CHM 1321 Assignment 5 Answers

1) Name the following compounds

a) 6-methylheptene or 6-methylhept-1-ene

b)

2-ethylpentene or 2-ethylpent-1-ene

c)

4-methylhepta-1,6-diene 4-vinylcyclohexene

d)

e)

3(S),4(R)-dimethylcyclopentene

f)

E-2-methyloct-4-ene

g)

5Z-2,7-dimethylocta-1,5-diene

2) Predict the products of E1 elimination for the following compounds. Predict the relative amounts of each product.
OH H2SO4 a) heat OH + H
+

OH2 H

b)

H3PO4 OH heat + OH + H+ OH2 H H minor (least substituted) + H+ H+

c)

Br

HOCH3

major (most substituted) H + H + HOCH3 HOCH3 + HOCH3 + HBr minor (least substituted) + HOCH3 + HBr major (most substituted)

H Br

d)

Br

HOC(CH3)3 H

H Br H

HOC(CH3)3

HBr minor (least substituted) HBr Major (most substituted)

+ HOC(CH3)3

HOCH3 e) Br H + H Br + HOCH3 HOCH3 + HBr minor (least substituted) + HBr major (most substituted) + HBr major (most substituted)

+ HOCH3 H

f)

Br

HOCH3

H Br + HOCH3

+ HBr major (most substituted)

+ HOCH3 H

+ HBr

3) When 1-bromomethylcylcohexene is heated in ethanol, three products are observed. Give mechanisms to account for each product.

Br

ethanol heat

+ OCH2CH3

OCH2CH3

Br

resonance hybrid HOCH2CH3 OCH2CH3 + H2OCH2CH3

OCH2CH3 H HOCH2CH3 + H2OCH2CH3

HOCH2CH3 HOCH2CH3 OCH2CH3 H HOCH2CH3 + H2OCH2CH3 OCH2CH3

4) The reaction of sodium ethoxide with methyl iodide is sensitive to the polarity of the solvent. Draw an energy diagram for this reaction in a protic solvent and in a dipolar aprotic solvent. Use the energy diagram to predict which reaction will be faster.
I + I H + H H OCH3 O + I

H3C

OCH3

dipolar aprotic solvent

H + H H

OCH3

+ I

H3C

I OCH3 protic solvent

reaction co-ordinate

reaction in the dipolar aprotic solvent will be faster because the activation energy is lower in this solvent

5) a) Design an alkyl halide that will give only 2, 4-diphenyl-2-pentene upon treatment with potassium tert-butoxide (a strong hindered base).
Note: Cis/trans are still possible, but only one isomer will be obtained depending on the stereochemistry of the starting material (see parts below)

Br

placing the bromine at any other carbon is incorrect as this leads to 3 products

Br

b) What relative stereochemistry is required in your alkyl halide so that only the following stereoisomer of the product is formed?
H Br

Newman Projection

R H3C

H Ph

to get this projection, add H and Br antiperiplanar

R H Br

R H3C

H Ph

Br

note: Relative stereochemistry is important at all positions. verify by Newman projection

6) When 2-bromo-3-phenylbutane is treated with sodium methoxide, alkenes result in addition to the substitution product. a) Draw a mechanism for the reaction showing the major and minor products. Clearly indicate the source of each product (mechanism)
Br + OCH3 OCH3

2-bromo-3-phenylbutane Br H + OCH3

Br

H + OCH3 or stereochemistry will depend on the configuration of the starting material

b) When one pure diastereomer of the starting material reacts, one pure isomer of the major product results. Predict which diastereomer will produce the isomer that has the methyl groups cis.
Br H + OCH3

Look at the Newman Projection add H and Br antiperiplanar Ph H CH3 CH3 product

Br Ph H

Br CH3 H CH3 starting material

c) Draw a Newman projection of the transition state to justify your choice in part b. see above d) Draw a Newman projection of the transition state to show the formation of the trans isomer from the other diastereomer.
Br H + OCH3

Look at the Newman Projection add H and Br antiperiplanar Ph H3C CH3 H product

Br Ph H3C

Br CH3 H H starting material

e) Predict the stereochemistry of the product produced from the enantiomer of part b. The enantiomer of the material in part b will give the same alkene. Remember that enantiomers have identical properties except their interaction with plane polarized light and their reactivity with other chiral compounds.
Br NaOMe

Ph H

Br CH3 H CH3 Ph H CH3 CH3

Br NaOMe

H3C H3C

Br Ph H H H3C H3C Ph H

7) Some of the following can exist as stereoisomers and some cannot. For the ones that can, draw the isomers and assign names.
a) 2-bromo-3-chloro-2-pentene Br Br Cl E b) 3-ethylhexa-2,4-diene Z Cl

2E-4E c)

2E-4Z

2Z-4Z

2Z-4E

2-bromo-3-methyl-2-butene

Br d) 1,3-pentadiene

e)

E Z 4-tert-butyl-5-methyl-4-octene

Z f) 3, 7-dichloroocta-2,5-diene 2Z-5E-7S Cl Cl 2E-5E-7S Cl only Z possible Cl

E 2Z-5Z-7R Cl 2Z-5E-7R Cl 2E-5E-7R Cl Cl 2Z-5Z-7S Cl

Cl

Cl Cl

Cl g)

