Chm 222
Spring 2016, Exercise Set 3
Addition to Carbonyls and the Pillars
Mr. Linck
c
Boniface
Beebe Productions
January 5, 2016
Version 5.2.
NOTE: An asterisk in the problem title indicates that it is a continuing problem from
the previous one. Two asterisk tells you the problem depends on the last two, etc.
3.1. Learning Organic Chemistry
Review your notes from the last six lectures. Summarize the subjects that were
covered. Present that summary to another student in the class.
3.2. Acids, Bases, Conjugate Acids, and Conjugate Bases
For the reaction
CH3 SH + OH− = CH3 S– + H2 O
identify the acid, the base, the conjugate acid, and the conjugate base.
3.3. Acids, Bases, Conjugate Acids, and Conjugate Bases
What is the conjugate base of HBr, CH3 OH, NH+
4?
3.4. A Material May be an Acid and a Base
Show that NH3 can act as a base. Show that NH3 can act as an acid.
3.5. Acids, Bases, Conjugate Acids, and Conjugate Bases
What is the conjugate acid of NH3 , NH–2 , Cl– , (CH3 )2 C(O)? Draw the Lewis structure
for the last.
3.6. Equilibrium Constants
Write the equilibrium constant in terms of concentrations for the reaction (in water)
CH3 OH = CH3 O– + H+
NOTE: Equilibrium constants for reactions in which a substance produces a proton
are usually called Ka .
3.16
2
3.7. Equilibrium Constants
What does a large value of an equilibrium constant mean? HINT: Give an answer in
terms of concentrations of various species.
3.8. What is a Ka
Express the mathematical equation that defines a Ka . Do so specifically for phenol,
C6 H5 OH. Before you proceed, be sure you can write the Lewis structure of phenol.
HINTS: (1) Recall compounds with ihd of four often have benzene rings. (2) Express
the Ka in terms of the phenoxide ion, phenol, and hydrogen ion.
3.9. pKa
What is a pKa ?
3.10. Information from pKs
Consider the reaction
CH3 C(O)OH
=
CH3 C(O)−
+
H+
for which we can write
Ka =
[CH3 C(O)− ][H+ ]
[CH3 C(O)OH]
Show that this is equivalent to the expression
[CH3 C(O)− ]
pKa = pH − log(
[CH3 C(O)OH]
3.11. Information from pKa *
If the pKa of phenol, C6 H5 OH, is 10, what is the ratio of phenoxide ion to phenol
at equilibrium if the pH is 10? If the pH is 8? If the pH is 12? HINT: See the last
problem.
3.12. Concentrations and pKa **
Articulate what you learned in the last problem. “If the pH is below the pKa , then
the ratio of . . . If the pH is above the pKa , then the ratio . . . ” Use general words like
acid, conjugate base, base, conjugate acid.
3.13. Information from pKa
Show that in the general case of an acid HX, that if the pH = pKa , the ratio [X− ]/[HX]
is unity.
3.14. Information from pKa
Ethanol has a pKa of about 16. What is the dominant species, CH3 CH2 OH or
CH3 CH2 O– at a pH of 12? At a pH of 8?
Chm 222, Section 1
Exercise Set 3
3.25
3
3.15. pKa
Is a compound with a very positive pKa a strong acid or a weak acid?
3.16. Use of pKa
Will the conjugate base of an acid with a large pKa react with another acid with a
small pKa ? HINT: If the answer is not completely obvious to you, then write out the
reactions and figure it out.
3.17. Use of pKa
Will the conjugate base of an acid with a small pKa react with another acid with a
large pKa ? HINT: To do organic chemistry successfully, you have to use pKa values
like your toothbrush, without much thought.
3.18. Ka , pKa , and Reaction Prediction
The pKa of NH3 is 35. That of ethyne is 25. Will NH–2 react with HCCH to produce
ammonia and HCC– ? HINT: Write out the equation in terms of the two reactions
defining the Ka ’s.
3.19. Ka , pKa , and Reaction Prediction
The pKa of CH4 is about 48. That of ethyne is 25. Will CH–3 react with HCCH to
produce methane and HCC– ? HINT: Learn this concept.
3.20. Ka , pKa , and Reaction Prediction
The pKa of CH4 is 48. That of ethanol is 16. Will CH–3 react with CH3 CH2 OH to
produce methane and CH3 CH2 O– ?
3.21. Ka , pKa , and Reaction Prediction
You are going to carry out a Grignard reaction on a carbonyl containing molecule
which also has an alcohol group. Do you have to worry about acid/base chemistry? Explain. HINT: Reactions involving the transfer of a proton, acid/base
reactions, from -NH and -OH bonds are generally much faster than other nucleophile/electrophile reactions. If an acid/base reaction can screw you up, it generally
will.
3.22. pKa Values
Look at Table 1 and get a sense for which substances are strong acids, which weak.
We will work to refine that relationship in what follows. HINT: This table is trying
to get you to classify acid strength with a broad brush. If you want details, there is
a nice table of 600 acids at:
www.chem.wisc.edu/courses/116/OtherDoc/pKas_of_Organic_Acids_and_Bases.
pdf
3.23. Use of pKa Values
Use Table 1 to determine if OH– will substantially deprotonate H2 O2 .
Chm 222, Section 1
Exercise Set 3
Chm 222, Section 1
Horrible Acids
pKa above 30
Extremely Weak
pKa 20 to 30
Very Weak
pKa 10 to 20
Weak acids
pKa 0 to 10
Strong acids
pKa below 0
pKa Range
CH3 C(O)CH2 C(O)OC2 H5 , 10.7
C2 H5 OC(O)CH2 C(O)OC2 H5 , 13
cyclopentadiene, 16
CH3 C(O)H, 16.7
ketone, 19.2
HCCl3 , 24
HCCH, 25
CH3 C(O)OR, 25.6
(Ph)3 PCH+
3 , 30
dithiane, 31.1
(Ph)3 CH, 31.5
toluene, 40
CH2 CH2 , 44
CH4 , 48
1,3-propanedial, 5
2,4-pentadione, 9
HCN, 9.2
C acids
NH3 , 35
R2 NH, 36
aniline, 27
protonated aniline, 4.6
protonated pyridine, 5.2
HONH+
3 , 5.8
NH+
,
4 9.2
succinimide, 9.6
(C2 H5 )3 NH+ , 10.7
(H2 N)2 CNH+
2 , 13.6
amide, 17
N acids
RCNH+ , -10
H2 O2 , 11.6
CF3 CH2 OH, 12.4
CH3 OH, 15.5
H2 O, 15.7
O acids
HClO4 , -10
protonated ketone, -7
protonated acid, -6
protonated alcohol, -2.4
H3 O+ , -1.7
protonated amide, -0.5
CF3 C(O)OH, 0.5
H3 PO4 , 2.2
CF3 CH2 C(O)OH, 3.1
CH3 C(O))H, 4.8
C2 H5 SH, 10.6
(Ph)3 PH+ , 2.7
HF, 3.2
H2 Se, 3.9
H2 S, 7.0
Misc. acids
HI, -10
HBr, -9
HCl, -7
RSH+
2 , -7
3.25
4
Table 1: Various pKa values for compounds. Note the labels “weak” etc. are subjective.
Exercise Set 3
3.34
5
3.24. Use of pKa Values
Use Table 1 to determine if OH– will substantially deprotonate NH+
4.
3.25. Use of pKa Values
Use Table 1 to determine if SH– will substantially deprotonate CH3 OH.
3.26. Use of pKa Values
With the help of Table 1, find a base that will deprotonate a ketone.
3.27. Use of pKa Values
Study Table 1 as you do the following problems to see if your conclusions make sense.
If there is anything about organic chemistry that requires memorization, it is learning
the relative magnitudes of pKa values.
3.28. Predicting Acidity: The First Step
Write out the reaction for HF acting as an acid. Write out the reaction for H2 O
acting as an acid.
3.29. Predicting Acidity: The First Step*
For the two reactions in the last problem, which anion is most easily able to accommodate the negative charge? HINT: Use periodic position.
3.30. Predicting Acidity: The First Step**
Based on your answer to the last problem, which material, HF or H2 O is the strongest
acid?
3.31. Predicting Acidity: The First Step
Which is the strongest acid, NH3 or H2 O?
3.32. Predicting Acidity: The First Step
Which is the strongest acid, CH4 or NH3 ?
3.33. Preparation of Alkyne Anions
Alkyne anions are generally produced by reaction of the alkyne with NaNH2 . Will
this work with 2-butyne? Why or why not? HINT: We will return to why an alkyne
with a proton on the carbon of the triple bond is a stronger acid than a proton on a
alkane carbon.
3.34. Predicting Acidity: The First Step
There are several important factors in determining the acidity of an HX compound
as X varies around the periodic table. One of these is the stability of negative charge
on the resultant X– species. We have been using that in the last few problems. The
second is the bond strength of the HX bond, which, after all, must be broken in the
acidity reaction. The first row elements have bond strengths that are about equal,
so we can ignore the second feature as long as our acids are in the first row, as we
have been doing. But when we go down the table, bond strengths tend to get weaker.
Chm 222, Section 1
Exercise Set 3
3.45
6
Assume for the moment that the bond strength factor is the only consideration (and
that it gets weaker as we go down the table). Which would be the strongest acid,
HCl or HF?
