Synthesis And Reduction Of Functional Alkyl Disulfides Under Phase-transfer Catalysis

Disulfides play an important role in organic synthesis and activities in vivo,the reversible transformation between disulfide bond and thiol in vivo makes disulfide-based biodegradation materials show a wide significance as chemosensors,prodrugs,hydrogels and nanocarriers.In this work,the synthesis of functional disulfides by phase transfer catalysis were studied under various reaction conditions,the phase-transfer mechanism were proposed and bis(11-hydroxyundecyl)disulfide were synthesized by this method.Then,bis(11-hydroxyundecyl)disulfide was reduced by different reducers and the reducing ability of DTT to the disulfide in different solvent systems were addressed.The reduction mechanism of DTT to disulfide was hypothesized.The main conclusions include:1.The reaction temperature,reaction time,feeding-ratio and other factors in the process of phase transfer synthesis of various alkyl disulfides were studied,the feeding ratio of sulfur to sodium sulfide in the first step reaction determined the reaction equilibrium of the producing disulfide anion,as well as the concentration of monosulfide,disulfide and trisulfide ions after the completion of the reaction.2.In the second step of the phase transfer catalysis synthesis of alkyl disulfides,the order of binding capability of these sulfur anions with dimethyldidodecyl-ammonium(DDA+)cation increases in the order of monosulfide < disulfide < trisulfide.In the process of phase-transfer catalysis synthesis of disulfide,the concentration of sulfur ions and their ability to bind to phase transfer active ions determine which ions can be transferred and produce the corresponding product.3.The bis(hydroxyundecyl)disulfide with high purity can be prepared under optimized reaction conditions of phase-transfer catalysis reaction.In addition,poly(decyldisulfide)as a colorless and transparent polymer can be prepared under proper molar ratio of Na2S2 to 1,10-dibromodecane.4.In the reduction reaction of bis(hydroxyundecyl)disulfide,the reduction yield with sodium borohydride as the reducing agent is 70 %.The reduction rate of 80 % can be achieved by Zn-acetic acid reducing system though the hydroxyl in the substrate is easily to be esterified with acetic acid,while the reduction yield using Zn-HCl reducing system is 53 %.Tributyl phosphine showed basically no reduction activity.5.The reduction of disulfide bonds using DTT as a reducer depends closely on solvent properties.When THF is used as a main solvent,the reduction rate becomes higher with more content of proton solvent(water and methanol)in THF,and the highest value reaches to 95.6 %.When dichloromethane is used as a main solvent,the reduction reaction cannot occur in completely anhydrous solvent,while the reduction yield reaches to 73.6 % as water content is only 0.05 %,then the reduction yield decreases with the increase of water content.6.For the reaction mechanism,the two mercapto groups of dithiothreitol are ionized into sulfur ions under alkaline condition.In the presence of water,methanol and other proton solvent promote sulfur ion acts as a nucleophile to attack the sulfur atom of disulfide bond,and the disulfide bond is broken to form sulfur ions.Meanwhile,two sulfur atoms in dithiothreitol close into a disulfide loop and is oxidized.