Term
| What is the stereochemistry of carbon, nitrogen, and oxygen in each of the hybridisation states? |
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Definition
| In sp3 they are tetrahedral, in sp2 they are trigonal planar, and in sp they are linear |
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Term
| What is the priority of the 12 simple functional groups from highest to lowest? |
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Definition
| Carboxylic acid, sulfonic acid, ester, acyl chloride, amide, nitrile, aldehyde, ketone, alcohol, thiol, amine, then ether |
|
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Term
| What are the three IUPAC rules for acceptable structures? |
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Definition
| Stereobonds must be orientated with the narrow ends pointing towards an asymmetric centre, avoid connecting stereogenic centres with stereogenic bonds, no solid, and hash in a line. |
|
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Term
| What is an aliphatic compound? |
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Definition
| A non-aromatic compound such as butane which is in chain form |
|
|
Term
| What is an acyclic compound? |
|
Definition
| A compound which is aliphatic and has an open chain structure. |
|
|
Term
| What is a dihedral angle? |
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Definition
| The angle between two planes ie in a molecule such as ethene we can visualise it as two crossed planes |
|
|
Term
| What is a Newman Projection? |
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Definition
| A Newman projection is created by viewing the molecule down the carbon-carbon sigma bond to show the arrangement of substituents in space. This is useful for sawhorse formula. |
|
|
Term
| What is the sawhorse formula? |
|
Definition
| The sawhorse formula is when two sp3 hybridised carbon atoms are connected and the substituents tend to form a sawhorse formation |
|
|
Term
| Draw a staggered Newman projection for ethane? |
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Definition
|
|
Term
| Draw the Newman projection for the chair conformation of cyclohexane? |
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Definition
|
|
Term
| Draw the Newman projection for the boat conformation of cyclohexane? |
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Definition
|
|
Term
| How do staggered and overlapped conformations come about which can be visualised in the Newman Projection? |
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Definition
| Groups bonded to a sigma bond are able to undergo rotation about that bond with relation to one another. When staggered the angle is 180° and when overlapped the angle is 0° |
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Term
|
Definition
| Temporary molecular forms where the Newman projection overlaps |
|
|
Term
| What is a torsional barrier in terms of ethane? |
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Definition
| Not all possible conformations are of equal stability and in the case of a staggered conformation there is less potential energy while in an eclipsed form there is more. The barrier is the difference. |
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Term
| How is the torsional barrier affected in the case of butane? |
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Definition
| Butane does not just have hydrogen bonds and thus steric hindrance also plays a part in the ideal conformation. The lowest energy is when the two methyl are 180° and highest is when they are 0° |
|
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Term
| What is a flagpole interaction? |
|
Definition
| Where there are hydrogen atoms in close proximity within an alicyclic molecule |
|
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Term
| What are the main two conformations of cyclohexane and which is favoured and why? |
|
Definition
| Chair and boat with chair being favoured due to the lack of flagpole interactions and more staggered conformation which can be seen in the Newman projection. |
|
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Term
| How many chair-boat interconversions of cyclohexane occur per second and what percentage is in chair conformation at a given time? |
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Definition
| 106 interconversions per second and 99% are in chair conformation at any time. |
|
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Term
| How many components do light waves consist of and what is their relationship? |
|
Definition
| Light waves consist of two perpendicular components: electric and magnetic |
|
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Term
| How do the two components of light waves vibrate in relation to the direction of propagation? |
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Definition
| Both components vibrate in all possible planes perpendicular to the direction of propagation with all three components being mutually perpendicular. |
|
|
Term
| What happens in unpolarised light? |
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Definition
| In unpolarised light, the oscillations occur in random directions perpendicular to the direction of the light wave. |
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Term
| What happens in plane polarised light and how does this occur? |
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Definition
| Polarised light has oscillations in only one plane. The oscillations in all other planes are filtered out by the polarising filter. |
|
|
Term
| What are optically active compounds? |
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Definition
| Naturally occurring compounds and some types of crystal (quartz) which can rotate plane polarised light. |
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Term
|
Definition
| An instrument used to measure the degree of optical rotation “α”. |
|
|
Term
| How does the polarimeter work and what is the rotation referred to as? |
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Definition
| In a polarimeter light travels from a light source in all directions until it reaches a polarising filter and forms a plane of light. As this plane travels through the sample it is rotated by optically active compounds. Light can be rotated either counter clockwise or clockwise. This is referred to as dextrorotation and laevorotation. |
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Term
| In a polarimeter what happens if the compound is a racemate? |
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Definition
| In the case of more than one optically active compound being in the sample tube, the degree of rotation is summative hence why racemates (a mixture of enantiomers) are considered to be optically inactive. |
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|
Term
| How is the rotation of light measured in a polarimeter? |
|
Definition
| The sample is placed between one plane and the next. The two planes are initially placed parallel and if light can be seen then the sample is optically inactive. If light cannot be seen then the sample is optically active and the analyser can be rotated clockwise or anticlockwise until light can be seen again and this gives the optical rotation. |
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|
Term
| What is optical activity and how is measurement taken? |
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Definition
| Optical activity is a molecular property and measurement is taken under standard conditions. The wavelength must be constant (a sodium vapour lamp is often used with a wavelength of 589.3nm), the concentration of the investigated compound must be known, along with the polarimeter tube length (generally 5, 10, or 20cm), and temperature (typically 20-25°C). |
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Term
| How are dextrorotatory and laevorotatory compounds distinguished? |
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Definition
| Dextrorotatory compounds are given the sign (+) and laevorotatory compounds are given the sign (-). |
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|
Term
| What is standardisation and how is this acheived? |
|
Definition
Standardisation is required to ensure all measurements follow the same conditions. The relationship between “specific” rotation [α]D and observed rotation α is defined as:
[image]
Where α and [α]D are measured in degrees, l (tube length) is measured in decimetres, and c (concentration is measured in gmL-1 or density for a pure liquid. |
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Term
|
Definition
| Connectivity is the order in which atoms are connected to one another. |
|
|
Term
| What are structural isomers? |
|
Definition
| Structural isomers are compounds with the same molecular formula whose atoms have different connectivity. |
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|
Term
|
Definition
| Stereoisomers are isomers that have the same connectivity, but differ in the arrangement of their atoms in space. Stereoisomers are not superposable. There are several different types of stereoisomer. |
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|
Term
|
Definition
| Stereocentres (stereogenic centres, chiral centres, asymmetric centres) are atoms that cannot have any symmetry operations performed on them. A carbon atom must be sp3 hybridised (tetrahedral stereochemistry) to form a stereocentre. The carbon atom must also have four different substituents (ligands) to act as stereocentres. Optically active compounds have at least one stereocentre. |
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Term
|
Definition
| Enantiomers are stereoisomers which have the same connectivity that are non-superposable mirror images of one another. Most enantiomers have at least one stereocentre. |
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Term
| What are the differences between a pair of enantiomers in an achiral medium? |
|
Definition
| In an achiral medium the physicochemical properties of the pairs of enantiomers are the same, except for the rotation of plane polarised light. Enantiomers rotate plane polarised light in equal but opposite directions which is shown by a (+) – dextrorotatory or a (-) – laevorotatory before their names. |
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Term
| How many stereoisomers will an enantiomer with n stereocentres have? |
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Definition
| Enantiomers with “n” stereocentres will have a maximum of 2^n stereoisomers. |
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|
Term
|
Definition
| A racemic mixture or racemate is a 50-50 mixture of a pair of enantiomers. |
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|
Term
| For an enantiomer with n stereocentres how many stereoisomers are there if some of the stereocentres are connected by a ring? |
|
Definition
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|
Term
| What are the advantages and disadvantages of a racemate in a pharmaceutical formulation? |
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Definition
| The advantages of a racemate are that it is cheaper to synthesize than individual enantiomers. The disadvantages are that 50% of the drug may be inactive (ballast) and there may be unwanted effects of one of the enantiomers. Note that side effects may be wanted or unwanted depending upon the clinical situation (eg antihistamines). |
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Term
|
Definition
| Diastereomers are stereoisomers (same connectivity) which are non-superposable and not mirror images. For example if a molecule has two stereocentres with one being a mirror image and the other identical then the two compounds are considered to be diastereomers. |
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Term
| What are the physicochemical properties of a pair of diastereomers? |
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Definition
| Diastereomers often have similar but different physicochemical properties. Their rotation of plane polarised light is not equal nor opposite as is the case with enantiomers. |
|
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Term
| What are geometric/constitutional/structural isomers? |
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Definition
| Geometric isomers are diastereomers that have hindered rotation about a double bond. Cis-trans isomerism may also occur in the absence of double bonds in the case of a cyclic compound or metal coordination. Trans is more stable than cis due to less steric interaction and has higher melting and boiling points. |
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Term
|
Definition
| Meso compounds are compounds that have two or more stereocentres but have a plane of symmetry. They are mirror images within the same molecule and are thus achiral (mirror image indistinguishable from original) and optically inactive. |
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Term
| How can you determine the number of stereoisomers for a mesocompound with n stereocentres and are meso compounds and their mirror images superposable? |
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Definition
| A meso compound and its mirror image are superposable as they are the same compound. Some compounds may have more than one meso structure and for each meso structure there will be one less stereoisomer. Thus to calculate stereoisomers we use (2^n)-1 |
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Term
| What are Haworth Formulae and how are ligands drawn in relation to one another? |
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Definition
| Haworth formulae are a method of representing a ring in a manner where it appears to be poking out of the page with darkened lines (plane conformation). Ligands are then considered to be attached equatorially (side to side) or axially (up and down). Ligands pointing down are then considered to be on the right side of a Fischer projection. Depending on steric hindrance for a given conformation, axial or equatorial can be more stable. |
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Term
| How can multi-ring structures be considered cis or trans? |
|
Definition
In cases where two rings are directly next to each other it is considered Trans and when kinked cis. This can be seen below with H in same direction also indicating cis and in differing directions indicating trans.
