Chm 222 Spring 2016, Exercise Set 3 Addition to Carbonyls ...rlinck/Chm222/sec/pset3.pdf · Chm 222...

Chm 222Spring 2016, Exercise Set 3

Addition to Carbonyls and the Pillars

Mr. Linck

c©Boniface Beebe ProductionsJanuary 5, 2016

Version 5.2.

NOTE: An asterisk in the problem title indicates that it is a continuing problem fromthe 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 werecovered. Present that summary to another student in the class.

3.2. Acids, Bases, Conjugate Acids, and Conjugate Bases

For the reaction

CH3SH + OH− = CH3S– + H2O

identify the acid, the base, the conjugate acid, and the conjugate base.


What is the conjugate base of HBr, CH3OH, 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.


What is the conjugate acid of NH3, NH–2, Cl–, (CH3)2C(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)

CH3OH = CH3O– + H+

NOTE: Equilibrium constants for reactions in which a substance produces a protonare usually called Ka.

3.16 2

3.7. Equilibrium Constants

What does a large value of an equilibrium constant mean? HINT: Give an answer interms of concentrations of various species.

3.8. What is a Ka

Express the mathematical equation that defines a Ka. Do so specifically for phenol,C6H5OH. 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) Expressthe 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

CH3C(O)OH = CH3C(O)− + H+

for which we can write

Ka =[CH3C(O)−][H+]

[CH3C(O)OH]

Show that this is equivalent to the expression

pKa = pH − log([CH3C(O)−]

[CH3C(O)OH]

3.11. Information from pKa*

If the pKa of phenol, C6H5OH, is 10, what is the ratio of phenoxide ion to phenolat equilibrium if the pH is 10? If the pH is 8? If the pH is 12? HINT: See the lastproblem.

3.12. Concentrations and pKa**

Articulate what you learned in the last problem. “If the pH is below the pKa, thenthe ratio of . . . If the pH is above the pKa, then the ratio . . . ” Use general words likeacid, 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, CH3CH2OH orCH3CH2O

– 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 asmall pKa? HINT: If the answer is not completely obvious to you, then write out thereactions 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 alarge pKa? HINT: To do organic chemistry successfully, you have to use pKa valueslike 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 reactionsdefining the Ka’s.


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.


The pKa of CH4 is 48. That of ethanol is 16. Will CH–3 react with CH3CH2OH to

produce methane and CH3CH2O–?


You are going to carry out a Grignard reaction on a carbonyl containing moleculewhich also has an alcohol group. Do you have to worry about acid/base chem-istry? Explain. HINT: Reactions involving the transfer of a proton, acid/basereactions, from -NH and -OH bonds are generally much faster than other nucle-ophile/electrophile reactions. If an acid/base reaction can screw you up, it generallywill.

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 tryingto get you to classify acid strength with a broad brush. If you want details, there isa 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 H2O2.


3.25 4

pK

aR

ange

Cac

ids

Nac

ids

Oac

ids

Mis

c.ac

ids

Str

ong

acid

sp

Ka

bel

ow0

RC

NH

+,

-10

HC

lO4,

-10

HI,

-10

pro

ton

ated

keto

ne,

-7H

Br,

-9p

roto

nat

edac

id,

-6H

Cl,

-7p

roto

nat

edal

coh

ol,

-2.4

RS

H+ 2

,-7

H3O

+,

-1.7

pro

ton

ated

amid

e,-0

.5

Wea

kac

ids

pK

a0

to10

1,3-

pro

pan

edia

l,5

pro

ton

ated

anil

ine,

4.6

CF3C

(O)O

H,

0.5

(Ph

) 3P

H+

,2.

72,

4-p

enta

dio

ne,

9p

roto

nat

edpyri

din

e,5.

2H

3P

O4,

2.2

HF

,3.

2H

CN

,9.

2H

ON

H+ 3

,5.

8C

F3C

H2C

(O)O

H,

3.1

H2S

e,3.

9N

H+ 4

,9.

2C

H3C

(O))

H,

4.8

H2S

,7.

0su

ccin

imid

e,9.

6

Ver

yW

eak

pK

a10

to20

CH

3C

(O)C

H2C

(O)O

C2H

5,

10.7

(C2H

5) 3

NH

+,

10.7

H2O

2,

11.6

C2H

5S

H,

10.6

C2H

5O

C(O

)CH

2C

(O)O

C2H

5,

13(H

2N

) 2C

NH

+ 2,

13.6

CF3C

H2O

H,

12.4

cycl

open

tad

ien

e,16

amid

e,17

CH

3O

H,

15.5

CH

3C

(O)H

,16

.7H

2O

,15

.7ke

ton

e,19

.2

Extr

emel

yW

eak

pK

a20

to30

HC

Cl 3

,24

anil

ine,

27H

CC

H,

25C

H3C

(O)O

R,

25.6

(Ph

) 3P

CH

+ 3,

30

Hor

rib

leA

cid

sp

Ka

abov

e30

dit

hia

ne,

31.1

NH

3,

35(P

h) 3

CH

,31

.5R

2N

H,

36to

luen

e,40

CH

2C

H2,

44C

H4,

48

Table 1: Various pKa values for compounds. Note the labels “weak” etc. are subjec-tive.


