2012 H3 Lecture Test 2 Practice Questions 1 Pheniramine, chlorpheniramine, brompheniramine and clemastine are antihistamines which are used

to treat allergic conditions. They are often taken as their maleate or fumarate salts.
Cl
N N

Br N

N N

pheniramine

chlorpheniramine
Cl

brompheniramine

O O
O O O O

O O
fumarate

clemastine

maleate

A mixture of the above antihistamines and their salts, dissolved in a suitable solvent, was analysed using high performance liquid chromatography. The chromatogram is shown below.

pheniramine

recorder response

maleate fumarate

chlorpheniramine A

1.0

2.0

3.0

4.0

5.0

6.0

retention time / min (a) With the aid of a labeled diagram, outline the important parts of the apparatus used for high performance liquid chromatography. Suggest whether normal or reverse-phase HPLC was used. Suggest a suitable mobile phase for this separation. Decide, giving a reason, which of the two antihistamines, brompheniramine or clemastine, was responsible for peak A. Find the ratio of the amount of pheniramine to chlorpheniramine in the mixture. State any assumptions made. Maleate and fumarate ions have the same mass and carry the same charge. Explain why it is nonetheless possible to separate maleate and fumarate ions using electrophoresis. [4] [2] [1] [2] [2]

(b) (c) (d)

(e)

(f)

[1]

2(a)

Explain the following observations with the help of suitable diagrams (where appropriate) . (i) The infrared spectrum of a dilute solution of cis3fluorocyclohexanol shows a lower frequency OH stretching frequency peak than the transisomer. [2] Substitution of an amino group on the 4position of acetophenone shifts the C=O frequency from about 1685 to 1652 cm1, whereas a nitro group attached to the 4position yields a C=O frequency of 1693 cm1.

(ii)

CH3

CH3

CH3

NH2 acetophenone
(b) (i)

NO2 4-nitroacetophenone
[2]

4-aminoacetophenone

The reference standard used in NMR spectroscopy should give a single intense peak on the spectrum well away from the peaks owing to the compound analysed. Explain why deuterated sodium trimethylsilyl propanoate (sodium TMSP) is suitable as the reference standard in this respect. [2]

D Si

O O Na

deuterated sodium TMSP Suggest why deuterated sodium TMSP is sometimes used in preference to TMS as the reference standard. [1]

(ii)

3(a) An unknown anaesthetic has the formula C13H20N2O2. C13H20N2O2 was hydrolysed by heating with dilute HCl, followed by careful neutralisation to form compounds B and C. H+ C13H20N2O2 + H2O C7H7NO2 + C B (i) (ii)
1

State the molecular formula of C. The 1H NMR and IR spectra data of B are given below. Deduce the structure of B, giving your reasoning.

[1] [6]

H NMR spectrum data of B: / ppm 12.00 7.70 6.50 5.90 Integral ratio 1 2 2 2 Multiplicity Broad singlet; disappeared upon the addition of D2O Multiplet Multiplet Broad singlet; disappeared upon the addition of D2O

IR spectrum of B:

(iii) The 1H NMR and IR spectra of C are given below. Deduce the structure of C, giving your reasoning.
1

[5]

H NMR spectrum of C:

Note: The NMR peak at ~ 7.4ppm disappears in the presence of D2O. Note: The peak at 2.5ppm is an overlap between 2 signals. You need not discuss about the splitting pattern of this peak.

IR spectrum of C:

(iv) Hence, deduce the structure of the unknown anaesthetic, C13H20N2O2. (c) The reaction below is an important step in the synthesis of amino acids.
CH3 C2H5 H C O O C N H R CF3CO2H O C CH3CH=CHCH3 R N H

[1]

HO

(i)

Assign the R/S configuration of the chiral centre in the starting compound. Explain your answer. In the presence of CF3CO2H catalyst, the starting compound can react to form CH3CH=CHCH3 and RNHCO2H. This reaction involves bimolecular kinetics. Suggest a possible mechanism for the reaction, indicating clearly whether the E or Z isomer of CH3CH=CHCH3 is the major product. You should use Newman projection to account for the stereochemistry of the major product.

