What Is Camphor And How Is IT Used Biology Essay

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Camphor is a white solid which is waxy and crystalline in character. It is extracted from the oil of the Camphor Laurel tree, and such plantation is cultivated in parts of Asia (India and China in particular). The tree has small, clustered white flowers and bear red berries similar to cinnamon [1]. Recipe of this substance was first discovered in the 9th Century by the Arab chemist, Al-Kindi[2].

C:\Users\Patel\Desktop\Cinnamomum camphora.jpgC:\Users\Patel\Desktop\cincam09.jpg

Figure - The Cinnamomum Camphora Tree[3,4]

The compound can be obtained by one of three ways:

Freezing out

Complexation with strong acids eg) Sulphuric acid (H2SO4)

Fractional Distillation

Camphor can also be synthesised commercially from α-Pinene, which is now used in industry[5].

The natural product has a strong, pleasant and aromatic odour, making it suitable as an ingredient in desserts. Fadiaev describes the taste to be "bitter" at first and then "refreshing"[6].

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Camphor is widely used for religious celebrations in Hinduism by means of a holy flame for worshipping the Hindu God Shiva.

It is also highly valued for its availability in Chinese medicine. Natural products like this have many medicinal applications, in terms of herbal and therapeutic use as the active ingredient. A common example is the VICKS vapour rub (for chest inhalation and coughs). C:\Documents and Settings\06174083\Desktop\vicksvaporub.jpg

Figure - VICKS Vapour Rub[7]

Other treatments include for itching, bacterial infection, bruises, sprains and rheumatism. Therefore it can be used as a local anaesthetic as a result of the ability to numb nerve endings, since the compound has the power to absorb rapidly across mucous membranes (once through the skin), and to produce a cooling effect similar to that of menthol[8].

Camphor can also be used as:

An Insect Repellant

An Explosive of smokeless gunpowder

The manufacture of photographic film and celluloid.[1,6]

Despite all the good things mentioned, high toxicity levels of this compound can lead to certain adverse effects. Such examples include neuromuscular hyperactivity, jerky movements, irritation and mental confusion. The most extreme cases involve coma and death in toddlers[9]. Thus it is best avoiding consumption orally.

Physical Properties[10]

IUPAC name = 1,7,7-Trimethylbicyclo[2.2.1]heptan-2-one

Molecular Formula = C10H16O

Molecular Weight = 152 g mol-1

Melting Point = 176-180oC

Boiling Point = 204oC Figure - (+) and (-) Camphor

Ignition Temperature = 466oC

Vapour Pressure = 4 mmHg at 70oC

Log P = 3.04

Camphor is soluble in many Organic solvents. However, it does not dissolve in water because of the log P value. This is a measure of the hydrophobicity of the molecule, relative to the concentration ratio of Octanol and Water. Octanol is used for comparison as it relates to the hydrophobic level needed to pass through cell membranes in fish.

At standard room temperature and pressure, Camphor can undergo sublimation. In addition, there is a possible fire risk if the compound is exposed to sources of ignition.

Chemical Properties

Camphor goes under the class of Organic compounds known as the Terpenes. These are naturally occurring substances found in plants. This product is referred to as a bicyclic monoterpene due to cyclisation of two isoprene units, followed by hydrolysis and oxidation. The source of these units come from Geranyl Pyrophosphate.

C:\Documents and Settings\06174083\Desktop\700px-CamphorBiosynthesis.png

Figure - Biosynthesis pathway to Camphor from Geranyl Pyrophosphate[11]

The natural form has a strained bridged system as a result of steric hindrance, with the inclusion of an electron withdrawing effect from the carbonyl group.

Figure 5 - Molecular model of camphor showing the bicyclic system that existsIt contains two chiral centres at C1 and C4 (although two asymmetric carbons exist) and therefore a pair of diastereoisomers are formed (no enantiomers, so no R and S isomers).

Convention used for these types of isomers is the direction of plane polarised light after exposure to the molecule.

Hence (+) (Dextrorotatory) and (-) (Levorotatory) signs are used to signify clockwise and anti-clockwise rotation respectively, in relation to glyceraldehyde (see Figure 3). In general, the (+) isomer is the natural form, whereas the (-) isomer is the synthetic version[12].