3.34 5


Use Table 1 to determine if OH– will substantially deprotonate NH+4 .


Use Table 1 to determine if SH– will substantially deprotonate CH3OH.


With the help of Table 1, find a base that will deprotonate a ketone.


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 learningthe 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 H2Oacting 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 accom-modate 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 H2O is the strongestacid?


Which is the strongest acid, NH3 or H2O?


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. Willthis work with 2-butyne? Why or why not? HINT: We will return to why an alkynewith a proton on the carbon of the triple bond is a stronger acid than a proton on aalkane carbon.


There are several important factors in determining the acidity of an HX compoundas X varies around the periodic table. One of these is the stability of negative chargeon the resultant X– species. We have been using that in the last few problems. Thesecond is the bond strength of the HX bond, which, after all, must be broken in theacidity 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 wehave been doing. But when we go down the table, bond strengths tend to get weaker.


3.45 6

Assume for the moment that the bond strength factor is the only consideration (andthat 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 thanelectronegativity 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–? H2S, C6H5CH3,CH3NH2

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 fromrural 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 ofattacks. So think acid/base before you think other nucleophilic chemistry.


Rank each of the following sets in order of increasing acidity.

A. NH3, H2O, H2SB. CH3OH, CH3NH2, CH3CH3

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?


What kind of product results from attack of hydroxide ion on an aldehyde?


What kind of product results from attack of ozone on an alkene, followed by treatmentwith Zn?

3.44. Synthesis Review

From what would prepare an alcohol? How?


3.54 7

3.45. Synthesis Review

Give an example of the synthesis of an alcohol from a ketone in which the number ofcarbon 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

H2O + F– = HF + OH–

HS– + NH3 = H2S + NH–2

CH4 + OH– = CH–3 + H2O

H2S + OH− = HS− + H2O

3.47. Hybridization Review

What is the hybridization of C in C2H6, C2H4, and C2H2?

3.48. Character of C-H Bond*

What is the amount of “s character” in each carbon of the last problem? HINT: Iam 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 afree 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 47can 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 toleratesnegative charge best?

3.52. Application of Corrollary

Which species in problem 47 is the strongest acid?


3.63 8


Will butyl lithium react with propyne? To produce what?


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 youmake?

3.56. Acid/Base, Epwa, Mechanism, and Reactions

Propyne is treated first with butyl lithium, then with 2-butanone, finally with diluteH+. Write a mechanism for the reaction and show final products. HINT: To be ableto solve this kind of problem (albeit of increasing complexity) is the aim of organicchemistry courses.

3.57. Acidity of a Alkyne and the Resulting Reagent

Propyne is treated with butyl lithium. What happens? What kind of reagent havewe made? Like any compound of this type, it wants to find a center that is polarizedhow?

3.58. Acidity of a Alkyne and the Resulting Reagent

Propyne is treated with butyl lithium. What kind of reagent have we made? Thisreagent that we produced is then added to oxirane (the epoxide of ethylene, a cyliccompound), C2H4O. Finally the solution is treated with H+ to neutralize charge.What is the product? Give a mechanism. HINT: Always make a Lewis structure ofyour 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 haveseen. 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 notadd acid. Instead, we add more oxirane, C2H4O, and then, after some time, dilutehydrogen ion. What now is the product? Give a mechanism with epwa. HINT: Lookat what you can do with epwa!

3.61. The First Rule and Corrollary

State the first rule of acidity and its corrollary.


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.


3.74 9

3.63. Predicting Acidity: The Second Step

Write the reaction in which H2S 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 H2S or HS– is thestrongest acid. State your reasoning.

3.65. Relative Acid Strength

Which is the strongest acid, (C2H5)2NH+2 or (C2H5)2NH?

3.66. Relative Base Strength*

Which of the two substances in the last problem is the strongest base?


Will the following reaction occur significantly to the right?

O2− + HF = OH– + F−


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 CH3CH2OH (to produce?) but not with CH3CH3. What is the orderof base strength of H−, CH3CH2O

–, and CH3CH–2? HINT: Write reactions.


Malonic acid is HOC(O)CH2C(O)OH. It can give up two protons relatively read-ily; one has a pKa of 2.86, the second a value of 5.7. Comment. HINT: A usefulcomparison would bring in the value(s) of other species, such as, for example, aceticacid.


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 areusing.


3.82 10

3.74. A Nucleophilic Substitution

Is there an position in the molecule CH3I that is positively polarized? Let Br–, actingas a nucleophile, attack CH3I. This starts to form a new bond from bromide to thecarbon (use epwa to see this), but carbon cannot have five bonds, so at the sametime, the electrons in the bond to the iodine atom must be leaving carbon and goingto 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: SN2

The attack described in the last problem occurs with the bromide ion coming towardthe CH3I 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 thebromide is looking for an empty orbital on the CH3I in which to put its electrons.The lowest empty orbital is the σ* level of the C-I bond, which is more concentratedon the carbon.

