vi solvent effects on organic rates and equilibria · 2017-03-06 · chapter 2 solvent effects on...

CHAPTER 2 SOLVENT EFFECTS ON ORGANIC

RATES AND EQUILIBRIA

References

1. Carey and Sundberg, 5th ed section 3.8

2. Carroll, p. 329

3. L & R pp. 177-189; 335-340

4. Isaacs Chapter 5

5. E. Buncel and H. Wilson, J. Chem. Ed., 57, 629(1980).

Importance

a) Changes in solvent can produce changes in reaction rate of up to 1010 or more.

Some understanding of solvent effects is therefore useful in minimizing reaction

times, or maximizing yields where two or more products are formed by competing

pathways

b) Solvent effects on reaction rate can yield information about the reaction

mechanism (specifically, information about the TS structure).

I SOLVENTS AND SOLVATION

Classification of solvents:

a) polar dielectric constant (ε) greater than about 15

nonpolar ε < about 15

b) protic contain a proton attached to N or O that is usually rapidly-

exchangeable in D2O and that can form a hydrogen bond with an

electron pair donor.

aprotic no rapidly-exchangeable proton

ORGANIC REACTIVITY - CHEM*4720 - COURSE NOTES W2010 2 - 1

Some common solvents are classified in this way in the Table.

Classification of Solvents

Dipolar Protic ε Nonpolar Protic ε H2O 78.5 CH3CO2H 6.2

HCO2H 58.5 (CH3)3COH 12.5

CH3OH 32.7 cyclohexanol 15.0

CH3CH2OH 24.6 phenol 9.8

HC(O)NH2 111.0

Dipolar Aprotic Nonpolar Aprotic

acetone 20.7 CCl4 2.2

HC(O)N(CH3)2 (DMF) 36.7 pyridine 2.4

CH3S(O)CH3 46.7 n-hexane 1.9

CH3CN 37.5 cyclohexane 2.0

CH3NO2 35.9 ethyl ether 4.3

[(CH3)2N]3PO (HMPA) 30 dioxane 2.2

CH3OCH2CH2OCH3 (DME) 7.2

benzene 2.3 THF 7.6

Solvation involves the same forces as are involved in all intermolecular interactions,

namely dispersion (London), dipole-dipole, and ion-dipole forces. In general, solutes

and solvents in which the intermolecular forces are of the same kind and similar in

magnitude are mutually-miscible (i.e., "like dissolves like").


Two generalizations:

a) Uncharged solutes are usually more soluble in organic solvents than in water,

while ionic solutes are usually more soluble in water.

b) Salts (at least at lower concentrations) tend to make ionic solutes more soluble

and uncharged solutes less soluble.

Ions are solvated by ion-dipole interactions. Consider, for example, a solvent such as

methanol or water:

M+-

-

--

+

+

+

+ X-+

++

+-

-

-

--+

OR

H

Solvation of ions is stronger the more concentrated the charge. Ionic or dipolar solutes

are stabilized by ion-dipole or dipole-dipole attractions in dipolar solvents. With anions,

particularly small anions, hydrogen bonding is particularly important. The hydrogen

bond is a dipole-dipole attraction but is stronger than other dipole-dipole attractions

because the positive end of the bond dipole (the proton) is very exposed and permits

very close approach. Dipolar aprotic solvents such as dimethyl sulfoxide (DMSO)

are not nearly as effective at solvating anions because the positive end of the dipole is

less exposed.

SO

CH3CH3

δ-

δ+


II QUALITATIVE ELECTROSTATIC MODEL OF SOLVENT EFFECTS ON RATES

(Hughes & Ingold)

The largest solvent effects are seen where reactant and transition state differ greatly in

polarity, i.e., when charges are developed or neutralized in going from reactants to the

transition state. Hughes and Ingold reasoned that reactions leading to increased charge

separation in the transition state should be increased in rate by increased "solvent

polarity" (increased ion-solvating ability) while those leading to decreased charge

separation should respond in the opposite way. These ideas were developed for

nucleophilic substitution reactions and are summarized in the Table.