Reactions With Camphor

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Camphor can undergo a number of reactions, given the susceptibilities to attack from nucleophiles and electrophiles given from figure 6:

Nucleophillic Addition from C=O followed by elimination of H2O

Electrophillic Addition from enolate anion at C3[13]

Electrophillic Substitution at C10[14]

Oxidation and Reduction[5,15]

Figure 6 - Nucleophillic (left) & Electrophillic (right) areas of attack of Camphor

In electrophillic addition reactions, the products are formed from the α carbon. The protons at C3 are slightly acidic, due to electron withdrawing power from the carbonyl group. Thus a proton can be removed by an acid or base catalyst forming a resonance stabilised carbanion, ready for addition of an electrophile.

e.g)

Br2, CH3COOH

Figure 7 - Synthesis of Bromocamphor by an Electrophillic Addition Reaction[13]

For electrophillic substitution reactions, the electrophile approaches the methyl group at C10 via an addition reaction, followed by elimination of a hydrogen atom.

e.g)

H2SO4, CH3COOH

Figure 8 - Synthesis of Camphor-10-Sulphonic Acid via an Electrophillic Substitution Reaction[14]

Oxidation of Camphor leads to the cleavage of the bond between C2 and C3 in the bicyclic ring using Nitric acid.

Figure 9 - Synthesis of Camphoric Acid through Oxidative Cleavage[5,15]

Reduction of the starting material to Borneol via Sodium Borohydride (a source of H-) forms a pair of diastereoisomers. They are expressed as the syn and anti syn forms, formed from the endo (Bottom) and exo (Top) faces of C=O at C2 respectively[15].

Figure 10 - The bridged structure of camphor enables reducing agents to attack stereoselectively

The dominant form of the product is determined from obtaining yields of both isomers through gas chromatography[16]. In general, the endo (Cis) configuration is the most stable as it avoids the steric hindrance coming from the bicyclic ring, wheras the exo (Trans) form does not.

Nucleophillic addition reaction will be explained later in section 2 from a derivative of camphor.

Aims and Relation To Penicillin

The objective of this work is to synthesise an Aminocamphor Sulphonate Ester derivative used for medicinal applications and testing:

Figure 11 - Aminocamphor Sulphonate Ester Derivative is the target molecule to the synthesis

It is said that the derivative possesses anti bacterial and structural properties, similar to that of penicillin.

Penicillin is the first anti bacterial drug known since at the time of the famous Scottish scientist, Sir Alexander Fleming in 1928.

C:\Users\Patel\Desktop\Idris's Project Stuff\01-05_penicillin_1.jpg

Figure 12 - A bacterium colony containing the active drug, Penicillin G[17]

This discovery was seen in one of his experiments from a bacterium colony, grown on agar medium (left over for several weeks). He noticed that the fungi that contaminated the dish (from exposure to air) caused cell lysis to many bacteria. Fleming concluded that an antibacterial agent was surrounding the colony[18].

Penicillin is only treatable for gram positive bacterial infections and not for gram negative, due to differences in thickness of cell walls. Figure 10 explains reasons behind the cell wall structure for these type of bacterium:

Gram Positive

Gram Negative

Type Of Structure

Strong, rigid & highly porous (no barriers)

Includes a lipopolysaccharide Membrane

(a membrane that contains lipids and carbohydrates linked onto a polymer chain)

Thickness

Wide

Thin

Number Of Peptidoglycan Layers

(A polymer layer consisting of proteins and sugars)

50-100

2

Example

Mycobacteria

E.Coli

Figure 13 - Comparison between gram positive and gram negative cell walls[18]

Comparing between the two structures resembles similarities and differences.

Figure 14 - 3D Structures of Aminocamphor Sulphonate Ester Derivative (Top) & Penicillin G (Bottom)

The structure of penicillin has two stereogenic centres, just like the derivative. Difference is that the chiral system is in the β-lactam ring, positioned at C3 and C6, in contrast to the derivative at C1 and C4.

