Activity WM3 "Investigating the chemistry of the -OH group in various environments"

• All the background chemistry is covered in Chemical Ideas 13.4 part b.

• You need to know the results of testing ethanol, phenol, ethanoic acid and 2-hydroxybenzoic acid with (i) universal indicator, (ii) sodium carbonate solution and (iii) iron(III) chloride solution. Might be a good idea to do aspirin as well.

  • also be able to write equations for the two acids reacting with NaHCO₃.

• You should know the simple tests for a

  • phenol: neutral FeCl_3(aq) purple colour]

  • carboxylic acid: NaHCO_3(aq) => CO_2(g) => limewater => white ppt.].

• The questions are also good revision.

Chemical Storylines WM4 "INSTRUMENTAL ANALYSIS"

• Three powerful tools for investigating molecular structure of organic compounds eg salicylic acid:

  • Mass spectroscopy (m.s.): molecular ion peak M⁺ of 138, M = 120 due to H₂O loss (this is due to the proximity of two OH groups in 2-hydroxybenzoic acid, BUT the peak does not occur in the 3- or 4- isomer).

  • Infrared spectroscopy (i.r.): shows wavenumbers corresponding to C=O (1700 cm^-1), -OH in phenol (3600 cm^-1), -OH in -COOH (3300 cm^-1) and aromatic C-H (3100 cm^-1)[Fig 6, Assignment 1].

  • Nuclear magnetic resonance spectroscopy (n.m.r.): You do not study this in detail until Unit EP in the A2 course. What you should be aware of is that n.m.r. gives the ratio of hydrogen atoms (protons) in different electronic environments' in the molecule (Fig 7, Assignment 2). Its 2:4 for the H's on the OH's and 4 'similar' on the aromatic or benzene ring.

• Drawing all the evidence together:

  • from WM3 -COOH and phenolic -OH

  • i.r. shows -OH (phenol and carboxylic acid), aromatic C-H and C=O groups

  • n.m.r. in high resolution spectrum shows: 1 proton in a -COOH group; 1 proton in an -OH group directly attached to ring; 4 protons in C-H where the carbon is part of a benzene ring.

  • the mass spectrum 'fingerprint pattern' matches 2-hydroxybenzoic acid, and not the 3- or 4-hydroxybenzoic acid structural isomers. 

Chemical Ideas 6.4 "Infrared spectroscopy"

• When electromagnetic radiation interacts with matter there can be changes in electronic, vibrational or rotational energy levels, ie energy absorbed to raise something to a higher quantum level.

• Infrared radiation causes changes in vibrational levels, that is the rate of oscillation of usually two or three atoms in a molecule in a particular 'vibrational mode' eg symmetric/asymmetric stretching or bending modes (see Figs 12, 13 and 15).

• These frequencies of vibration are quantised and each set of atoms involved in a particular vibrational mode has its own characteristic frequency. So if radiation of the 'right energy' is passed through a substance, that is the radiation frequency matches the frequency of a vibration level, energy is absorbed.

• When a substance is 'scanned' with a range of infrared frequencies, characteristic absorption patterns are produced, and this 'finger print' is called the infrared absorption spectrum (Fig 14).

  • The absorption is registered as a reduction in the % transmittance to produce a series of 'troughs' in the spectrum.

  • The frequencies are expressed in infrared data/spectra as their wavenumber in cm^-1 (that is the reciprocal of the wavelength in cm, it just gives a reasonable range of numbers to deal with eg usually 700 - 4000 cm^-1)

  • Particular groups of atoms have quite well defined, and characteristic absorption wavenumbers and so an infrared spectrum is an important analytical tool in deducing molecular structure (see Fig 14, and tables 3-4, p139-140)

• Fig 16, p137, shows how an infrared spectrometer works.

  • The infrared beam is split in two, one beam goes through the sample solution (or salt disc containing compound).

  • The second beam is for reference ie a 'blank', and goes through the pure solvent (or pure salt disc).

  • The difference between the two beams is what the sample actually absorbs.

  • The frequency or wavenumber is varied by passing the resulting beams through a rotated prism or diffraction grating.

• Interpreting the spectra to identify particular molecular structure features requires problem solving experience, its the only way to learn it!, and you will given a table like Table 3, p139, in the exam data booklet.

  • Note that the same group of vibrating atoms can have more than one characteristic wavenumber

  • AND the intensities of absorption can be quite variable eg strong S or moderate M.