Solvent Effects in Nucleophilic Substitutions (Hughes & Ingold)

Reactants T.S. change in charge distribution

effect of increased “solvent polarity” (ion solvating

ability)

R X R Xδ-δ+

increased charge

separation large increase

R X+ R Xδ

+δ+

charge dispersal small decrease

R XY- + R XY

δ−

δ−


R XY + R XY δ−δ

+

increased charge

separation large increase

R X+Y- + R XY

δ+

δ−

decreased charge separation

large decrease

Y- + C O

C OYδ

− δ−


These rules very often lead to a correct qualitative prediction of a change in solvent

polarity on the rate. The reason they work is that they usually correctly predict the

solvent effect on the difference G‡ - G reactants (ΔG‡) even though both may increase


or decrease. For example, in the solvolysis of benzyl chloride in methanol-water

mixtures, the rate increases by a factor of 200 in going from 100% methanol to 100%

water. Increasing the % H2O actually increases both γR-Cl and γT.S., but γT.S. is

increased less than γR-Cl.

More examples of kinetic solvent effects follow.

Me3S+ + OH- → MeOH + Me2S (Et)3N + EtI → (Et)4N+ + I-

% EtOH (v/v) in H2O/EtOH system

rel. rate (100 °C) solvent ε rel. rate (100 °C)

0 1.00 hexane 1.9 1 60 4.01 X 10 benzene 2.3 8.1 X 10 80 4.82 X 102 acetone 20.5 8.4 X 102

100 1.96 x 10 4 nitrobenzene 34.6 2.8 X 103

Acetyl Peroxide Decomposition nBu-I + *I-→ nBu-I* + I-

medium rel. rate (85 °C) solvent ε rel. rate (25 °C)

gas 1.0 methanol 32.7 0.20 cyclohexane 0.57 ethanol 24.2 1.00

isooctane 0.67 n-butanol 17.3 5.1 benzene 0.72 n-hexanol 12.8 5.7

acetic acid 0.58 n-dodecanol 6.15 6.8

propionic acid 0.74 carbon tetrachloride 0.54


tBuCl → tBuOS + HCl (solvolysis in SOH)

MeI + Cl- → MeCl + I-

SOH rel. rate (25 °C)

solvent rel. rate (25 °C)

EtOH 1 methanol 1.0 MeOH 9.3 formamide 1.6 X 10

EtOH/H2O = 80/20 (v/v) 1.08 x 102 N-methyl formamide

4.5 X 10

EtOH/H2O = 60/40 (v/v) 1.43 x 103 N,N-dimethyl formamide

7.9 X 105

EtOH/H2O = 40/60 (v/v) 2.02 x 104 N,N-dimethyl acetamide

2.5 X 106

H2O 5.5 x 105 N-methylpyrrolidine 7.9 X 106

acetonitrile 4.0 x 104 acetone 1.6 X 106 nitromethane 1.6 X 104

The qualitative rules do not correctly predict the large differences between aprotic and

protic solvents in reaction involving anions (see CH3I + Cl- example). The term "solvent

polarity" is not precisely defined. Several solvent properties, particularly the ability of

the solvent to solvate anions and cations, must be considered. The origin of the

dramatic increase in reactivity of anions in changing from a protic to an aprotic solvent is

the poor solvation of anions in aprotic solvents.

The qualitative rules can also lead to an incorrect prediction for reactions of ionic

nucleophiles Y- unless the reactions compared actually involve free Y-. In very poorly

ion-solvating media the nucleophile may be present entirely as ion pairs, M+Y-, or higher

aggregates. In such situations reaction of Y- with a substrate RX can be strongly


increased in rate by an increase in solvent ion-solvating ability by increasing the

concentration of much more reactive Y- ions.

III EMPIRICAL SCALES OF ION-SOLVATING ABILITY

The solvent dielectric constant is in general a very poor indicator of ion-solvating ability

unless the solvents are very similar in structure.

H Br H OS

+ HBr

H Br

δ+

δ-

via this T.S.:

SOH

SOH = H2O, EtOH, CH3CO2H, etc.

Nitrobenzene (ε = 35) added to ethanol (ε = 25) decreases the rate. Acetic acid (ε =

6.1) solvent reacts faster than ethanol (ε = 25). The reason for these seemingly

anomalous observations is that solvation of the anion and cation are both important.

Ethanol (protic solvent) solvates the incipient Cl- better than nitrobenzene, while acetic

acid is a better anion-solvating solvent than ethanol.