[image] |
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|
Term
| How is a benzene ring named as a compound, side chain, -CH2- substituted, and -OH substituted? |
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Definition
| A benzene ring can be called many names. As a compound in its own entirety it is benzene compound, as a side chain it is a phenyl substituent, with the attachment of a CH2- it is benzyl, and as an alcohol it is a phenol compound. |
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Term
| What are the specifications for a stereocentre? |
|
Definition
| Stereocentres must be tetrahedral and have sp3 hybridisation. They are mainly carbon but can also be S, P, or N etc. A lone pair of electrons does not count as a ligand and thus these elements are only stereocentres when attached to four different ligands. A stereocentre is not always optically active. |
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Term
|
Definition
| TLC (Thin layer chromatography) is where a sample and a control are spotted onto a TLC plate which is useful for testing the purity of a sample. The TLC plate has a stationary phase, in the case of our labs zinc sulfide, which coats an inert support. The plate is then added to a jar of the solvent which is known as the mobile phase and tends to move up the stationary phase. According to the relative polarity and lipophilicity of the sample it will either move up with the solvent or remain unmoved like the stationary phase. The physical characteristics of the solvent will determine the speed at which it moves up the plate and thus the position it will end in when the plate is removed from the solvent. The mobility is measured using the RF value which is the distance between the start point and the solvent front. If a sample has the same RF as the control then it suggests high purity and similarity between the two samples. |
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|
Term
| What are the precautions that must be taken for TLC to work and what happens if these aren't adhered to? |
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Definition
| Precautions that need to be taken include ensuring the sample is dilute otherwise there will just be a line up the plate that tells us nothing. The samples also need to be discrete to avoid confusion and overlap in results. When drawing the line for the samples to be added the stationary phase should ideally not be disrupted in any way (light pencil line) as this can make it more difficult for sample to move and for mobile phase to move up the plate. The point at which the sample is added also needs to be above the level of the solution reservoir to ensure the sample can only move in the same direction as the mobile phase. |
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|
Term
| What is the purpose of CIP rules? |
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Definition
| To assign an R or S descriptor to each stereocentre and an E or Z descriptor to each double bond so the configuration of the entire molecule can be specified using the descriptors in the name. |
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Term
| How do you draw a Fischer projection for an amino acid? |
|
Definition
| Orientate the amino acid so the carboxylic acid group is up and the R group is facing into the page then flatten it and redraw in a planar cross formation with H and NH2 groups being to either side. If the NH2 group is to the left it is an L configuration and if on the right it is an R configuration. |
|
|
Term
| What do R and S stand for? |
|
Definition
| R stands for Rectus and S stands for Sinister |
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|
Term
| How is the priority system of ligands on a stereocentre determined? |
|
Definition
| The priority system is assigned on the basis of the atomic number of each atom attached to a stereocentre where the higher the atomic number of the first atom of the ligand, the higher the priority assigned. |
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|
Term
| How is the priority of ligands on a stereocentre decided when the first atoms of two different ligands are the same? |
|
Definition
| The next three atoms in each assigned ligand are examined and this is continued until a priority is established meaning priority is established at the first point of difference. |
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|
Term
| How is a stereocentre classified as R or S? |
|
Definition
| If the locus (pathway) from the highest to lowest priority is clockwise then the specification is R and if anti-clockwise then it is S. |
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|
Term
| Draw how you would rearrange multiple bonds in a ligand attached to a stereocentre in order to assign priority? |
|
Definition
|
|
Term
| How do we classify a double bond when all four of the ligands on either side of a double bond are different? |
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Definition
| We use CIP rules based on atomic mass. If the ligands of the highest priority are on the same side it is classified Z and if on opposite sides it is an E. |
|
|
Term
| What shape are S orbitals? |
|
Definition
|
|
Term
|
Definition
| The probability of where an electron will be at a given point in time |
|
|
Term
| How many P orbitals are there, what shape are they, and what is there energy like compared to S orbitals? |
|
Definition
| There are three P orbitals per level and these lie in orthogonal axes at right angles to one another. These are dumbbell shaped and have higher energy than corresponding S orbitals |
|
|
Term
| Where do the d orbitals lie and what shape are they? |
|
Definition
| The d orbitals also lie in orthogonal planes and are double dumbbell shaped with higher energy than corresponding S orbitals |
|
|
Term
| What is the Pauli Exclusion Principle? |
|
Definition
| The Pauli Exclusion Principle is where each atom has a unique set of quantum numbers. An orbital may contain a maximum of two electrons which are paired with opposite spin. |
|
|
Term
| What is the Aufbau principle? |
|
Definition
| This refers to the order of filling orbitals ie 1s 2s 2p 3s 3p 4s 3d 4p 5s 4d 5p 6s 5d 6p 7s 6d 7p. Essentially you list the same numbers out and draw diagonal lines |
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|
Term
|
Definition
| The Hund’s Rule is the way in which electrons occupy orbitals of equal energy. The lowest energy configuration has the maximum number of electrons with the same spin orientation. Only once there are two electrons in an orbital are both electrons in opposite spin. |
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|
Term
| What are resonance structures and what are the rules around them? |
|
Definition
| Resonance structures exist only on paper. The hybrid of the resonance forms best represents the actual molecule, ion, or radical. We are only allowed to move electrons and all resonance forms must have the same number of unpaired electrons. All atoms that are part of the delocalised pi system must lie in a plane (or be nearly planar). |
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|
Term
| What are the basic properties of Benzene? |
|
Definition
| Benzene (C6H6) is a volatile, flammable liquid with a melting point of 6°C and a boiling point of 80°C. It is soluble in water and relatively inert (flammable but only reactive under certain conditions) as well as carcinogenic. |
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|
Term
| Why is benzene not an alkene? |
|
Definition
| Benzene contains three double bonds and one ring. This could potentially also be called cyclohexatriene. However, benzene does not behave like cyclohexatriene as there is decreased reactivity than alkenes for example no addition reaction with chlorine and instead benzene undergoes substitution reactions. This means that the benzene structure we see isn’t the correct structure but it is more convenient. All of the carbon to carbon bond lengths are equal. The heat of hydrogenation is far less that that expected for three double bonds which means there is an unexpected increased stability of benzene. Nothing supports being an alkene. |
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|
Term
| How do we visualise Benzene? |
|
Definition
| We think of benzene as a planar cyclic compound. It is an sp2 hybridised compound with a cloud of electrons above and below its plane. |
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|
Term
| What are ortho, meta, and para? |
|
Definition
| When there is one substituent the carbons either side are ortho, the next two are Meta, and the last one is para. |
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|
Term
| What determines whether a structure is aromatic? |
|
Definition
| It is planar with an uninterrupted conjugated pi system, all the atoms in the ring are sp2 hybridised, its conjugated pi system has an odd number of paired electrons, and it must obey the Huckel 4n+2 rule for the number of pi electrons |
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Term
|
Definition
| Electrophiles are electron loving and thus electron deficient. Electrophiles have a partial or full positive charge and are attracted to sites of electron density. |
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|
Term
| What is the general mechanism for electrophilic aromatic substitution? |
|
Definition
| The general mechanism is that the electrophile is electrostatically attracted to the pi cloud of the aromatic ring and the electrons from the double bond are thus transferred to the electrophile breaking the double bond and leaving a positive charge. The positive charge is then spread by resonance throughout the ring. The charge dispersal is a stabilising effect. Ultimately (rapidly) a proton is abstracted from the ring and Aromaticity is re-established. |
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|
Term
| What are inductive effects? |
|
Definition
| If a substituent that is bonded to a benzene ring is less electron withdrawing than hydrogen, the electrons in the sigma bond that attaches the substituent to the benzene ring will move towards the ring more readily than those in the sigma bond that attaches to the hydrogen. Donation of electrons through a sigma bond is called inductive electron donation. Alkyl substituents such as methyl donate inductively (+I). If a substituent that is bonded to a benzene ring is more electron withdrawing than hydrogen it will draw the sigma electrons away from the benzene ring more strongly than hydrogen will. Withdrawal of electrons through a sigma bond is called inductive electron withdrawal (-I). The +NH3 group is an example of a substituent that withdraws electrons inductively because it is more electronegative than hydrogen. These effects weaken over distance. |
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|
Term
| What are resonance effects? |
|
Definition
| Resonance is mediated through conjugated pi systems. Electrons move out of pi bonds to or from substituents. This may occur over greater distances than inductive effects. The resonance effect is thus greater than the inductive effect except for halogens. Substituents with a -R effect are o, p-deactivators (m-directors) and substituents with a +R effect are o, p-activators. |
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|
Term
| What are examples of +R substituents? |
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Definition
| –OR, -OH, -SR, -NR2, -NCOR2. These are generally electron rich and thus a site for electron attack. |
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|
Term
| What are examples of electron withdrawing substituents? |
|