3.35. Predicting Acidity: The First Step*
Of the two factors discussed in the last problem, bond strength has more effect than
electronegativity when you compare acids related vertically in the periodic table.
Which is the strongest acid, NH3 or PH3 ?
3.36. Relative Acidity
Which of the following can be significantly deprotonated by OH– ? H2 S, C6 H5 CH3 ,
CH3 NH2
3.37. Acidity Rule One
What is the first thing you consider in deciding relative acidity?
3.38. Acidity and Reactions
In an attempt to synthesize 1, Boniface Beebe, the esteemed natural philosopher from
rural Arkansas, reacted one mole of ethyl Grignard with one mole of HC(O)C(O)OH,
glyoxylic acid, then added acid. Was his product 1? If not, what did he make? HINT:
You have learned the Grignard reaction, but acid/base reactions, proton transfers
(especially involving-OH bonds), are generally much more rapid than other kinds of
attacks. So think acid/base before you think other nucleophilic chemistry.
3.39. Relative Acidity
Rank each of the following sets in order of increasing acidity.
A. NH3 , H2 O, H2 S
B. CH3 OH, CH3 NH2 , CH3 CH3
C. HBr, HF, NH3
3.40. Concepts for Acidity*
What is the only acidity factor important in the rankings in the last problem?
3.41. Reactions Review
What kind of product results from the attack of BH–4 on a ketone?
3.42. Reactions Review
What kind of product results from attack of hydroxide ion on an aldehyde?
3.43. Reactions Review
What kind of product results from attack of ozone on an alkene, followed by treatment
with Zn?
3.44. Synthesis Review
From what would prepare an alcohol? How?
Chm 222, Section 1
Exercise Set 3
3.54
7
3.45. Synthesis Review
Give an example of the synthesis of an alcohol from a ketone in which the number of
carbon atoms in the alcohol is greater than that in the ketone.
3.46. The Direction of an Acid/Base Reaction
Will these reactions take place (significantly) to the right?
NH–2 + propyne = NH3 + propyne anion
H2 O + F– = HF + OH–
HS– + NH3 = H2 S + NH–2
CH4 + OH– = CH–3 + H2 O
H2 S + OH− = HS− + H2 O
3.47. Hybridization Review
What is the hybridization of C in C2 H6 , C2 H4 , and C2 H2 ?
3.48. Character of C-H Bond*
What is the amount of “s character” in each carbon of the last problem? HINT: I
am looking for a percent of the bond from C to H that is “s.”
3.49. Carbon Atom Toleration of Negative Charge**
In a carbon atom, what orbital is more stable, 2s or 2p? In which orbital would a
free electron prefer to be?
3.50. Carbon Atom Toleration of Negative Charge***
Given your answers to the last two problems, which of the compounds in problem 47
can tolerate a negative charge most readily?
3.51. A First Rule Corrollary
What element tolerates negative charge best, F or C? What “kind” of C tolerates
negative charge best?
3.52. Application of Corrollary
Which species in problem 47 is the strongest acid?
Chm 222, Section 1
Exercise Set 3
3.63
8
3.53. Relative Acidity
Will butyl lithium react with propyne? To produce what?
3.54. Relative Acidity
Will methyl Grignard react with propyne? To produce what?
3.55. Formation of a “C− ” Reagent*
In the last two problems you start with a “C− reagent. What kind of reagent do you
make?
3.56. Acid/Base, Epwa, Mechanism, and Reactions
Propyne is treated first with butyl lithium, then with 2-butanone, finally with dilute
H+ . Write a mechanism for the reaction and show final products. HINT: To be able
to solve this kind of problem (albeit of increasing complexity) is the aim of organic
chemistry courses.
3.57. Acidity of a Alkyne and the Resulting Reagent
Propyne is treated with butyl lithium. What happens? What kind of reagent have
we made? Like any compound of this type, it wants to find a center that is polarized
how?
3.58. Acidity of a Alkyne and the Resulting Reagent
Propyne is treated with butyl lithium. What kind of reagent have we made? This
reagent that we produced is then added to oxirane (the epoxide of ethylene, a cylic
compound), C2 H4 O. Finally the solution is treated with H+ to neutralize charge.
What is the product? Give a mechanism. HINT: Always make a Lewis structure of
your reagents as you think about things.
3.59. Learning Organic Chemistry*
Relate the process in the reaction in the last problem to some other reaction you have
seen. HINT: Always.
3.60. Plunging Forward with Epwa, Mechanism, and Reactions**
Let’s repeat the process in problem 58. This time we do the same process but do not
add acid. Instead, we add more oxirane, C2 H4 O, and then, after some time, dilute
hydrogen ion. What now is the product? Give a mechanism with epwa. HINT: Look
at what you can do with epwa!
3.61. The First Rule and Corrollary
State the first rule of acidity and its corrollary.
3.62. Learning Organic Chemistry
Propyne is mixed with NaNH2 and the mixture is added to acetone; after some time,
H+ is added. Use epwa to find the products. Show the mechanism.
Chm 222, Section 1
Exercise Set 3
3.74
9
3.63. Predicting Acidity: The Second Step
Write the reaction in which H2 S acts as an acid. Write the reaction in which HS–
acts as an acid.
3.64. Predicting Acidity: The Second Step*
Examine the reactions of the last problem and determine whether H2 S or HS– is the
strongest acid. State your reasoning.
3.65. Relative Acid Strength
Which is the strongest acid, (C2 H5 )2 NH+
2 or (C2 H5 )2 NH?
3.66. Relative Base Strength*
Which of the two substances in the last problem is the strongest base?
3.67. Relative Acid Strength
Will the following reaction occur significantly to the right?
O2− + HF = OH– + F−
3.68. Relative Acid Strength
Which is the strongest acid, HOC(O)C(O)OH or HOC(O)C(O)O– ?
3.69. Second Acidity Rule
Using the results of the last several problems, state the second rule for acidity.
3.70. Acidity Rules
What are the first two rules for acidity?
3.71. Relative Basicity
NaH reacts with CH3 CH2 OH (to produce?) but not with CH3 CH3 . What is the order
of base strength of H− , CH3 CH2 O– , and CH3 CH–2 ? HINT: Write reactions.
3.72. Relative Acidity
Malonic acid is HOC(O)CH2 C(O)OH. It can give up two protons relatively readily; one has a pKa of 2.86, the second a value of 5.7. Comment. HINT: A useful
comparison would bring in the value(s) of other species, such as, for example, acetic
acid.
3.73. Relative Acidity
Write Lewis structures for P(CH3 )3 and P(CH3 )+
4 . If these materials are to act as
acids, what kind of bond must break? Which of the two is the strongest acid? HINT:
Whenever you answer an acidity problem you should be deciding what rule you are
using.
Chm 222, Section 1
Exercise Set 3
3.82
10
3.74. A Nucleophilic Substitution
Is there an position in the molecule CH3 I that is positively polarized? Let Br– , acting
as a nucleophile, attack CH3 I. This starts to form a new bond from bromide to the
carbon (use epwa to see this), but carbon cannot have five bonds, so at the same
time, the electrons in the bond to the iodine atom must be leaving carbon and going
to the iodine. Use epwa to show this also. These two things happen at the same time,
so draw one epwa showing both. What is the net chemistry?
3.75. A Nucleophilic Substitution: SN 2
The attack described in the last problem occurs with the bromide ion coming toward
the CH3 I as far away from the iodine atom as possible. Why might this be true?
NOTE: In addition to the obvious reason you just gave, it is also true that the
bromide is looking for an empty orbital on the CH3 I in which to put its electrons.
The lowest empty orbital is the σ* level of the C-I bond, which is more concentrated
on the carbon.
3.76. A Characteristic of SN 2 Reactions
The process you just described in the last problem requires that the C-I bond break.
Hence these so-called SN 2 reactions are more facile when there is a good “leaving”
group. Generally, as we shall see repeatedly later, good leaving groups are, generally,
poor bases. Which would be the best leaving group, I– or Cl– ?
3.77. Leaving Groups
Which would you guess is the best leaving group, Cl– or OH– ?
3.78. Deduction of a Reaction
Triphenylphosphine is a molecule with a lone pair of electrons. (“Phenyl” is the name
for C6 H–5 ; so chlorobenzene, C6 H5 Cl could also be called phenyl chloride.) Draw a
Lewis structure to show this. If it is to react with something as a nucleophile, what
will that lone pair of electrons look for? Where in 1-butyl bromide is that kind of
thing? Use epwa to show the reaction of triphenylphosphine with 1-butyl bromide;
be sure to indicate the product. HINT: Use the last couple of problems.
3.79. Bonds to Carbon
How many bonds does carbon usually make? Does your product in the last problem
agree with this?
3.80. Bonds to Carbon
Review from Problem Set One. Carbon makes four bonds unless it is . . . .
3.81. Bonds to Carbon
When a carbon is charged positively, how many bonds does it make? When a carbon
is charged negatively, how many bonds does it make? If the answers are not evident
to you, draw Lewis structures and be sure.