3.76. A Characteristic of SN2 Reactions

The process you just described in the last problem requires that the C-I bond break.Hence these so-called SN2 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 namefor C6H

–5; so chlorobenzene, C6H5Cl could also be called phenyl chloride.) Draw a

Lewis structure to show this. If it is to react with something as a nucleophile, whatwill that lone pair of electrons look for? Where in 1-butyl bromide is that kind ofthing? 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 problemagree with this?


Review from Problem Set One. Carbon makes four bonds unless it is . . . .


When a carbon is charged positively, how many bonds does it make? When a carbonis charged negatively, how many bonds does it make? If the answers are not evidentto you, draw Lewis structures and be sure.


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 thatcharge do to the acidity of a C-H bond next to it? What kind of reagent is ethyllithium? HINT: There are two answers; give both. What happens if you treat theproduct of the last problem with the base ethyl lithium? Use epwa. HINTS: (1)Remember, generally speaking, proton transfers to a good nucleophile (base) are fastcompared to other nucleophilic attacks. (2) The product of this reaction is said tobe a “zwitterion,” meaning it has both negative and positive charges in the samemolecule. An earlier example of this that you have seen is NH+

3 CH2C(O)O–. Drawthe 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 istrue, 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 〈 P+-O−,P=O 〉 bond. No matter what pair of electrons you use to do this, sticking to thefour 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 originallyin the aldehyde one color and those that were originally in the butyl bromide an-other. Draw a line between the two colors. That is how you determine what startingmaterials are necessary to make a given alkene.

3.86. Synthesis

From what compounds would you synthesize 3-methyl-2-pentene? HINT: Draw thestructure of the desired product and draw the “retrosynthetic” line you establishedin the last problem. What fragments do you have? Now note one fragment startedas an aldehyde or ketone and the other as an alkyl bromide (or chloride or . . . ). Useepwa from those starting materials to establish everything is OK.

3.87. Synthesis

How would you synthesize 2-ethyl-2-hexene? Use epwa. HINT: Generally, becausethe SN2 reaction in the first step of this process occurs much more easily on a primaryalkyl halide, that is the issue that determines which side of the retrosynthetic line isthe 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?


3.102 12

3.90. Synthesis Summary

What is one way to make alkenes? HINT: Alas, there will be other methods we willlearn.

3.91. Nucleophiles

Which do you think is the better nucleophile, (CH3)3P or (CH3)2S? Why?

3.92. Synthesis of a Good Acid

How would you prepare (CH3)3S+ from (CH3)2S and CH3I?


Why is (CH3)3S+ a better acid than (CH3)2S?


A strong enough base will surely deprotonate (CH3)3S+. What base might you use?

3.95. Deducing a Reaction

Use epwa to write the chemical reaction of (CH3)3S+ with a strong base.

3.96. Deducing a Reaction*

What kind of reagent have you made in the last problem? HINT: We are mostlyconcerned 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 atomseparated from the positive sulfur. Sulfur is not a good atom to be positive, butbecause the affinity of sulfur for an oxygen atom is considerably less than the affinityof phosphorous for oxygen, it turns out that we need to find another atom for thenegative oxygen to attack that will still move charge to sulfur. Since epwa only occursover 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 inthe propanone with one color and those that were originally in the CH3I with anothercolor. Draw a line between those two sets of color. that is how you figure out whatmolecules 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)?


3.111 13

3.102. Review of Two Syntheses

What acidity feature do we take advantage of in order to synthesize alkenes andoxiranes?

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, C4H9NH+

3 has a pKa of about 11. We make a mixture of thetwo four-carbon species (butanoic acid and butyl amine) in water and adjust the pH asindicated 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 butylamine is in the CH2Cl2 layer? c. In what range of pH will butanoic acid be in thedichloromethane 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 solublein the organic layer. (2) This is a simple problem using the relationship you derivedin problem 10

3.105. Charge and Relative Acidity

On the basis of charge only, which would you expect to be the strongest acid, ethanol(CH3CH2OH) 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 thiscomparison?

3.107. Charge and Relative Acidity**

On the basis of the nature of the element and charge, which compound, acetic acid,CH3C(O)OH, or NH+

4 would you expect to be the strongest acid? HINT: You mightuse 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 isthe stronger acid?

3.109. Relative Acidity****

In problem 105 charge was sufficient to overcome the nature of the element carryingthe 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?


3.113 14

Figure 1: Reaction coordinate curves for two acids, HA and the resonance stabilizedHB.

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 thesame charge (What does that say about acidity rules one and two?). If there isresonance stability in HB, but not in HA, then HB is stabilized. Will HA or HB bethe stronger acid? See Figure 1.