There are several quantitative scales of ion-solvating ability based on model reactions

or physical processes (analogous to σ values for substituent effects). These ion-

solvating power or "polarity" scales can be used to develop linear free energy

relationships for solvent effects.


A GRUNWALD-WINSTEIN Y VALUES

model reaction:

CH3C

H3CH3C Cl C

H3C

H3CH3C OS

+ HCl

25 °CSOH

CH3C

CH3H3CClδ+ δ-

T.S.

Y = log (k/ko)t-BuCl, 25°

where k = rate constant in the solvent whose Y value is to be measured.

ko = rate constant in the standard solvent, 80% aqueous ethanol, i.e., 80/20 (v/v)

ethanol/water.

Y = 0 (by definition) for 80% ethanol-water, positive for solvents of greater ionizing

power, and negative for solvents of lower ionizing power.

The Y scale is limited to solvolyzing (i.e., protic) solvents. It therefore cannot be used to

correlate or predict rate constants in aprotic solvents. Y values for some common

solvents are listed in the table on p. 2-11.

B KOSOWOR Z VALUES

I-+

charge-transfer complex

NCH2CH3

COMeO

+NCH2CH3

COMeO

+ I-

N-ethyl-4-carbomethoxypyridinium iodide


The spectrum of N-ethyl-4-carbomethoxypyridinium iodide (and also some other

quaternary pyridinium and related halides) shows a strong maximum in the UV-visible

which is very sensitive to solvent (examples: λmax = 342 nm in methanol, 450 nm in

CHCl3). The new maximum is absent in the chloride or bromide and the absorbance

does not follow Beer's law. The absorption corresponds to a charge-transfer transition

corresponding approximately to

Py+I- Py.I.hν

Excited State

Ground State

Py.I..Py+I-

minor major

Py.I..Py+I-

major minor

hν (charge transfer

Since the ground state is stabilized by solvation of ions, the energy of the transition

increases with increasing ion-solvating ability.

Z = ΔE = Nhν = Nhc

λin kcal/mol hνct

CHCl3

hνct

MeOH Some values are listed in the Table on p. 2-11. (reference: E.M. Kosowor, J. Am.

Chem. Soc. 80, 3253(1958).)


C DIMROTH ET VALUES

reference: C. Reichardt, Angew. Chem. Intl. Ed. Engl., 4, 29(1965)

(a review of solvent "polarity" scales)

Again, the long wavelength maximum is very

sensitive to solvent because there is less

charge separation in the excited state than in

the ground state. ET is the transition energy in

kcal mol-1 (as with Z values).

N

Ph

Ph

Ph

Ph

Ph-O +

For reactions of unknown mechanism a plot of log k vs Y, Z, or ET gives some idea of

the sensitivity of reaction rate to ion-solvating ability and therefore some indication of

the difference in charge separation between the reactant(s) and transition state.

Interpretation of the slopes of such plots requires a comparison with slopes for reactions

of "established" mechanisms or well-characterized transition states. The slopes are

analogous to ρ values, which measure sensitivity to substituent effects. Again, we are

comparing the reaction to some model reaction or model process. If the correlation is

good, the model is a good one.

The original Dimroth solvent parameters are called ET(30) values in more recent

papers. Several new betaine dyes having different substituents on the pyridinium and

phenoxide rings (compared to the structure noted above) have been synthesized and

the new compounds have permitted considerable extension of the original scale.

Reichardt & Harbusch-Görnet Liebigs (Ann., 721 (1983)) have defined a scale called

ETN values based on all of these compounds. In the ETN scale, tetramethylsilane is

assigned a value of 0.00 and water a value of 1.00, so that all other values fall between

0 and 1.0. ETN values for 243 solvents are listed.