Chm 222, Section 1
Exercise Set 3
3.90
11
3.82. Acidity and Deduction of a Reaction
What kind of charge does the product molecule of problem 78 have? What does that
charge do to the acidity of a C-H bond next to it? What kind of reagent is ethyl
lithium? HINT: There are two answers; give both. What happens if you treat the
product of the last problem with the base ethyl lithium? Use epwa. HINTS: (1)
Remember, generally speaking, proton transfers to a good nucleophile (base) are fast
compared to other nucleophilic attacks. (2) The product of this reaction is said to
be a “zwitterion,” meaning it has both negative and positive charges in the same
–
molecule. An earlier example of this that you have seen is NH+
3 CH2 C(O)O . Draw
the Lewis structure of this and convince yourself it is reasonable.
3.83. Deduction of a Reaction*
The product of the reaction in problem 82 is a “C− ” reagent of sorts. Given that is
true, deduce what the result is if that “C− ” reagent reacts with propanal? Use epwa.
3.84. Finishing a Reaction**
The product of the last problem can rearrange to form the very stable h P+ -O− ,
P=O i bond. No matter what pair of electrons you use to do this, sticking to the
four bonds to carbon rule, you will end up with an alkene. Use epwa to show this.
3.85. Preparing for a Synthesis***
Take your product from the last problem and color the atoms that were originally
in the aldehyde one color and those that were originally in the butyl bromide another. Draw a line between the two colors. That is how you determine what starting
materials are necessary to make a given alkene.
3.86. Synthesis
From what compounds would you synthesize 3-methyl-2-pentene? HINT: Draw the
structure of the desired product and draw the “retrosynthetic” line you established
in the last problem. What fragments do you have? Now note one fragment started
as an aldehyde or ketone and the other as an alkyl bromide (or chloride or . . . ). Use
epwa from those starting materials to establish everything is OK.
3.87. Synthesis
How would you synthesize 2-ethyl-2-hexene? Use epwa. HINT: Generally, because
the SN 2 reaction in the first step of this process occurs much more easily on a primary
alkyl halide, that is the issue that determines which side of the retrosynthetic line is
the original carbonyl and which side is the halide.
3.88. Synthesis
How would you synthesize 4-octene?
3.89. Synthesis Summary
From what kind of compounds do you make alkenes?
Chm 222, Section 1
Exercise Set 3
3.102
12
3.90. Synthesis Summary
What is one way to make alkenes? HINT: Alas, there will be other methods we will
learn.
3.91. Nucleophiles
Which do you think is the better nucleophile, (CH3 )3 P or (CH3 )2 S? Why?
3.92. Synthesis of a Good Acid
How would you prepare (CH3 )3 S+ from (CH3 )2 S and CH3 I?
3.93. Relative Acidity
Why is (CH3 )3 S+ a better acid than (CH3 )2 S?
3.94. Relative Acidity
A strong enough base will surely deprotonate (CH3 )3 S+ . What base might you use?
3.95. Deducing a Reaction
Use epwa to write the chemical reaction of (CH3 )3 S+ with a strong base.
3.96. Deducing a Reaction*
What kind of reagent have you made in the last problem? HINT: We are mostly
concerned with interesting carbon fragments in this course.
3.97. Deducing a Reaction**
Write a mechanism for the reaction of the product of the last problem with propanone.
3.98. Deducing a Reaction***
The product of the last problem is again a zwitterion, with the negative oxygen atom
separated from the positive sulfur. Sulfur is not a good atom to be positive, but
because the affinity of sulfur for an oxygen atom is considerably less than the affinity
of phosphorous for oxygen, it turns out that we need to find another atom for the
negative oxygen to attack that will still move charge to sulfur. Since epwa only occurs
over short distances, there is only one choice. Do it.
3.99. Preparing for Synthetic Thought****
Take the product from the last problem and color the atoms that were originally in
the propanone with one color and those that were originally in the CH3 I with another
color. Draw a line between those two sets of color. that is how you figure out what
molecules are needed to make the oxirane.
3.100. Synthesis
What starting materials would you use to make 1a (several pages previous)?
3.101. Synthesis
What starting materials would you use to make 1b (several pages previous)?
Chm 222, Section 1
Exercise Set 3
3.111
13
3.102. Review of Two Syntheses
What acidity feature do we take advantage of in order to synthesize alkenes and
oxiranes?
3.103. Review
Give the first two rules of acidity.
3.104. Separation on Basis of Acidity
Water and dichloromethane are immiscible. Butanoic acid has a pKa of about 5.
Butylammonium ion, C4 H9 NH+
3 has a pKa of about 11. We make a mixture of the
two four-carbon species (butanoic acid and butyl amine) in water and adjust the pH as
indicated in what follows. This aqueous solution is then shaken with dichloromethane.
Determine: a. In what range of pH will both materials be found in the water layer?
b. In what range of pH will butanoic acid be in the water layer while the butyl
amine is in the CH2 Cl2 layer? c. In what range of pH will butanoic acid be in the
dichloromethane layer while the ammonium salt is in the water layer? HINTS: (1)
Assume that ions are more soluble in water and neutral molecules are more soluble
in the organic layer. (2) This is a simple problem using the relationship you derived
in problem 10
3.105. Charge and Relative Acidity
On the basis of charge only, which would you expect to be the strongest acid, ethanol
(CH3 CH2 OH) or NH+
4 ? Write the reactions that show the acidity of each.
3.106. pKa and Relative Acidity*
The pKa of the two materials in the last problem are 15.9 and 9.2, respectively.
Which is the stronger acid? How would you apply the first two rules of acidity to this
comparison?
3.107. Charge and Relative Acidity**
On the basis of the nature of the element and charge, which compound, acetic acid,
CH3 C(O)OH, or NH+
4 would you expect to be the strongest acid? HINT: You might
use what you just learned.
3.108. Relative Acidity***
The pKa of the two materials in problem 107 are 4.7 and 9.2, respectively. Which is
the stronger acid?
3.109. Relative Acidity****
In problem 105 charge was sufficient to overcome the nature of the element carrying
the negative charge. In problem 107, it was not. What is special about the compounds
(actually, only one of the compounds) in problem 107 causes this change?
3.110. The Third Rule for Acidity
What is the third rule for acidity?
Chm 222, Section 1
Exercise Set 3
3.113
14
Figure 1: Reaction coordinate curves for two acids, HA and the resonance stabilized
HB.
3.111. The Third Rule
Consider the acidity of two arbitrary compounds HA and HB (that is NOT boron):
HA = H + + A−
HB = H + + B −
where we assume that the hydrogen atom is attached to the same element with the
same charge (What does that say about acidity rules one and two?). If there is
resonance stability in HB, but not in HA, then HB is stabilized. Will HA or HB be
the stronger acid? See Figure 1.
3.112. The Third Rule
Consider the acidity of two arbitrary compounds HC (that is NOT carbon) and HD
(and that is NOT deuterium):
HC = H + + C −
HD = H + + D−
where we assume that the hydrogen atom is attached to the same element with the
same charge (What does that say about acidity rules one and two?). If there is
resonance stability in D− , but not in C− , then D− is stabilized. Will HC or HD be
the stronger acid? See Figure 2.
Chm 222, Section 1
Exercise Set 3
3.118
15
Figure 2: Reaction coordinate curves for two acids, HC and HD; the conjugate base
D− is resonance stabilized.
3.113. The Third Rule
Articulate what you have to do to find out if an acid is stronger or weaker because
of resonance. HINT: Many, many students look at a problem, see resonance, and say
“That is the stronger acid.” To me, that sounds like something Boniface Beebe would
say!
3.114. The Third Rule
Consider the same two compounds as in problem 111. If both HA and HB are
resonance stabilized, what would you do to determine which is the stronger acid?
HINT: Nothing beats thinking.
3.115. The Third Rule
Consider the same two compounds as in problem 111. If both HA and A− are resonance stabilized, what would you do to determine whether HA or HB is the stronger
acid? HINT: Same as last problem.
3.116. Site of Basicity
Consider N-methyl-ethanamide, CH3 C(O)NHCH3 . It is treated with a strong acid.
Where will it protonate? HINT: Write the Lewis structure (as usual) and consider
any resonance (as usual).
3.117. Site of Basicity
If you brought H+ up to CH3 CH3 , where could it protonate? HINT: Trick question!
Chm 222, Section 1
Exercise Set 3
3.130
16
3.118. Site of Basicity
If you brought H+ up to CH2 CH2 , where could it protonate? HINT: Not a trick
question. Think about loosely held electrons for the hydrogen ion to use to bond.
3.119. pKa and Relative Acidity, Review
Which is the stronger acid, pyruvic acid (pKa = 2.49) or lactic acid (pKa = 3.08)?
3.120. Relative Basicity, Review
Which is the stronger base, pyruvate anion or lactate anion? HINT: See last problem
for pKa s.
3.121. Relative Acidity Coupled with Relative Basicity, Review
If HX and HY are two acids, formulate a statement about their relative strengths
(You can make up anything you like) and then make the corresponding conclusion
about the relative basicity of X− and Y− .
3.122. Reactions and Learning Organic Chemistry
What do you need to do to convert lactic acid into pyruvic acid? In nature, an enzyme
called lactate dehydrogenase catalyzes this interconversion. HINT: You should have
looked up the structures in problem 119, but if you didn’t, now is the time. Thinking
this way is an easy way to remember what those two acids are.
3.123. Acidity Rules
What are the first three rules for acidity? Also, state the corollary for rule one.
3.124. The Fourth Rule
The Ka of 2-chlorobutyric acid (2-chlorobutanoic acid) is 1.39 x 10−3 . Why is this
value greater than the Ka of butyric acid (butanoic acid)? NOTE: This effect on
acidity, the least important of the four we have, is called the “inductive effect”.