A lactam is defined as a cyclic amide, and the number of carbon atoms joined with the NHCO bond classifies the type of lactam ring present[12]. In general, only three types exist:

β - lactam = 2 carbon atoms (4 membered ring)

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γ - lactam = 3 carbon atoms (5 membered ring)

δ - lactam = 4 carbon atoms (6 membered ring)

Another feature is the bicyclic system, but it is made from the β-lactam ring, joined with a thiazole ring (A five membered ring with a Sulphur atom).

Both structures have the same peptide (amide) bond attached to the main ring. The structures only differ by their molar masses:

Penicillin G = 333g mol-1 (C16H17N2O4S)

Aminocamphor Sulphonate Ester Derivative = 379 g mol-1 (C19H25NO5S)

Proposed Synthesis

2.1) Camphorquinone

Given that the original synthesis of the Aminocamphor Sulphonate Ester Derivative is composed of 4 steps, another route (which is shorter and efficient) needs to be devised.

The proposed route is composed of using a starting material similar to Camphor known as Camphorquinone.

Figure - CamphorquinoneThis derivative is a diketone positioned at C2 and C3 and is more stable than its enol form. It is because the latter form violates an important rule, where the double bond in bridged structures cannot be located in the bridgehead known as Bredt's rule[15]. Therefore the quinone shows properties of a diketone[5].

Camphorquinone can be synthesised from Camphor using Selenium dioxide and Acetic Anhydride[19].

Figure - Synthesis To Camphorquinone by Oxygen Activation

Due to health and safety reasons, SeO2 is highly toxic (smells like garlic) and a possible carcinogen. So instead, Camphorquinone is bought commercially.

The synthesis will involve three steps:

Formation of the oxime, Camphorquinone Monoxime

Figure - Synthetic routes to Camphorquinone Monoxime

Reduction to an Amine, Aminocamphor

Figure - Reduction of the oxime leads to the amine

Acylation of Aminocamphor to produce an amide derivative of Camphor

Figure - Acylation of Aminocamphor using an acid chloride]

2.2) Formation Of Camphorquinone Monoxime

In this reaction, Camphorquinone reacts with Hydroxylamine as the nucleophile. The conditions used are in Pyridine catalyst and Ethanol as the solvent[19].

However, using Hydroxylamine alone is unstable as it is easily oxidised by air. Thus Hydroxylamine Hydrochloride (the salt form) is used as an alternative, which is readily available[20,21]. Having mentioned this, the Nitrogen atom in the salt has no lone pairs (making it electron deficient). So nucleophillic character of hydroxylamine is lost[21].

Figure - Differences in chemical properties between two equivalent forms of Hydroxylamine

An advantage of using Pyridine in these cases is the proton removal of the Nitrogen, which is in equilibrium given below:

Pka = 5.2

Pka = 8.03

Figure - The abilty of Pyridine to remove a proton of the salt is dominant when it is used in excess[22]

At equilibrium, the starting material is favoured. But excess Pyridine will form some Hydroxylamine. Reason for this is that salts of Pyridine and Hydroxylamine are sources of protons, and so the anion of Hydroxylamine (-NHOH) is unlikely to form. Pka values of the changes in Pyridine emphasise this point.

In conclusion, the Oxygen atom at C3 of Camphorquinone is protonated prior to nucleophillic reaction[22]. Figure 16 explains the mechanism for this reaction:

Figure - Mechanism to the synthesis of Camphorquinone Monoxime using Pyridine

Another route to obtain the oxime is replacement of Pyridine to Sodium Acetate. This is also in equilibrium with the salt to release free Hydroxylamine[20], and nucleophillic reaction with the quinone proceeds as before. Solvents used are Ethanol and Water[23].

Figure - Mechanism to the synthesis of the oxime using Sodium Acetate

2.3) Reduction To Aminocamphor

This reaction involves a 4 electron reduction of Camphorquinone Monoxime to Aminocamphor using zinc dust and acetic acid[24].

Zinc in its neutral species is Zno. This is a d10 configuration plus 2 electrons (possibly from access to f orbitals).

After reaction, Zno becomes oxidised to Zn2+ and the oxime is converted to the secondary amine. The acid helps to form water (as a good leaving group), and the carboxylate anion generated will chelate with Zinc to produce Zinc Acetate.

