol, glycerol, and the like, C2 to C8 ethers and polyethers, cyclic ethers such as tetrahydrofuran, dioxane, and the like, acetonitrile, acetone, esters of Cl to C6 acids (e.g., acetates, propionates, butanoates, etc.) and Cl to C8 alcohols, and the like.

Cross-aldol condensations may include one or more polar cosolvents at a percent by weight (wt%) of the total aldehyde content of 10 wt% or more, 20 wt% or more; 70 wt% or less. 60 wt% or less, or 50 wt% or less, such as in a range between 1 wt% to 60 wt%, 5 wt% to 55 wt%, or 5 wt% to 50 wt%.

In some cases, a solid-supported basic catalyst may be regenerated following use by contact with a regenerating solvent to wash away aqueous and polar deactivating contaminants. Regenerating solvents may include glycol ethers such as anisole (methyl phenyl ether), tert-butyl methyl ether, dibenzyl ether, diethyl ether, dioxane, diphenyl ether, methyl vinyl ether, tetrahydrofuran, triisopropyl ether, diethylene glycol diethyl ether, diethylene glycol dimethyl ether (diglyme), diethylene glycol monobutyl ether, diethylene glycol monomethyl ether, 1,2-dimethoxyethane (monoglyme), ethylene glycol monobutyl ether, triethylene glycol dimethyl ether (triglyme), triethylene glycol monomethyl ether, acetone, diisobutyl ketone, methyl n-propyl ketone, methyl ethyl ketone, methyl isobutyl ketone, methyl formate, methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, and combinations thereof.

Methods may include batch and continuous processes that contain the general steps of providing a reactant mixture containing a first alkyl aldehyde and a second alkyl aldehyde, the first alkyl aldehyde having a lower carbon number than the second alkyl aldehyde, and the feed stock having a molar ratio of 1:1 or more of the first alkyl aldehyde to the second alkyl aldehyde; and contacting the reactant mixture with a solid- supported basic catalyst in a reactor; operating the reactor to generate a product mixture containing a cross-aldol product of the aldehydes.

The cross-aldol condensations described herein may be carried out in any reactor of suitable design, including batch, semi-batch reactors, and continuous flow reactors, without limitation as to design, size, geometry, flow rates, etc. (e.g., plug-flow reactors, continuous stirred-tank reactors, and the like). Example reaction parameters are given below and in the examples. Generally, reaction pressures run from atmospheric to about 100 atm, with temperatures ranging roughly from 0° C to 300° C. Cross-aldol condensations may be performed at suitable temperatures. For example, a reaction mixture or stream may be maintained at 60 °C or more during the condensation reaction.

Aqueous fluids may deactivate the solid- supported basic catalyst by associating with active sites. Prior to cross-aldol condensation, solid-supported basic catalysts may be activated by drying at 90°C to 100 °C (or higher depending on the catalyst) to remove adsorbed water. Moreover, the solid- supported basic catalysts may be regenerated in batch or continuous settings by contacting the catalyst (in situ or removed from the reactor) with a regenerating solvent. The selected catalysts arc then loaded into the desired reactor and the reactant mixture is added or fed into the reaction zone at the specified temperature for the specified time.

The cross-aldol product may be separated from a reaction mixture by any suitable method, such as solvent extraction, crystallization, distillation, vaporization, wiped film evaporation, falling film evaporation, phase separation, and filtration. For example, in a continuous process the liquid reaction mixture (containing aldehyde product, etc.), i.e., reaction fluid, removed from the reaction zone can be passed to a separation step, e.g., distillation column, wherein the desired aldehyde product can be separated via distillation, in one or more stages, under normal, reduced or elevated pressure, from the liquid reaction fluid, and further purified. The portion of the liquid reaction mixture that is not removed in the product stream from the separation step, containing aldehyde products, aldehyde feed, solvent, water, reaction byproducts, feedstock impurities, and the like, may then be recycled back to the reactor either in total or in part.

Systems for forming cross-aldol condensates may include a reactor (batch or continuous) containing a solid- supported basic catalyst; a reactor input for providing a reactant mixture containing a first alkyl aldehyde and a second alkyl aldehyde, the first alkyl aldehyde having a lower carbon number than the second alkyl aldehyde; and a reactor output for obtaining a product mixture comprising 20 wt% or more of the cross-aldol product of the first alkyl aldehyde and the second alkyl aldehyde.