HINT: Don’t use it to answer questions until the first three rules yield no difference.
3.125. Predicting Ka and pKa *
Given the result in the last problem, predict the Ka of 3-chlorobutyric acid (3chlorobutanoic acid). HINT: The pKa of butyric acid is 4.82.
3.126. Predicting pKa
Predict the pKa of acetic acid (ethanoic acid) given the value for butyric acid in the
last problem.
3.127. The Factors Influencing Acid Strength
What are the four factors (and the corollary) that influence acidity?
3.128. Conjugate Acids and Bases
What is the conjugate acid of 3? The conjugate base?
Chm 222, Section 1
Exercise Set 3
3.135
17
3.129. Relative Acidity, Review
Which is the strongest acid, CH3 CH(SH)CH3 or CH3 CH(OH)CH3 ?
3.130. Relative Acidity, Review
Which of the following reactions takes place extensively to the right?
CH3 CC– + CH3 CHCH2 = CH3 CHCH– + CH3 CCH
CH3 CH2 OH + CH3 C(O)O– = CH3 CH2 O– + CH3 C(O)OH
3.131. What Is Written
I read in an organic chemistry text about the factors that influence acidity. They
were, in the order listed: Hybridization, electronegativity, inductive effect, resonance,
hydrogen bond, and aromaticity. What do you think?
3.132. Strange Acidity?
nitromethane, (CH3 )NO2 , releases H+ to make (CH2 )NO–2 with a pKa of 10. From
the Lewis structure (which you drew, right?) the hydrogen ion had to come from the
carbon atom. Is this more or less acidic than a “normal” C-H bond?
3.133. Strange Acidity Must Have a Reason*
Why is this C-H bond in the molecule in the last problem so acidic? HINT: You know
what I am going to say; if not, it involves a pencil.
3.134. Strange Relative Acidity
Diethyl malonate ester is CH3 CH2 OC(O)CH2 C(O)OCH2 CH3 . It can give up a proton
with a pKa of about 9. Why should this “C” acid be so much stronger than, say,
C3 H8 with a pKa of about 50?
Chm 222, Section 1
Exercise Set 3
3.141
18
3.135. Epwa, Mechanism, and Acidity
Many processes in organic chemistry are catalyzed by H+ and/or OH− . These generally involve acid/base reactions. See if you can provide a series of steps (a mechanism),
with epwa, that account for the reaction below, which is catalyzed by OH− . HINT:
Hydroxide ion is a base, which will react with an acidic hydrogen atom. Find a site
in the molecule where you need to break a bond to hydrogen. Start there and then
proceed.
3.136. Nucleophilicity is Sometimes Related to Basicity
What makes a good base often makes a good nucleophile. So OH– is a better nucleophile than F– , just as is true for basicity. However, a second important factor for
nucleophiles is the ease of polarization of the electrons, so generally speaking, species
further down the table are better nucleophiles, even though they are not as good as
bases: I– is a better nucleophile than F– . Which would you imagine is a better base,
OCH–3 or SCH–3 ? Which is the better nucleophile?
3.137. Nucleophilicity
Order the following in terms of increasing C− nucleophilicity: ethyl Grignard, ethyl
lithium, and 4. HINT: Use the periodic table to figure out which metal-carbon bond
is polarized the most.
3.138. Nucleophilicity
Good nucleophiles are often strong bases. Articulate (try for less than five words)
how you would prepare a good nucleophile.
3.139. Epwa, Reaction Prediction, and Learning Organic Chemistry
The compound 4 is a weak C− reagent. It will not react with ketones or aldehydes,
but does react with acid chlorides, compounds of the type RC(O)Cl to produce a
ketone. Use epwa to suggest a mechanism. HINT: After your first step you should
have a tetrahedral carbon with an atom of good leaving ability, i.e., a weak base.
Which would that be? Let it leave, driven by a negative oxygen atom making a
strong C=O double bond.
3.140. Epwa, Reaction Prediction, and Learning Organic Chemistry
Consider CH3 C(OH)2 CH3 in acid solution. Where on this molecule would a proton
sit? Does that change a group from a poor leaving group (strong base) into a good
leaving group (i.e., a weak base)? If that good leaving group does leave, what do you
have? Can you move the positively charged site on this compound to a site where a
hydrogen ion could leave to produce a neutral compound. Use epwa to show all of
these steps (four epwas, I think).
Chm 222, Section 1
Exercise Set 3
3.154
19
3.141. Reactions with Epwa, Review
What is the product of butanal with ethyl Grignard? HINT: No acid is added at the
end.
3.142. Reactions with Epwa
What is the product of butyric acid with excess methyl lithium? HINT: No acid is
added at the end. HINT: Methyl lithium, in contrast to methyl Grignard, is a very
powerful C− reagent.
3.143. Reaction Prediction and Learning Organic Chemistry
Use the information from problem 140 to establish what happens when the product
of the last problem is treated with H+ .
3.144. Formulating a Synthesis
What kind of compound is 2-methyl-2-butanol?
3.145. Formulating a Synthesis*
From what kind of compound can you make the kind of compound that 2-methyl-2butanol is?
3.146. The Synthesis**
How would you make 2-methyl-2-butanol from 2-butanone? Use epwa.
3.147. Formulating a Synthesis
How would you make 2-butanol from 2-butanone?
3.148. Formulating a Synthesis
What kind of compound is 2-methyl-1-butene?
3.149. Formulating a Synthesis*
From what kind of compound can you make the kind of compound that 2-methyl-1butene is?
3.150. The Synthesis**
How would you make 2-methyl-1-butene from 2-butanone? Use epwa.
3.151. Synthesis
How would you prepare 2-methyl-2-butene?
3.152. Reactions
Compound 5 is treated with excess ethyl lithium, then acid. What is the product?
3.153. Reactions
Compound 6 is treated with ethyl Grignard, then acid. What are the products?
HINT: Note the verb tense and that the noun is plural; in this case I really want all
the products.
Chm 222, Section 1
Exercise Set 3
3.161
20
3.154. Relative Acidity
The compound 7 is a stronger acid than 8 by a factor of about 40. Suggest a reason.
HINT: It is not the electron withdrawal by the -OH group; but it is a favorite topic
of biologists.
3.155. Relative Acidity
Which is the stronger acid, 9 or 10? HINT: Go through the rules.
3.156. Relative Acidity
Compound 11 is a stronger acid than a normal amine. Suggest a reason.
3.157. Relative Basicity
If you brought a proton up to CH3 CH2 CH(OH)CH3 , where would you expect it to
“sit”? Use epwa to show.
3.158. Consequence of Protonation*
When the compound of the last problem is protonated, does that turn some group
into a better leaving group? What is changed to a better leaving group?
3.159. Leaving Group Ability**
Why is H2 O a better leaving group than OH– ?
3.160. Driving Out the Leaving Group***
For the -OH+
2 group attached to C-2 of the carbon chain in problem 157 to leave, C-2
must gain some electrons. One place for those to come from is the pair of electrons
in a C-H bond of C-3. Use epwa to show how those electrons can form a C-2 to C-3
double bond, release a proton, and satisfy the positive charge polarization on C-2 (or
on the oxygen, depending on how you look at it).
Chm 222, Section 1
Exercise Set 3
3.173
21
3.161. Classifying–The Type of Process****
What would we call the process of the last several problems: a substitution, an
addition, a subtraction?
3.162. Forming Alkenes
How many ways do we know to form alkenes? Name them. In your mind (or, better,
on paper) outline the important steps in those pathways.
3.163. Epwa and Reaction Mechanism
Write the mechanism for the formation of 2-methylpropene from propanone and
methyl iodide using a Grignard reaction and, at the end, strong acid. HINT: More
than one step.
3.164. Synthesis
Outline a synthesis of 2-methylpropene starting with 2-propanol and methyl iodide.
HINT: Multi-step.
3.165. Synthesis
What kind of compound is 12?
3.166. Synthesis*
From what kind of compounds do you form 12?
3.167. Epwa, Mechanism, and Synthesis
Write the mechanism for the synthesis of the epoxide 12.
3.168. Epwa, Mechanism, and Reactions
Propyne is treated with butyl lithium. What kind of reagent have we made? If you
brought that kind of reagent up to 1-bromobutane, what is going to happen? What
is the product? Give a mechanism with epwa. HINT: No more than four bonds to
carbon.
3.169. Mechanistic Restrictions
What alkyne anion and what alkyl halide would you use to prepare 16? Is that your
only choice? Why or why not?
3.170. Type of Compound
What kind of compound is 17?
3.171. How Do We Get a ...?*
From what compound(s) would you prepare the kind of compound that 17 is?
3.172. Synthesis**
Outline the steps in a synthesis of 17 from acetylene and other compounds.
Chm 222, Section 1
Exercise Set 3
3.181
22
3.173. Relative Acidity and Leaning Organic Chemistry
What are the factors that determine acidity? How many are there? Give an example
where each causes one compound to be more acidic than another.
3.174. Relative Acidity and Leaning Organic Chemistry
Discuss with another student the fundamental reason(s) for the importance of each
of the factors in the last problem.
3.175. Relative Acidity
What factors are important in determining if 13 or butyric acid is the strongest acid.