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 thesame charge (What does that say about acidity rules one and two?). If there isresonance stability in D−, but not in C−, then D− is stabilized. Will HC or HD bethe stronger acid? See Figure 2.


3.118 15

Figure 2: Reaction coordinate curves for two acids, HC and HD; the conjugate baseD− is resonance stabilized.


Articulate what you have to do to find out if an acid is stronger or weaker becauseof 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 wouldsay!


Consider the same two compounds as in problem 111. If both HA and HB areresonance stabilized, what would you do to determine which is the stronger acid?HINT: Nothing beats thinking.


Consider the same two compounds as in problem 111. If both HA and A− are reso-nance stabilized, what would you do to determine whether HA or HB is the strongeracid? HINT: Same as last problem.

3.116. Site of Basicity

Consider N-methyl-ethanamide, CH3C(O)NHCH3. It is treated with a strong acid.Where will it protonate? HINT: Write the Lewis structure (as usual) and considerany resonance (as usual).


If you brought H+ up to CH3CH3, where could it protonate? HINT: Trick question!


3.130 16


If you brought H+ up to CH2CH2, where could it protonate? HINT: Not a trickquestion. 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 problemfor pKas.

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 conclusionabout 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 enzymecalled lactate dehydrogenase catalyzes this interconversion. HINT: You should havelooked up the structures in problem 119, but if you didn’t, now is the time. Thinkingthis 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 thisvalue greater than the Ka of butyric acid (butanoic acid)? NOTE: This effect onacidity, 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 (3-chlorobutanoic 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 thelast 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?


3.135 17

3.129. Relative Acidity, Review

Which is the strongest acid, CH3CH(SH)CH3 or CH3CH(OH)CH3?

3.130. Relative Acidity, Review

Which of the following reactions takes place extensively to the right?

CH3CC– + CH3CHCH2 = CH3CHCH– + CH3CCH

CH3CH2OH + CH3C(O)O– = CH3CH2O– + CH3C(O)OH

3.131. What Is Written

I read in an organic chemistry text about the factors that influence acidity. Theywere, 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 thecarbon 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 knowwhat I am going to say; if not, it involves a pencil.

3.134. Strange Relative Acidity

Diethyl malonate ester is CH3CH2OC(O)CH2C(O)OCH2CH3. It can give up a protonwith a pKa of about 9. Why should this “C” acid be so much stronger than, say,C3H8 with a pKa of about 50?


3.141 18

3.135. Epwa, Mechanism, and Acidity

Many processes in organic chemistry are catalyzed by H+ and/or OH−. These gener-ally 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 sitein the molecule where you need to break a bond to hydrogen. Start there and thenproceed.

3.136. Nucleophilicity is Sometimes Related to Basicity

What makes a good base often makes a good nucleophile. So OH– is a better nucle-ophile than F–, just as is true for basicity. However, a second important factor fornucleophiles is the ease of polarization of the electrons, so generally speaking, speciesfurther down the table are better nucleophiles, even though they are not as good asbases: 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, ethyllithium, and 4. HINT: Use the periodic table to figure out which metal-carbon bondis 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 aketone. Use epwa to suggest a mechanism. HINT: After your first step you shouldhave 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 astrong C=O double bond.

3.140. Epwa, Reaction Prediction, and Learning Organic Chemistry

Consider CH3C(OH)2CH3 in acid solution. Where on this molecule would a protonsit? Does that change a group from a poor leaving group (strong base) into a goodleaving group (i.e., a weak base)? If that good leaving group does leave, what do youhave? Can you move the positively charged site on this compound to a site where ahydrogen ion could leave to produce a neutral compound. Use epwa to show all ofthese steps (four epwas, I think).


3.154 19

3.141. Reactions with Epwa, Review

What is the product of butanal with ethyl Grignard? HINT: No acid is added at theend.

3.142. Reactions with Epwa

What is the product of butyric acid with excess methyl lithium? HINT: No acid isadded at the end. HINT: Methyl lithium, in contrast to methyl Grignard, is a verypowerful C− reagent.

3.143. Reaction Prediction and Learning Organic Chemistry

Use the information from problem 140 to establish what happens when the productof 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-2-butanol is?

3.146. The Synthesis**

How would you make 2-methyl-2-butanol from 2-butanone? Use epwa.


How would you make 2-butanol from 2-butanone?


What kind of compound is 2-methyl-1-butene?


From what kind of compound can you make the kind of compound that 2-methyl-1-butene 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 allthe products.


3.161 20


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 topicof biologists.


Which is the stronger acid, 9 or 10? HINT: Go through the rules.


Compound 11 is a stronger acid than a normal amine. Suggest a reason.

3.157. Relative Basicity

If you brought a proton up to CH3CH2CH(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 groupinto a better leaving group? What is changed to a better leaving group?

3.159. Leaving Group Ability**

Why is H2O 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 electronsin a C-H bond of C-3. Use epwa to show how those electrons can form a C-2 to C-3double bond, release a proton, and satisfy the positive charge polarization on C-2 (oron the oxygen, depending on how you look at it).


