11Hardik MistryHardik MistryL M college of pharmacyL M college of pharmacyPharmaceutical chemistry dept.Pharmaceutical chemistry dept.
22SOLVENTSOLVENTIt is the component of the reaction system thatseldom appear in our equation , but that isnearly always present.
33Importance of the solventImportance of the solventThe presence of the solvent can speed up or slowdown the reaction by a factor 1020Change from the one solvent to another can bringabout millionfold change in reaction rate.Solvent effect is more powerful than any other factorslike steric factor,polarity factor or symphoric factor.
44Solute molecules and ions do not exist in the solutionas nacked particles but always solvated and eachdissolved particles is a cluster of solvent molecules.
55Any solvent cluster help to make up the structure anddetermine their stabilities which help us to predict thechemical behavior of the structure.Through the secondary bonding ,solvent help us todetermining the shape of the of large molecules likeprotein and nucleic acids and inturn their biologicalactivities.
99Role of solvent inRole of solvent inSOLUBILITYSOLUBILITY1) Non ionic solute:Solubility of it depends upon their polarity and inparticular their ability to form hydrogen bond.
1010“Like dissolves like “ apply hereExample : hydrocarbons dissolve in benzene while alkylhalide dissolve in solvent like chloroform or carbontetrachloride.
1111In case of alcohol , it composite alkane-like alkyl groupand water like hyroxyl group.Hydroxyl group is polar with high electronegativity ofoxygen element.So alcohols are soluble in other hydroxyl compounds likewater.
12122) Ionic solutes.Here the forces holding together an ionic lattice arepowerful, and to break them ,energy is supplied by theformation of the ion-dipole bonds and the solvent.
1313To dissolve ionic compounds- solvent must be highly polar- it must have high dielectric constantMeans it must be good insulator to lower theattraction between oppositely charged Ions once theyare solvated.
1414Water is the universal and most superior solvent due toits polarity and high Dielectric constant.Solvating power(the ability to form strong bonds todissolved ions) is very important and so there are otherliquids having large dipole moments and highDielectric constant are still poor solvent.
1515Cations are attracted to theCations are attracted to thenegative pole of the solventnegative pole of the solventLook in water hereOHH+δ+δ-δ+
1616Anions are attracted to theAnions are attracted to thepositive pole of the solventpositive pole of the solventH OH_+δ-δ+δ
1919Types of the solventTypes of the solvent1) Protic solventsolvents containing hydrogen that is attached to theoxygen and nitrogen and hence acidic enough to formhydrogen bond.Example: water and methanol
2020Other protic solvents solvate ions in the same manner asthat water does:Cations: through unshared pairsAnions: through hydrogen bonding
21212) Aprotic solventssolvents with moderately high dielectric constantand do not contain acidic hydrogen.Example: DMSO,DMF,HMPT
2222The aprotic solvents dissolve ionic compounds, butthey cannot form hydrogen bond to anions as inprotic solvents.Aprotic solvents are highly polar and thus theydissolve ionic compounds through their solvation ofthe cations.
2323Selection of the solventSelection of the solventExample: water and methanolWater dissolves ionic compounds very well but poorfor organic onewhile non polar solvents dissolves organic compoundsbut poor for inorganic salts.
2424Alcohol ,particularly smaller ones like methanol andethanol due to their alkyl group dissolve non polarorganic compounds and due to their hydroxyl groupdissolve polar compounds.
2525Problem with alcoholProblem with alcoholWater and alcohol are protic solvents and through thehydrogen bonding they solvates the anions stronglyso they stabilizes the anions and lower theirreactivity and so weakens its basicity and nucleophilicpower.
2626So we require aprotic solventand reaction that ,in protic solvent proceed slowlyat high temperature to give low yields may be found,In aprotic solvent, to proceed rapidly often at roomtemperature-to give high yields.
2727Role of solvent in SRole of solvent in SNN1 reaction1 reactionHere one substrate reacts faster than another chieflybecause of a lower Eact .In SN1, for example the difference in rate betweentertiary and secondary substrate corrosponds to adifference in Eact of about 15 kcal.C CH3CH3H3CBr+ OH-C CH3CH3H3COH+ Br-Rate= k[RBr]
2828In the SN1 reaction in transition state there is aheterolysis means bond breaking takes place withoutany bond forming to balance it to provide energy.And in the gas phase bond dissociation energy showsthat heterolysis of an alkyl halide requires great dealof energy of about 149 Kcal/mole for tert-butylbromide.