HINTS: This is a question requiring thought; there may be several factors, perhaps
not all working in the same direction. The process is more important than the answer.
3.176. Relative Acidity
Propanone has a pKa of about 22, whereas 2,4-pentanedione has a pKa of about 9.
Show your knowledge with an intelligent comment.
3.177. Relative Acidity
Which is the strongest acid, 13 or 14? Why?
3.178. Reactions
What is the product of the reaction of 1-chlorobutane with acetylide anion?
3.179. Reactions
What is the product of the reaction of acetylide anion with 2-pentanone, followed by
acid?
3.180. Stability for an Empty Orbital
Imagine CH+
3 . How many atoms is the carbon bonded to? What hybridization would
you invoke to explain the bonding? What orbital is left over? How many electrons
in that orbital? What is the shape of the molecule?
Chm 222, Section 1
Exercise Set 3
3.191
23
3.181. Stability for an Empty Orbital*
In the CH+
3 from the last problem, what kind of orbital on the H is necessary to donate
electrons to the empty orbital on the carbon atom? Is such an orbital available on a
hydrogen atom?
3.182. Stability for an Empty Orbital
If you consider CH2 (NH2 )+ , a three-coordinate carbon compound, does the bonded
-NH2 group have an orbital of the correct symmetry to bond to the empty orbital
on the carbon? Make a sketch showing this interaction. Draw the equivalent Lewis
structure.
3.183. Stability for an Empty Orbital*
Given your answer to the last problem, what is one way to stabilize a positive charge
on a carbon atom?
3.184. Stability for an Empty Orbital
Draw the Lewis structure of CH2 X+ where X is a vinyl group, -CH−CH2 . Does the
vinyl group have an orbital of the correct symmetry to bond to the empty orbital?
Make a sketch showing this interaction. Draw the equivalent Lewis structure.
3.185. Stability for an Empty Orbital
If you consider CH2 (CH3 )+ , a compound with a carbon bonded to two hydrogen
atoms and a -CH3 group, does the bonded -CH3 group have an orbital of the correct
symmetry to bond to the empty orbital? Careful. This is a little tricky. Make a
sketch showing this interaction (which clearly implies an answer to the last question).
Draw the equivalent Lewis structure, which you will not like because it contains a
“no-bond” structure. NOTE: This kind of stability of a carbocation is known as
“hyperconjugation”.
3.186. Stability for an Empty Orbital
Given the last four problems, what are ways to stabilize a positive charge on a carbon
atom?
3.187. Stability of Carbocations
Which of the cations 18-20 are stabilized by adjacent double bonds? Use epwa to
prove your point.
3.188. Resonance Stability
Which of the cations 18-20 has the most resonance stability? Why?
3.189. Stability of Cations
Which cation, 21 or 22 is most stable?
3.190. Stability for an Empty Orbital
What are three ways to stabilize a positive charge?
Chm 222, Section 1
Exercise Set 3
3.201
24
3.191. Subtle Resonance Stability
Which cation, 19 or 23 is most stable? HINT: Look carefully at the resonance
structures that you drew. You did draw them, didn’t you?
3.192. Stability of Cations
Which cation, 24 or 25 is most stable?
3.193. Learning Organic Chemistry
What factors influence the stability of carbocations?
3.194. Reactions and Chemical Intuition
What is the product of the reaction of 12 with acetylide anion, followed by treatment
with dilute acid? HINT: A new wrinkle here: Which side will be attacked? Find a
reason to prefer one side over the other.
3.195. Using Knowledge to Predict Reactions*
If you treat the product of the last problem with NH–2 and then with more 12, what,
if there is one, is the product?
3.196. Learning Organic Chemistry
Review your notes from the last lecture. How many topics were covered? How are
they interconnected? How do they relate to what has proceeded them in the course?
Talk to another student about those connections.
3.197. Reactions
Compound 26 is treated first with ethyl magnesium bromide, then with a weak acid.
What is the final product?
3.198. Reactions and Resonance Stability*
Compound 26 is treated first with ethyl magnesium bromide, then with strong acid.
What is the final product? HINT: Surely something is different here relative to the
last problem (or your are forced to the unmentionable alternative about my marbles).
3.199. Reactions**
Compound 27 is treated first with ethyl magnesium bromide, then with acetic acid,
a weak acid, but not as weak as NH+
4 . What is the final product?
3.200. Reactions and Learning Organic Chemistry***
Express the difference for the reactions in last three problems. Formulate how you
will solve problems in the future to take these issues into consideration.
Chm 222, Section 1
Exercise Set 3
3.209
25
3.201. Stability and the Double Bond
Draw the Lewis structure of propene. Now draw a minor resonance structure in which
a pair of electrons in a C-H bond of the -CH3 group makes a double bond between the
-CH3 carbon and one of the vinyl carbon atoms. HINT: Remember to keep carbon to
four bonds or less. This resonance is not present when the double bond is attached
only to hydrogen atom substituents; hence stability of a double bond is obtained by
substitution of a methyl group (or other alkyl group) for a hydrogen atom.
3.202. Quantitative Stability Considerations of Double Bonds
The heat of hydrogenation of an alkene (heat absorbed by the compound at constant
pressure when H2 reacts with it) of 1,3–pentadiene is -222.6 kJ/mole and that of
1,4-pentadiene is -253.1 kJ/mole. Which is most stable; by how much, and why?
HINT: The negative sign means that heat is really released, not absorbed; that is,
the products are more stable than the reactants. So if you make a diagram (which is
always the safe thing to do in stability problems), the alkanes are below the alkenes.
Note also the alkane is the same in both cases.
3.203. Quantitative Stability Considerations of Double Bonds
The heat of combustion (heat absorbed by the system at constant pressure when the
compound reacts with O2 to produce CO2 and H2 O) of 1,3–pentadiene is -3010.7
kJ/mole and that of 1,4-pentadiene is -3041.2 kJ/mole. Which is most stable; by how
much, and why?
3.204. Quantitative Stability Considerations of Double Bonds
The heat of isomerization to spiropentane, 28, of 1,3–pentadiene is 109.3 kJ/mole
and that of 1,4-pentadiene is 78.8 kJ/mole. Which of the dienes is most stable; by
how much, and why? HINT: Are products up or down?
3.205. Quantitative Stability Considerations of Double Bonds*
Compare your answers to the last three problems. Why are they the same? What is
the difference in the three treatments. HINT: Ever hear of the “freedom to choose a
zero of energy”?
3.206. Resonance Stability
Compare the resonance in benzene with that in butadiene. Which is most important?
Why?
3.207. Resonance Stability
Draw the resonance structure present in acetate anion, CH3 C(O)O– . Compare it to
any resonance in acetic acid, CH3 C(O)OH. Which is most important? Why?
3.208. Synthetic Thinking
What kind of compound is 29? HINT: There are two answers.
Chm 222, Section 1
Exercise Set 3
3.217
26
3.209. Synthetic Thinking*
From what kind of compound do you make the kind of compound that 29 is? HINT:
There are still two answers but one of them is problematic because of that -OH group,
which often give trouble: WHY?
3.210. Synthetic Thinking
Do we need to add carbons to acetone in order to make 29 from it? How many?
3.211. Synthesis*
How would you prepare 29 from 30 and acetone?
3.212. Synthesis
How would you make 4-methyl-2-pentene?
3.213. Reactions and Predictive Thought
Boniface Beebe, the famous chemist from rural Arkansas, reacted (C6 H5 )2 (CH3 )P
with ethyl iodide. He took the product of this reaction, treated it with butyl lithium,
and then added acetone. Much to his surprise, he isolated two products containing
only C and H. “Leapin’ lizards,” he shouted, “what are those products? Why are
there two products?” And you would answer?
3.214. Reasoning Like an Organic Chemist*
Generalizing from the last problem, when might there be multiple products in a
Wittig or sulfur ylide synthesis?
3.215. NMR Review
Consider the five compounds: cyclohexane, cyclopropane, ethane, 2,3-dichlorobutane,
and 31. One of these has one signal in the 1 H nmr and two signals in the 13 C nmr
spectra. Which is it?
3.216. Carbon Level
Generally speaking, what kind of reagent changes a compound from carbon level 2 to
carbon level 1?
Chm 222, Section 1
Exercise Set 3
3.229
27
3.217. Carbon Level
Generally speaking, what kind of reagent changes a compound from carbon level 1 to
carbon level 2?
3.218. Synthetic Thinking
What kind of compound is 1-pentene?
3.219. Synthetic Thinking*
From what kind of compound(s) do you prepare the kind of compound that 1-pentene
is?
3.220. Synthetic Thinking**
Do we have to add carbon atoms to butanal to make 1-pentene? How many?
3.221. Synthesis***
How would you make 1-pentene from methyl iodide and butanal?
3.222. Synthesis
How would you prepare 32 from 2-bromopropane and 3-methyl-but-2-enal?
3.223. Always Question Your Synthesis*
In the last problem, there is are two possible routes in the last step. Why is the one
you want the most efficient path?
3.224. Always Wonder!**
Is there a synthesis of 32 other than that you suggested in the last problem? If so,
what is it? Which synthesis would you use? Why?
3.225. Epwa, Mechanism, and Projected Thinking
When a ketone is treated with diazomethane, one resonance structure of which is
given in 33, an oxirane is sometimes formed. See if you can epwa (verb usage) your
way through a mechanism. HINT: Firstly, identify a “C− ” reagent to attack the
carbonyl. Then look for a very good leaving group in the intermediate that you form.