Definition
|
|
Term
| Why are halogens different in terms of inductive and resonant effects? |
|
Definition
| Halogens have been found experimentally to inductively withdraw electrons from the ring more strongly than they donate electrons into the ring by resonance. |
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Term
| What do activating and deactivating substituents do? |
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Definition
| The activating substituents make the benzene ring more active toward electrophilic substitution while the deactivating substituents make the benzene ring less reactive. |
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|
Term
| Draw resonance structures for ortho and meta electrophilic substitution to show why ortho is much more likely to occur than meta? |
|
Definition
Ortho substitution has one more resonance structure which is more stable as seen below:
[image]
While meta substitution does not have the final and most stable resonance structure:
[image] |
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|
Term
| What are the limitations of Friedel-Crafts Alkylation? |
|
Definition
| The ring can be too deactivated to react with the electrophiles due to -I and -R effects particularly if the carbocation undergoes an alkyl shift. This occurs because primary carbocations are much less stable than secondary and tertiary so where possible a carbocation will switch to secondary or tertiary which will mean the carbocation is no longer as reactive with a deactivated ring. Polyalkylation can also occur which may be undesirable if the alkylbenzene has greater or equal reactivity following the Friedel Crafts Alkylation process again. |
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Term
| What happens if we react chlorobenzene with methoxide and how does the presence of nitro groups affect this? |
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Definition
| We form methoxy benzene due to the chloro group being a good leaving group. This reaction is increased if we have nitro groups substituted at the para and ortho positions but will not proceed with a nitro at the meta position. The more nitro groups the more deactivated and essentially positive the ring and thus the faster the reaction. This is an example of nucleophilic aromatic substitution. |
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|
Term
| What is required for nucleophilic aromatic substitution to occur? |
|
Definition
| A halogen with a strong electron withdrawing group in the ortho or para positions. |
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|
Term
| How does nucleophilic aromatic substituion occur? |
|
Definition
| The halogen group is strongly electron withdrawing giving the attached carbon a large slightly positive charge which attracts nucleophiles whiles the nitro group withdraws electrons from the ring to itself increasing the positive charge. |
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Term
| What is the rate of nucleophilic aromatic substitution and what does this mean? |
|
Definition
| The rate of a nucleophilic aromatic substitution is K[aryl halide][nucleophile] and is thus second order kinetics and is thus a bimolecular reaction mechanism not a SN1 mechanism. |
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|
Term
| What increases the reactivity of a nucleophilic aromatic substitution and how? |
|
Definition
| The electronegativity of the halogen atom increases reactivity and the number of electron withdrawing groups also increases reactivity. Both of these affect the slightly positive charge of the halogen carbon atom. Chlorine is a good leaving group and the nitro group(s) facilitates the stabilisation of the incoming negative charge from the nucleophile. |
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|
Term
| What is the name of the intermediate structure of a nucleophilic aromatic substitution? |
|
Definition
|
|
Term
| How is paracetamol (acetaminophen) synthesised? |
|
Definition
| p-chloronitrobenzene is reacted with OH- to form p-nitrophenol which is then reduced to form p-aminophenol. Ethanoic anhydride (combination of two carboxylic acids with the loss of a water molecule) Is then reacted in the presence of acid to form N-(4-hydroxyphenyl) ethanamide. |
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|
Term
| What is paracetamol (acetaminophen)? |
|
Definition
| It is an over the counter drug which acts as an analgesic (pain-killing) and an antipyretic (reduces fever) but is not an NSAID. This can be taken in tablet form, liquid form, or as suppositories. |
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|
Term
| What is a Bronsted-Lowry acid? |
|
Definition
| A Bronsted-Lowry acid is considered a proton donor. Some examples include sulphuric acid, ethanoic acid, and phenol. These acids have a highly polarised Z-H bond meaning there is a large slightly positive charge and/or there is a weak Z-H bond. There must always be a stabilised conjugate base. Z is usually a group 15, 16, or 17 atom (N, O, S, Cl, or Br). These acids are either uncharged or positively charged. |
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|
Term
|
Definition
| A Lewis acid is an electron acceptor because Lewis acids are electron deficient. This may be due to transition elements (ZN); elements with unfilled d-orbitals (Al); or carbocations. Lewis acids are uncharged or positively charged. |
|
|
Term
| What is a Bronsted-Lowry base? |
|
Definition
| A Bronsted-Lowry base is considered a proton acceptor. Some examples include methanamine (aliphatic amine) and aniline (aromatic amine). These bases have a non-bonding pair of electrons and thus a site with a large slightly negative charge such as C-Z where Z is usually a group 15 or 16 atom (N, O, or S). These bases are either uncharged or negatively charged. |
|
|
Term
|
Definition
| A Lewis base is an electron donor as they are sites of electron excess. Lewis bases can have non-bonding pairs, be uncharged, or negatively charged. |
|
|
Term
| What is a neutral compound? |
|
Definition
| Neutral compounds have functional groups that do not readily accept or lose protons except under extremes of pH. There is however a double meaning of neutral in terms of both charge and acidity. |
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|
Term
| What is pKa and how can it be understood? |
|
Definition
| The smaller the pKa the stronger the conjugate acid (and the weaker the conjugate base) while the larger the pKa the weaker the conjugate acid and thus the stronger the conjugate base. The pKa of an acid refers to the dissociation of the conjugate acid to the conjugate base. In bases pKa still refers to the conjugate acid. Essentially if the conjugate base is stronger it accepts protons more readily so its conjugate acid must be weaker in order to lose protons less readily. The pKa is the pH at which the ratio of the molar concentration of a compounds conjugate acid to its conjugate base is 1:1. |
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|
Term
|
Definition
|
|
Term
| What is the relationship between pH and pKa? |
|
Definition
| The pKa is the pH at which the ratio of the molar concentration of a compounds conjugate acid to its conjugate base is 1:1. A compound’s conjugate acid and the conjugate base are in pH dependant equilibrium with one another. Changing the concentration of hydrogen will change the equilibrium. When the compound is in a solution where the pH is greater than the pKa then there is a decreased hydrogen concentration leading to increased conjugate base formation. In contrast when the compound is in a solution where the pH is less than the pKa then there is an increased hydrogen ion concentration and thus this will increase conjugate acid formation. |
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|
Term
| How can percentage ionisation be calculated? |
|
Definition
| This can be worked out using the pH=pKa+log(base/acid). This can be rewritten as pH=pKa+log(1/x) then according to whether the base (1) or acid (x) is ionised you put either 1 or x over (x+1) to get the percentage ionised. |
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|
Term
| What six things make a functional group a Bronsted-Lowry acid? |
|
Definition
| Slightly positive effect of an acidic proton, the Z-H bond strength (Z is an electronegative atom), -I effects near the functional group, -R effects near the functional group, stability of the conjugate base, and the size of the atom to which an acidic proton is bonded. |
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Term
| How does increased positivity of the acidic proton affect the equilibrium? |
|
Definition
| An increased slightly positive charge on the proton leads to increased ease of attack by the non-bonding electron pairs of water. This pushes the equilibrium to the right leading to increased acidity and decreased pKa. |
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|
Term
| In the case of carboxylic acids how does the presence of an electronegative substituent affect the pKa? |
|
Definition
| Increased substituent electronegativity leads to increased OH bond polarisation and thus an increased slightly positive charge on the OH proton leading to increased acid strength and decreased pKa. The closer the substituent to the carboxylic acid group the lower the pKa. |
|
|
Term
| What do inductive effects depend on? |
|
Definition
| Inductive effects depend on the electronegativity and number of substituents near acidic protons as this effect operates over short distances. |
|
|
Term
| How are electron withdrawing groups involved in inductive effects? |
|
Definition
| Electron withdrawing groups have a –I effect and will also stabilise the conjugate base. If A-Z- is more stable that A- then pKa (HAZ) is less than pKa (HA). |
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|
Term
| What is the range that pKa can be altered and what are examples of groups with +I and -I effects? |
|
Definition
| The range that the pKa can change due to inductive effects is approximately 5. Groups with a –I effect include R3N+-, O2N-, -CN, -CO2H, -CO2R, -COR, -X, and –CF3. Groups with a +I effect include Alkyl, CO2-, and O-. |
|
|
Term
| How are the strengths of resonance and inductive effects comparable and how do each work? |
|
Definition
| Resonance effects may occur over many atoms unlike –I effects. The R effects are thus much stronger than the I effects on acid and base properties and aromatic ring activity. The I effect leads to polarisation of the electron pair within a single bond. The R effect leads to movement of an electron pair out of a double bond toward the electronegative atom. |
|
|
Term
| How are the pKas of an aliphatic alcohol, phenol, and carboxylic acid comparable? |
|
Definition
In aliphatic alcohols there are no substituents in the conjugate base with a –I or a –R effect present. The negative charge of the conjugate base is not stabilised by –I or –R effects. The pKa of simple aliphatic alcohols is typically about 15.
In the case of phenol resonance structures have charge separation. This means there is a large slightly positive charge of the on the oxygen atom and then an even more slightly positive effect on the bound hydrogen due to the –I effect of the oxygen atom on the hydrogen atom. This increases the rate of attack by water on the OH proton. A phenolic OH proton is more acidic than an aliphatic OH proton. The phenoxide negative charge is spread around the ring due to increased conjugate base stabilisation (this isn’t as stable as the carbon is not very electronegative) which shifts the equilibrium to the right leading to an increased acid strength and a decreased pKa of about 10.