Cl

Cl 2E-5Z-7R

Cl 2E-5Z-7S

cyclohexene

h)

cyclodecene

i) E, Z E,E Z,Z cyclodeca1,5-diene

8) Explain why a strong base such as tert-butoxide cannot dehydrate an alcohol through an E2 mechanism. What can be done to the alcohol to dehydrate it (give 2 methods)? The strong base removes the hydrogen from the hydroxyl group making a terrible leaving group. To dehydrate the alcohol, use acidic conditions or convert the alcohol to a sulfonyl ester. 9) Predict the elimination products that result when the following are heated in alcoholic KOH. When more than one product is possible, predict the relative amounts.

a) Br KOH Br 3 b) Br KOH Br 3 c) Cl 1 = major 3 = minor 1 2 4 1 = major 4 = minor 1 2

Cl Cl + H H H's antiperiplanar to Cl major minor

d) Cl

(Hint: for parts c and d build models)

Cl Cl H H OCH3 this hydrogen is antiperiplanar to the Cl, can get E2 reaction this hydrogen is not antiperiplanar to the Cl, cannot get E2 reaction

10) Explain the difference in the following reactions.

Br

NaOH

CH3CH2OH

OH

(1)

Br

NaSH

CH3CH2OH

(2)

sulfur is a much better electron donor than oxygen is (lower in the periodic table). Therefore it is a much better nucleophile. The product of the first displacement in reaction 2 is still a very good nucleophile and can do a second reaction. The product of the first reaction can do a second displacement, but it will happen much slower (ROH now more hindered than OH-).

Br

SH

CH3CH2OH

SH

SH S Br + S

11) Give the major product of the following reactions. Include a mechanism for each, and name the type of reaction (SN1, SN2, E1 or E2).
a) Br Br + + KOH OH SN2 b) Br Br + + I SN2 Br Br CH3CH2OH H2 N KI DMF DMF OH

c)

+ +

NH3 NH3

SN2

NH3

NH2 d) H Br + OC(CH3)3 E2 Br + NaOC(CH3)3 HOC(CH3)3

e)

Cl

NaOC(CH3)3

HOC(CH3)3

H Cl + OC(CH3)3 E2

f)

KI

DMF

no reaction

g)

NH3

NH3

NH3

H H2N

NH3

SN2 NH2 NH2

h) Br + CH3CH2OH

Br

O H -H SN1

CH3CH2OH

i)

OSO2CF3 + NaOCH3

HOCH3

OSO2CF3 OCH3 H major E2

12) For each of the following reactions, indicate if the reaction will work well, poorly or not at all. Give mechanisms and brief justifications.

Br a) Br + OH DMF + NaOH DMF

OH

OH

work well - good nucleophile and leaving group, dipolar aprotic solvent CH3OH

b)

Cl

Cl

CH3OH O H

-H O

work poorly. Uncharged nucleophile, no strong base leaving group is not the best I c) I + CN + NaCN DMF

CN

CN

work well - good nucleophile and leaving group, dipolar aprotic solvent HOC(CH3)3 d) O S OO CH3 OH O

S OO

CH3

OC(CH3)3 O S OO CH3

O work well - intramolecular reaction (nucleophile and alpha carbon on same molecule)

e)

Br

NaSCH3

HOC(CH3)3

Br

SCH3

HOC(CH3)3

will work - good nucleophile and leaving group however the electrophile is hindered and the solvent is protic.

f)

DMF CH3I

H3C I

will not work - the nucleophile is poor HOC(CH3)3 g) Cl + KOC(CH3)3

HOC(CH3)3 + Cl H OC(CH3)3 will work well - strong hindered base

13) Propose syntheses of the following molecules from the indicated starting materials. You may use any reagents or solvents needed. Give mechanisms for all transformations. Provide a retrosynthetic analysis for each.
a) O Retrosynthesis O OR OR = good leaving group from OH and HO

OH Synthesis

+ ClO2S

OH

+ Cl

base S O O

H O

S O O

base

S O O

OH b) Retrosynthesis X H Synthesis OH H2SO4 H OH2 H -H from

c)

S S Retrosynthesis S S Synthesis Br SNa +

from 1, 3-dibromopropane X SH S X Br SH SH Na2S S SH Br S SH Br Na2S S S Br X

X S S X From Na2S S S

X SH

Br

SNa

S S d) NCH3 Retrosynthesis X NCH3 Synthesis Br NH2CH3 Br Br NHCH3 H NH2CH3 Br NHCH3 NHCH3 X from CH3NH2

X NH2CH3

NCH3 H

NH2CH3

CF3 e) Retrosynthesis CF3

from any alcohol

CF3 H

HO

CF3 H

Synthesis HO CF3 H H2O H H2SO4 CF3 H CF3 H CF3

f) Retrosynthesis

from any non-alkene (the Ph is not considered an alkene)

X H

Synthesis Br NaOC(CH3)3 H Br Bonus: The required stereochemistry is:

14) Draw mechanisms and energy diagrams for the following reactions.

a)

(CH3)3CCl +

CH 3NH2

Cl

NH2

-H NH2 H NH2

Cl NH3 NH2

reaction co-ordinate
b) (CH3)2CHCH2Br + Br KOH

OH

OH

E Br

OH OH

reaction co-ordinate

c)

BrCH2CH2CH2CH2OH

heat

BrCH2CH2CH2CH2OH

H O

-H

E H O

BrCH2CH2CH2CH2OH

reaction co-ordinate

15) Explain the following result:

NaOCH2CH3 D Br D

NaOCH2CH3 D Br Note: D = deuterium, an isotope of hydrogen Hint: build models

Br D D Br Br H D Br D base H H base elimination is antiperiplanar D elimination is antiperiplanar