  • AND some show up as sharp troughs (eg C=O, Fig 18, at 1630-1740 cm^-1) or cover a broader band of wavenumbers (eg O-H, Fig 19, at 3100-3500 cm^-1)

• Study the examples on pages 138-141 and realise that there are limitations to its use as a 'molecular investigative tool'.

  • For but-1-ene you get C=C (1620-1680 cm^-1) but most organic molecules will have C-H!

  • For propanone, similarly, all you get is C=O (1705-1725 cm^-1), but you can sometimes say its in a ketone or an amide.

  • For ethanol you get C-O (1050-1300 cm^-1) and O-H (3200-3640, broadish in liquids due to hydrogen bonding).

  • For butane you get little, but does clearly illustrate the point that if a characteristic significant peak is missing, then the molecule doesn't have that functional group!

  • For methylbenzene you can get the benzene ring from particular C-H vibrations at >3000 cm^-1)

  • For benzoic acid you can get O=H (sharp 3580 cm^-1, not H bonded), C=O (1760 cm^-1) and C-H in aromatic ring (>3000 cm^-1).

  • Generally the infrared spectrum is used as a 'finger print' to identify a molecule, its rarely used to identify functional groups, except in helping to solve A level chemistry molecular structure problems!

Chemical Ideas 2.1 "A simple model of the atom" (revision)

• Revision of how a mass spectrometer works by separating particles of different mass after converting them to positive ions, which follow different paths in a magnetic field. By changing the magnetic field strength, ions of a particular mass can be focused on a detector and their relative intensity measured.

• In WM the idea is extended from ions from atoms to ions from whole molecules eg C₆H₅COOH⁺ (m = 122) or a fragment from such a molecule eg C₆H₅⁺ (m = 77) because the molecules break up when hit by the electrons from the -ve source.

Chemical Ideas 6.5 "Mass spectrometry"

• The mass spectrometer is another tool for deducing molecular structure (a few details of revision above).

• In mass spectrometer, a molecule is initially converted into its molecular ion M⁺, this is the whole molecule just stripped of one electron. Its detection is useful for providing the molecular mass M_r of the compound.

• However this is unstable and breaks down under further electron bombardment into smaller pieces in a process called fragmentation.

• Any fragment that forms a positive ion can be detected, and when the intensity of each ion is measured by the detector, it was possible to produce the whole fragmentation pattern (and molecular ion peak) in the form of a mass spectrum:

  • this is a chart of relative ion peak intensity versus mass, the intensity is the relative amount of the ion of that mass

  • quite often the tallest peak, for the most abundant ion, is called the base peak, is given the value of 100% as an arbitrary value, against which the other peaks are measured.

  • the spectra can be quite complicated to interpret because of the 'strange' chemistry of the unstable fragments, however for each compound there is a 'finger print' pattern which can be used to identify a compound

  • AND particular fragments, of particular mass, can be identified as particular molecular structure feature (see Fig 28, p143 and table 5 p144).

  • however it is rare to completely deduce the whole molecular structure, but it can help to distinguish between two different compounds of different molecular formula and even structural isomers.

  • It is possible to distinguish between two different molecular formula with the same value of M_r⁺, when the molecular ion peak is very accurately measured (see Q7).

• The presence of isotopes is another complication in interpreting mass spectra.

  • For chlorine compounds, any fragment containing a Cl atom, gives double peaks with a difference of two mass units, due to the ³⁵Cl and ³⁷Cl isotopes and there is a 'tell tale' ratio of the 'twin peaks' is 3:1 because of their relative isotopic abundance.

    • (note A_r(Cl)=35.5 because of this isotope ratio)

  • For bromo compounds there will be similar twin peaks, 2 mass units apart, but of equal height, due to a 1:1 ratio in naturally occurring bromine of ⁷⁹Br:⁸¹Br

    • (note A_r(Br)=80.0 because of this isotope ratio)

  • For the exam I would not worry about using the ¹²C to ¹³C fragment ratio to deduce molecular formulae or number of C atoms in the molecule, but be aware that as the C number increases, there is a greater chance of seeing a small peak at 1 mass unit higher than the main molecular ion peak.

• Interpreting the spectra to identify particular molecular structure features and deduce the molecular structure requires a problem solving experience, its the only way to learn it!

Activity WM4 "Interpretation of the mass spectrum of salicylic acid"

• The exam Q's on mass spectroscopy will not be this demanding, but the ideas of the molecular ion peak [M]⁺, [M+1]⁺ peak due to ¹³C, prominent fragment ions and finger print patterns are all important (see Chemical Ideas 6.5 above).