In a carboxylic acid resonance produces a large slightly positive charge on the OH proton which causes a decreased pKa and increased acid strength due to –I and –R effects. (If you have to explain write in terse sentences). This also has charge separation. The negative charge of the conjugate base is spread over two electronegative oxygen atoms which increase the carboxylic acid stabilisation. The pKa compared to ROH is approximately 5. |
|
|
Term
| What are some examples of acidic functional groups and their pKa? (Sulfonic acids, thiols, enols, amides, imides, and sulfonamides) |
|
Definition
Sulfonic acids - 1
Thiols - 9
Enols - 5
Amide - 14 (generally neutral)
Imide - 8
Sulfonamide - 5 |
|
|
Term
| What is the most essential part needed for something to be a base? |
|
Definition
| A non=bonding pair of electrons |
|
|
Term
| What makes something more basic? |
|
Definition
| +I and +R effects near the functional group with the resonance effects being stronger than inductive. |
|
|
Term
| What helps to determine the strength of a base? |
|
Definition
| The stability of the conjugate acid |
|
|
Term
| What is the effect of reducing the availability of non-bonding pairs on a basic compound and vice versa? |
|
Definition
| The main component that determines basicity is the availability of non-bonding pairs of electrons. Anything that decreases non-bonding pair availability decreases basicity and thus decreases the pKa while anything that increases the non-binding pair availability will increase basicity and thus increase the pKa. |
|
|
Term
| What is the effect of increased substituent negativity in a basic compound? |
|
Definition
| Essentially increased substituent electronegativity leads to decreased non-bonding pair availability and hence decreases base strength and in turn pKa. If the electronegative substituent is further away it has less effect on the pKa and thus basicity. |
|
|
Term
| What is the effect of electron releasing substituents in basic compounds and how does this compare to electron withdrawing substituents? |
|
Definition
| Electron releasing groups with a +I effect increase basicity but this is relatively weak compared to the –I effect caused by electron withdrawing groups. |
|
|
Term
| What effect may electron withdrawing groups have on the conjugate acid? |
|
Definition
| Electron withdrawing groups may destabilise the conjugate acid which is the opposite situation to acids. This is because the conjugate acid is generally more positively charged. |
|
|
Term
| What is the effect of resonance on basicity? |
|
Definition
| In the case of aniline the N atom goes from sp3 hybridisation to sp2 hybridisation due to resonance and has p orbital overlap which leads to double bond formation and ring activation as well as being o, p-directing. A decreased availability of non-bonding pairs leads to decreased basicity and a pKa of about 4.5. The addition of a nitro group to form p-nitroaniline would decrease the pKa further due to the electron withdrawing effects of the nitro group. |
|
|
Term
| What is the affect of multiple bonds on basicity? |
|
Definition
| A multiple bond attached to a basic nitrogen atom for example decreases basicity and thus decreases pKa. This occurs when no resonance effects are present. Increased s character of the hybridised orbitals leads to non-bonding pairs of electrons being held more closely and thus basicity decreases. |
|
|
Term
| What is the main effect of differing pH on a compound? |
|
Definition
| Essentially at low pH any proton that can leave will and at higher pH any proton that can be accepted will. |
|
|
Term
| What are acids and bases and which resonance and inductive effects make them a stronger acid or base and why? |
|
Definition
| Acids are proton donors and –I and –R effects lead to increased acidity of conjugate acids and thus decreased pKa (increased polarisation of O-H and N-H bonds). Bases are proton acceptors and –I and –R effects lead to decreased basicity of conjugate bases and in turn decreased pKa (decreased availability of nitrogen atom non-bonding pairs). |
|
|
Term
| What are neutral functional groups? |
|
Definition
| Neutral functional groups and compounds have no significant acid or base properties. Usually (under milder conditions) they will not accept or donate protons. |
|
|
Term
| What are examples of neutral functional groups? |
|
Definition
| These include aldehydes, ketones, esters (esters that are in a ring are called lactones and are not unstable in water), amides, nitriles, ethers, nitro groups, and sulfonates. |
|
|
Term
| What is the salt of an acid and how is it named? |
|
Definition
| Salts of acids are usually an inorganic cation and the conjugate base of a drug which is the major part of the compound. These are named by placing the name of the ions before the conjugate base name. |
|
|
Term
| If an organic cation is part of a drug name then what is the drug moiety? |
|
Definition
| If an inorganic cation is part of a drug name then the drug moiety is the conjugate base of that drug. |
|
|
Term
| What is the salt of a base and how are they named? |
|
Definition
| Salts of bases are usually an inorganic anion and the conjugate acid of a drug where these are generally chlorides (hydrochloride), bromides (hydrobromide), nitrates, sulfates, and phosphates. These are named by putting the drug name before the ion. |
|
|
Term
| If an organic anion is part of a drug name then what is the drug moiety? |
|
Definition
| If an inorganic anion is part of that drug name then the drug is the conjugate acid of that drug. |
|
|
Term
| What are examples of carbonyl containing compounds? |
|
Definition
| Carbonyl containing compounds include aldehydes, ketones, amides (primary to tertiary), carboxylic acids, esters, and acyl chlorides. |
|
|
Term
| What is the carbonyl group and what is the structure? |
|
Definition
| The carbonyl group is a carbon double bonded to oxygen. The bond is planar and contains one sigma bond and one pi bond. Both the carbon and oxygen atoms are sp2 hybridised with trigonal planar stereochemistry and a bond angle of 120°. |
|
|
Term
| Is the carbonyl bond polar and if so why? |
|
Definition
| Oxygen has two lone pairs of electrons and is more electronegative than carbon. This means that a larger share of the bonded electrons go towards the oxygen in addition to the lone pairs of electrons on oxygen. The bond is thus not symmetrical but is polar as oxygen has a slightly negative charge and carbon has a slightly positive charge. |
|
|
Term
| What are the carbonyl carbon and alpha carbon in a carbonyl compound? |
|
Definition
| The carbon double bonded to the oxygen is known as the carbonyl carbon while the next carbon is known as the alpha carbon. The proton attached to the alpha carbon is known as the alpha proton. |
|
|
Term
| What is special about esters, carboxylic acids, and amides in terms of carbonyl compounds? |
|
Definition
| Esters, carboxylic acids, and amides all contain a substituent with non-bonding pairs of electrons attached to the carbonyl carbon. This means they can undergo resonance. The nitrogen in amides makes the greatest contributor of these as nitrogen is less electronegative and thus holds a positive charge better. |
|
|
Term
| What is the order of functional group priorities? |
|
Definition
1. Carboxylic Acid
2. Sulfonic Acid
3. Ester
4. Acid Chloride
5. Amide
6. Nitrile
7. Aldehyde
8. Ketone
9. Alcohol
10. Thiol
11. Amine
12. Ether |
|
|
Term
| How is an aldehyde named when it is the highest priority? |
|
Definition
| When the aldehyde is the highest priority the word alkane is replaced with alkanal and always given the number one when numbering the carbon chain. |
|
|
Term
| How is an aldehyde named when it is not the highest priority? |
|
Definition
| When the aldehyde group is not the highest priority it is referred to as an oxo-substituent. |
|
|
Term
| When a ketone is the highest priority how is it named? |
|
Definition
| When the ketone is the highest priority alkane becomes alkanone. |
|
|
Term
| When a ketone is not the highest priority how is it named? |
|
Definition
| When ketone is not the highest priority group it is referred to as an oxo substituent. |
|
|
Term
| What are the properties of the carbonyl group in terms of melting and boiling points? |
|
Definition
| The carbonyl group is polar as there are unevenly shared bonding electrons. There are thus polar interactions which means there is a higher melting and boiling point and good aqueous solubility. |
|
|
Term
| Can nucleophilic attack occur on a carbonyl compound and if so which part of the compound does it attack? |
|
Definition
| Nucleophilic attack of the carbonyl carbon can also occur. |
|
|
Term
| What are the hydrogen bonding properties of ketones and aldehydes? |
|
Definition
| While the carbonyl bond is polar and thus capable of hydrogen bonding, no intermolecular bonds are possible for simple, pure aldehydes and ketones as the alpha carbon to hydrogen bond is not polarised enough as carbon and hydrogen have similar electronegativities. The carbonyl oxygen atom may, however, hydrogen bond with protic solvents such as water and simple alcohols etc. This increases aqueous solubility due to solvation by the solvent. |
|
|
Term
| What are the acid and base properties of aldehydes and ketones? |
|
Definition
| Because the carbonyl group bind is polar, the alpha proton to alpha carbon bond is also slightly polarised due to inductive effects (-I) by the carbonyl group. Though the alpha proton is more acidic therefore than a proton bound to an ordinary sp3 hybridised carbon it is still less acidic than a water proton. The acidity is due to the asymmetrical nature of bond sharing in a polar bond which makes it easier for the alpha hydrogen to leave. The deprotonated version of an aldehyde or ketone, due to the carbonyl group, is a relatively stable base as the negative charge from the proton leaving can be spread via resonance through to the carbonyl oxygen. Aldehydes and ketones are more acidic than esters as the oxygen in the OR group attached to the carbonyl group also has a lone pair of electrons which compete with the electrons of the alpha carbon to be distributed through to the oxygen. If the alpha carbon is flanked between two carbonyl groups then the acidity increases further as there are two oxygen’s to delocalise charge to. The acidic alpha proton of an aldehyde and ketone may react with a strong base to lose the alpha carbon due to the aforementioned stabilising effects. The pKa of a ketone and aldehyde is still quite high though so the base does have to be very strong for example OH-. |
|
|
Term
| Why is PCC/CH2Cl2 used when oxidising a primary alcohol to an aldehyde? |
|
Definition
| Aldehydes can be prepared through the oxidation of alcohols using an oxidising agent such as H+, H2O, or Na2Cr2O7. The problem however is that the oxidation reaction can’t easily be stopped at the aldehyde as the aldehyde one formed is in equilibrium with a hydrate. Even if hydrate equilibrium is to the left, the hydrate is more easily oxidised so a carboxylic acid is formed. In order to overcome this we must make sure no hydrate forms. We do this by using an oxidising agent that is soluble in anhydrous solvents. If there is no water there can be no hydrate formation and thus no over oxidation to a carboxylic acid. An example is using CrO3 in HCl to convert pyridine to pyridinium chlorochromate (PCC). PCC is soluble in CH2Cl2 at 25°C and this can be used to oxidise a primary alcohol to an aldehyde without a hydrate forming due to the absence of water. |
|
|
Term
| What are the three main ways that ketones can be prepared? |
|
Definition
| Oxidation of secondary alcohols, ozonolysis of alkenes or Friedal-crafts acylation through the use of a carbonyl compound to form an electrophile and thus undergo electrophilic aromatic substitution. |
|
|
Term
| Why does PCC/CH2Cl2 not need to be used when oxidising a secondary alcohol to a ketone? |
|
Definition
| Because there is no risk of over-oxidation |
|
|
Term
| What reactions can ketones and aldehydes undergo? |
|
Definition
| Hydrate formation, hemiacetal/hemiketal/acetal/ketal formation, reduction to secondary and primary alcohols respectively, and reductive amination to form an imine intermediate in the presence of a trace amount of acid which is then reduced to an amine. |
|
|
Term
| What is required for the formation of a hydrate from a ketone or aldehyde? |
|
Definition
| Water and an acid catalyst |
|
|
Term
| Out of ketones and aldehydes which is more hydrated at equilibrium? |
|
Definition
| Aldehydes at 99% while ketones are at 1%. |
|
|
Term
| What decreases the percentage of hydration at equilibrium? |
|
Definition
| Bulky substituents and electron donating groups such as the methyl substituents on propanone. |
|
|
Term
| What increases the percentage of hydration at equilibrium? |
|
Definition
| Small substituents and electron withdrawing substituents such as halogens attached to the alpha carbon. |
|
|
Term
| What is the difference between an acetal and a hemiacetal? |
|
Definition
| In a hemiacetal there is one OR group (alcohol) and one OH group while in an acetal there are two OR groups. |
|
|
Term
| Why is an acid catalyst required in both hydration and acetal formation? |
|
Definition
| Because alcohols and water are poor nucleophiles. |
|
|
Term
| How stable is an acetal/ketal and can it be isolated, if so how? |
|
Definition
| A ketal/acetal is unstable as the tetrahedral carbon is bound to two oxygen atoms. In order to isolate the acetal or ketal they must be removed from water as the prescece of water can allow the formation of the more stable carboxylic acid. Without water the only compound that can be formed is the less stable O-alkylated intermediate. |
|
|
Term
| What is the reducing agent used to reduce aldehydes and ketones back to their respective alcohols? |
|
Definition
| NaBH4 - sodium borohydride |
|
|
Term
| What is the stability of aldehydes and ketones in formulation? |
|
Definition
Aldehydes and ketones can:
• React with water in the presence of acids to form hydrates
• React with alcohols in the presence of acid to form hemiacetals and acetals
• React with amines with trace amounts of acid to form imines
• Be oxidised often via complex free radical mechanisms.