3.173 21

3.161. Classifying–The Type of Process****

What would we call the process of the last several problems: a substitution, anaddition, 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 andmethyl iodide using a Grignard reaction and, at the end, strong acid. HINT: Morethan 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 youbrought that kind of reagent up to 1-bromobutane, what is going to happen? Whatis the product? Give a mechanism with epwa. HINT: No more than four bonds tocarbon.

3.169. Mechanistic Restrictions

What alkyne anion and what alkyl halide would you use to prepare 16? Is that youronly choice? Why or why not?

3.170. Type of Compound


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.


3.181 22

3.173. Relative Acidity and Leaning Organic Chemistry

What are the factors that determine acidity? How many are there? Give an examplewhere 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 eachof the factors in the last problem.


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, perhapsnot all working in the same direction. The process is more important than the answer.


Propanone has a pKa of about 22, whereas 2,4-pentanedione has a pKa of about 9.Show your knowledge with an intelligent comment.


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 byacid?

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 electronsin that orbital? What is the shape of the molecule?


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 ahydrogen atom?


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 orbitalon the carbon? Make a sketch showing this interaction. Draw the equivalent Lewisstructure.

3.183. Stability for an Empty Orbital*

Given your answer to the last problem, what is one way to stabilize a positive chargeon a carbon atom?


Draw the Lewis structure of CH2X+ 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.


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 correctsymmetry to bond to the empty orbital? Careful. This is a little tricky. Make asketch 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”.


Given the last four problems, what are ways to stabilize a positive charge on a carbonatom?

3.187. Stability of Carbocations

Which of the cations 18-20 are stabilized by adjacent double bonds? Use epwa toprove 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?


What are three ways to stabilize a positive charge?


3.201 24

3.191. Subtle Resonance Stability

Which cation, 19 or 23 is most stable? HINT: Look carefully at the resonancestructures that you drew. You did draw them, didn’t you?

3.192. Stability of Cations

Which cation, 24 or 25 is most stable?


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 treatmentwith dilute acid? HINT: A new wrinkle here: Which side will be attacked? Find areason 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?


Review your notes from the last lecture. How many topics were covered? How arethey 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 thelast 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 youwill solve problems in the future to take these issues into consideration.


3.209 25

3.201. Stability and the Double Bond

Draw the Lewis structure of propene. Now draw a minor resonance structure in whicha 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 tofour bonds or less. This resonance is not present when the double bond is attachedonly to hydrogen atom substituents; hence stability of a double bond is obtained bysubstitution 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 constantpressure when H2 reacts with it) of 1,3–pentadiene is -222.6 kJ/mole and that of1,4-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 isalways the safe thing to do in stability problems), the alkanes are below the alkenes.Note also the alkane is the same in both cases.


The heat of combustion (heat absorbed by the system at constant pressure when thecompound reacts with O2 to produce CO2 and H2O) of 1,3–pentadiene is -3010.7kJ/mole and that of 1,4-pentadiene is -3041.2 kJ/mole. Which is most stable; by howmuch, and why?


The heat of isomerization to spiropentane, 28, of 1,3–pentadiene is 109.3 kJ/moleand that of 1,4-pentadiene is 78.8 kJ/mole. Which of the dienes is most stable; byhow 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 isthe difference in the three treatments. HINT: Ever hear of the “freedom to choose azero of energy”?


Compare the resonance in benzene with that in butadiene. Which is most important?Why?


Draw the resonance structure present in acetate anion, CH3C(O)O–. Compare it toany resonance in acetic acid, CH3C(O)OH. Which is most important? Why?

3.208. Synthetic Thinking

What kind of compound is 29? HINT: There are two answers.


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?


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 (C6H5)2(CH3)Pwith 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 containingonly C and H. “Leapin’ lizards,” he shouted, “what are those products? Why arethere 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 aWittig 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 1H nmr and two signals in the 13C nmrspectra. Which is it?

3.216. Carbon Level

Generally speaking, what kind of reagent changes a compound from carbon level 2 tocarbon level 1?


3.229 27

3.217. Carbon Level

Generally speaking, what kind of reagent changes a compound from carbon level 1 tocarbon level 2?


What kind of compound is 1-pentene?


From what kind of compound(s) do you prepare the kind of compound that 1-penteneis?

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 oneyou 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 isgiven in 33, an oxirane is sometimes formed. See if you can epwa (verb usage) yourway through a mechanism. HINT: Firstly, identify a “C−” reagent to attack thecarbonyl. 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.


What kind of compound is 2-pentene?


How do we prepare compounds of the type that you gave as your answer to the lastproblem? HINT: Duh?


Do we need to add carbon atoms to compounds with three carbons in order to make2-pentene?


3.240 28

3.229. Synthesis***

How would you prepare 2-pentene from compounds with three carbon atoms or less?


Without looking, go through the steps in the last several problems that establish aconceptual method for you to think about the synthesis of a compound. HINT: Thisis one of the important exercises of the semester.