Chemical Storylines WM5 "THE SYNTHESIS OF SALICYLIC ACID"

• When a 'complex' natural compound's structure is known, and it, or a modification of it, proves a useful compound, the search begins for molecules to synthesise it from (Assignment 3).

• Compounds similar in structure to the 'lead' molecule from nature are synthesised and tested for pharmacological properties (on people!). This is what Hoffmann did, and came up with 'Aspirin'.

• It is possible to combine phenol with carbon dioxide to synthesise 2-hydroxybenzoic acid. This is reacted with ethanoic anhydride to make 2-ethanoylhydroxybenzoic acid (Aspirin). Its not very soluble in water and was eventually sold in 'tablet' form.

• 'HISTORIC' NOTE: Before the days of modern instrumental techniques, the only real way to prove the structure of a molecule, was to synthesise it with well-known chemistry, and when the 'known' synthesised compound's properties matched the original molecule, you'd cracked it!

Activity WM5.1 "A preparation of aspirin"

• You should be able to outline the general method of preparation ...

  • be able to describe reduced pressure (vacuum) filtration, wash out some of the impurities with a little iced water

  • be able to describe recrystallisation - dissolve crude product in minimum hot solvent (water), allow to cool to reform purer crystals (hopefully, the impurities stay in solvent), re-filter, collect onto clean watch glass and leave to dry.

  • write the reaction equation

  • calculate a % yield, ie the % actually obtained of the maximum possible as calculated from a theoretical reactant and product masses.

• Note the methods of testing for impurities, the most prominent being the original 2-hydroxybenzoic acid.

  • neutral iron(III) chloride solution - phenol group (not present in aspirin)

  • thin-layer chromatography, one spot only if pure?

  • melting point, sharp narrow range eg 138-140 if aspirin pure, lower wider melting range if impure

Activity WM5.2 "Using spectroscopy"

• This is a good exam question activity

Chemical Storylines WM6 "DELIVERING THE PRODUCT"

• It costs a lot of money to develop a new medicine so the price charged by the pharmaceutical company must cover the cost of research, production and marketing.

• Patents are taken out to protect the company's commercial interests in the new medicine.

• There can be a range of formulations of a particular medicine when you buy it over the counter eg tablet of 100% aspirin, soluble aspirin (via Na⁺ salt of the acid from neutralisation) and aspirin might form part of a mixture including substances that have other beneficial effects.

Activity WM6 "An aspirin assay"

• Be able to describe the basic method: weighing out aspirin, dissolve in ethanol (because aspirin not very soluble in water), titrate with standard sodium hydroxide using phenolphthalein (end-point is first permanent pink).

• Assay calculation: If a 300mg aspirin tablet dissolved in ethanol required 16.5 cm³ of 0.1M NaOH for neutralisation. If you get 99.1%, you know how to do em'! (or tell me I'm wrong!, 1st WM edition is being rushed!!!!!)

Chemical Storylines WM7 "THE MIRACULOUS MEDICINE"

• The main point here is that aspirin, like many drugs, can have multi-functional effects, hopefully all beneficial.

• BUT this, sadly, is not always the case, because with any new drug there is always the danger of unknown side-effects.

• Therefore there is a tremendous responsibility on pharmaceutical companies to ensure the development of safe and effective drugs ... which leads into Storylines WM8

Storylines WM8 "DEVELOPING AND SAFETY TESTING OF MEDICINES"

• Lots of time and money spent on discovering and developing new drugs.

• The green 'box' on p118-119 needs a thorough read! some of the main ideas are ...

  • from the discovery of a potentially useful molecule (sometimes called the 'lead molecule' can be from natural source, produced in some other project etc.) .....

  • is there room in the commercial market place for it?

  • do research to see if its safe, otherwise further development is a waste of time and money?

  • or if not safe, can its molecular structure be modified?

  • can the modification be safe? and more effective?

  • in what form, can it be/needs to be, administered in?

  • carefully clinical trials in various phases, noting particularly if any side-effects

  • does it finally pass all the tests and so become legally licensed for patient consumption?

Activity WM8 "Which product should a pharmaceutical company develop?"

• One good read for revision should be enough to reinforce the ideas from Storylines WM

This page should cover all of: WM9 SUMMARY, WM9 Check your notes on "What's in a Medicine" and the WM learning objective list to prepare you for the WM Unit Test and hence the module examination 2851.

GENERAL REVISION NOTES

 * Salters Advanced Level Chemistry * Salters Advanced Level Chemistry * Salters Advanced Level Chemistry * Salters Advanced Level Chemistry * Salters Advanced Level Chemistry *