The physicochemical properties such as hydrogen bonding relate to the compound solubility. |
|
|
Term
|
Definition
| A set of isomers that are in rapid equilibrium |
|
|
Term
| What are keto-enol tautomers and comment on the relative stability of the keto and enol tautomers? |
|
Definition
| Keto-enol tautomers differ in the location of a double bond and hydrogen where enols are an alkene and an alcohol combined. Generally the keto tautomer is much more stable than the enol tautomer and makes up 99.9% of the solution while the enol only makes up 0.1%. |
|
|
Term
| What is the one exception to the relative stability of the keto and enol tautomers? |
|
Definition
| Generally the keto is more stable but in the case of phenol the enol is more stable as it is resonance stabilised whereas the keto tautomer is not. |
|
|
Term
| What is required for Keto-enol tautomerism to occur? |
|
Definition
| An alpha proton on the ketone or aldehyde ie methanal cannot undergo tautomerism but the other natural aldehydes and ketones can. |
|
|
Term
| What is an aldol reaction and what is another name for an aldol? |
|
Definition
| In the case of this course it is specifically two aldehyde or ketone groups reacting to give an aldol (aldehyde/ketone and alcohol). The aldol can then react to give other producrs and is also called a betahydroxyketone or a betahydroxyaldehyde. |
|
|
Term
| How do we describe atom position? |
|
Definition
| We use Greek letters to describe the atom position with the carbonyl group being the reference point even though this is not actually part of the systemic, proper name. A carbonyl group doesn't necessarily need to be the reference as it could be said that a chloro group is alpha to a hydroxyl group. |
|
|
Term
| What is the pKa of a ketone and aldehyde and are these acidic/basic/neutral? |
|
Definition
| We know that the carbonyl bond is polarised and through the inductive effects of oxygen this also makes the alpha carbon and hydrogen slightly polarised. This makes the alpha proton slightly positive and it can thus react with a base with the conjugate base being resonance stabilised. Stabilisation forms an enolate (enol with no hydroxyl proton). The alpha proton is thus very different to the proton on an alkane as a ketone and aldehyde normally have a pKa of about 20. The carbonyl compound must have at least one alpha proton for this to occur and the alpha carbon must be sp3 hybridised. |
|
|
Term
| Can the conjugate base of an aldehyde/ketone react as a nucleophile? If so why? |
|
Definition
| The conjugate base which has a negative charge where the alpha proton used to be is a nucleophile and attracted to sites of electron deficiency. A strong base, however, such as OH- or R-O- (eg ethoxide) is required to abstract the proton. In summary we can abstract an alpha proton using a strong base to make the conjugate base of a ketone or aldehyde. This can then react as a nucleophile and attack electron deficient site. |
|
|
Term
| What are the basic steps of an aldol condensation? |
|
Definition
| Generate a nucleophile using a strong base to form an enolate ion, nucleophilic addition of the enolate ion to the other aldehyde/ketone through attraction to the carbonyl carbon to form the aldol, then dehydration/elimination of water to form the final alpha, beta unsaturated compound. |
|
|
Term
| What is the difference between an aldol reaction and an aldol condensation? |
|
Definition
| An aldol reaction forms an aldol from a pair of ketones or aldehydes while the condensation also involves the dehydration of the aldol to form the alpha, beta-unsaturated compound. |
|
|
Term
| In an aldol condensation why can't the enolate negative charge be the leaving group? |
|
Definition
| The hydroxyl group is the leaving group even though it is usually a bad leaving group because the driving force is the formation of the carbon-carbon double bond in conjunction with the carbonyl group. Sometimes high temperatures (or extended conjugated systems) are required to achieve this dehydration.The reason for the enolate ion not being used is that it can act as a nucleophile but the reaction is slower and the product is reversible back to enolate and ketone. The alpha, beta-unsaturated aldehyde or ketone is also more stable. |
|
|
Term
| What is the Claisen-Schmidt Reaction? |
|
Definition
| This is an Aldol cross condensation where an aromatic aldehyde reacts with an aliphatic aldehyde or ketone containing a pair of alpha protons on the same carbon atom. The aldol is then rapidly dehydrated. |
|
|
Term
| Why is there only one product in a Claisen-Schmidt reaction? |
|
Definition
| There is only one product because the aliphatic ketone is the only nucleophile as the aromatic aldehyde has no alpha protons free to be removed by a strong base due to the resonance ring structure. The aromatic aldehyde is also a better electrophile as the carbonyl carbon is more electron deficient due to the aromatic ring which is also electron withdrawing. |
|
|
Term
| Why is an aromatic aldehyde rather than an aromatic ketone in a Claisen-Schmidt reaction? |
|
Definition
| It is better to use an aromatic aldehyde rather than an aromatic ketone for steric reasons. |
|
|
Term
|
Definition
| No and it will thus precipitate out driving the equilibrium to the product side. |
|
|
Term
| What determines whether the ketone attacks the aromatic aldehyde rather than another ketone? |
|
Definition
| The aliphatic ketone could attack another molecule of unenolized ketone but it doesn’t because ketones are less reactive than aldehydes and the aromatic aldehyde is a better electrophile. How sterically hindered the apparently better electrophile is also determines whether self-condensation or cross-condensation occurs. |
|
|
Term
| What is the Claisen condensation reaction? |
|
Definition
| An Aldol reaction between two esters. |
|
|
Term
| Why is a carbomate more stable to hydrolysis than an ester? |
|
Definition
| Because the nitrogen in the carbamate can donate its non-bonding pair of electrons resonantly to the carbonyl carbon and in turn carbonyl oxygen as well as the oxygen in the chain. This means there is reduced polarity of the carbonyl bond decreasing the susceptibility of the carbonyl bond to nucleophilic attack by the water. |
|
|
Term
| What is the most abundant carbohydrate? |
|
Definition
|
|
Term
| How is a carbohydrate defined? |
|
Definition
| A carbohydrate is defined as a hydrate of carbon and most follow the formula Cn(2O)n. Not all stick to this formula, however, as some have differing numbers of oxygen and some contain nitrogen. Carbohydrates are essentially aldehydes and ketones with multiple hydroxyl groups or compounds that yield these after hydrolysis. |
|
|
Term
| What is the difference between simple and complex carbohydrates and what is the difference between monosaccharides, disaccharides, oligosaccharides, and polysachharides? |
|
Definition
| There are two types of carbohydrates: simple carbohydrates and complex carbohydrates. Simple carbohydrates are monosaccharides while complex carbohydrates contain two or more monosaccharides linked together. Disaccharides have two monosaccharides linked together, oligosaccharides have three to eight monosaccharides linked together, and polysaccharides have more than eight monosaccharides linked together. |
|
|
Term
| Are monosaccharides able to be hydrolysed? |
|
Definition
| Monosaccharides are the simplest form of carbohydrates and are unable to be hydrolysed. |
|
|
Term
| How are monosaccharides categorised and what is an example of a polyhydroxy aldehyde versus a polyhydroxy ketone? |
|
Definition
| A monosaccharide can be a polyhydroxy aldehyde such as D-glucose which is referred to as an aldose, or a polyhydroxy ketone such as D-fructose which is referred to as a ketose. Monosaccharides are also classified according to the number of carbons they contain. Those with three carbons are trioses, those with four carbons are tetroses, those with five carbons are called pentoses, those with six carbons are called hexoses, and those with seven carbons are heptoses. A six carbon polyhydroxy aldehyde such as D-glucose would thus be an aldohexose while a six carbon polyhydroxy ketone such as D-fructose would be a ketohexose. |
|
|
Term
| How can hemiacetals and acetals be formed in terms of carbohydrates? |
|
Definition
| We can also get hemiacetals and acetals which are formed by carbohydrates. A hemiacetal is when the aldehyde carbonyl bond is broken to form a hydroxyl group and an alcohol is added while an acetal is where a further alcohol is added to a hemiacetal to replace the hydroxyl group. A hemiacetal is formed when a straight chain carbohydrate forms a ring while the acetal is present when many monosaccharides join together as the glycosidic bond is essentially the addition of an alcohol through the removal of water. |
|
|
Term
| How do you classify a carbohydrate as D or L? |
|
Definition
| In the straight chain form If the hydroxyl group attached to the second to last carbon (the penultimate carbon) is to the left then the compound is an L sugar and if it is on the right then it is D sugar. The mirror image of a D sugar is an L sugar and most sugars are D sugars. This notation assumes that the aldehyde/ketone is always at the top or as close to the top as possible. |
|
|
Term
|
Definition
| Diastereomers which differ in configuration at only one stereocentre are called epimers. |
|
|
Term
| What are the three most common aldohexoses? |
|
Definition
| D-glucose, D-mannose, D-galactose |
|
|
Term
| What are the structures of D-glucose, D-mannose, and D-galactose? |
|
Definition
| D-glucose is a hexose which goes OH, H, OH, and OH on the right side in the D conformation. D-mannose is the C-2 epimer (1st stereocentre) (H H OH OH), and D galactose is the C-4 epimer (3rd stereocentre) (OH H H OH) |
|
|
Term
| Where is the ketone on a naturally ketose and how does the number of stereocentres relate to an aldose? |
|
Definition
| Naturally occurring ketoses have the carbonyl group on Carbon two and thus have one less stereocentre than an aldose of the same chain length. |
|
|
Term
| What is the structure of fructose? |
|
Definition
| Fructose is a ketohexose and is essentially the ketone version of glucose without the top OH. (H OH OH) |
|
|
Term
|
Definition
| Glucose with the top OH replaced by an amino group |
|
|
Term
|
Definition
| Mannose with the top OH replaced by an amino group |
|
|
Term
|
Definition
| Galactose with the top OH replaced by an amino group |
|
|
Term
| What is N-acetyl-D-glucosamine? |
|
Definition
| Glucose with the top OH replaced by an amide group (NHCOCH3) |
|
|
Term
|
Definition
| Interconversions of the alpha and beta forms of a sugar via mutarotation |
|
|
Term
| What are the relative proportions of alpha, beta, and open chain during mutarotation and why? What is the relationship between these forms? |
