Molecular Shape & Reactivity Flashcards
What is drug structure controlled by?
Structure + orientation of functional groups
What is functional group structure controlled by?
Electronic arrangement
= individual atoms
= valency
= hybridisation
Describe ethane
C2H6 2 carbons = both tetrahedral C-H formed by overlap sp3 C + H s orbital C-C formed by overlap of 2 C sp3 109.5 degrees
How can ring structures be simply made?
By having 2 sp3-sp3 C-C bonds
Describe bonds in ethene
C2H4
Each C has 4 bonds
Hybridisation of s with 2x 2p = 1 p orbital left non-hybridised
120 degrees
What is e- repulsion minimised by in ethene?
3x sp2 orbitals
point corners of equilateral triangle
Where is the unhybridised p orbital?
Perpendicular to plane
How is the double bond formed in ethene?
1st = overlap of sp2 from each C = sigma bond 2nd = side to side overlap of unhybridised p orbital = pi bond
Describe the bonds in ethyne
C2H2
Triple bond
Hybridisation of only 2 orbitals (sp) = 2 p orbitals left (2p)
Describe sp orbitals in ethyne
C2H2
2 side to side overlap = 2 pi bonds
C form 1 sigma bond
Describe bonding in methyl cation
C positively charged
Bonded to 3x H
sp2 hybridisation
Non-hybridised p remains empty + perpendicular to plane
Describe bonding in methyl radical
C bonded to 3x H
sp2 hybridised
What is the difference between methyl cation and methyl radical?
Radical has one more e- that resides in non-hybridised p orbital
Describe bonding in methyl anion
C bonded to 3x H
3 bonding pairs + 1 L.P
Negatively charged C = sp3
L.P resides in sp3
How are the 3 bonds formed in methyl anion?
sp3-s overlap
What does nitrogen hybridise to form?
4x sp3 orbitals
1 = occupied by 2x non-bonding e-
How are N-H formed?
sp3-s overlap
Describe bonding in amines
N has same geometry as in NH3
C-N bonds formed by sp3-sp3 overlap
What can Hs be replaced by in amines?
1 alkyl or aryl group = primary amine
2 alkyl or aryl group = secondary amine
3 alkyl or aryl group = tertiary amine
Why can H2O + NH3 act as bases (nucleophiles)?
Use L.P to bond H+
Formal charge of +1
What is the bond angle of N-H?
109.5 degrees
How are O-H bonds formed?
sp3-s orbital overlap
How are C-O bonds formed?
sp3-sp3 orbital overlap
How are S-H bonds formed?
sp3-s orbital overlap
How are S-C bonds formed?
sp3-sp3 orbital overlap
What can O + N form?
Double bonds
What can N form?
Triple bonds
What does phosphorus use for bonding?
3rd shell e-
Why does phosphorus use 3rd shell e- for bonding?
Smaller energy gap between the occupied 3p orbitals + vacant 3d orbitals
Where is the bond formed in HF?
Between H 1s orbital + F 2sp3 orbital
Where is the bond formed in HCl?
Between H 1s + Cl 3sp3
What happens to e- density in region of s-sp3 overlap as size of hydrogen halide increases?
Decreases
= H-X bond becomes weaker
What happens to hydrogen halide bond strength down the group?
Decreases
How is the C-X bond formed in alkyl halides?
sp3-sp3 orbital overlap
What happens as size of halogen increased in alkyl halides?
sp3 orbital from higher shell used in bond decreased in e- density
= longer + weaker
What is electronegativity?
Tendency of an atom to pull bonding e- towards itself
What is a polar covalent bond?
Covalent bond in which e- distribution between atom is unsymmetrical
Describe inductive effect
Atom’s ability to polarise a bond
e- -attracting or e- -withdrawing effect transmitted through S bonds
What do electronegative elements have?
e- -withdrawing inductive effect
What is dipole moment a measure of?
Net polarity of a molecule
What are covalent compounds composed of?