2929Where does this great amount of energy comes from?Where does this great amount of energy comes from?This great amount of energy comes from formation ofthe many bonds: bonds between the ions producedand solvent.The ions are not generated as the naked particles butthey are generated as the solvated ions.
3030Ions are products of heterolysis.Individually, each of these ion-dipole bonds isrelatively weak, but altogether they provide greatdeal of energy.+++++++_______+ ____+_++++_
3131The reactant has dipole moment, and forms dipole-dipole bonds to solvent molecules.R R XX R++ X-+δ −δReactant transition stateproduct
3232Transition state has great dipole moment than reactantand can form strong dipole-dipole bonds to thesolvent.The solvent thus stabilizes the transition state morethan it does the reactant, lowers the Eact and speeds upthe reaction.
3333Clearly the effect of the solvent :it lowers the Eact by130 Kcal or more and thus allow the reaction to takesplace.
3434Kinds of the solvent that is best for SKinds of the solvent that is best for SNN1 reaction1 reactionMore polar solvent, the stronger the ion-dipolemoment.So the SN1 reaction of neutral substrates in waterthan ethanol. they go faster in 20% ethanol than80% ethanol.
3535Role of solvent in SRole of solvent in SNN2 reaction2 reactionSN2 reaction: reaction between alkyl halide and hydroxyl ionMost of the energy needed to break the bond to the leavinggroup is supplied by the making of the bond to thenucleophile. in attach by OH-, C-X bond is being brokenand simultaneously C-O bond is being formed.CH3Br + OH- CH3OH + Br-Rate = k [CH3OH] [OH-]
3636Among the protic solvents, ionizing power is highestfor those solvent which can form most strongerhydrogen bond among all of them.example:- 2,2,2 tri fluoroethanol- formic acid- trifluoroacetic acid
3737Solvents which speeds up the SN1 reaction enormouslyslows down the SN2 reaction by the factor 1020!The alkyl halide has dipole moment and forms weakdipole-dipole bonds with the solvent. hydroxyl ionhas fully negative charge and forms very powerfulion-dipole bond to the solvent.
3838The transition state carries a full negative charge tooand charge is divided between alkylhalide andhydroxyl ion and so the solvent stabilizes the reactantsmore than that in the transition state and raises theEact and slows down the reaction.R R XX OH + X-−δReactant transition stateproductOH-+ HO+δR
3939Solvation of the anionic nucleophile is thus overridingfactor here. By stabilizing it-relative to the transitionstate-the solvent deactivates the nucleophile.
4040Kinds of the solvent that is best for SKinds of the solvent that is best for SNN22reactionreactionThe greater the polarity slower the SN2 reaction.SN2 reaction in the solvents like dimethyl sulphoxide(DMSO), dimethylformamide (DMF) orhexamethylphosphorotriamide (HMPT) go millionstimes faster than in alcohol or alcohol-water mixture.
4141The SThe SNN2 reaction:2 reaction:Phase transfer catalysisPhase transfer catalysisExample:The reaction of an alkyl halide with sodium cynide toyield alkyl cynide (nitrile).Traditional way is to use solvent which dissolves bothreagents.
4242Consider solution of alkyl halide in nonpolar organicsolvent and a solution of sodiumcynide in water.ThenThe solvents are immisible, two separate layers andon heating also no reaction takes place.
4343On the addition of small amount of quaternaryammonium salt to the reaction mixture, alkyl halideand cynide still seperated in its own phase-reactrapidly and give high yield of the nitrile.This type of the reaction is called as the phasetransfer catalysis.
4545Ions of the alkyl halides are in the organic phase whilecynide ions are in the aqueous phase.Q+ion carry cynide ion from aqueous to organic phaseand reaction of alkyl halide and cynide ion takesplace and form alkyl cynide.And Q+carry halide displaced from alkylhalide back tothe aqueous phase.