|
Definition
| Mutarotation refers to the equilibrium between alpha and beta forms which are cyclic via the straight chain. These are all anomers. At equilibrium 64% is beta as the hydroxyl group as the largest substituent is in an axial position when in chair conformation making it more stable. 36% is in the alpha form and 0.02% is in the open chain at any one point in time. |
|
|
Term
| What is the anomeric carbon? |
|
Definition
| The carbon in a monosaccharide that was the carbonyl carbon in the open chain form |
|
|
Term
|
Definition
| Ring structures that have differing conformations at the anomeric carbon. |
|
|
Term
| How do you determine if a sugar is alpha or beta? |
|
Definition
| The configuration of the anomeric carbon determines whether alpha or beta. Relative the terminal CH2OH group if the OH on the anomeric carbon is on the same side then the compound is beta and if it is on the other side it is alpha. Cis is beta and trans is alpha. |
|
|
Term
| What are six membered rings containing oxygen called? |
|
Definition
| Pyran meaning the carbohydrate would be pyranose. |
|
|
Term
| What are five membered rings containing oxygen called> |
|
Definition
| Furan meaning the carbohydrate would be furanose. |
|
|
Term
| What is the solubility of various carbohydrates like? |
|
Definition
| Monosaccharides such as glucose are colourless, crystalline solids which are all very water soluble such as glucose. Small carbohydrates show very good water solubility. There is, however, lower solubility of larger forms such as starch due to branching and thus usage of the polar hydroxyl bonds in the formation of acetals and hemiacetals. |
|
|
Term
| How is the carboxylic acid named? |
|
Definition
| The carboxylic acid is the highest ranked functional group and is named by substituting the alkane for alkanoic acid. |
|
|
Term
|
Definition
| An ester has two halves or R groups. We name the R group connected to the oxygen first followed by the COR. The naming instead of alkane becomes alkyl alkanate. |
|
|
Term
| How do we name a cyclic ester? |
|
Definition
| A lactone is a cyclic ester and in order to name it we count the longest carbon chain and then give it the name alkanolactone starting the numbering from the carbonyl carbon and stating the carbon number where the oxygen in the ring joins the chain. |
|
|
Term
| Why do carboxylic acids have much higher melting and boiling points compared to ketones and esters? |
|
Definition
| Carboxylic acids can have intramolecular “dimer” hydrogen bonding between the carbonyl carbon and the hydroxyl hydrogen. They have a much higher melting and boiling point compared to ketones and esters etc because of this. |
|
|
Term
| How soluble is an ester and what increases solubility? |
|
Definition
| Esters are soluble in protic solvents where the solvent has a proton to donate or share. Solubility varies according to acid strength and ionisation where ionisation increases solubility and substituents on an aromatic ring increase it further when ortho and para to the carboxylic acid and electron withdrawing. Hydrogen bonding intramolecular stabilisation in the conjugate base form helps increase the acidity as in salicylic acid whereas hydrogen bonding in the acid form makes it more difficult to remove the proton making it less acidic with a higher pKa ie ciproflaxin. |
|
|
Term
| What is the general pKa for carboxylic acids? |
|
Definition
|
|
Term
| Why does 2, 4, 6-trinitrobenzoic acid have a pKa of 0.42? |
|
Definition
| Due to the aromatic ring and the strong electron withdrawing groups in the ortho and para positions. |
|
|
Term
| Why are carboxylic acids good acids? |
|
Definition
| Because the conjugate base or carboxylate is resonance stabilised. |
|
|
Term
| Why do esters have a lower boiling point that carboxylic acids? |
|
Definition
| Esters are still polar as they contain a carbonyl group but cannot form intermolecular “dimer” hydrogen bonds as is the case with carboxylic acid. |
|
|
Term
| Why are esters less soluble than carboxylic acids? |
|
Definition
| They can, however, hydrogen bond with protic solvents but not quite as well as carboxylic acids. |
|
|
Term
| Why are the alpha protons of an ester not that acidic? |
|
Definition
| The oxygen within the chain also contributes to resonance and thus the alpha protons are not as acidic as in the conjugate base the negative charge must compete with the non-bonding pairs of the oxygen for resonance stabilisation decreasing acidity and increasing the pKa. |
|
|
Term
| How are carboxylic acids prepared? |
|
Definition
| By oxidation of primary alcohols, aldehydes, or alkyl benzenes or through the hydrolysis of esters. |
|
|
Term
| What are the conditions for hydrolysis of esters? |
|
Definition
| You need water. It can be done under acidic or basic conditions. |
|
|
Term
| How can esters be prepared? |
|
Definition
| Through Fischer esterification which is the reaction of a carboxylic acid and an alcohol under acidic conditions or the more reactive acyl chloride and alcohol. Acyl chloride and alcohol is not considered Fischer esterification and does not require acidic conditions. |
|
|
Term
| Why is an acyl chloride more reactive than a carboxylic acid? |
|
Definition
| Acyl chloride is more reactive as the chloride ion is a good leaving group due to its high electronegativity and non-bonding pairs of electrons compared to the hydroxyl group of the carboxylic acid which needs to be protonated by an acid in order to be able to act as a leaving group. |
|
|
Term
| What are the three main reactions of carboxylic acids and what are important things to consider in regards to nucleophilic substitution? |
|
Definition
| Acid base reactions at the hydroxyl group, carbonyl oxygen protonation under acidic conditions, and nucleophilic substitution at the carbonyl carbon. Nucleophilic substitution in acidic conditions the carbonyl oxygen is generally protonated prior to nucleophilic substitution. This works best under basic conditions but under basic conditions a nucleophile or base will usually react to the acidic proton in preference to the carbonyl carbon. |
|
|
Term
| What are the two main reactions of esters? |
|
Definition
| Claisen condensation and acid catalysed ester hydrolysis. |
|
|
Term
| Why do carbamic acids not exist? |
|
Definition
| Because the spontaneously decompose into an amino group and carbon dioxide |
|
|
Term
| Why are carbamate esters more stable to hydrolysis than normal esters? |
|
Definition
| Carbamate esters, however, are much more stable to hydrolysis than ordinary esters because of the difference in slightly positive charge on the alpha carbon atom. This is due to the fact that nitrogen is also an electron donating atom and thus competes with the ester oxygen for resonance making it harder for hydrolysis to occur particularly acid hydrolysis as it is more difficult to protonate the carbonyl oxygen. On a prodrug oxidative metabolism must occur which is different to hydrolysis. |
|
|
Term
| What is an inorganic ester? |
|
Definition
| The combination of an alcohol with an inorganic acid. An example is a phosphate ester. |
|
|
Term
| Why are drugs administered as prodrugs? |
|
Definition
• Improve IV formulation (make more hydrophilic)
• Improve membrane permeability (make more lipophilic)
• Mask taste
• Delay metabolism or adjust drug half life
• Drug delivery to diseased tissue only (site specificity)
• Prolonged release (eg physical barrier or gel) |
|
|
Term
| How to you name an amide? |
|
Definition
|
|
Term
|
Definition
| A cyclic amide named in the same way as lactones |
|
|
Term
| Why are amides less reactive? |
|
Definition
| Amides are polar and contain polarised bonds, however they are relatively unreactive. The non-bonding electron pair of the nitrogen is delocalised into the adjacent carbonyl group. Therefore amides are much less reactive towards nucleophiles at the alpha carbon that ketones, aldehydes, and esters. |
|
|
Term
| Why are amides soluble in polar solvents? |
|
Definition
| Because amides are polar they can hydrogen bond with polar solvents which is good for improving water solubility. |
|
|
Term
| When can amides be acidic or basic? |
|
Definition
| Amides can be acidic or basic only if nitrogen non-bonding electrons cannot be resonance shared. For resonance stabilisation to occur the nitrogen goes from sp3 to sp2 hybridised and the p orbitals of N-C-O atoms must all be coplanar for molecular orbital overlap. If a nitrogen is sp3 hybridised as in some lactams then resonance cannot occur due to a lack of ability to switch to sp2 hybridisation. This would occur for example when holing together two rings. |
|
|
Term
| How are amides prepared and why can't we use carboxylic acid?? |
|
Definition
| Acylation of amines with acyl chlorides. Carboxylic acids have OH groups which are bad leaving groups and thus would not react. Only acyl chlorides and activated esters can be used in the reaction. |
|
|
Term
| What reactions can an amide undergo? |
|
Definition
| Amides are relatively unreactive but under strong forcing conditions such as a highly acidic or basic solution and heat then they can be hydrolysed. In the acid condition a strong acid, water, and heat are required to remove the amino group to form a carboxylic acid and ammonium salt. In the base condition it is the carbonyl group that is removed to form an amine and a carboxylate salt. Both of these reactions can be seen below: |
|
|
Term
| Under forcing basic conditions and heat what is formed by hydrolysis of an amide? |
|
Definition
| A carboxylate salt and an amine |
|
|
Term
| Under forcing acidic conditions and heat what is formed by hydrolysis of an amide? |
|
Definition
| An ammonium salt and a carboxylic acid. |
|
|
Term
| Is a sulfonamide acidic, basic, or neutral? |
|
Definition
| A sulfonamide is considered weakly acidic and will lose a proton from the nitrogen atom if an N-H bond is present as due to the acidity of the N-H bond. pKa is 5-10. 5 if the R group is electron withdrawing and 10 if it is not. |
|
|
Term
|
Definition
| Essentially a sulfamide with one less double bonded oxygen and one more R group. This is also a weak acid |
|
|
Term
| What happens in the case of protein misfolding? |
|
Definition
| It is believed that misfolding of the native polymer causes all of the beta strands to clump together in a beta sheet and then the beta sheets together aggregate to form amyloid fibrillar aggregates. |
|
|
Term
| What is believed to happen in the case of Alzheimers? |
|
Definition
| . It is believed that the beta sheet may play a part in Alzheimer’s disease where the usually soluble amyloid-beta peptide aggregates into beta-sheet-rich oligmeric structures which are neurotoxic and then intermolecular hydrogen bonds form between the strands. |