Methods disclosed herein may be performed in batch or continuous conditions with a cross- aldol selectivity, defined as the concentration of the cross-aldol product in the product mixture over the concentration of the self-aldol product of the second alkyl aldehyde in the product mixture (or stream), of 2.3 or more, 2.5 or more, or 3.0 or more, or in a range of 2.3 to 4.0, or 2.3 to 3.5.

The numerical ranges disclosed herein include all values from, and including, the lower and upper value and all values in between. Unless stated to the contrary, implicit from the context, or customary in the ail, all parts and percentages are based on weight and all test methods are current as of the filing date of this disclosure. EXAMPLES

The following examples are provided to illustrate the embodiments of the invention, but are not intended to limit the scope thereof. Materials used in the following examples are shown in Table 1. Solid-supported basic catalysts arc shown in Table 2, where abbreviations arc used for strong basic anion (SBA), Type I SBA indicates resins contain trimethylammonium functional groups, Type II SBA indicates resins containing dimethylethanolammonium functional groups, weak basic ion (WBA), and divinyl benzene (DVB). Matrix designations refer to porosity, where microporous indicates higher porosity than gel resin.

Cross-aldol condensation products were generated using batch or flow reactor (continuous) methods as described below. In these examples, conversion of a selected analyte (A) is defined as: Z , (4)

Yield of Cl 3 is defined as:

... . , Moles C13 Produced

Y leidr cay _tr_oo ccti 3d = - Mol : -es C9 Fed 7 — ( ^v5)

Unless otherwise specified in the examples, samples were tested using the following flow reactor method.

Flow Reactor Method

Flow reactions were performed in a custom-built flow reactor. Briefly, the reactor is a Fz” OD stainless steel reactor connected up and downstream with 1/16” stainless steel tubing. There is PTFE tubing from selection valve 1 to the Gilson HPLC 305 pump equipped with a 5SC pump head. The reactor is placed vertically within a continuously N2 purged oven and solution flow is upwards. A catalyst bed is packed within the reactor by loading catalyst diluted with quartz beads to achieve an approximate 6” bed height. Above and below the catalyst bed, quartz wool was added to the reactor. A Type K thermocouple was placed in the reactor coaxial to the catalyst bed within the bed or at the top of the bed and the temperature was recorded continuously. Samples were collected periodically during a run for product analysis by GC.

Gas chromatography of flow reactor samples was performed on an Agilent 7890A GC equipped with a flame ionization detector using an Agilent J&W DB-17 column (Part Number 123- 1732LTM). The GC method involves a 5 min hold at 50°C followed by a 10°C/min ramp to 280°C and a 2 min hold for a total run time of 30 min.

Calibration of butanal, nonanal, octenal, and octadecenal were completed by dilution of the pure materials in toluene to obtain standards of 40, 30, 15, 5 and 1 wt%. Octenal (92% purity) and octadecenal (88% purity) were calibrated at the same levels. A response factor for the tridecenal (product of the cross-aldol condensation of butanal and nonanal) was estimated based on linear interpolation from plotting response factors of the available aldehydes versus number of carbons. Decane was used as an internal standard for all components at 2 wt% decane and toluene was used as the diluent. Comparative Example 1

In this example, a cross-aldol condensation was performed using a solid- supported basic catalyst without a cosolvent. Using a flow reactor setup, conversion of C4 and C9, and Cl 3 yield were measured as a function of time. Reactant feed included 2:1 C4:C9 (37/37/3/23 wt% C4/C9/decane/octene) over a catalyst bed containing 2 g Amberlyst A26OH (diluted in quartz to achieve 6” bed height). The catalyst was regenerated and activated prior to testing with 1 M NaOH, H2O, isopropanol, and 1 -octene. The reactor column was operated in flow at 0.15 mL/min (1 hour residence time), an initial temperature of 22°C and a final temperature of 50°C, and at 2: 1 weight ratio of C4:C9.

Comparative example 1 demonstrates that using a 2:1 C4:C9 feed without an additional cosolvent with Amberlyst A26OH results in near complete conversion of C4 but loss of C9 activity is observed over time. There is a correspondingly low yield of C13.

Inventive Example 1 In this example, a cross-aldol condensation was performed using a solid-supported basic catalyst with isopropanol as a polar cosolvent. The flow reactor column was loaded to a 6” bed height with 2.0 g Amberlyst A26OH in quartz beads and regenerated prior to use with 1 M NaOH, H2O, isopropanol and 1 -octene. The reactor column was operated at an initial temperature of 22 °C to a final temperature of 50 °C in flow at 0.15 mL/min (1 hour residence time), with a feed containing 24 wt% C4, 24 wt% C9, 36 wt% isopropanol, 14 wt% octene, and 2.0 wt% decane (as internal standard). The feed was pretreated with excess Amberlyst A21 to minimize acid content stemming from oxidation of the aldehyde with exposure to air. .