This leaving group leaves because it is not only energy driven but entropically driven,
that is, forms a gas.
3.226. Synthetic Thinking
What kind of compound is 2-pentene?
3.227. Synthetic Thinking*
How do we prepare compounds of the type that you gave as your answer to the last
problem? HINT: Duh?
3.228. Synthetic Thinking**
Do we need to add carbon atoms to compounds with three carbons in order to make
2-pentene?
Chm 222, Section 1
Exercise Set 3
3.240
28
3.229. Synthesis***
How would you prepare 2-pentene from compounds with three carbon atoms or less?
3.230. Learning Organic Chemistry
Without looking, go through the steps in the last several problems that establish a
conceptual method for you to think about the synthesis of a compound. HINT: This
is one of the important exercises of the semester.
3.231. Synthetic Thinking
What kind of compound is cyclohexene?
3.232. Synthesis*
Give two methods of preparing cyclohexene, one starting with and the other starting
without, the ring structure.
3.233. Synthesis
We have (at this stage) two ways to make an alkene. Start with cyclohexanone and
prepare alkenes with formula C7 H12 by each of these methods. Use epwa. What is
the difference between your products?
3.234. Stability of Alkenes
Consider the three compounds, 2,4,7,9-undecatetraene, 2,4,6,8-undecatetraene, and
1,4,6,9-undecatetraene. Which is most stable? Why? HINT: undeca is the name for
an eleven carbon chain.
3.235. Reactions
The ketone, 2-butanone, is reacted with methyl lithium and then with strong acid.
What is the product?
3.236. Epwa and Mechanism*
Write a mechanism for the reaction in the last problem, which is how you should have
solved it in the first place.
3.237. Carbon Level Review
Give the carbon level of the carbon atoms in 12-13.
3.238. Carbon Level Review
Give the carbon level for each carbon atom in 34.
3.239. Synthesis
How would you synthesize 15 from 3-methyl-2-butanone?
Chm 222, Section 1
Exercise Set 3
3.245
29
3.240. Reactions and Reversibility
How would you synthesize 2-methyl-2-butene from 2-methyl-2-butanol? To do so you
would want conditions with low concentration of water to make it easier to remove
that water molecule. How might you make the reverse reaction take place? Would
you need water? Would you need H+ ? HINT: Think backwards, exactly backwards.
There is even a name for that: microscopic reversibility.
3.241. Formulating a Synthesis*
How would you synthesize 2-methyl-2-butanol from 2-methyl-2-butene?
3.242. Reaction Type**
What kind of reaction did you use in the last problem, an addition, . . . ?
3.243. Opening Oxiranes
Why should the oxirane ring be rather easily “opened”?
3.244. Opening Oxiranes
To open the oxirane ring requires that a new group come forward to bond to one of
the two carbon atoms. This attack occurs as the oxygen atom leaves the carbon. Such
a process requires both the oxirane and the incoming group to collide with sufficient
energy to cause reaction. If both the oxygen atom and the incoming group are to be
partially bonded to the carbon atom, we have to use one orbital on carbon to bond to
two atoms. Since the 2p orbital on a carbon atom more easily extends away from the
carbon atom, that is the orbital of preference. What would you imagine is the best
way for two atoms to simultaneously bond to a carbon atom? Make a rough sketch
of this bonding situation. HINTS: (1) Here is a case where you will have five bonds,
or at least five partial bonds, to a carbon atom: an unstable, high energy, transition
state between two normal four-bonded carbon atoms. (2) We have done this reaction
before in the Wittig reaction; we are just looking at it in a slightly different way.
Chm 222, Section 1
Exercise Set 3
3.254
30
3.245. Opening Oxiranes*
From your sketch in the last problem, assess the difficulty in getting a nucleophile
close to the oxirane carbon when it has two hydrogen atoms as its substituents versus
the situation where it has two methyl groups as substituents. NOTE: This is called
steric interference. HINT: You may have discovered this previously: see problem 194.
This will play an important role in the study of SN 1 and SN 2 reactions next semester.
3.246. The Nature of the Products of Opening an Oxiranes
Take methyl-oxirane and open it with SH– , then treat the resultant material with
dilute acid. Will the nucleophile attack one side preferentially? What is the nature
of the product? How would you classify it in generic terms? HINT: Might we (and
only we) call it an α-DIN?
3.247. Opening Oxiranes in Acid
Can methyl-oxirane be protonated? On what site? Draw the Lewis structure of this
material and consider a couple of possible resonance structures. Order your resonance
structures in terms of increasing importance.
3.248. Opening Oxiranes in Acid*
If a protonated methyl-oxygen backs away from one of the two carbons, which carbon
will it leave as the most highly positively polarized?
3.249. Opening Oxiranes in Acid**
Given your result from the last problem, which carbon atom would a nucleophile be
most likely to attack under these acid conditions?
3.250. Opening Oxiranes in Acid
Show that the result of opening an substituted oxirane depends on the acidity of the
medium. Use Br– as a good nucleophile for neutral attack and HBr, which is, of
course, a strong acid and dissociated, for acidic attack.
3.251. Opening Oxiranes
Outline the two competing factors important to consider in the opening of an oxirane.
3.252. Opening Oxiranes
What kind of compound results when an oxirane is opened?
3.253. Epwa, Reactions and Mechanism
The compound 2-butanone is treated with the sulfur ylide, (CH3 )2 S+ CH–2 and product
A is isolated. That material is reacted with ethyl Grignard, followed by dilute acid
to give B. What are A and B? Give the mechanism and use epwa. HINT: Think
about steric issues with this powerful nucleophile.
Chm 222, Section 1
Exercise Set 3
3.268
31
3.254. Epwa, Reactions and Mechanism
The compound 2-pentanone is treated with the sulfur ylide, (CH3 )2 S+ CH–2 and product C is isolated. That material is reacted with bromide ion in the presence of acid
to give D. What are C and D? Give the mechanism and use epwa. HINT: Think
about the role of acid in opening an oxirane.
3.255. Synthetic Thinking
What kind of compound is 35? How do we make the kind of compound that 35 is?
3.256. Worrying about Regioselectivity*
To get 35 we have to open an epoxide the right way. Which way is that? And how
do we open the oxirane that way?
3.257. Synthesis**
Show how you could make 35 and 36 from propanal.
3.258. Reaction and Regioselectivity
What is the product of the reaction of HBr with 37?
3.259. Reaction and Regioselectivity
What is the product of the reaction of HS- with 37?
3.260. Reaction and Regioselectivity
What is the product of the reaction of ethanol with 38 under conditions of sulfuric
acid catalysis?
3.261. Reaction and Regioselectivity
What is the product of the reaction of methoxide ion with 38?
3.262. Reactions
What is the product when (1) methyl iodide is treated with (CH3 )2 S, (2) this product
is treated with butyl lithium, and (3) that last product is added to acetone.
3.263. Synthetic Thinking
What kind of compound is 39?
3.264. Synthetic Thinking*
From what immediate precursor do you synthesize the kind of compound that 39 is?
3.265. Synthetic Thinking**
What kind of compound is the precursor of 39? See last problem.
3.266. Synthetic Thinking***
From what immediate precursor do you synthesize the answer to the last problem?
3.267. Synthesis****
Prepare 39 from butanone and ethyl iodide.
Chm 222, Section 1
Exercise Set 3
3.281
32
3.268. Synthesis
Prepare 40 from butanone and ethyl iodide.
3.269. Review of Carbon Level
Find a three carbon species that has a carbon level of zero at each carbon atom.
3.270. Review of Carbon Level
Find two compounds that contain three carbon atoms and have a carbon atom with
a carbon level of 1.
3.271. Review of Carbon Level
Find a compound that contain three carbon atoms and has a pair of carbon atoms
with a delocalized carbon level of 1.
3.272. Review of Carbon Level
Find two compounds that contain three carbon atoms and have a carbon atom with
a carbon level of 2.
3.273. Review of Carbon Level
Find two compounds that contain three carbons and have a carbon atom with a
carbon level of 3.
3.274. Review of Carbon Level
Find a compound that has a carbon atom of carbon level 4.
3.275. Carbon Level and Extrapolated Thinking
What happens to the carbon level of the carbonyl carbon when a Grignard reacts
with acetone? What happens to the carbon level of the Grignard carbon? HINT:
Trick question in the sense that the carbon level of the Grignard carbon must be
assigned logically, not strictly by our rules.
3.276. Synthetic Thinking
What kind of compound is 2,3-dihydroxypentane?
3.277. Synthetic Thinking*
From what precursor do you synthesize the kind of compound that 2,3-dihydroxypentane
is?
3.278. Synthetic Thinking**
What kind of compound is the precursor of 2,3-dihydroxypentane? See last problem.
3.279. Synthetic Thinking***
From what precursor do you synthesize the answer to the last problem?
3.280. Synthesis****
How would you make 2,3-dihyroxypentane? HINT: Think several steps.
Chm 222, Section 1
Exercise Set 3
3.293
33
3.281. Epwa, Reactions, and Mechanism
Show the product of the Wittig reaction starting with 1-iodo-2-methylpropane, (C6 H5 )3 P,
(added strong base), and acetone. Use epwa and trace out the mechanism.
