chem1002 2014-n-9 november 2014...chem1002 2014-n-9 november 2014 • consider compound a, whose...

CHEM1002 2014-N-9 November 2014

• Consider compound A, whose structure is shown below.

List the substituents on the stereogenic (chiral) carbon in compound A, in descending order as determined by the sequence rules.

Highest priority Lowest priority

Marks 8

-CH2OH -CH2CH3 -CH3 -H

Give the full name that unambiguously describes the stereochemistry of compound A.

(R)-2-methylbutan-1-ol or (R)-2-methyl-1-butanol

When compound A is reacted with racemic compound B, two compounds are formed as shown below.

Circle the stereogenic centre in compound B.

Draw the stick structures of the two compounds formed in this reaction. Make sure you clearly show all of the stereochemistry in your structures.

Are the two compounds formed in this reaction enantiomers, constitutional isomers or diastereoisomers?

They are diastereoisomers (stereoisomers which are not mirror images).

O

O

H H

O

O

H H


• Convert the following structure into a sawhorse projection.

3

What does the D in the name D-threose designate?

The OH on the last stereogenic carbon on the Fischer projection (i.e. the third carbon from the top) is on the right hand side.

OHH

CH2OH

CHO

HHO


• Methylphenidate, also known as Ritalin, is a psychostimulant drug approved for the treatment of attention-deficit disorder. Identify all stereogenic (chiral) centres in methylphenidate by clearly marking each with an asterisk (*) on the structure below.

Marks 7

Using a stereogenic centre you have identified, draw the (R)-configuration of that centre.

How many stereoisomers are there of methylphenidate? Describe the relationships between these isomers.

4: each isomer has 1 enantiomer and 2 diastereoisomers

Ritalin is generally sold as the hydrochloride salt, formed when methylphenidate is treated with dilute hydrochloric acid. Draw the structure of this salt and suggest why this is the preferred compound for sale.

The hydrochloride salt is soluble in water, which generally means better bioavailability. Salt will have better stability - amines are prone to aerial oxidation.

methylphenidate


• Convert the following structure into a Fischer projection. Marks

3


• Butanone is treated first with lithium aluminium hydride, LiAlH4, in dry ether and then with aqueous acid to yield the alcohol, A.

State whether A is obtained as the (R)-enantiomer, the (S)-enantiomer or as a racemic mixture. Give a reason for your answer.

Marks 4

Racemic mixture. The geometry around the carbonyl group is trigonal planar, so the H– nucleophile is equally likely to attack from either the top or bottom. This leads to equal amounts of the (R) and (S) enantiomers.

List below the substituents on the stereogenic (chiral) carbon atom in A, in descending order as determined by the sequence rule.

Highest priority Lowest priority

-OH -CH2CH3 -CH3 -H

Draw the stereoformula for the (R)-enantiomer with the lowest priority substituent at the back.


• The structure of (+)-citronellal, a widely occurring natural product, is shown below.

Marks 2

Which of the following best describes (+)-citronellal? achiral compound, racemic mixture, (R)-enantiomer, or (S)-enantiomer

(R)

Is it possible to obtain (Z) and (E) isomers of (+)-citronellal? Give a reason for your answer.

No. One end of the double bond has two identical groups (methyl) attached to it.


• 1,2-Dibromocyclopentane has two stereogenic carbon atoms, each marked with an asterisk (*) on the structure below.

The maximum number of configurational stereoisomers is given by the formula 2n, where n is the number of stereogenic centres. 1,2-Dibromocyclopentane has only three configurational stereoisomeric forms, not four. Explain briefly why this is the case. Include drawings of the relevant stereoformulas in your answer.

Marks 3

There are 4 possibilities: (1R,2R)-, (1S,2S)-, (1R,2S)- and (1S,2R)-. The first two of these are enantiomers. The last two are the same compound, a meso- isomer.


• Convert the following structure into a Fischer projection.

Marks 3


• Compound (X) is a derivative of a naturally occurring Japanese beetle pheromone.

OCH3

O

H

H3CO

Marks 7

What is the molecular formula of (X)? C16H30O3

What is the stereochemistry of the C–C double bond in (X)? (Z)

List the substituents attached to the stereogenic centre in descending order of priority according to the sequence rule.

highest priority lowest priority

OCH3 (CH2)7CH3

H

H3CO O

> > >

What is the absolute stereochemistry of (X)? Write (R) or (S).

(R)

On heating with 4 M H2SO4, one of the products obtained is compound (Y), whose structure is shown on the right. Explain the formation of this product.

O

OCH3

O

The 4 M H2SO4 catalyses 2 reactions; (i) hydrolysis of the ester to a carboxylic acid and (ii) addition of water across the C=C double bond to give the following intermediate:

ANSWER CONTINUES ON THE NEXT PAGE

OCH3

O

H

HO1

23

456

HO

(X)

(Y)


This intermediate can undergo an intramolecular esterification (the OH on carbon 5 reacts with the carboxylic acid group at carbon 1) to give the cyclic ester (Y).

How many different stereoisomers are possible for compound (Y)?

4*

*There are stereogenic centres at C4 and C5.

O

OCH3

O

12

3

4

5

6


• Bupivacaine is the active molecule in some local anaesthetics. Of the two enantiomers, the one shown below (X) is the more effective.