|
|
Term
| How are amines classified when ordinary aliphatic and when protonated?? |
|
Definition
| Aliphatic amines are classified according to the number of substituents on the nitrogen such as primary, secondary, and ternary. When protonated these amines become known as aminium and are again classified as primary, secondary, or tertiary. There is also a special case of aminium called quaternary aminium where there are four carbon substituents attached to the nitrogen with a counter ion attracted to the positive nitrogen. |
|
|
Term
| How is an amine named when highest priority and not highest priority? |
|
Definition
| When amines are the highest priority the amine is put at the end of the name with the carbon the amine is attached to. In contrast when the amine is not highest priority the amino group is labelled as an amino substituent. |
|
|
Term
| How is an amine named if there are one or more amino substituents on a benzene ring? |
|
Definition
| If there are one or more direct N-substituents on a benzene group then the aromatic amine is known as aniline or when protonated is anilinium. |
|
|
Term
| What are the two main heterocyclic aliphatic amines? |
|
Definition
| Pyrrolidine (five) and piperidine (six |
|
|
Term
| What are the two main heterocyclic aromatic amines? |
|
Definition
| Pyrrole (five) and pyridine (six) |
|
|
Term
| What determines the solubility of amines? |
|
Definition
| Polar means an uneven shared pair of electrons and due to the comparatively higher electronegativity of nitrogen, the N-H bond is polarised. Because of this polar bond hydrogen boning is able to occur. The greater the number of hydrogen bonds in a pure solution of the amine means a higher melting/boiling point. The greater the number of hydrogen bonds with a solvent the more soluble the compound. Most amines with a low molecular mass are soluble in protic solvents such as water. |
|
|
Term
| How are the boiling points of amines comparable to alkanes of similar weight? |
|
Definition
| Both primary and secondary amines form hydrogen bonds and so these amines have higher boiling points than alkanes with similar molecular weights. |
|
|
Term
| Are the hydrogen bonds stronger in amines or alcohols and what does this mean in terms of boiling points? |
|
Definition
| Nitrogen is not as electronegative as oxygen, however, which means that the hydrogen bonds between amine molecules are weaker than the hydrogen bonds between alcohol molecules. An amine therefore has a lower boiling point than an alcohol of similar molecular mass. |
|
|
Term
| Why do primary amines have a higher boiling point than similar molecular mass tertiary amines? |
|
Definition
| primary amines have two N-H bonds, hydrogen bonding is more significant in primary amines than secondary amines. Tertiary amines cannot form hydrogen bonds because they do not have hydrogen attached to the nitrogen. Consequently, when we compare amines with the same molecular weight and similar structures, we find that a primary amine has a higher boiling point than a secondary amine and a secondary amine in turn has a higher boilng point than a tertiary amine. |
|
|
Term
| How do substituents affect the basicity of an amine? |
|
Definition
| An electronegative substituent close to the nitrogen atom will tend to draw the non-bonding pairs away making it a weaker base (lower pKa). |
|
|
Term
| What are the acid base properties of amine and what is the pKa? |
|
Definition
| An amine can behave as an acid and donate a proton or behave as a base and receive one. Due to the high pKa values of amines, however, they rarely behave as acids. Amines are much more likely to act as bases and in fact amines are the most common organic bases. The high pKa refers to the fact that they do not tend to act as acids and thus must be stronger bases with pKas around 40. The pKas of protonated amines are about 10 to 11. |
|
|
Term
| When can nitrogen be a stereocentre? |
|
Definition
| Nitrogen can be a stereocentre but only when protonated (in quaternary state). Even though an amine is sp3 hybridised the lone pair of electrons cannot be counted as a ligand because inversion occurs readily at room temperature with nitrogen lone pairs moving to the other face. This means it is thus not possible to isolate the stereoisomers. |
|
|
Term
| How can amines be prepared? |
|
Definition
| Through the reduction of an azide (three nitrogen atoms in a row double bonded to one another) by palladium/carbon and hydrogen, reduction of a nitro group in the presence of hydrogen and nickel, and via reductive amination. |
|
|
Term
| What happens to an imine in acidic aqueous solution? |
|
Definition
| In acidic aqueous solution, an imine is hydrolysed back to the carbonyl compound and amine. |
|
|
Term
| How is an enamine formed? |
|
Definition
| A secondary amine reacts to form an enamine instead of an imine and as there are no protons attached to the nitrogen to lose, a proton is instead lost from the alpha carbon breaking the double bond to the nitrogen and thus forming a double bond from the amino carbon to the alpha carbon instead of maintaining the double bind to the nitrogen and losing an amino hydrogen as in an imine. |
|
|
Term
| What is imine formation called? |
|
Definition
| The first reaction amines undergo is Schiff base (imine) formation which is the first step of the two step reductive amination reaction where there is nucleophilic addition of the amine to the aldehyde or ketone. |
|
|
Term
| What are the reactions of amines? |
|
Definition
| Schiff base formation/reducive amination, amide formation, acid/base, and reaction to form diazonium salts and azo compounds. |
|
|
Term
| What conditions are required to form diazonium chloride? |
|
Definition
| Aniline can react with sodium nitrate and HCl at 0° to form diazonium chloride. |
|
|
Term
| How does the diazonium chloride reaction occur? |
|
Definition
| This reaction occurs by sodium nitrate and two molecules of HCl first reacting to form water, NaCl, and the nitrosonium ion. The nitrosonium ion then acts as an electrophile to form an intermediate compound where water is then released to form the final product |
|
|
Term
| When is diazonium stable? |
|
Definition
| Diazonium is only stable when kept cold, in water, and in salt form. This is made in situ and reacted immediately. If a diazonium solution is warmed up or dried to remove water it becomes very sensitive to touch, heat, and pressure and can go boom. |
|
|
Term
| What reactions can diazonium salts undergo and why are aryl diazonium salts more stable than acyl diazonium salts? |
|
Definition
| Aryl diazonium salts are more stable than alkyl as charge and electron can be delocalised by resonance. These are very useful synthetic intermediates for example coupling with an activated aromatic ring to give azo compounds. This is an example of electrophilic aromatic substitution and the substitution will occur preferentially at the para position or failing that at ortho. |
|
|
Term
|
Definition
| The azo group is a pH-sensitive chromophore and azo dyes are common in textiles. Azo benzenes have an extended conjugated system that causes them to absorb light from the visible region of the spectrum. Varying the extent of conjugation and the substituents attached to the conjugated system creates a large number of different colours. |
|
|
Term
| What is the pKa of aniline and why? |
|
Definition
| Anilines are less basic than aliphatic amines due to resonance where the nitrogen lone pair of electrons is delocalised within the ring. This makes the nitrogen less nucleophilic and lowers the pKa making it a weaker base. Imine and amide formation is possible for anilines but the reaction requires more forcing conditions compared to aliphatic amines. These have a pKa of approximately 5. Protonated aniline is a relatively strong acid due to the high stability of deprotonated aniline as a result of resonance. |
|
|
Term
| What type of substitution can occur for aniline? |
|
Definition
| Electrophilic aromatic substitution can occur on the ring. The lone pair of electrons on the nitrogen atom gets delocalised within the ring activating the ortho and para positions for substitution. However, in strong acidic conditions the nitrogen is protonated and the protonated amino group is deactivating. |
|
|
Term
| How stable is an amine in formulation? |
|
Definition
| Amines may react with aldehydes/ketone to produce imines and can behave as nucleophiles if electrophiles are present. Often the acid salt is used in formulation as it is easier to handle, stable, more soluble in water, and not as volatile. |
|
|
Term
| What is an alcohol and how is it classified?? |
|
Definition
| An alcohol is a compound where a hydroxyl group is bonded to a sp3 hybridised carbon. Oxygen is also sp3 hybridised and tetrahedral with two pairs of non-bonding electrons. This is classified according to the number of substituents on the adjacent carbon as to whether it is primary, secondary, or tertiary. |
|
|
Term
| How do we name an alcohol when it is highest priority and when it isn't? |
|
Definition
| When the alcohol is the highest priority we insert “ol” into the longest chain and thus instead of alkane it becomes alkanol. When the alcohol is not the group of highest priority it is named hydroxyl. |
|
|
Term
|
Definition
| A compound containing two hydroxyl groups is called a diol. |
|
|
Term
| Why are phenol, ethers, enols, and inorganic salts not alcohols? |
|
Definition
| Phenol is not an alcohol but is rather a hydroxyl group bound to an aromatic benzene ring. Ether is when as alcohol hydroxyl group is C-O-C substituted. An inorganic salt is where the hydroxyl group is not bound to a sp3 hybridised carbon but is instead bound to a cation. An enol is where the hydroxyl group is bound to a sp2 hybridised carbon instead of a sp3 hybridised carbon. |
|
|
Term
| What do the polar C-O and O-H bonds in alcohol mean? |
|
Definition
| Both the C-O and O-H bonds of an alcohol are polar due to the high electronegativity of the oxygen atom. This allows hydrogen bonding between like molecules and also between alcohols and other polar molecules. This leads to an increased melting point and boiling point compared to alkanes and allows alcohols to dissolve more easily than alkanes in aqueous solvents such as ethanol and water. |
|
|
Term
| What affects the melting and boiling points of an alcohol? |
|
Definition
| A longer carbon chain will also increase the melting and boiling points while branching of the chain will decrease melting and boiling points. This is due to increasing van der Waals forces. |
|
|
Term
| What are the acid/base properties of alcohol? |
|
Definition