What kind of compound is cyclohexene?

3.232. Synthesis*

Give two methods of preparing cyclohexene, one starting with and the other startingwithout, the ring structure.

3.233. Synthesis

We have (at this stage) two ways to make an alkene. Start with cyclohexanone andprepare alkenes with formula C7H12 by each of these methods. Use epwa. What isthe difference between your products?

3.234. Stability of Alkenes

Consider the three compounds, 2,4,7,9-undecatetraene, 2,4,6,8-undecatetraene, and1,4,6,9-undecatetraene. Which is most stable? Why? HINT: undeca is the name foran 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 havesolved 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?


3.245 29

3.240. Reactions and Reversibility

How would you synthesize 2-methyl-2-butene from 2-methyl-2-butanol? To do so youwould want conditions with low concentration of water to make it easier to removethat water molecule. How might you make the reverse reaction take place? Wouldyou need water? Would you need H+? HINT: Think backwards, exactly backwards.There is even a name for that: microscopic reversibility.


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”?


To open the oxirane ring requires that a new group come forward to bond to one ofthe two carbon atoms. This attack occurs as the oxygen atom leaves the carbon. Sucha process requires both the oxirane and the incoming group to collide with sufficientenergy to cause reaction. If both the oxygen atom and the incoming group are to bepartially bonded to the carbon atom, we have to use one orbital on carbon to bond totwo atoms. Since the 2p orbital on a carbon atom more easily extends away from thecarbon atom, that is the orbital of preference. What would you imagine is the bestway for two atoms to simultaneously bond to a carbon atom? Make a rough sketchof 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, transitionstate between two normal four-bonded carbon atoms. (2) We have done this reactionbefore in the Wittig reaction; we are just looking at it in a slightly different way.


3.254 30

3.245. Opening Oxiranes*

From your sketch in the last problem, assess the difficulty in getting a nucleophileclose to the oxirane carbon when it has two hydrogen atoms as its substituents versusthe situation where it has two methyl groups as substituents. NOTE: This is calledsteric interference. HINT: You may have discovered this previously: see problem 194.This will play an important role in the study of SN1 and SN2 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 withdilute acid. Will the nucleophile attack one side preferentially? What is the natureof the product? How would you classify it in generic terms? HINT: Might we (andonly 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 thismaterial and consider a couple of possible resonance structures. Order your resonancestructures 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 carbonwill 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 bemost 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 themedium. Use Br– as a good nucleophile for neutral attack and HBr, which is, ofcourse, a strong acid and dissociated, for acidic attack.


Outline the two competing factors important to consider in the opening of an oxirane.


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)2S+CH–

2 and productA is isolated. That material is reacted with ethyl Grignard, followed by dilute acidto give B. What are A and B? Give the mechanism and use epwa. HINT: Thinkabout steric issues with this powerful nucleophile.


3.268 31

3.254. Epwa, Reactions and Mechanism

The compound 2-pentanone is treated with the sulfur ylide, (CH3)2S+CH–

2 and prod-uct C is isolated. That material is reacted with bromide ion in the presence of acidto give D. What are C and D? Give the mechanism and use epwa. HINT: Thinkabout the role of acid in opening an oxirane.


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 howdo 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?


What is the product of the reaction of HS- with 37?


What is the product of the reaction of ethanol with 38 under conditions of sulfuricacid catalysis?


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)2S, (2) this productis treated with butyl lithium, and (3) that last product is added to acetone.




From what immediate precursor do you synthesize the kind of compound that 39 is?


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.


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.


Find two compounds that contain three carbon atoms and have a carbon atom witha carbon level of 1.


Find a compound that contain three carbon atoms and has a pair of carbon atomswith a delocalized carbon level of 1.


Find two compounds that contain three carbon atoms and have a carbon atom witha carbon level of 2.


Find two compounds that contain three carbons and have a carbon atom with acarbon level of 3.


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 reactswith 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 beassigned logically, not strictly by our rules.


What kind of compound is 2,3-dihydroxypentane?


From what precursor do you synthesize the kind of compound that 2,3-dihydroxypentaneis?


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.


3.293 33

3.281. Epwa, Reactions, and Mechanism

Show the product of the Wittig reaction starting with 1-iodo-2-methylpropane, (C6H5)3P,(added strong base), and acetone. Use epwa and trace out the mechanism.


What kind of compound is 2-methyl-butan-2-ol?


From what four carbon compound can you make 2-methyl-butan-2-ol?


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 carbonsor less. HINT: This requires a different process than that outlined in your answersto the last few problems, but apply the same principles, which you should be used toby now.

3.286. Reactions

Compound 41 is treated with CrO3 in acid, the organic material is isolated andreacted with CH3MgBr 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 underacid 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. Whatmight they be?


What kind of compound is 4-methyl-2-pentene?


How many ways do we have to prepare compounds of the kind you specified in thelast problem?


If you were to prepare 4-methyl-2-pentene from compounds with four or fewer carbonatoms, would you have to form C-C bonds?