2.4) Conversion To The Amide Derivative

The Amine produced from step 2 reacts with Benzoyl Chloride, yielding the Amide Derivative of Camphor. It proceeds via a nucleophillic acyl substitution reaction (SN2), with Toluene as the solvent.

This reaction is particularly useful with primary and secondary amines and is known as the Schotten-Baumann reaction[25].

Figure - Mechanism of the Nucleophillic attack of the amine with an acid chloride

3) Experimental Procedure

3.1) Experiment 1 - Preparation Of Camphorquinone Monoxime Using Pyridine [19]

Apparatus

Camphorquinone = 1.00g (6.02Ã-10-3 mol)

2Ã-50ml round bottom flask

24ml Ethanol

4ml Pyridine

Hydroxylamine Hydrochloride = 0.544g (7.80Ã-10-3 mol)

Magnetic stirrer

Rotary Evaporator

10ml Hexane

10ml Ethyl Acetate

100ml Separating Funnel

12.5ml Hydrochloric Acid (2M)

30ml Water (Deionised)

30ml Saturated Sodium Chloride (Brine Water)

Magnesium Sulphate

6.5ml Petroleum Ether (60-80)

Dessicator with vacuum chamber

Phosphorus Pentoxide (In a beaker)

Tin foil

Method

In a 50ml round bottomed flask, Camphorquinone (1g, 6.02Ã-10-3 mol), Hydroxylamine Hydrochloride (0.544g, 7.8Ã-10-3 mol), 4ml Pyridine and 24ml Ethanol were mixed together. The flask was covered with tin foil and the mixture was stirred for 30 minutes. Ethanol was removed by rotary evaporation and the remaining oil was diluted with 10ml of Hexane and Ethyl Acetate. The oil was transferred to a 100ml separating funnel (taking care to remove the magnetic stirrer) and the organic phase was washed with 12.5ml Hydrochloric Acid (2M), 30ml Water and Brine water. The yellow solution was dried over Magnesium Sulphate, filtered by gravity filtration and concentrated again under reduced pressure. Petroleum Ether (6.5ml) was added to the remaining residue, refluxed for 10 minutes and was left to cool down to room temperature. A white solid was observed (can also be orange as the crude form) and was left to desiccate for 24 hours. Camphorquinone Monoxime was yielded as a mixture of syn and anti-syn isomers.

3.2) Experiment 2 - Preparation Of Camphorquinone monoxime Using Sodium Acetate [23]

Apparatus

Camphorquinone = 1g (6.02Ã-10-3 mol)

Hydroxylamine Hydrochloride = 0.418g (6.02Ã-10-3 mol)

Sodium Acetate = 0.415g (5.02Ã-10-3 mol)

30ml Ethanol

24ml Water

2Ã-30ml Dichloromethane

Magnesium Sulphate

Petroleum Ether

2 Round bottomed flasks (1Ã-100ml and 1Ã-50ml)

100ml Separating funnel

Rotary evaporator

Water Bath

Method

In a 100ml round bottomed flask, Camphorquinone (1g, 6.02Ã-10-3 mol), Hydroxylamine Hydrochloride (0.418g, 6.02Ã-10-3 mol), and Sodium Acetate (0.415g, 5.02Ã-10-3 mol) were mixed in Ethanol (30ml) and Water (24ml) and was refluxed on a water bath for 1 hour. The reaction mixture was then concentrated by rotary evaporation and then transferred to a 100ml separating funnel. The organic phase was washed and separated with Dichloromethane (2Ã-30ml) and the aqueous phase was dried over MgSO4 and filtered by gravity filtration. The resulting filtrate was transferred to a 50ml round bottomed flask and then evaporated again under reduced pressure. It was then recrystallised in Petroleum ether to give Camphorquinone Monoxime (as a mixture of syn and anti-syn isomers).