3.282. Synthetic Thinking
What kind of compound is 2-methyl-butan-2-ol?
3.283. Synthetic Thinking*
From what four carbon compound can you make 2-methyl-butan-2-ol?
3.284. Synthetic Thinking**
From what compound can you make the answer to the last problem?
3.285. Synthesis***
Devise a synthesis of 2-methyl-butan-2-ol using compounds containing two carbons
or less. HINT: This requires a different process than that outlined in your answers
to the last few problems, but apply the same principles, which you should be used to
by now.
3.286. Reactions
Compound 41 is treated with CrO3 in acid, the organic material is isolated and
reacted with CH3 MgBr and then weak H+ . What is the product?
3.287. Reactions*
What side product may be formed in the process described in problem 286?
3.288. Epwa and Mechanism
Show the mechanism for the formation of 42 from 2,4-dimethyl-3-pentanone under
acid catalysis. Use epwa. HINT: What is the nucleophile?
3.289. Nomenclature*
The compound you made in the last problem is a gem-diol. In more general terms, we
(and only we) might call it a gem-DIN. How does a gem-DIN differ from an α-DIN?
HINT: While we are thinking about this, we shall be exposed to β-DINs too. What
might they be?
3.290. Synthetic Thinking
What kind of compound is 4-methyl-2-pentene?
3.291. Synthetic Thinking*
How many ways do we have to prepare compounds of the kind you specified in the
last problem?
3.292. Synthetic Thinking**
If you were to prepare 4-methyl-2-pentene from compounds with four or fewer carbon
atoms, would you have to form C-C bonds?
Chm 222, Section 1
Exercise Set 3
3.305
34
3.293. Synthesis***
How would you prepare 4-methyl-2-pentene from substances with four or fewer carbon
atoms?
3.294. Synthesis and Learning Organic Chemistry
How would you prepare 43 from 2-methyl-1-propanol? To pursue this, ask yourself
the kind of questions that I have been asking you in this exercise set. HINT: I am
soon going to quit asking those questions.
3.295. Synthetic Thinking
What kind of compound is 44?
3.296. Synthesis*
How many ways do we have to prepare compounds of the type that 44 is? What are
they?
3.297. Synthesis**
Do we need to make C-C bonds in going from 45 to 44?
3.298. Synthesis***
How would you prepare 44 from 45 and other simple compounds? HINT: Think
several steps.
3.299. Epwa and Mechanism
Use epwa to show the mechanism of the reaction of OH– with 43.
3.300. Learning Organic Chemistry*
How does the reaction in the last problem differ from reaction of H− (or BH–4 ) with
43?
3.301. Epwa and Mechanism
Use epwa to show the mechanism of the reaction of water with 43 in the presence of
acid.
3.302. Learning Organic Chemistry*
How does the reaction in the last problem differ from reaction of H− (or BH–4 ) with
43? How is it the same? HINT: “Contrast and compare. Compare and contrast.”
3.303. Epwa and Mechanism, and Learning Organic Chemistry
Use epwa to show the mechanism of the reverse reaction of problem 301. HINT: If
you recognize that this is a dumb question, don’t do it. If not, proceed and learn.
3.304. Epwa, Reactions, and Mechanism
Write the mechanism (use epwa) for the reaction of PCC with 3-pentanol in CH2 Cl2 .
Chm 222, Section 1
Exercise Set 3
3.312
35
3.305. Epwa, Reactions, and Mechanism
Write the mechanism (use epwa) for the reaction of H2 CrO4 in H+ /water with 3pentanol.
3.306. Epwa, Reactions, and Mechanism*
Write the mechanism (use epwa) for the reaction of H2 CrO4 in H+ /water with 1pentanol.
3.307. Epwa, Reactions, and Mechanism**
What factor causes the difference in the mechanism (and products) of the reactions
in problems 305 and 306.
3.308. Epwa and Mechanism
Use epwa to show the reaction product of cyclopentanone with ethanol in acid solution
with water removal.
3.309. Learning Organic Chemistry*
In your product of the last problem, color the carbon atoms that originated in the
cyclopentanone one color and those that originated in the ethanol, and the oxygen
atoms of the ethanol, another. Draw a line between the two colors. Look hard at
that sketch and be able to recognize how that structural form is synthesized.
3.310. Synthesis
What kind of compound is 46? HINT: This has an official name and our name; both
would be nice.
3.311. Synthesis*
From what kind(s) of compound(s) do we make compounds of the “kind” you specified
in the last problem?
Chm 222, Section 1
Exercise Set 3
3.321
36
3.312. Reaction, Epwa and Mechanism
What happens when you treat 46 with acidified water? Use epwa to write a mechanism. HINT: Do you recognize this as the reverse of something. If so, the question is
trivial.
3.313. Learning Organic Chemistry, a Slight Twist
The next six problem are a set that teaches similarities. Write the mechanism for the
acid catalyzed attack of an alcohol on acetone.
3.314. Learning Organic Chemistry*
Write the mechanism for the acid catalyzed dehydration of the acetal of acetone, that
is the reverse of the last reaction. HINT: Duh.
3.315. Epwa and Mechanism, Similiarities**
Write the mechanism for the acid catalyzed attack of NH3 on acetone to form what
is officially called a hemi-aminal (NOT animal, but from amine and “al” because it
works for aldehydes as well), but which we (and only we) might call a gem-DIN. What
are the similarities between this reaction and the one in problem 313?
3.316. Learning Organic Chemistry***
Aminals, see the last problem, are generally not very stable. They undergo acid
catalyzed dehydration, which is the exact process that you are familiar with, see
problem 314. Use epwa to show this process by following what you did in problem 314.
You should end up with an imine, a “carbon double bonded nitrogen” compound.
3.317. Learning Organic Chemistry****
What would happen to the aminal if it underwent acid catalyzed loss of NH3 . Use
epwa to describe.
3.318. Learning Organic Chemistry*5
Imines, see problem 316, are also rather unstable and can revert back to the ketone
(or aldehyde) under acid conditions. What would drive a mixture of NH3 , H+ , and
acetone to the imine form? What would drive it to the ketone form? Can you see a
general picture here?
3.319. Leaning Organic Chemistry*6
What do you see that is common among the compounds NH2 H, NH2 CH3 , NH2 OH,
and NH2 NH2 , where I have written the first in an odd way to promote your recognition
of the similarity. Draw Lewis structures of all these species.
3.320. Learning Organic Chemistry*7
Look at the last problem and then show that if you understand how NH3 reacts (under
acid catalysis) with a ketone or aldehyde, you also know how any of the other NH2 X
compounds do. Do you know how NH3 reacts? If now, go back a few problems and
start again.
Chm 222, Section 1
Exercise Set 3
3.327
37
3.321. Synthesis
How would you prepare 47 from an ketone?
3.322. Another Slight Twist
Repeat the general process for acid catalyzed reaction of NH2 X compounds with
a ketone, see problems 313-320 with a compound of the type NHX2 , for instance
NH(CH3 )2 . HINT: You should be able to get almost to the end of the synthesis, but
will be forced to stop before the final step. Why? Articulate your answer in less than
eight words.
3.323. Learning Organic Chemistry*
Examine the final material in your epwa from the last problem, a species with a
positive charge on a nitrogen atom double bonded to a carbon. There is a way to
put a lone pair back on the nitrogen atom, and thereby relieve the positive charge.
It involves using a C-H bond α to the carbonyl (or what was the carbonyl) carbon.
See if you can produce this “enamine.”
3.324. Learning Organic Chemistry
Review your notes from the last lecture. What reactions were discussed? For each of
these, compare it to some reaction you learned in the past and establish the similarities and the differences (if any). Ask another student if she sees any similarities or
differences that you missed. Discuss it. If necessary, argue about it.
3.325. Attacking an Imine
Show that if you attack an imine with CN– in the presence of water that you can
produce an pseudo-gem-DIN with electronegative elements -NH2 and -CN (the latter
being the pseudo one; why?). NOTE: As we shall show before the end of the semester,
this compound offers an entrance to the biologically important amino-acids.
3.326. Reactions
What would happen if you treated 1-butyne with NaNH2 , followed by treatment with
4-hydroxy-2-pentanone? HINT: Remember that generally speaking proton transfer
reactions are very rapid.
3.327. IR, NMR, Reactions, and, in the HINT, Learning Organic Chemistry
A compound is reacted with NH2 OH using acid catalysis and generates a product with
IR peaks at 3247 (broad) and 1665 cm−1 . The product has an 1 H nmr that shows
a triplet at 1.09 δ (3), a singlet at 1.87 δ (3), a quartet at 2.34 δ (2), and a broad
singlet that is exchangeable at 9.3 δ (1); and the decoupled 13 C nmr shows peaks at
10.84 δ, 13.27 δ, 29.19 δ, and 159.4 δ. What is the original compound? HINTS: (1)
Where would a carbon-nitrogen double bond appear in the IR? This double bond is
weaker than the carbonyl bond, but has a lighter mass. I could live with 1665 cm−1 .
Pursue! (2) When I re-worked this problem I wondered about the 9.3 δ peak in the
1
H nmr; seems high for the anticipated -OH peak. I looked it up and found that is
where it occurs and, while looking at that data, found that a hydrogen attached to
Chm 222, Section 1
Exercise Set 3
3.336
38
the carbon level 2 carbon of a oxime absorbs in the 6.5-8 δ region, considerably less
than an aldehydic hydrogen. Interesting.