3.305 34

3.293. Synthesis***

How would you prepare 4-methyl-2-pentene from substances with four or fewer carbonatoms?

3.294. Synthesis and Learning Organic Chemistry

How would you prepare 43 from 2-methyl-1-propanol? To pursue this, ask yourselfthe kind of questions that I have been asking you in this exercise set. HINT: I amsoon going to quit asking those questions.



3.296. Synthesis*

How many ways do we have to prepare compounds of the type that 44 is? What arethey?

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: Thinkseveral steps.


Use epwa to show the mechanism of the reaction of OH– with 43.


How does the reaction in the last problem differ from reaction of H− (or BH–4) with

43?


Use epwa to show the mechanism of the reaction of water with 43 in the presence ofacid.


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: Ifyou recognize that this is a dumb question, don’t do it. If not, proceed and learn.


Write the mechanism (use epwa) for the reaction of PCC with 3-pentanol in CH2Cl2.


3.312 35


Write the mechanism (use epwa) for the reaction of H2CrO4 in H+/water with 3-pentanol.

3.306. Epwa, Reactions, and Mechanism*

Write the mechanism (use epwa) for the reaction of H2CrO4 in H+/water with 1-pentanol.

3.307. Epwa, Reactions, and Mechanism**

What factor causes the difference in the mechanism (and products) of the reactionsin problems 305 and 306.


Use epwa to show the reaction product of cyclopentanone with ethanol in acid solutionwith water removal.


In your product of the last problem, color the carbon atoms that originated in thecyclopentanone one color and those that originated in the ethanol, and the oxygenatoms of the ethanol, another. Draw a line between the two colors. Look hard atthat 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; bothwould be nice.

3.311. Synthesis*

From what kind(s) of compound(s) do we make compounds of the “kind” you specifiedin the last problem?


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3.312. Reaction, Epwa and Mechanism

What happens when you treat 46 with acidified water? Use epwa to write a mecha-nism. HINT: Do you recognize this as the reverse of something. If so, the question istrivial.

3.313. Learning Organic Chemistry, a Slight Twist

The next six problem are a set that teaches similarities. Write the mechanism for theacid catalyzed attack of an alcohol on acetone.


Write the mechanism for the acid catalyzed dehydration of the acetal of acetone, thatis 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 whatis officially called a hemi-aminal (NOT animal, but from amine and “al” because itworks for aldehydes as well), but which we (and only we) might call a gem-DIN. Whatare 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 acidcatalyzed dehydration, which is the exact process that you are familiar with, seeproblem 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. Useepwa 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+, andacetone to the imine form? What would drive it to the ketone form? Can you see ageneral picture here?

3.319. Leaning Organic Chemistry*6

What do you see that is common among the compounds NH2H, NH2CH3, NH2OH,and NH2NH2, where I have written the first in an odd way to promote your recognitionof 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 (underacid catalysis) with a ketone or aldehyde, you also know how any of the other NH2Xcompounds do. Do you know how NH3 reacts? If now, go back a few problems andstart again.


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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 NH2X compounds witha ketone, see problems 313-320 with a compound of the type NHX2, for instanceNH(CH3)2. HINT: You should be able to get almost to the end of the synthesis, butwill be forced to stop before the final step. Why? Articulate your answer in less thaneight words.


Examine the final material in your epwa from the last problem, a species with apositive charge on a nitrogen atom double bonded to a carbon. There is a way toput 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.”


Review your notes from the last lecture. What reactions were discussed? For each ofthese, compare it to some reaction you learned in the past and establish the similar-ities and the differences (if any). Ask another student if she sees any similarities ordifferences 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 canproduce an pseudo-gem-DIN with electronegative elements -NH2 and -CN (the latterbeing 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 with4-hydroxy-2-pentanone? HINT: Remember that generally speaking proton transferreactions are very rapid.

3.327. IR, NMR, Reactions, and, in the HINT, Learning Organic Chemistry

A compound is reacted with NH2OH using acid catalysis and generates a product withIR peaks at 3247 (broad) and 1665 cm−1. The product has an 1H nmr that showsa triplet at 1.09 δ (3), a singlet at 1.87 δ (3), a quartet at 2.34 δ (2), and a broadsinglet that is exchangeable at 9.3 δ (1); and the decoupled 13C nmr shows peaks at10.84 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 isweaker 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 the1H nmr; seems high for the anticipated -OH peak. I looked it up and found that iswhere it occurs and, while looking at that data, found that a hydrogen attached to


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the carbon level 2 carbon of a oxime absorbs in the 6.5-8 δ region, considerably lessthan 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 H2CrO4, isolate the organic material, andthen treat it with ethyl magnesium bromide and then dilute acid. What is the prod-uct?

3.330. IR and Reaction

A compound has IR peaks at 2900-3000 cm−1, a weak peak at 2720 cm−1, and a peakat 1750 cm−1. When treated with water and an acid catalyst, the second and thirdof these peaks disappear and are replaced by a broad peak at 3300 cm−1. How wouldyou 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 3340cm−1. Use epwa to show what happens.