3.3) Experiment 3 - Preparation Of Aminocamphor[24]

Apparatus

Zinc dust = 0.333g (5.12Ã-10-3 mol)

9ml Glacial Acetic Acid

Camphorquinone Monoxime = 0.2g (1.10Ã-10-3 mol)

Magnetic Stirrer

50ml Round Bottomed Flask

10ml Chloroform

2Ã-20ml Water

100ml Separating Funnel

Sintered Funnel

Magnesium Sulphate

Rotary Evaporator

Method

In a 50ml round bottomed flask, Zinc dust (0.333g, 5.12Ã-10-3 mol), 9ml Glacial Acetic Acid and the oxime generated from experiment 1 or 2 (0.2g, 1.1Ã-10-3 mol) was stirred for 30 minutes at room temperature. Most of the inorganic material was removed by vacuum filtration using a sintered glass funnel, and the filtrate was diluted with 10ml Chloroform. The mixture was then transferred to a 100ml separating funnel and extracted with 2Ã-20ml Water to remove any remaining unreacted dust. The product phase was dried over MgSo4, filtered by gravity filtration and heated up on a hot plate at 110oC to eliminate any glacial acetic acid and solvent present. A yellow oil was observed which means that Aminocamphor has been produced.

3.4) Experiment 4 - Preparation Of Amide Derivative of Camphor[25]

Apparatus

Aminocamphor = 0.13g approx (4.80Ã-10-4 mol)

0.2ml Benzoyl Chloride

2ml Pyridine

4ml Toluene

10ml Hydrochloric Acid (2M)

25ml Water

2ml Sodium Carbonate (5%)

100ml Separating Funnel

Water Bath

Magnesium Sulphate

Hot Plate

Ethanol

Desiccator with vacuum chamber

Phosphorus Pentoxide (in a beaker)

Method

In a 50ml round bottomed flask, Aminocamphor (approx 0.13g, 4.8Ã-10-4 mol), 0.2ml Benzoyl Chloride, 2ml Pyridine were mixed in 4ml Toluene and was refluxed in a water bath for 30 minutes. The reaction mixture was diluted in 20ml water and was transferred to a 100ml separating funnel. 10ml HCl (2M) was added and the mixture was shaken to get rid of any excess benzoyl chloride and also dissolving the pyridine. The organic phase was washed with 2ml Water and 2ml NaCO3 (5%). The resulting product phase was dried over MgSO4, filtered by gravity filtration and was transferred to a hot plate. The hot plate was set to 120oC to boil off any remaining toluene. A white solid was observed suggesting formation of the amide derivative of Camphor. It was recrystallised in Ethanol and left in a desiccator to dry.

Results & Analysis

4.1) Experiment 1

A browny yellow oil was observed after stirring and evaporation under reduced pressure. The overall product appeared as an off-white solid, sometimes orange (the crude form, so needs further purification).

Mass of Camphorquinone Monoxime = 0.84g

Mr = 181 g mol-1

Theoretical yield = 1.09g

% Yield = 77 %

Melting Point = 150-152oC

TLC of the compound in Ethanol gave a spot with an Rf value of 0.78. Detection of the oxime came as a light green spot when dipped in 1% CuSO4 solution.

1% CuSO4

Infrared Analysis Of Camphorquinone Monoxime

Absorption (cm-1)

Bond Vibrating

Structural Feature

3442

O-H Stretch

Oxime

2958

C-H Stretch

Aliphatic Chain

1744

C=O Stretch

Ketone

1642

C=N Stretch

Oxime

861

C-H Bend

Substitued oxime?

From the infrared spectrum, it suggests that an oxime has been formed. However, use of H1 and C13 NMR spectra will help determine if the compound is generated.

H1 NMR Analysis Of Camphor

Peak

Chemical Shift (ppm)

Integration Reading (mm)

Number Of H Atoms

Multiplicity

Structural Feature

A

2.39, 2.32

15

1

Triplet (Ã-2)

CH

B

2.09

14

1

Triplet

CH2

C

1.88, 1.81

27

2

Multiplet, Singlet

CH2

D

1.69

9

1

Multiplet

CH2

E

1.62

6

1

Singlet

CH2

F

1.37

13

1

Multiplet

CH2

G

0.96

45

3

Singlet

CH3

H

0.92

47

3

Singlet

CH3

I

0.84

46

3

Singlet

CH3

H1 Analysis Of Camphorquinone

Peak

Chemical Shift (ppm)

