Seminaron

Greener methods for batch sulfonation

Presentedby

Anuja A. Sawant

Under the guidanceof

Prof. G. S. Shankarling

IntroductionSulfonation is introduction of These groups attach toSO2OH SO2X

C N

Classification of sulfonates

Aliphatic&Alicyclic Aromatic Heterocyclic N-sulfonatesOrSulfamates

C C C N

Types of Sulfonates● Dyes● Dye Intermediates● Naphthalene sulfonates● Alkylated Aromatics● Aliphatic Sulfonates or Hydroxysulfonates● Sulfosuccinates and Sulfosuccinamates

● Paraffin sulfonates● Fatty acid ester sulfonates● Petroleum Sulfonates● Lignosulfonates● Monomer and Polymer Sulfonates

Applications of Sulfonates

Sulfonating agents

Sulfonating Agents Sub-typesSulfur trioxide and compounds thereof Sulfur trioxide, oleum, concentrated sulfuric acid (SO3 plus water)Chlorosulfonic acid (SO3 plus HCl)Sulfur trioxide adducts with organic compoundsSulfamic acidThe sulfur dioxide group Sulfurous acid, metallic sulfitesSulfur dioxide with chlorineSulfur dioxide with oxygenSulfoalkylating agents Sulfomethylating agents (hydroxyl- and aminomethanesulfonates)Sulfoetylating agents (hydroxyl-, chloro-, and methylaminoethanesulfonates; ethylenesulfonic acid)Miscellaneous sulfoalkylating agents; sulfoacylation; sulfoarylation; sulfatoalkylation

Advantages of Batch Processes

Small scale productionRange of different products to be produced in the same equipmentReactions requiring long reaction timesReactions with superior selectivity

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Design Features for Sulfonation

Heat Transfer Agitation

Sulfonation reaction mixtures areViscousinefficient heat exchangepoor product quality and/or reduced productivity

Non-green aspects of Sulfonation methods

Dilute sulfuric acid

Neutralization of acid

Inherent propertiesof sulfonating agents

Large inventoriesof sulfonating agents

Swelling agents By-products like sulfone

Recylingof sulfonating agents

High temperatureconditions

UndesirableSalt waste streams

Formation of toxic reactionalresidues

Aims of Green Batch Sulfonation● Reactions that can be carried out at room temperature and consume less energy.● Reactions that use raw materials those are easily available.● Lowers waste stream issues.● Simplicity of the process.● Shorter reaction time.● Enhancement in reaction rates.

● Improved yields.● Improved conversions.● Improved selectivity.● Reduction or elimination of by-products such as sulfones.● Use of stoichiometric quantities of sulphonating agents.● Reactions that can be carried out at in solvent-free conditions.

Literature Survey

Sulfonating agents Conditions Process CatalystSulfonation with silica sulfuric acidChemical Recycling of Polystyrene. Sulfonation with Different Sulfonation AgentsSulfonation using SO3-DMF complex

Microwave Assisted SulfonationUltrasound assisted regioselective sulfonation

Sulphonated Polymer ResinSulfonation process forming crystalline productSulfonation process forming free-acid form of the product

Sulfonation of an aromatic compound

Sulfonating agents

A novel method for sulfonation of aromatic rings with silica sulfuric acid

With solvent (1,2-dichloroethane) Without solvent/excess substrateLower yield Higher yield

A novel method for sulfonation of aromatic rings with silica sulfuric acid

Conventional methods for sulfonation of aromatic compounds Newer greener methodSulfonic acids are often in equilibrium with sulfones as a by-product Sulfones are not produced at allSulphuric acid causes destruction of acid sensitive functional groups Silica sulphuric acid does not cause destruction of acid sensitive functional groups

Procedure

ArH + SIOArH + SIO22O-SOO-SO33H --> ArSOH --> ArSO33H +SIOH +SIO22-OH-OH

● RBF charged with silica sulfuric acid + aromatic compound● Magnetic stirrer● Conditions: 80˚C for 30min● Mixture then was filtered, washed with dichloromethane, and the solvent was removed under reduced pressure.● The residue was washed with n-hexane and dried in air to produce white solid (75% yield)

Chemical Recycling of Polystyrene. Sulfonation with Different Sulfonation Agents

Newer greener method using silica sulfuric acid as compared to the conventional method using sulfuric acid

Reaction SimplifiedSeparation of productsfrom acid and solvent

Easier

Method for the sulfonation of compounds comprising free hydroxyl (OH) groups or primary or secondary amines

Conventional methods Newer greener methodFormation of potentially toxic reactional residues Avoids introduction of toxic substances that are difficult or impossible to eliminate completely.SO3-pyridine ●Uses SO3:DMF complex●Pyridine's toxicity to humans is well knownPerformed at a very acid pH value Avoids the use of excessively acidic pH values by using an acid capture agent(2-methyl-2-butene).●Structural integrity of the initial polymer is not altered.