Selected Solvent Polarity Parameters

Solvent ET Z Y

water 63.1 94.6 3.49 formic acid - - 2.05 trifluoroacetic acid - - 1.84 trifluoroethanol - - 1.06 80/20 (v/v) EtOH/H2O 53.6 84.8 0.00

methanol 55.5 83.6 -1.09 ethanol 51.9 79.6 -2.03 acetic acid 51.2 79.2 -1.64 1-propanol 50.7 78.3 -2.73 nitromethane 46.3 71.3 - acetonitrile 46.0 71.2 - DMSO 45.0 71.1 - DMF 43.8 68.4 -3.5 acetone 42.2 65.5 - chloroform 39.1 63.2 - ethyl acetate 38.1 59.4 - THF 37.4 58.8 - ethyl ether 34.6 - - benzene 34.5 54 - carbon tetrachloride 32.5 - - n-hexane 30.9 - -

Y values: Fainberg & Winstein, JACS 78, 2770(1956)

ET values: Reichardt Angew. Chem. Int. Ed. Engl. 4, 29(1965)

Z values: Kosower JACS 78, 3253(1956)


IV PHASE TRANSFER CATALYSIS

references: W.P. Weber and G.W. Gokel, Phase Transfer Catalysis in Organic

Synthesis, Springer-Verlag, Berlin, 1977.

C.M. Starks and C. Liotta, Phase Transfer Catalysis, Principles and

Techniques, Academic Press, N.Y. 1978.

Phase transfer catalysis is a way of carrying out reactions between an organic

compound, soluble in an organic solvent, and an ionic compound not appreciably

soluble in the organic solvent. The reaction is carried out in a two-phase

organic/aqueous system using a large quaternary ammonium or related salt (phase

transfer catalyst) which carries the ionic reactant into the organic phase as an ion pair.

Using this method it is possible to carry out reactions ordinarily requiring a scrupulously

anhydrous medium.

example:

aqueous phase

organic phase

Na+OH- in H2O

PhCH2CN + CH3I in CH2Cl2 No reaction occurs until PhCH2N+Et3 Cl- is added. After addition of the phase transfer

catalyst the reaction is over in a few minutes. product: Ph CH(CH3)CN

Procedure: Add aqueous Na+OH- + R4N+OH- to a solution of PhCH2CN + CH3I in

CH2Cl2 and stir.

General Mechanism:

aqueous phase

organic phaseQ+PhCHCN + H2O [Q+OH-] + PhCH2CN

-

Q+Cl- + -OH [Q+OH-] + Cl-

PhCHCN

CH3

+ [Q+I-]Q+PhCHCN + CH3I -


The method depends on the fact that R4N+OH- is much more soluble in organic

solvents than Na+OH-.

another example:

C C

Cl ClNa+OH-, PhCH2N+Et3, in H2O

in CHCl3C C

aqueous phase

organic phase

Crown ethers and cryptands can also be used a phase transfer catalysts:

Na+OH- + crown [crown.Na+] OH-

(soluble in organic phase

V SOLVENT EFFECTS ON PRODUCT COMPOSITION

The solvent can have a large effect on the product composition in reactions where two

or more products are produced by competing pathways that respond differently to

changes in solvent. One familiar example is competition between concerted nucleophilic

substitution (SN2) and nucleophilic substitution by a stepwise ionization (SN1)

mechanism. Depending on the substrate and nucleophile, the solvent can effect the %

rearrangement or % racemization, both of which require a carbocation intermediate.

Two other examples are shown:

(i) Concerted vs Ionic Cycloaddition


CC

CN

Cl

+

NC Cl

+Cl

CN

Cl

CN+

1 2 3 in: benzene 50% 9% 38%

acetonitrile 26% 2% 64%

Adduct 1 is produced by a thermally-allowed π2s +

π2s + π2s cycloaddition, while 2 and 3 are

presumed to arise from the accompanying

zwitterionic intermediate. C

C-

Cl

CN+

(ii) Reactions of Ambident Anions

Ambident anions have two or more nucleophilic sites and can react with alkyl halides,

acyl halides, etc. at two or more positions.

examples:

-CN NO O-

O- O

-etc.

R C R

O O

H

-

H

OO-

RCR etc.

enolate anions

General rule: the more free the anion the greater the tendency to react at the

most electronegative atom


For enolate anions, protic solvents strongly solvate the oxygen site favouring C-

alkylation. Polar aprotic solvents, by leaving the anion relatively unsolvated, favour O-

alkylation.