Integration Reading (mm)

Number Of H Atoms

Multiplicity

Structural Feature

A

2.38, 2.32

21

1

Triplet (Ã-2)

CH

B

2.09

21

1

Triplet

CH2

C

1.87

24

2

Multiplet

CH2

D

1.61

18

1

Multiplet

CH2

E

1.37

18

1

Multiplet

CH2

F

1.11

39

2

Doublet

CH3

G

0.91

65

3

Triplet

CH3

H

0.83

65

3

Singlet

CH3

H1 Analysis Of Camphorquinone Monoxime

Peak

Chemical Shift (ppm)

Integration Reading (mm)

Number Of H Atoms

Multiplicity

Structural Feature

A

7.84

1

1

Singlet

N-OH

B

2.39, 2.32

1

1

Triplet (Ã-2)

CH

C

2.17

1

1

Triplet

CH2

D

2.03

20

2

Multiplet

CH2

E

1.83

5

1

Doublet

CH2

F

1.79

13

1

Doublet

CH2

G

1.60

12

2

Singlet

CH3

H

1.58

17

3

Singlet

CH3

I

1.54

21

3

Singlet

CH3

From comparison between Camphor and Camphorquinone, it seems that the orange product is contaminated. So a perfect spectrum cannot be deduced, apart from it looking similar to the standard chemicals. In conjunction to this, the oxime is formed because the NOH bond is located at 7.84ppm. Therefore the next analysis will confirm the occurance of the oxime product.

C13 Analysis Of Camphor

Peak

Chemical Shift (ppm)

Hybridisation

Structural Feature

1

220

SP2

C=O

2

77

SP3

Quaternary Carbon

3,4

43.4, 43.1

SP3,SP3

CH2,CH

4

30

SP3

CH2

5

27

SP3

CH2

7,8

19.8,19.2

SP3,SP3

CH3,CH3

9

9

SP3

CH3

C13Analysis Of Camphorquinone

Peak

Chemical Shift (ppm)

Hybridisation

Structural Feature

1

131

SP2

C=O

2

77

SP3

Quaternary Carbon

3

58

SP3

CH

4

47

SP3

Quaternary Carbon

5,6

43.3,43.0

SP3,SP3

CH2,CH

7

30

SP3

CH2

8

27

SP3

CH2

9,10

22,21

SP3

CH2,CH

11,12

19.7,19.1

SP3

CH3,CH3

13

9

SP3

CH3

C13Analysis Of Camphorquinone Monoxime

Peak

Chemical Shift (ppm)

Hybridisation

Structural Feature

1

204

SP2

C=O

2

163

SP2

C=NOH

3

77

SP3

Quaternary Carbon

4

47

SP3

CH2

5

45

SP3

Quaternary Carbon

6

31

SP3

CH3

7

24

SP3

CH3

8

21

SP3

CH2

9

19

SP3

CH3

10

9

SP3

CH2

11

0

SP3

CH2

Again, the contamination of Camphorquinone Monoxime is prevalent in the spectrum. In contrast to the H1 NMR, it is much clearer to see. Comparison with the two standards indicates that the oxime is produced after all.

As a precaution, a mass spectrum of the compound was taken for analysis.

Mass Spectral Analysis Of Camphorquinone Monoxime

M/Z

Fragmentation

93

CQMO-CH3(x2)-C=O-OH-NH

106

CQMO-CH3(x2)-C=O-OH

121

CQMO-CH3-C=O-OH

136

CQMO-OH-C=O

153

CQMO-C=O

164

CQMO-OH

181

Camphorquinone Monoxime

The mass spectrum finally deduces the identification of Camphorquinone Monoxime without any problems with contamination.

Due to lack of time, the oxime synthesised in experiment 2 was not taken for analysis. But obsersavions were the same as in this experiment (i.e) Experiment 1), when describing the appearance of the oxime.

4.2) Experiment 3

After reduction, extraction and purification (as much as possible), a yellow oil was produced, indicating that Aminocamphor has been synthesised.