Procedure

● Solubilization or preparation of a homogeneous solution of the compound to be sulfonated in an anhydrous solvent or cosolvent such as dimethylformamide (DMF) ● Addition at ambient temperature (about 20-22˚C) of a molar excess of an acid capture agent such as 2-methyl-2-butene, miscible in the cosolvent.● Rapid addition of the SO3-DMF complex under agitation.● Stopping the reaction by progressive addition of the mixture to an

alkaline solution, e.g., a 2% solution of sodium bicarbonate (NaHCO3) or another alkali● Purification of the sulfonated compound obtained by tangential ultrafiltration against water

Conditions

Microwave Assisted Sulfonation of 2-Naphthol by Sulfuric Acid: Cleaner Production of Schaeffer’s Acid

Without microwave With microwaveAt least 200 times excess sulfuric acid is employed for monosulfonation Effect of MW irradiation on Performance of 2-Naphthol sulfonationMolar Ratio 2-N conversion % Molar Ratio 2-N conversion %

S:2-N = 1.5:1S:2-N =2.5:1

did not achieve specified conversion73S:2-N = 1:1S:2-N = 2:1O:2-N = 2:1

878154Requires more time Requires lesser timeActivation energy required is more Activation energy required is lesser

Procedure

Frequency: 2450 MhzFor each run, sulfuric acid (S)or oleum (O)and 2-naphthol (2-N)were mixed to prepare a homogeneous slurryby maintaining 15-20°CReactions were carried out at different temperaturesand powers.

Advantages● Efficient and rapid transformation of energy and heating throughout the volume● Reduction in reaction time● Utilizes only a stoichiometric quantity of sulfuric acid leading to minimum effluent generation ● Increase in conversion● Enhanced selectivity

Ultrasound assisted regioselective sulfonation of aromatic compounds with sulfuric acid

Substrate Condition Time Conversion(%)

Selectivity(%)

Product

Toluene Silent 24h 70 90 Toluene-4-sulfonic acidToluene ))))) 45min 76 100 Toluene-4-sulfonic acid

Procedure

RBF was placed at the center of Ultrasonic BathSulfonating agent: sulfuric acidToluene was addedSulfuric acid (98 wt%) was addedReaction mixture sonicated at 25˚CFrequency: 33 kHzPower: 100 WHPLC analysis of samples

Advantages

● Solvent free conditions● Ultrasound is the promoter● Enhancement in reaction rate● Improved selectivity● Improved conversion

Process

Sulphonated Polymer Resin and Preparation Thereof

Conventional methods for preparing a sulphonated polymer resin Newer greener methodUses swelling agent, such as chlorohydrocarbon Avoids the use of a swelling agentProducts obtained are not physically stable but they tend to break Products obtained are stableConventional resins sulphonated with sulphuric acid have lesser activity Macroporous resins prepared have been found to have better activity

Procedure● Reaction Conditions:

– 50 and 100 Pa– 40 to 80˚C

● The polymer resin: typically sulphonated in a particle form● Sulfonating agent: pure gaseous sulphur trioxide● After-treatment to prevent breakage of the resin structure

Sulfonation of Polyhydroxyaromatics

Conventional methods Newer greener methodProcess with catechol

Uses oleum or fuming sulfuric acid ●Avoids the use of oleum or fuming sulfuric acid●Neutralization required

Process with pyrogallol

●Lead to product mixtures, or make an alkali metal salt product●Complicates recycling of the sulfonylation agent●Often requires high temperature for a significant time

●Lower waste production●Runs at RT or elevated temperature●Neutralization required

Process with Protocatechuic acid (PCA)

●PCA is obtained from microbial synthesis●The product precipitates from the reaction solution as the free acid.●No neutralization

Sulfonation of Polyhydroxyaromatics

Formula I:R’ = SO3H or CO2H, R2 = H or OHWhen R’ = SO3H or CO2H, R2 = H, product is Tiron TMWhen R’ = SO3H or CO2H, R2 = OH, product is 4,5,6-trihydroxy-1,3-benzenesulfonic acidWhen R’ = CO2H, R2 = H, product is 3,4-dihydroxy-5-sulfobenzoic acid

Formula II:R’ = H OR CO2HR2 = H OR OHWhen R’ & R2 = H, compound is catechol.When R’ is H, R2 is OH, compound is pyrogallol.When R’ is CO2H, R2 is H, compound is protocatechuic acid.