Examples:

+ CH3I

OC

Ph CPhPh

CH3

OCH3

CPh C

Ph

Ph

+

OC

Ph CPh

Ph-

in tBuOH 96% 4%

DME/DMSO 50% 50%

O- OCH2Ph OHCH2Ph

+ PhCH2Br

in: DMF 97% 0%

methanol 57% 24%

CF3CH2OH 7% 85%


PRACTICE PROBLEMS 3 1. Predict the effect on the rate accompanying a change to a more polar solvent. Is the rate change considered to be large or small? a)

Et3S+Br- Et2S EtBr+

b)

-OH Et4N+ H2O CH2 CH2 Et3N+ + +

c)

CH2 CH2 + Br2 BrCH2 CH2Br

via rate determining bromonium ion formation 2. Account for the trends in Keq for the following equilibrium.

O O O OHKeq solvent Keq % enol

n-hexane 19 95

1,4-dioxane 4.6 82

methanol 2.8 74

3. Consider the accompanying substitution reaction, which follows the addition-elimination mechanism introduced in CHEM*3750.

+ Na+Br-

NO2

Br N3

-

N3

NO2

+ Na+N3-

Br

NO2 When the reaction is done in DMF, the rate of disappearance of the starting material is rapid. If increasing incremental amounts of water are added to the mixture, the reaction slows down. Please explain. 4. Rank the following compounds for their propensity to solvolyze under the conditions indicated (fastest to slowest). Give reasons for your rankings. The temperature is the same in each instance.


Situation A Situation B Situation C Situation D Situation E

CH3

CH3

Cl

CH3

CH3

ClCH3OCH3

CH3

ClCH3OCH3

CH3

Cl

CH3O

CH3

CH3

Cl

CH3O

80% EtOH/20% H2O 80% EtOH/20% H2O 50% EtOH/50% H2O 80% EtOH/20% H2O 90% iPrOH/10% H2O

5. For the following reaction that proceeds by way of a dipolar (or zwitterionic) intermediate, a) Match the relative rate with the appropriate solvent.

N C OClSO2 + C CH2

CH3

CH3

C CH2

ClSO2OCN

CH3CH3

measured relative rates reaction solvents

1, 31, 5000 diethyl ether, n-hexane, nitrobenzene

a) Draw the structure of the probable intermediate. 6. You have been introduced to the Hughes-Ingold model for predicting solvent polarity effects on reaction rates. Consider the following reaction: Et3N + Et-I Et4N+ + I- which is for the 2nd table of page 2-5 of the course notes. Draw a potential energy level diagram (as on course notes p. 3-10 at the top) demonstrating the reaction path when this reaction proceeds in benzene vs. nitrobenzene. Place both curves on one diagram and be sure to label each curve.


7. Although it was only briefly mentioned in class, the solvent susceptibility parameter m can assume a negative value, as shown in the two similar reactions below. Me3S+ + -OH MeOH + Me2S m = -0.78

Et3S+ + -OH EtOH + Et2S m = -0.84 a) Briefly explain, in general, what kinds of chemical reactions give a positive m value and hence the kinds of chemical reactions that give provide a negative m value. b) Briefly justify the negative m value in the particular instance of the reactions

above. 8. As indicated by the symbolic drawing below, benzyltrimethyl ammonium chloride is complexed by a crown ether (18-crown-6) and the equilibrium constant (K) for the complexation is solvent dependent (298 K). The interaction of the ether oxygens with the ammonium ion is through hydrogen bonding. The table showing the data also shows the entropy change for the reaction, ΔSr, which is presented as TΔS; that is, the temperature component has been incorporated.

O

O

O

O

O

O

+ PhCH2NH3+ O

OO

OO

OH3N CH2 Ph

+K

solvent log K TΔS (kJ/mol)

H2O 1.44 --

iPrOH 4.14 -26.4

DMSO 1.34 -23.7

You are required to: a) Explain why the entropy for the complexation equilibrium is negative. b) Explain why the log K for iPrOH is much larger than that for water.


Explain why water and DMSO have comparable equilibrium values despite being solvents of such different structure.