Mass of Aminocamphor = 0.13g

Mr = 167g mol-1

Theoretical yield = 0.18g

% Yield = 72%

TLC of the product was done in Ethanol, giving an Rf value of 0.76.

Detection of the amine was carried out with Ninhydrin spray, and upon drying for 5 minutes with a blowdryer, a yellow spot verifies the conversion to the required product.

Ninhydrin Spray and drying

Now knowing this, spectral analysis of the compound can be determined.

H1 NMR Of Aminocamphor

Peak

Chemical Shift (ppm)

Integration Reading (mm)

Number Of H Atoms

Multiplicity

Structural Feature

A

4.5

32

2

Singlet

NH2

B

2.1

8

1

Triplet

CH

C

1.9

7

1

Triplet

CH2

D

1.8

20

1

Multiplet

CH2

E

1.3

20

1

Singlet

CH

F

1.2

15

1

Triplet

CH2

G

1.1

47

3

Doublet

CH2

H

1.0

60

3

Doublet

CH3

I

0.9

55

3

Singlet

CH3

J

0.6

15

1

Singlet

CH3

From the spectrum, the compound seems to be contaminated, due to difficulty of removing the glacial acetic acid. Comparing to the spectrum of Camphor enables the relationship between the two to be good overall. Analysis using C13 NMR was taken for consideration.

C13 Analysis Of Aminocamphor

Peak

Chemical Shift (ppm)

Hybridisation

Structural Feature

1

188

SP2

C=O

2

77

SP3

Quaternary Carbon

3

66

SP3

CH

4

54

SP3

CH

5

37

SP3

CH2

6

32

SP3

CH2

7

22

SP3

CH2

8,9

20.1,19.9

SP3,SP3

CH2,CH3

10

19

SP3

CH3

11

11

SP3

CH3

As before, the peaks are much clearer than in H1 NMR. But a number of peaks are too close to be observed due to contamination. Relation to the spectra of Camphor is overall good, indicating the identification of the required compound.

Mass Spectral Analysis Of Aminocamphor

M/Z

Fragmentation

110

AC-CO-NH2-CH

124

AC-CO-NH

135

AC-CH3

150

AC-NH3

167

Aminocamphor

The results show a perfect identification to Aminocamphor without any contamination of other materials present in the mixture. Therefore the zinc reduction step is a reliable reaction, remembering to remove difficult solvents like glacial acetic acid. For instance, using a hot place at 110oC (Boiling point of acid).

Infrared spectrum of Aminocamphor cannot be applied because the procedure was done under a 0.2g scale

Due to lack of time, the amide from Experiment 3 cannot be analysed by TLC and spectroscopic methods. Observation was a white solid after purification and dessication.

Conclusion

The intended work originally was to synthesise an Aminocamphor Sulphonate Ester Derivative for medicinal properties and testing. From spectral analysis of results, a synthetic route leading to the Amide Derivative of Camphor seems promising. However, further purification steps are needed to be taken in practice to reveal ideal spectra. But overall, a total of 3 routes so far have been established, compared to 5 steps to make the target molecule.

If the Amide derivative is formed, then it is possible to sulphonate the compound at C10 from a mixture of Sulphuric Acid and Acetic Acid (given from Dr.D'Silva as a teaching preparation). Enabling a SO3H group can be esterifyied using Ethanol and will help to form the Sulphonate Ester.

There are other methods to obtain the oxime and amine which may produce in better yields than the respective values of 77 and 72%. For Camphorquinone Monoxime:

Susmita Roy and and Asit K. Chakraborti[26] used Camphor in dry THF (Tetrahydrofuran) mixed in Potassium tertiary butoxide, tBuOK. The conditions must be absolutely dry or the solution will turn blue, indicating the failure of the experiment.

Bredt and Perkin[27] placed Camphor in an ether solution and was mixed with Sodamide and isoamylnitrite under 0oC.

The reduction step to Aminocamphor was also followed by their method for replacing Glacial Acetic Acid with NaOH.

An alternative to using Zinc would be to use other inorganic reagents like Raney Nickel[28] and ZrCl2[29].

Applying a different procedure to the amide derivative (if no product is yielded) would involve changing solvents and vigorous shaking[30,31].