Discrete molecules
What are the 4 main type of interactions?
Van der Waals
Dipole-dipole interactions
Hydrogen bonding
Ion-ion
Describe Van Der Waals
Weak interactions caused by momentary change in e- density
Present in non-polar compounds
What determines the strength of Van Der Waals?
SA of molecule
What is polarizability?
Measure of how e- cloud around an atom responds to changes in its electronic environment
What are dipole-dipole interactions?
Attractive forces between the permanent dipoles of 2 polar molecules
Describe H bonding
Most important
Short range, directional, inter or intramolecular no-bonded interaction
Describe how H bonding works
Non-bonded interaction between H atom bonded to electronegative atom + another electronegative atom
What is the e- deficient H called?
Hydrogen bond donor
What is the e- rich H called?
Hydrogen bond acceptor
What is H bonding important for?
Drug molecule - receptor interactions
What are the conformational strains for alkanes?
Ethane
Staggered
Eclipsed
What is the torsional strain?
Alkanes
Repulsion felt by bonding e- as they pass close to bonding e- of an adjacent substituent
What is conformational analysis?
Alkanes
Investigation of a compound’s conformations + their relative stabilities
Describe conformation of butane
Rotation can occur around all 3 bonds
Staggered conformers of equal energy
Eclipsed conformers of equal, BUT higher energy
What does rotation around the C2-C3 bond of butane give?
6 important conformations Staggered gauche Eclipsed Staggered anti Eclipsed Staggered gauche Eclipsed
What is gauche conformation compared to anti?
Less stable due to repulsive Van Der Waals between 2 CH3
Describe conformation of cycloalkanes
Molecules not static = rotation around each C-C continuous
= many interconverting conformers can exist at any 1 time
=separation of conformers not possible
Why is separation of conformers not possible in cycloalkanes?
Due to paid speed of inter-conversion
What is the relative no. of molecules in a particular conformation of cycloalkanes dependent on?
Conformer stability with majority in staggered conformations
What is the difference with cycloalkane formation?
Ring rotation is limited = molecules twist + bend to minimise source of strain
What are the different sources of strain?
Angle strain
Torsional strain
Steric strain
What is angle strain?
Deviation from ideal tetrahedral bond angle
What is torsional strain?
Repulsion of proximate bonding e-
What is steric strain?
Where atoms/groups approach too closely
Describe conformations of cyclopropane
Torsional strain = C-H bonds eclipsed
Angle strain = orbitals overlap at slight angle
What does the conformations do to cyclopropane?
Weaker + more reactive than typical alkane bonds
Describe conformations of cyclobutane
Torsional strain= 1 C lies 25 degrees above plane of other 3
Is the angle strain of cyclobutane less or more than cyclopropane?
MORE
= larger number of ring H
Describe conformations of cyclopentane
Twists to non-planar conformation
= C-C 108 degrees
= C5 out of plane
Is the angle strain of cyclopentane less or more than cyclobutane + cyclopropane?
LESS
What would the planar cyclopentane exhibit?
Minimal angle strain
Large torsional strain = H eclipsed
Describe conformations of cyclohexane
No angular strain = C-C-C 111.5, close to 109.5
No torsional strain = neighbouring C-H staggered
What conformation does cyclohexane adopt?
Chair conformation/ boat conformation
What can happen to chair conformations?
Interconvert = exchanging axial + equatorial positions
Describe monosubstituted cyclohexane conformations
2 chair conformations not equal stability
Bulkier substituent = greater preference for equatorial substitution
Why is there an energy difference between axial + equatorial conformations?
Steric strain caused by 1,3-diaxial interactions
Describe disubstituted cyclohexane conformations
1,2-dimethylcyclohexane
Trans-isomer
2 methyl groups on opposite faces
Exist in diequatorial conformation
What are all substituents in glucose?
Equatorial
What are all substituents in mannose?
1 OH group axial
= mannose more strained