SOLUTIONS TO PRACTICE PROBLEMS 3

1. a)

Et3S+Br- Et2S EtBr+

-an example of decreased charge separation -large decrease in rate b)

-OH Et4N+ H2O CH2 CH2 Et3N+ + +

-another example of decreased charge separation -large decrease in rate c)

CH2 CH2 + Br2 BrCH2 CH2Br

via rate determining bromonium ion formation -an example of increased charge separation -large increase in rate

2.

solvent Keq % enol

n-hexane 19 95

1,4-dioxane 4.6 82

O O O OHKeq

methanol 2.8 74

Much like one of the labs in CHEM*3750, we see a dependence of internal H-bonding on solvent. With the least polar solvent, there in no opportunity for solvent participation through H-bonding or dipole alignment, so the molecule satisfies itself somewhat by tautomerizing to the enol and doing the internal H-bonding. With 1,4-dioxane, increased stabilization of

O OH

H-bonding arrangemen


the polar carbonyl form is possible through interaction with the solvent, (but not H-bonding). With MeOH there is good chance to H-bond to the carbonyl and to solvate it well through polar interaction. Hence self-stabilization by enol formation is reduced. 3. When sodium (or K+) azide is added to DMF, the sodium is solvated due to the direction of the dipole moment of the solvent. The azide is poorly solvated and readily does chemistry; hence the efficient addition elimination reaction. The addition of water creates a new solvent system that can assist in the stabilization of the positive sodium ion, but will probably have a greater effect on the azide which is poorly solvated in DMF alone. Water can perform H-bonding to the azide, which stabilizes it and reduces its reactivity. 4.

Situation A Situation B Situation C Situation D Situation E

CH3

CH3

Cl

CH3

CH3

ClCH3OCH3

CH3

ClCH3OCH3

CH3

Cl

CH3O

CH3

CH3

Cl

CH3O

80% EtOH/20% H2O 80% EtOH/20% H2O 50% EtOH/50% H2O 80% EtOH/20% H2O 90% iPrOH/10% H2Oranks third,

boring substituent and common solvent

system

2nd fastest case, is in common solvent system and bears

+R group for through resonance stabilization in the

TS for Cl loss

fastest case, is in most ionizing

solvent and bears +R group for

through resonance stabilization in the

TS for Cl loss

2nd slowest case, bears -I group and is in

common solvent system

slowest case, bears -I group and is in least ionizing

solvent

5. a) A dipolar intermediate would suggest that more polar solvents would accelerate the reaction.

CCH2

ClSO2OCN

CH3CH3

-

+

The accompanying molecule is the proposed intermediate. Note that the tertiary carbon bears the cation while the collection of electronegative atoms bears the anion.

Measured relative rates reaction solvents

1 n-hexane,

31 diethyl ether,

5000 nitrobenzene


6. Here is my thought. The important issues are that the starting materials should be close, the overall ΔG‡ should be less for nitrobenzene and the ionic products in nitrobenzene should be of lower energy that in benzene. I also believe the energy difference between the products in the different solvents should be greater than the energy difference between the two transitions states in the different solvents

7.

Me3S+ + -OH MeOH + Me2S m = -0.78

Et3S+ + -OH EtOH + Et2S m = -0.84

a) The concept of m arises from solvolysis reactions. One can take the rate of solvolysis of a standard reaction, determine its’ rate in a number of solvents and then establish a solvent parameter, m. Since in a solvolysis, there is creation of charge, so more polar solvents create a large m and anything that creates charge will have a positive m based on how m was established in the first place.

So when m is measured for a reaction that destroys charge, then m comes out to be negative.

b) In the case of the reactions at hand, the negative m value is applicable since charged ion are reacting to create neutral compounds.



8.

a) Two reasons: Two molecules come together to form one. The flexibility of the ring is lost when it closes to complex with the

ammonium ion. b) iPrOH is not as good of an H-bonding solvent as water because of steric reasons,

polarity and the number OH bonds per molecule. Note that for the ammonium ion to bind with the crown ether, it must give up its interaction with the solvent. In water more so than iPrOH, that interaction is through H-bonding and hence it is more difficult to leave that H-bonding interaction behind in favour of the crown ether. The weaker interaction of the ion with iPrOH therefore will more readily concede the ammonium to the crown ether.

Both water and DMSO have oxygens capable of offering electron density towards cations. When that cation is something like an ammonium ion, then both can participate in H-bonding. Despite their structural differences, both can H-bond very well.

vi solvent effects on organic rates and equilibria · 2017-03-06 · chapter 2 solvent effects on...

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