[2]

(ii)

[7]

An unknown compound A, which contains 11 carbon atoms, was synthesized in the laboratory. Its 1H NMR, MS, IR and UV spectra data are given below. Deduce the structure of A giving your reasoning.
1

H NMR spectrum of A / ppm 7.30 7.50 2.30 1.50 Integral 2 3 9 Multiplicity Multiplet Singlet Singlet

Major fragments in MS spectrum of A m/z 15 57 247 304 306 308 IR spectrum of A Wavenumber / cm1 1610, 1650 2900 to 3050 Description Sharp, medium bands Strong bands [10] Intensity 100 80 70 25 50 25

The UV spectrum of A shows absorption above 220 nm.

5 Dorzolamide is an anti-glaucoma agent and topically applied in the form of eye drops. Glaucoma is a condition in which the pressure in the eye is increased due to the accumulation of fluid. Following administration of dorzolamide to the eye, intraocular pressure is lowered and the risk of nerve damage and vision loss is decreased.
H3C NH O S O NH2 .HCl

H3C

S O

dorzolamide

Dorzolamide is synthesized in the laboratory based on the following reaction scheme.

O H 3C O H 3C OCH2Ph step I H 3C O H3C S S OH step IV H 3C O S O O 1) HCl 2) (CF3CO)2O step II H3C O

S O O

OH step III H 3C S S

O O CH3COCCH3 step V S H3C O

CH3

S O

H 3C

NH O S O NH2 .HCl

H 3C

S O

(a)

A chemist needs to synthesize dorzolamide in the laboratory. However, he only has

O H3CO O CH3

as the starting material.

O O CH3 O OCH2Ph CH3

Propose a 3-step synthesis to convert H3CO (b)

O H3CO

to H3CO

[3]

An alternative starting material for the synthesis of dorzolamide is to use the thioether,
SCH2Ph CH3

, in step I. [2] [3] [3]

Which of the starting material, thioether or ether, is more reactive? Give a reason to support your answer. (c) (d) State the reagents for step I. Account for the stereochemistry behind the reaction in step I. (i) Explain why electrophilic substitution of thiophene takes place preferentially at the 2position. Suggest why electrophilic substitution did not occur at the 2-position, but at the 4position in step II.

(ii)

O H3C O H3C S 4 S 2

[1]

(e) Identify the types of reaction and suggest suitable reagents and conditions for steps III and IV. [4] (f)
O O Outline the mechanism in step V and suggest why H3C C O C CH3 is a more suitable

reagent than CH3CO2H. 6 (a) Compound N is a penicillin derivative.

[4]

S NH2 N O O
N

N O

O O O

Predict the products of the reactions of N with each of the following: (i) (ii) (iii) (b) dilute hydrochloric acid concentrated aqueous ammonia lithium aluminium hydride. [7]

Pyrrole reacts readily in the Vilsmeier reaction to produce the aryl aldehyde, P. The Vilsmeier reaction is the chemical reaction of a substituted amide with phosphorus oxychloride and an activated arene to produce an aryl aldehyde. The reaction scheme of the Vilsmeier reaction is shown below.
CH3 N H O substituted amide Cl Cl P O Cl phosphorus oxychloride CH3 N N H H 2O step 3

CH3

CH3 step 1 CH3

N O POCl2

pyrrole step 2

CH3

Cl2OPO

OHC P

N H

(i) (ii)

Describe the mechanism involved for step 1.

[2]

Describe the mechanism for step 2 and explain, with the help of relevant mesomeric structures, why electrophilic substitution happens at position 2 instead of position 3 of the pyrrole ring. [5]

(c)

Guanine is one of the four main nitrogenous bases found in DNA and RNA. Arrange the nitrogens labeled NA to ND in guanine in order of decreasing basicity and explain your answer.
O HNA H2NB N guanine NDH NC

[4]
(d) Compound S is synthesized via a 2-step synthesis as shown below.

NH2 + OH

O
solvent reflux Step 1

H N
CBr4, Ph3P CH3CN, r.t

H N

OH

Step 2

Br

S
(i) (ii) Describe the reaction mechanism in step 1. [3]

Step 2 uses a novel method of substituting OH for Br. Briefly explain why mainstream [1] method such as using PBr3 may not be suitable.