N

NHO

H

(1)

(2)

(3)

(4)

N

NHO

H

(1)

(2)

(3)

(4)

N

N O

H

(1)

(2)

(3)

(4)

counter-clockwise

Marks 7

What is the molecular formula of (X)? C18H28ON2

Calculate the m/z value for the major peak you would expect to see for the molecular ion in the high resolution mass spectrum. [Atomic masses: 1H = 1.0078; 12C = 12.0000; 16O = 15.9949; 14N = 14.0031]

The molecular ion has m = molar mass:

Molar mass = (18 × 12.0000 (C) + 28 × 1.0078 (H)

+ 15.9949 (O) + 2 × 14.0031 (N)) g mol-1 = 288.2195 g mol-1

Answer: 288.2195 g mol-1

List the substituents attached to the stereogenic centre in descending order of priority according to the sequence rule.


N

R1

R2

CONHR CH2 H

What is the absolute stereochemistry of (X)? Write (R) or (S).

(S) (see above)

Name the functional groups present in (X).

(tertiary) amine, amide, aromatic ring

(X)


N

NHO

H

(1)

(2)

(3)

(4)

N

NHO

H

(1)

(2)

(3)

(4)

N

N O

H

(1)

(2)

(3)

(4)counter-clockwise


• Threonine (Y) is an amino acid. On the structure of (Y) below, identify all stereocentres in threonine with an asterisk (*).

Marks 4

OH

COOHH2N

*

*

How many possible stereoisomers of threonine are there?

Two chiral centres so 4 possible stereoisomers (RR, SS, RS and SR)

Give the structures of the products obtained when threonine is treated with the following reagents.

1 M HCl

OH

COOHH3N

(HCl is a strong acid so will protonate the amine – a weak base. It will not protonate the very, very weakly acidic oxygen atoms at this concentration).

1 M NaOH

OH

CO2H2N

OH- is a strong base and will deprotonate the carboxlic acid – a weak acid. It will not deprotonate the very, very weakly acidic N-H or alcohol O-H groups.

(Y)


• Classify the starting materials for each of the following reactions as nucleophile or electrophile in the boxes provided and indicate with δ and δ the polarisation of the H–Br and C–Br bonds in the starting materials.

Marks 4

• Draw the constitutional formula for each of the following compounds. 3

(Z)-4-methylhex-2-ene

trans-1,3-dichlorocyclohexane

ClCl

(R)-butan-2-ol

OHH

H Br H

H B r ++ B r

nucleophile electrophile

H 3C N

CH 3

CH 3

CBr

H

H

H N

CH 3

H3C

CH 3

CH3+

Br


δ- δ+

δ+ δ-


• Dopa is a non-proteinogenic amino acid used to treat Parkinson’s disease. Only the enantiomer (X) is effective in restoring nerve function. The other enantiomer is highly toxic.

OH

O

HO

HO

H2N H

ab

Marks 7

What is the molecular formula of (X)? C9H11O4N

List the substituents attached to the stereogenic centre in descending order of priority according to the sequence rules.


NH2

COOH CH2 OH

OH

H

What is the absolute stereochemistry of (X)? Write (R) or (S). (S)

Name the functional groups, highlighted by the boxes a and b, present in (X).

a = arene (aromatic ring)

b = carboxylic acid

Give the constitutional formula of the product obtained when (X) is treated with NaHCO3.

O

O

HO

HO

H2N H

(X)


• Classify the starting materials for the following reaction as nucleophile or electrophile in the boxes provided and draw the structure of the product.

Marks 3

N CH3

CH3

H3C

CH3

Br

• Draw the constitutional formula for each of the following compounds. 2

(E)-5-methylhex-2-ene

(2)(1) (Highest priority

substituents onopposite sides of thedouble bond: (E))

cis-1,2-dichlorocyclopentane

Cl

Cl

CH3 N

CH 3

CH 3B r C

H

H

H

+



• Phenylalanine is a naturally occurring amino acid. Only the enantiomer (X) is commonly produced in nature.

O

OHH2N

Ha

b

(X)

(1)(2)

(3)

(Anticlockwise: (S))

Marks 6


List the substituents attached to the stereogenic centre in descending order of priority according to the sequence rules.


-NH2

-COOH

CH2

-H

What is the absolute stereochemistry of (X)? Write (R) or (S). (S)


a = arene (aromatic ring)

b = carboxylic acid


Draw the constitutional formula for each of the following compounds. 3

3,5-dichlorophenol

OH

Cl

Cl

(E)-4-methyl-2-pentene

(S)-2-bromobutane

Br


Adrenaline (X) is a naturally occurring hormone and neurotransmitter that is released

by the human body in response to stress.

(1)

(2)(3)

Marks

6


List the substituents attached to the stereogenic centre in descending order of priority

according to the sequence rules.


OH

CH2 N CH3

H

(-C-N-C)

HO

HO

(C-C-C-)

H

What is the absolute stereochemistry of (X)? Write (R) or (S). (R)


a = aromatic ring (arene)

b = secondary amine


Salbutamol (X) is the active ingredient in the asthma treatment Ventolin™. Although

the drug is marketed as a racemic mixture, the enantiomer of (X) shown is solely

responsible for the beneficial pharmacological action (smooth muscle relaxation).

(1)

(2)

(3)

Marks

6


List the substituents attached to the stereogenic centre in descending order of priority

according to the sequence rules.


OH

CH2 N

H

HO

HO

H

What is the absolute stereochemistry of (X)? Write (R) or (S). (R)

Name the functional groups, highlighted by the boxes a and b present in (X).

a = phenol

b = secondary amine

Give the constitutional formula of the product formed when (X) is treated with

cold dilute sodium hydroxide solution.

HO

O

N

HOHH

The H+ is removed from the phenol OH group as the negative charge is

stabilized by delocalization onto the aromatic ring.

chem1002 2014-n-9 november 2014...chem1002 2014-n-9 november 2014 • consider compound a, whose...

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