A comparison of the results from Table 3 and Table 4 demonstrates that the addition of isopropanol as a polar cosolvent results in sustained C4 and C9 conversion without apparent deactivation. C13 yield is correspondingly improved. This result demonstrates that a continuous process for aldol condensation can be achieved. Inventive Example 2

In this example, a cross-aldol condensation was performed using Mitsubishi DIAION PA312LOH ion exchange resin with isopropanol added as a polar cosolvent. Catalyst was prepared by adding 2 g and diluting with quartz to achieve 6” bed height, and activated or regenerated using 1 M NaOH, H2O, isopropanol, and 1 -octene. The reactor column was operated at an initial temperature of 22 °C to a final temperature of 50 °C in flow at 0.15 mL/min (1 hour residence time), with a feed containing 24 wt% C4, 24 wt% C9, 36 wt% isopropanol, 14 wt% octene, and 2.0 wt% decane (as internal standard). The feed was pretreated with excess Amberlyst A21 to minimize acid content stemming from oxidation of the aldehyde with exposure to air.

Inventive Example 2 demonstrates comparable sustained activity can also be obtained with other solid-supported basic catalysts.

Inventive Example 3 In this example, a cross-aldol condensation was performed using Amberlyst A26OH with isopropanol added as a cosolvent at reduced concentration. Catalyst was prepared by adding 2 g and diluting with quartz to achieve 6” bed height, and activated or regenerated using 1 M NaOH, H2O, isopropanol, and 1 -octene. The reactor column was operated at an initial temperature of 22 °C to a final temperature of 50 °C in flow at 0.15 mL/min (1 hour residence time), with a feed containing 30 wt% C4, 30 wt% C9, 20 wt% isopropanol, 18 wt% octene, and 2.0 wt% decane (as internal standard).

The feed was pretreated with excess Amberlyst A21 to minimize acid content stemming from oxidation of the aldehyde with exposure to air.

A comparison of the results from Table 3, Table 4, and Table 6 demonstrates the effect of varying amounts of isopropanol in the feed on C9 conversion. When the concentration of isopropanol is reduced in Example 3, steady-state C9 conversion can still be obtained with some reduction in C9 conversion and C13 yield.

While the foregoing is directed to exemplary embodiments, other and further embodiments may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.

Claims

1 . A process for cross-aldol condensation of alkyl aldehydes, comprising: providing a reactant mixture comprising a first alkyl aldehyde, a second alkyl aldehyde, and a polar cosolvent, the first alkyl aldehyde having a lower carbon number than the second alkyl aldehyde, and the feed stock having a molar ratio of 1:1 or more of the first alkyl aldehyde to the second alkyl aldehyde; and contacting the reactant mixture with a solid- supported basic catalyst in a reactor; operating the reactor to generate a product mixture comprising a cross-aldol product of the first alkyl aldehyde and the second alkyl aldehyde.

2. The process of claim 1, wherein the solid- supported basic catalyst comprises trimethylammonium functional groups or dimethylethanolammonium functional groups

3. The process of claim 1, wherein the yield of the cross-aldol product does not decrease by more than 50% during a 5 hour run.

4. The process of claim 1, wherein the first alkyl aldehyde has a carbon number in the range of 2 to 6 and the second alkyl aldehyde has a carbon number in the range of 7 to 20.

5. The process of claim 1, wherein the polar cosolvent comprises a C2 to C8 alcohol.

6. The process of claim 1, wherein the polar cosolvent is added at a percent by weight (wt%) of the reactant mixture of 20 wt% or more.

7. The process of claim 1, wherein operating the reactor comprises maintaining the solid- supported basic catalyst to at least 1 mol% base content relative to the combined moles of the first alkyl aldehyde and the second alkyl aldehyde.

8. The process of claim 1, wherein the reactor is operated at a temperature of 50 °C or more.

9. The process of claim 1, further comprising regenerating the solid- supported basic catalyst with a glycol ether.

10. A system for cross-aldol condensation of aldehydes comprising: a reactor comprising a solid- supported basic catalyst; a reactor input for providing a reactant mixture comprising a first alkyl aldehyde, a second alkyl aldehyde, and one or more polar cosolvents, the first alkyl aldehyde having a lower carbon number than the second alkyl aldehyde; and a reactor output for obtaining a product mixture comprising 20 wt% or more of the cross- aldol product of the first alkyl aldehyde and the second alkyl aldehyde.