Problem Set 9 1.

Provide valid products for the following:

(a) Cl

1. NaCN/DMSO

CO2H

2. H2O, H2SO4 heat (b)

OH

NaCN

H3O+

DMF

!

NaCN

H3O+

DMF

!

OH CH2CO2H

CH2Br

(c)

Br

CH3 Br

(d)

(e)

Mg

1. CO2

ether

2. H3O+

CO2H

CH3 CO2H

O H

NaCN

H2O

H2SO4

H2SO4 conc.

OH CO2H H

OH CO2H H

C8H8O3 (f)

O

HCN

OH

H3O+

CO2H

KCN

(g)

CH3

1. Mg, Et2O

CCl4

2. CO2 3. H3O+

COOH

O

(h)

OH H

OCH3

1. LiAlH4 2. H2O

O

(i)

NBS

HO

O OCH3

1. LiAlH4 2.

H3O+

OH

(j)

O 1. LiAlH4

O

2. H2O

O

(k)

OH OH

O

O xs CH3OH

O O

OCH3

H2SO4 heat

CO2CH3

O

(l)

OH

CH3CCl pyridine O

(m)

OH

O CH3CCl

O

pyridine

(n)

H N

O CH3CCl

NH2

CH3

pyridine

CH3 (o)

Cl

O CH2COH CH2OH

(r)

NH2

O

1. LiAlH4

Cl

(q)

OCH3

K2CO3

N H

O

CH3

CH3OH

O

(c)

O

N

2. H2O

O H2SO4

O

benzene heat

O

CH3CCl pyridine

H N

CH3 O

(s)

OH

O

CH3COCl pyridine

CH3

O CH3

O

O

(t) OCH3

O

(u)

NH3

NH2

O

CH3OH

OCH3

Cl

H N

O

(v)

1. LiAlH4 Cl

N

2. H2O

O

(w)

H2O NH

(x)

O

H N

H3O+

CH3

OH (y)

H3N

COOH

CH3

H2O H2SO4 heat

+H

OH

3N

O

O OH

O

ClCCl

O

pyridine

(z)

CH3

NH2

O

O OH

ClCCl pyridine

H N

O O

(s)

OH

O

CH3COCl pyridine

CH3

O CH3

O

O

(t) OCH3

O

(u)

NH3

NH2

O

CH3OH

OCH3

Cl

H N

O

(v)

1. LiAlH4 Cl

H2O NH

O

H N

H3O+

CH3

OH (y)

H3N

COOH

CH3

H2O H2SO4 heat

(z)

N

2. H2O

O

(w)

(x)

CH3

+H

OH

3N

O

O OH

NH2

ClCCl

O

pyridine

O

O

O OH

ClCCl pyridine

H N

O O

2. Draw the principle organic product in each of the following reactions. Indicate all stereoisomers formed where appropriate. (a) Br CO2H NaCN H3O+ !

DMF

(b)

O

1. LiAlH4 O

OH

2. H2O

OH

O

(c)

O

O Cl

(d)

CO2H

N H

N

CO2CH3

CH3OH H3O+ O

(e) OH

(f)

O

O

O

O

O NH2

SOCl2

1. LiAlH4 2. H2O

NH2

3. (a) Which of the following products will be produced by thiohydrolysis of acetyl coenzyme A labeled with 35S at the sp3-hybridized oxygen as shown? (i) O CH3

1. NaSH

35

SCoA

2. H3S+

O (i) CH3

H35SCoA

SH O

(ii)

CH3

HSCoA

SH

O

(iii) CH3

(iv)

HSCoA

35

SH

a mixture of (i) and (ii)

(b) Which of the following tetrahedral intermediates is most likely to dissociate to give an ester? (iii) (i)

OCH3

(iii)

CH3 C NH2

CH3 C O2CCH3

OH

(ii)

Cl CH3 C O2CCH3 OH

OCH3 OH

(iv)

OH CH3 C NH2 Cl

(c) Which is the strongest acid? (iii) O

(i)

O

(iii) OH

OH

CH3

Cl

O

(ii)

O

(iv)

OH

OH

(d) Which of the following reactions will not give the acyl derivative shown? (iii) O

(i)

O CH3CO–

CH3CCl

CH3COCCH3

O

(ii)

O CH3NH2

CH3COH

(iii)

O O

O

CH3CNHCH3

O

Cl–

CH3COCH3

CH3CCl

O

(ii)