| Alcohols can act as a very weak acid or base and are thus amphiprotic. As an acid it loses a proton and as a base it accepts a proton. Its ability to act as a base is useful for activating the compound and making a good leaving group by forming a water substituent (oxonium ion) as water is less attracted to the carbon than the hydroxyl group as oxygen does not like having a positive charge. A protonated alcohol is a very strong acid. |
|
|
Term
| How can alcohols be prepared? |
|
Definition
| Acid catalysed addition of water to alkenes, nucleophilic substitution of a haloalkane in the presence of dilute NaOH, and through the reduction of aldehydes and ketones using NaBH4. |
|
|
Term
| What is the difference between an SN1 and an SN2 reation? |
|
Definition
| An SN1 reaction happens in two steps and has a unimolecular rate determining step where the strength of the nucleophile does not affect the rate of reaction. The reactivity order is tertiary then secondary and the products can either have the same or inverted configurations. An SN2 reaction is a one step mechanism with a bimolecular rate determining step where the better the nucleophile the faster the rate of reaction. The reactivity order is methyl then primary then secondary and the product has an inverted configuration relative to that of the reactant. |
|
|
Term
| When does Williamson Ether synthesis not occur? |
|
Definition
| On alkenes, tertiary alcohols, aromatic alcohols |
|
|
Term
| What type of reaction is Willamson Ether synthesis? |
|
Definition
|
|
Term
| Why is it difficult to perform Williamson Ether synthesis with a secondary alkyl halide? |
|
Definition
| Because alkoxides are strong bases (recall the pKa of alcohols is in the range 16-18), competition with elimination [E2] pathways becomes a concern once the alkyl halide becomes more sterically hindered. For this reason trying to perform a Williamson on a secondary alkyl halide is a bit more problematic than it is for a primary alkyl halide. One way to attempt to get the SN2 to be favoured over the E2 is to use a polar aprotic solvent (such as acetonitrile or DMSO) that will increase the nucleophilicity of the alkoxide. If heat is applied, however, the E2 will most likely dominate. |
|
|
Term
| How is Williamson ether synthesis carried out? |
|
Definition
| The most common way to present the Williamson is to show the alkoxide base being added to the alkyl halide in the presence of its conjugate acid as solvent. |
|
|
Term
| How is alcohol converted to a haloalkane? |
|
Definition
| Using HCl or HBr or HI etc where the proton protonates the alcohol to make the hydroxyl group a better leaving group. |
|
|
Term
| During conversion to a haloalkane why do methyl and primary alcohols need to use the SN2 reaction where secondary and tertiary use SN1? |
|
Definition
| Tertiary alcohols react the most quickly as they are the most stable carbocation followed by secondary alcohols. Primary alcohols must use the SN2 reaction mechanism as the primary carbocation is too unstable. In this case the strong acid protonates the strongest base in this case the hydroxyl group. Instead of leaving immediately the halide ion attacks the back of the oxonium ion displacing the protonated hydroxyl group in a single step so the carbocation is not formed. This means that the conformation of the haloalkane will be the opposite to the conformation of the alcohol while in the SN1 mechanism either conformation is possible. |
|
|
Term
| What is required for a williamson ether synthesis? |
|
Definition
| A strong base such as NaH to remove the proton and allow the protons to combine to form hydrogen gas then bubble away rather than sticking around and interfering with the rest of the reaction. The alkyl halide is then added (prefarably primary and with limited steric hindrance). |
|
|
Term
| What happens when an alcohol reacts with a protonated carboxylic acid or acyl chloride? |
|
Definition
| An ester is formed and this is acid catalysed. This is known as the Fischer-Speier method |
|
|
Term
| How stable are alcohols in formulation? |
|
Definition
| In formulation alcohols can be oxidised by oxygen in the air to form aldehydes and in turn carboxylic acids in the case of primary alcohols this is why alcohol can go bad. They can also be oxidised to form peroxides which can be explosive. |
|
|
Term
| How is a thiol named when it is highest priority and when it isn't? |
|
Definition
| When it is the highest priority the suffix is thiol. When the thiol group is of lower priority the prefix is mercapto |
|
|
Term
| Why are thioethers not thiols? |
|
Definition
| A thiol needs an SH group and thus thioethers are not thiols. These are instead named as sulfides where either side of the S is named and then the suffix sulfide is added. |
|
|
Term
| What are the similarities and differences between thiols and alcohols? |
|
Definition
| The physicochemical properties of thiols are similar to alcohols and they can form both thioethers and thioesters in the same manner than alcohols form esters and ethers. The main difference compared to alcohols is that S and H have a similar electronegativity and thus the S-H bond is non-polar and the electrons are evenly shared in the S-H bond. This means very little hydrogen bonding and lower boiling points as well as lower protic solvent solubility compared to the equivalent alcohol. In contrast thiols are stronger acids than alcohols with a pH of closer to 10 (8.5) than 15 (15.9). |
|
|
Term
| What is the difference between an alpha and a beta glycosidic linkage? |
|
Definition
| An alpha linkage has the non-hydrogen anomeric substituent on the opposite side to the linkage and is thus trans. A beta linkage has the linkage on the same side as the non-hydrogen anomeric linkage and is cis. |
|
|
Term
| What is the difference between a reducing and a non-reducing sugar? |
|
Definition
| Reducing is a hemiacetal while non-reducing is an acetal. |
|
|
Term
|
Definition
| A hemiacetal forms an acetal through the addition of alcohol. Hydrolysis of an acetal back to a hemiacetal occurs with dilute acid (aqueous acid). A cyclic acetal derived from a monosaccharide is known as a glycoside and will not be a reducing sugar. |
|
|
Term
| What is a glycosidic bond? |
|
Definition
| A glycosidic bond is one that converts a hemiacetal sugar into an acetal sugar for example adding methoxy in the place of the anomeric hydroxyl group on glucose. |
|
|
Term
|
Definition
| Anomers are two versions of a sugar where the direction of the anomeric non-hydrogen substituent is inverted. |
|
|
Term
| What is the naming when there is a sugar and a non-sugar part to a glycoside? |
|
Definition
| In the case where there is a sugar part and a non-sugar part in a glycoside then the sugar part is called a glycone while the non-sugar part is an aglycone. |
|
|
Term
| What linkages are used for straight chain and which for branching? |
|
Definition
| 1,4 for chain and 1,6 for branch |
|
|
Term
|
Definition
| Monosaccharides can be reduced to alditols (aldehyde reduced to alcohol). This occurs in the straight chain form and utilises NaBH4 to reduce the aldehyde by increasing the number of C-H bonds and breaking the double carbonyl bond. |
|
|
Term
|
Definition
| A reducing sugar is one that can adopt its aldehyde (or ketone) form and then act as a reducing agent getting oxidised in the process. This reaction is specific to aldoses and forms aldonic acid. This uses bromine and water at pH 6. |
|
|
Term
|
Definition
| Glucose can also be oxidised to its uronic acid form which is where the terminal alcohol is converted to a carboxylic acid. This is enzyme catalysed. |
|
|
Term
|
Definition
| Oxidation to aldaric acid is also possible where the oxidising agent HNO3 is used to convert aldoses into dicarboxylic acids. |
|
|
Term
| How can blood groups A, B, and O interconvert? |
|
Definition
| Blood group A can be converted to O by A-zyme and returned by GTA while Blood group B can be converted to O by B-zyme and back by GTB. |
|
|
Term
| What is the difference between blood groups A, B, and O? |
|
Definition
| O contains neither A nor B antigen but contains both antibodies, A contains A antigen and B antibodies, B contains B antigens and A antibodies, while AB contains both antibodies and neither antigen. Determined by antigen. |
|
|
Term
| What is the pKa of indole? |
|
Definition
| pKa 17 for acidic proton but considered neutral as non bonding pair not available |
|
|
Term
| Where does electrophilic aromatic substitution take place on indole and why? |
|
Definition
| Indole electrophilic aromatic substitution occurs at the 3 position and not at the 2 position because resonance forms of C2 substitution involve the loss of benzene Aromaticity and this is unfavourable. |
|
|
Term
| What happens in halogenation of indole? |
|
Definition
| Halogenation of indole is another example of electrophilic substitution which again occurs at C3. The first step to this is the generation of the electrophile. In the case of chlorine this is achieved through the addition of the Lewis acid FeCl3 where one of the chlorines from the chlorine gas (Cl2) attaches to the FeCl3 which has an electron deficit to form FeCl4- leaving Cl+ to act as an electrophile. |
|
|
Term
| What is the pKa of tetrazole and what does this mean? |
|
Definition
| 5 used as a biostere for carboxylic acid. |
|
|
Term
|
Definition
| A four membered ring structure with a carbonyl group adjacent to the hydrogen. Not aromatic. Easily hydrolysed by aqueous protons, aqueous base, and enzyme so useful for prodrugs. This not a normal amide. |
|
|
Term
| What is the pKa of pyrrole, is it acid/base/neutral, and where do SEAr and SNAr take place? |
|
Definition
| Neutral SEAr C2 preferred pver C3. No SNAr |
|
|
Term
| What is the pKa of pyridine, is it acid/base/neutral, and where do SEAr and SNAr take place? |
|
Definition
| 5.2 basic. SEAr only in harsh conditions at C3 and SNAr at C2 and C4 |
|
|
Term
| What is the pKa of imidazole, is it acid/base/neutral, and where do SEAr and SNAr take place? |
|
Definition
| 7.0 basic. SEAr C4 and C5 SNAr C2 |
|
|
Term
| What is the pKa of indole, is it acid/base/neutral, and where do SEAr and SNAr take place? |
|
Definition
| Neutral SEAr at C3 no SNAr |
|
|
Term
| What is the pKa of tetrazole, is it acid/base/neutral, and where do SEAr and SNAr take place? |
|
Definition
| 4.9 acidic no aromatic substitution |
|
|
Term
| What is the geometry of a platinum complex? |
|
Definition
|
|
Term
| In a metal complex what is used to balance the charge? |
|
Definition
|
|
Term
|
Definition
| Chelation is coordination through two or more atoms for example EDTA (6 points of coordination) |
|
|
Term
| What is the case of tautomerism in imidazole? |
|
Definition
| There is also the case of Tautomerism of imidazole where the un-substituted imidazole has no issue but when substituted as below the 4-methyl imidazole is in equilibrium with the 5-methyl imidazole: |
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|