3.328. Review of Reaction, Epwa and Mechanism*
Use epwa to show the mechanism of the reaction in the last problem.
3.329. Review of Reactions
You treat 2-butanol with acidic aqueous H2 CrO4 , isolate the organic material, and
then treat it with ethyl magnesium bromide and then dilute acid. What is the product?
3.330. IR and Reaction
A compound has IR peaks at 2900-3000 cm−1 , a weak peak at 2720 cm−1 , and a peak
at 1750 cm−1 . When treated with water and an acid catalyst, the second and third
of these peaks disappear and are replaced by a broad peak at 3300 cm−1 . How would
you describe what happens?
3.331. IR and Reaction
Butanal is treated with a mixture of HCN/CN− . Butanal has a peak at 1731 cm−1
which disappears and is replaced by peaks at 2247 cm−1 and a broad peak at 3340
cm−1 . Use epwa to show what happens.
3.332. NMR and Reaction
Chloral, CCl3 CHO, is also known as the “knock-out” drops, the famous “Mickey
Finn” used by gin runners in prohibition to put the competition flat on their backs.
To test for this in a glass of watered-down gin, the FBI asked Boniface Beebe, the
natural philosopher of distinction from Searcy, Arkansas, which is just down the road
from Beebe, AR, which is the town where the red-winged blackbirds plunged to their
death on New Year’s Eve day in 2010 and 2011, to investigate (that folks, is a run-on
sentence). He used nmr to look for the characteristic peak that occurs in aldehydes
between 8 δ and 10 δ. He found no sign of a peak. Bonnie was joyful in his conclusion
that chloral was not present? Was he right? Give your reasoning.
3.333. Reactions
Compound 50 is treated with CH3 Li followed by aqueous NH4 Cl (which acts as a
weak acid). What is the product?
3.334. Synthesis with Protection
How would you prepare 48 from 49? HINT: Two carbonyl groups: both would react
with most reagents, unless . . .
3.335. Epwa, Mechanism, and Projected Thinking
Compound 51 reacts with 2-hexanone in the presence of catalytic amounts of CN−
to form 52. Use epwa to show the mechanism. HINT: You haven’t seen this reaction;
I am asking you to use your knowledge to gain chemical intuition.
Chm 222, Section 1
Exercise Set 3
3.344
39
3.336. Reactions
Multistriatin, a pheromone for the elm bark beetle, has the structure 53. What is
the product when this material is treated with dilute aqueous acid?
3.337. Reactions
What do you obtain when you treat 54 with one equivalent of 1,3-propanediol in the
presence of acid with removal of water, followed by reaction of that product with
ethyl lithium, and then aqueous acid?
3.338. Reactions and Critical Chemical Thinking
If one takes 55 and dissolves it in water containing catalytic amounts of acid, one
finds the IR carbonyl peak disappears. What happens, and why, on the basis of
bonding, does it happen?
3.339. Synthesis
How would you synthesize 56 from cyclohexanone and other carbon containing compounds?
3.340. Epwa and Synthesis
How would you make 57 from compounds with four or fewer carbon atoms? Specify
your reaction(s) with epwa.
3.341. Synthesis
How would you prepare 58 from butanal?
3.342. Epwa and Mechanism
Use epwa to show the formation of the imine formed from 2-propanone and ethyl
amine.
Chm 222, Section 1
Exercise Set 3
3.356
40
3.343. Review of Reversible Addition to Carbonyls
Compare the reaction of acetone with, on the one hand, NH3 , and on the other with
NH(CH3 )2 . How are they the same? How do they differ?
3.344. Epwa and Mechanism
Use epwa to show the formation of the enamine from diethylamine and cyclohexanone.
3.345. Learning Organic Chemistry
We can make gem-diols, ketals, imines, and hydrazones from ketones. Think about
how these reactions are similar and how they are different. Talk with another student
about the similarities and the differences.
3.346. Synthetic Thinking
What kind of compound is 59?
3.347. Synthetic Thinking*
How do you make the kind of compound that you specified in the last problem?
3.348. Synthetic Thinking**
Do you need to make C-C bonds to make 59 from cyclohexanone and compounds
with two or fewer carbon atoms?
3.349. Synthesis***
How would you synthesize 59 from cyclohexanone and compounds with two or fewer
carbon atoms?
3.350. Reactions
What do you get if you treat 60 with CH3 MgBr followed by concentrated H2 SO4 ?
3.351. A Not Very Important Synthesis
How would you make 60 from 61? HINT: Looks impossible! Think outside the box;
consider the special reactions of carbonyls with NH2 X compounds. HINT: See the
title.
3.352. Reactions*
What can you say about the yield for your reaction in problem 351? Why?
3.353. Learning Organic Chemistry
Review (from your notes) the mechanism of the Wolff-Kishner reaction.
3.354. Epwa and Mechanism*
Close those notes and try to do the Wolff-Kishner reaction using 3-pentanone as your
ketone.
3.355. Reviewing Our Status
How many ways do we have to make a ketone?
Chm 222, Section 1
Exercise Set 3
3.362
41
3.356. Reactions
Compound 62 does not react with dilute aqueous acid, but compound 63 does. Account for this difference. HINT: What kinds of compounds would we call these two
materials?
3.357. Spectroscopy
A compound has a 13 C nmr spectrum with peaks at 13.30 δ , 19.04 δ , 19.26 δ , and
119.87 δ . Its 1 H nmr spectrum has peaks at 1.081 δ (t, 6), 1.699 δ (hextet, 4), and
2.339 δ (t, 4). The mass spectrum has a molecular ion peak at 110 with an intensity
of 37.7 and an (M+1)+ peak of intensity 3.5. What is the compound? HINT: This is
a tricky question; you need to pursue and use logic.
3.358. Epwa and Mechanism
Use epwa to show how an oxime is formed.
3.359. Reactions
What is the product of the reaction of 64 with (1) N2 H4 , (2) strong base with heat,
followed by (3) H+ /H2 O?
3.360. Synthesis
How would you prepare 65 from fragments with four carbons or less? HINT: There
are only two ways we know to get rid of a functional groups from a molecule.
3.361. Epwa, Mechanism, and Projected Thinking
See if you can use the formation of an enamine as a guide to figure out how an enol,
see 66, forms in acid solution from a ketone. Use epwa.
Chm 222, Section 1
Exercise Set 3
3.369
42
3.362. Epwa, Mechanism, and Learning Organic Chemistry*
Enols, see the last problem, go back to ketones by the reverse mechanism of their
formation. Use epwa to show this and learn once again that doing a reversible process
is easy once you can do it in one direction.
3.363. Epwa, Mechanism, and Projected Thinking
A variation of the Wittig reaction with aldehydes in the presence of formaldehyde
takes place by the following steps. Let the Wittig reagent formed from propyl bromide
and triphenylphosphine, after it is treated with butyl lithium, react with butanal to
form a compound we call A. Now let A react with butyl lithium to form B. B then
reacts with formaldehyde to form C, which in turn is treated with water to form 67.
Identify A, B, and C. Use epwa to show mechanism. HINT: In the first step, don’t
let triphenylphosphine oxide form.
3.364. Epwa, Mechanism, and Projected Thinking*
Is there a second product that you might expect in the last problem in addition to
67? What is it? If you can, give an explanation for why 67 might be the dominant
product.
3.365. Synthetic Thinking
What kind of compound is 68?
3.366. Retrosynthetic Thinking*
Draw the cleavage lines to indicate the materials from which 68 can be made.
3.367. Synthesis*
Starting with cyclohexanone, how would you make 68?
3.368. Epwa, Mechanism, and Reactions
Use epwa to show how acid catalyzes the conversion of 69 into 70.
Chm 222, Section 1
Exercise Set 3
3.374
43
3.369. Epwa, Mechanism, and Reactions
The ketone 71 in the presence of HCN and CN− does NOT form very much of 72.
Use epwa to show the mechanism of the small amount that does form.
3.370. Projected Thinking*
Suggest an explanation for the lack of substantial product in the last problem?
3.371. Reactions
What is the product when 73 is treated with H+ in water?
3.372. NMR
A compound has the formula C9 H10 O. The 1 H nmr has the following peaks: 1.2 δ (t,
3), 2.75 δ (q, 2), 7.3 δ (d, 2), 7.8 δ (d, 2), and 9.95 δ (s, 1). What is the compound?
3.373. NMR
A compound has the formula C9 H10 O3 . The IR features a broad peak at about 3000
cm−1 , and peaks at 1770 and 1680 cm−1 . The 1 H nmr has the following peaks: 1.41
δ (t, 3), 4.09 δ (q, 2), 6.9 δ (d, 2), 7.9 δ (d, 2), and 12.3 δ (s, 1) and the 13 C peaks
are at 15 δ, 63 δ, 115 δ, 128δ, 131 δ, 163 δ, and 167 δ. What is the compound?
3.374. NMR
A compound has the formula C6 H10 O. The 1 H nmr has the following peaks: 1.1 δ
(t, 3), 1.9 δ (d, 3) , 2.53 δ (q, 2), 6.15 δ (d, 1), and 6.8 δ (q of d, 1). What is the
compound?
Chm 222, Section 1
Exercise Set 3