Procedure● RBF: conc. sulfuric acid + catechol at RT● Mixture was heated to 95˚C for 5h● Mixture was cooled to 50˚C, NaOH was added● Precipitate 1,2-dihydroxy-3,5-benzenedisulfonate sodium salt.● Mixture was cooled to 15-25˚C ● Precipitate was filtered● The solid was washed with isopropanol (600 mL) and dried under vacuum at 60˚C to yield 312g (73% yield) of 1,2-dihydroxy-3,5-benzenedisulfonate sodium salt as an off-white solid.

Sulfonation of Catechol in Concentrated H2SO4

Sulfonation method for zonisamide intermediate in zonisamide synthesis and their novel crystal forms

Conventional methods Newer greener methodFormation of by-product Does not use dioxane and eliminates the problem of the waste.Reagent chlorosulfonic acid is used in large excessChlorosulfonic acid:dioxane complex is used which is not safe

Procedure● Reactor: ethyl acetate + H2SO4, 98% + acetic anhydride● Mixture was cooled to -5˚C● BOA (benzisoxazole acetic acid )was added ● Reflux: 4h● Cooled to RT and NaOH was added● Product: precipitates as sodium salt (Crystalline forms of

benzisoxazole methane sulfonic acid (BOS-H) and its salts (BOS-Na, NOS-Ca, and BOS-Ba))

● After 2h precipitate was filtered, washed and dried● The yield was 20.33 grams BOA-Na having 100% purity by HPLC

Catalyst

Process for sulfonation of an aromatic compound

Conventional method for sulfonation of aromatic compounds Newer greener methodUses aluminum chloride which is●Corrosive●Used in large amounts●Separation of AlCl3 is lengthy and expensive●Cannot be recycled

Uses catalytically effective amount of a mixture of bismuth tri-halide and of perfluoroalkanesulfonic acid

Procedure● Sulfonation of the aromatic compound● Hydrolysis● Reaction mixture: 20˚C and 200˚C, atmospheric pressure● Catalytic mixture, some part of which is in the salt form is filtered, dried and recycled● Desired product: is recovered from organic phase● sulfonated aromatic product is subsequently recovered from the organic phase according to known techniques, by removing the organic solvent, by distillation or by crystallization

ReferencesKarki A., Paatero E., Heikkila H., Mononen H., Paananen H., Tiihonen H. “Sulphonated polymer resin and preparation thereof.” US 6,664,340 B1.

(16 Dec., 2003)

Hajipour A. R., Mirjalili Bi. Bi. F., Zarei A.,Khazdooz L. and Ruoho A. E. "A novel method for sulfonation of aromatic rings with silica sulfuric

acid",Tetrahedron Letters, 45, 6607–6609, (2004)

Sułkowski W. W., Nowak K., Sułkowska A., Wolińska A., Bajdur W. M., Pentak D. and Mikuła B. “Chemical recycling of Polystyrene. Sulfonation

with different sulfonation agents”, Mol. Cryst. Liq. Cryst., 523, 218=[790]–227=[799], (2010)

Dubac J., Le Roux C., Repichet S. “Process for the sulfonation of an aromatic compound.” US 6,455,738. (24 Sep., 2002)

Umrigar V. M., Chakraborty M. and Parikh P. A. “Microwave Assisted Sulfonation of 2-Naphthol by Sulfuric Acid: Cleaner Production of

Schaeffer’s Acid”, Ind. Eng. Chem. Res., 46, 6217-6220,(2007)

Qureshi Z. S., Deshmukh K. M., Jagtap S. R., Nandurkar N. S., Bhanage B. M. “Ultrasound assisted regioselective sulfonation of aromatic

compounds with sulfuric acid”, Ultrasonics Sonochemistry,16,308–311,(2009)

U.S. Patent Application No. 12/859,922, Publication No. 2011/0046412 A1 (published Feb. 24, 2011) (Frost J., Bui V., applicant)

Petit E., Garcia-Papy D., Barbier-Chassefiere V. “Method for the sulfonation of compounds comprising free hydroxyl (OH) groups or primary or

secondary amines.” US 7,396,923 B2. (8 Jul., 2008)

Mendelovici M., Nidam T., Schwartz E., Wizel S. “Sulfonation method for zonisamide intermediate in zonisamide synthesis and their novel crystal

forms.” US 6,841,683 B2. (11 Jan., 2005)