O H2O

CH3CCl

CH3COH

(e) Order of increasing acidity: CO2H

CO2H

CO2H CH3CH2OH

CH3O A

(i) D, B, A, C

CN B

(ii) C, B, A, D

C

(iii) B, C, D, A

D

(iv) B, A, C, D

(f) Order of increasing pKa: Cl

Cl Cl

CO2H CO2H

F

CO2H

Cl

A

B

(i) B, A, C, D

F

(ii) D, C, A, B

CO2H

C

D

(iii) B, C, A, D

(iv) D, C, B, A

(g) Increasing reactivity towards nucleophilic acyl substitution: O CH3

O O

A

CH3

O OCH3

B

(i) A, B, D, C

CH3

O O

O CH3

CH3

C

(ii) D, C, B, A

(iii) A, D, B, C

NH2 D

(iv) C, B, A, D

(h) Which tetrahedral intermediates would most likely lead to an ester?: O

O

H3C C NH2

H3C C OH

H3C C OCH3

H3C C OCH3

Cl

Cl

Cl

NH2

A

B

C

D

(i) C and D

(ii) B and C

O

(iii) A and C

O

(iv) C only

(i) What is the principal product from the following reaction? O H3O+

CH3MgBr

OCH3

(excess)

O

(i)

O

(ii) CH3

OH

(iii)

OCH3

(ii)

CH3 CH3

OMgBr

OCH3

(j) Which of the following molecules yield benzoic acid when hydrolyzed? (iii) O CH2OCCH3

CNH2

A

(i)

O

O

A, B

(ii)

CCH2CCH3

CN

B

C

(iii)

C, D

O

D

B, C

(iv)

B, D

(k) Which of the following molecules yield benzyl alcohol when reduced with LiAlH4? (iv) O CH2OCCH3

CNH2

A

(i)

A, B

O O

O

B

(ii)

C, D

COCCH3

CN

C

(iii)

D

B, C

(iv)

A, D

4. Outline a sequence of reactions that is suitable for the preparation of each of the following compounds from the indicated starting material and any organic or inorganic reagents. The syntheses will require more than one step. (a) (McMurray 20.31) CH3

CH2

CO2H

HBr

1. Mg/ether 2. CO2 3. H3O+

CH3 Br

(b) (McMurray 21.52b)

CN

N

H3O+

LiAlH4

OH O

N SOCl2 O

Cl

HN

O

(c) (McMurray 21.56) H N

NO2 F

O

O

(d) CO2H

CH3O

1. 2. 3. 4. 5. 6.

Br2/FeBr3 Mg/ether i. Butyraldehyde; ii. H3O+ PBr3 Mg/ether CO2

Or 1. NaCN/DMF 2. H3O+

CH3O

5. Show how butanol (as the only source of carbon) may be converted into each of the following compounds using any needed inorganic or organic reagents. You will need more than one equivalent of butanol. O O OH

O H2CrO4

H3O+

OH

OH or equiv.

6. Propose reasonable mechanisms for the following transformations. (McMurray 21.46) (a) O

Cl

NaN3

O

O

N3 O

O

N3 Cl

O

(b) O

O +

OCH3 OH

H3O

O

7. Provide valid syntheses for the following compounds from the indicated starting materials. (a) N,N-Diethyl-m-toluamide (DEET) is the active ingredient in many insect repellent formulations. How might you synthesize this substance from m-bromotoluene? O H3C

Br

H3C

?

N

Mg ether

H3C

HNEt2

MgBr 1. CO2 H3C

CO2H SOCl H3C 2

COCl

2. H3O+

(b) Phenyl 4-aminosalicylate is a drug used in the treatment of tuberculosis. Propose a synthesis of this compound starting from 4-nitrosalicylic acid. CO2H O2N

O ?

O

OH H2N

OH

SOCl2

SnCl2 OH O

COCl

O O2N

OH O2N

OH

8. Provide the missing structures in the scheme below.

LiAlH4

CO2H

a.

b. OH

PCC

CHO

HCrO4 Ph3P=CH2

KMnO4 c.

d.

OH 1. BH

PCC

CHO

e.

3

2. H2O2 HO–

H4 Al i L

Ag2O NH4OH f.

H O K

PBr3 g.

Br

CO2H

h. Mg

MgBr

ether CH3I K2CO3

1. NaOH 2. H3O+

i.

O

NaCN

1. CO2 2. H3O+

DMF

j. CN

OCH3

H3O+

CO2H

! 1. CH3MgBr 2. H3O+

NH3 O NH2

k.

O

SOCl2 l. Me2CuLi

COCl