6) References

[1] = "Camphor" by M.Grieve from:

http://www.botanical.com/botanical/mgmh/c/campho13.html#des

[2] = D.M. Dunlop, Arab civilization, op. cit., p. 229.

Ibid, p. 230ff

[3] = http://www.jamesdeandesign.com/Slide_Show/Plant_Catalog/TREES/Cinnamomum%20camphora.jpg

[4] = http://aquat1.ifas.ufl.edu/images/cincam/cincam09.jpg

[5] = A.R Pinder, The Chemistry Of The Terpenes, Chapman & Hall, 1960, p97, 105-106

[6] = "Camphor properties" by Sergey P.Fediaev, from:

http://www.spinfields.hut2.ru/ALMANACH/N1_96/StormGlass.htm

[7] = www.patient-pharmacy.co.uk/.../vicksvaporub.jpg

[8] = "Camphor for Pain Relief" by Vincent Platania (2009) from:

http://www.disabled-world.com/medical/alternative/herbal/camphor-pain.php

[9] = Jeffrey N. Love, MD,* Maura Sammon, MD,† and Janet Smereck, MD*, J Em Med, 2004. 27, 49-54

[10] = "Sigma Aldrich" website from:

http://www.sigmaaldrich.com/catalog/ProductDetail.do?N4=21300|FLUKA&N5=SEARCH_CONCAT_PNO|BRAND_KEY&F=SPEC

http://www.sigmaaldrich.com/MSDS/MSDS/DisplayMSDSPage.do

[11] = Savage, T.J, Archives of Biochem and Biophys, 1993, 305(2), 581-587

[12] = J Daintith, A Dictionary Of Chemistry, OUP, 2004, definitions of "Lactam", "Diastereoisomers"ff.

[13] = Ager, D.J, Handbook Of Chiral Chemicals, CRC Press, 2008, p108

[14] = Maroto, B.L, Tet Let, 2000, 11(15), p3059-3062

[15] = Clayden, Greeves, Warren & Wothers, Organic Chemistry, OUP, 2001, p484,862-863

[16] = "Reduction of Camphor with Sodium Borohydride" from:

http://www.chemistry.mcmaster.ca/~chem2o6/labmanual/expt7/2o6exp7.html

[17] = http://www.socialfiction.org/?n=181

[18] = Graham L.Patrick, An Introduction To Medicinal Chemistry (3rd edn), OUP, 2005, p388ff

[19] = "CAMPHORQUINONE AND CAMPHORQUINONE MONOXIME" from:

http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v79p0125

[20] = Mei Tak Yip, David R.Dalton, Organic Chemistry In The Laboratory, D.Van Nostrand Company, 1979, p125-126

[21] = Morrison & Boyd, Organic Chemistry (6th Edn), Prentice Hall, 1992, p679-680

[22] = Audrey Miller, Phillipa H.Solomon, Writing Mechanisms In Organic Chemistry, Elsevier Science & Technology Books, 1999, p176ff

[23] = AM'Boungou-M'Passi, F Henin, J Muzart, JP Pete, Bull Soc Chim Fr , 1993, 130, p214-217

[24] = Yikang Wu, Per Ahlberg, J Org Chem (1992), 57, p6324

[25] = David C.Eaton, Laboratory Investigations In Organic Chemistry, McGraw-Hill Book Company, 1989, p783-785

[26] = Susmita Roy and and Asit K. Chakraborti, J Tet Let, 1998, 39, p6355-6356

[27] = Bredt & Perkin, J Chem Soc, 1913, 103, p2182ff

[28] = Albert Kascheres and Reinaldo A. F. Rodrigues, J Tet Let, 1996, 52(40), p12919-12930

[29] = David R. Williams, John W. Benbow, Thomas R. Sattleberg and David C. Ihle, J Tet Let, 2001, 42, p8597-8601

[30] = L.M.Harwood, C.J.Moody, J.M.Percy, Experimental Organic Chemistry - Standard And Microscale (2nd edn), Blackwell Science Ltd, 1999, p272-273

[31] = Charles F.Wilcox Jr, Experimental Organic Chemistry, Macmillan Publishing Company, 1988, p182