3.332. NMR and Reaction

Chloral, CCl3CHO, is also known as the “knock-out” drops, the famous “MickeyFinn” 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, thenatural philosopher of distinction from Searcy, Arkansas, which is just down the roadfrom Beebe, AR, which is the town where the red-winged blackbirds plunged to theirdeath on New Year’s Eve day in 2010 and 2011, to investigate (that folks, is a run-onsentence). He used nmr to look for the characteristic peak that occurs in aldehydesbetween 8 δ and 10 δ. He found no sign of a peak. Bonnie was joyful in his conclusionthat chloral was not present? Was he right? Give your reasoning.

3.333. Reactions

Compound 50 is treated with CH3Li followed by aqueous NH4Cl (which acts as aweak acid). What is the product?

3.334. Synthesis with Protection

How would you prepare 48 from 49? HINT: Two carbonyl groups: both would reactwith most reagents, unless . . .


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.


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3.336. Reactions

Multistriatin, a pheromone for the elm bark beetle, has the structure 53. What isthe 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 thepresence of acid with removal of water, followed by reaction of that product withethyl 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, onefinds the IR carbonyl peak disappears. What happens, and why, on the basis ofbonding, does it happen?

3.339. Synthesis

How would you synthesize 56 from cyclohexanone and other carbon containing com-pounds?

3.340. Epwa and Synthesis

How would you make 57 from compounds with four or fewer carbon atoms? Specifyyour reaction(s) with epwa.

3.341. Synthesis

How would you prepare 58 from butanal?


Use epwa to show the formation of the imine formed from 2-propanone and ethylamine.


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3.343. Review of Reversible Addition to Carbonyls

Compare the reaction of acetone with, on the one hand, NH3, and on the other withNH(CH3)2. How are they the same? How do they differ?


Use epwa to show the formation of the enamine from diethylamine and cyclohexanone.


We can make gem-diols, ketals, imines, and hydrazones from ketones. Think abouthow these reactions are similar and how they are different. Talk with another studentabout the similarities and the differences.




How do you make the kind of compound that you specified in the last problem?


Do you need to make C-C bonds to make 59 from cyclohexanone and compoundswith two or fewer carbon atoms?

3.349. Synthesis***

How would you synthesize 59 from cyclohexanone and compounds with two or fewercarbon atoms?

3.350. Reactions

What do you get if you treat 60 with CH3MgBr followed by concentrated H2SO4?

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 NH2X compounds. HINT: See thetitle.

3.352. Reactions*

What can you say about the yield for your reaction in problem 351? Why?


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 yourketone.

3.355. Reviewing Our Status

How many ways do we have to make a ketone?


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3.356. Reactions

Compound 62 does not react with dilute aqueous acid, but compound 63 does. Ac-count for this difference. HINT: What kinds of compounds would we call these twomaterials?

3.357. Spectroscopy

A compound has a 13C nmr spectrum with peaks at 13.30 δ , 19.04 δ , 19.26 δ , and119.87 δ . Its 1H nmr spectrum has peaks at 1.081 δ (t, 6), 1.699 δ (hextet, 4), and2.339 δ (t, 4). The mass spectrum has a molecular ion peak at 110 with an intensityof 37.7 and an (M+1)+ peak of intensity 3.5. What is the compound? HINT: This isa tricky question; you need to pursue and use logic.


Use epwa to show how an oxime is formed.

3.359. Reactions

What is the product of the reaction of 64 with (1) N2H4, (2) strong base with heat,followed by (3) H+/H2O?

3.360. Synthesis

How would you prepare 65 from fragments with four carbons or less? HINT: Thereare only two ways we know to get rid of a functional groups from a molecule.


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.


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3.362. Epwa, Mechanism, and Learning Organic Chemistry*

Enols, see the last problem, go back to ketones by the reverse mechanism of theirformation. Use epwa to show this and learn once again that doing a reversible processis easy once you can do it in one direction.


A variation of the Wittig reaction with aldehydes in the presence of formaldehydetakes place by the following steps. Let the Wittig reagent formed from propyl bromideand triphenylphosphine, after it is treated with butyl lithium, react with butanal toform a compound we call A. Now let A react with butyl lithium to form B. B thenreacts 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’tlet 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 to67? What is it? If you can, give an explanation for why 67 might be the dominantproduct.



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?


Use epwa to show how acid catalyzes the conversion of 69 into 70.


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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 C9H10O. The 1H 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 C9H10O3. The IR features a broad peak at about 3000cm−1, and peaks at 1770 and 1680 cm−1. The 1H nmr has the following peaks: 1.41δ (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 13C peaksare 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 C6H10O. The 1H 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 thecompound?


Chm 222 Spring 2016, Exercise Set 3 Addition to Carbonyls ...rlinck/Chm222/sec/pset3.pdf · Chm 222...

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