Organic Chemistry - Isomerism PDF

GEOMETRY & ISOMERISM of ORGANIC COMPOUNDS “Structure of a molecule is often crucial in determining its properties and biological behaviour” ISOMERS – compounds with the same molecular formula but different structural formula or spatial orientation of atoms Classification of Isome...

GEOMETRY & ISOMERISM of ORGANIC COMPOUNDS “Structure of a molecule is often crucial in determining its properties and biological behaviour” ISOMERS – compounds with the same molecular formula but different structural formula or spatial orientation of atoms Classification of Isomers: A. Constitutional or Structural Isomers ◦ Isomers that vary in the bonding attachments of atoms 1. Skeletal Isomers - isomers that differ in the arrangement of the carbon chain Butane (C4H10) 2-methylpropane (C4H10) Classification of Isomers: A. Constitutional or Structural Isomers ◦ Isomers that vary in the bonding attachments of atoms 2. Functional Isomers - isomers with structural differences that put them in different classes of organic compounds C2H6O CH3CH2OH CH3OCH3 Ethanol (C2H5OH) Dimethylether (C2H6O) alcohol (ether) Classification of Isomers: A. Constitutional or Structural Isomers ◦ Isomers that vary in the bonding attachments of atoms 3. Positional Isomers - isomers that differ in the location of a noncarbon group or double bond or triple bond Br Br 1-bromopropane 2-bromopropane (C3H7Br) (C3H7Br) Classification of Isomers: A. Stereoisomers ◦ Isomers with the same bonding attachment of atoms but different spatial orientation 1. Optical Isomers - isomers which are identical in structure except where they differ as mirror images. Classification of Isomers: A. Stereoisomers ◦ Isomers with the same bonding attachment of atoms but different spatial orientation 2. Conformational Isomers - isomers that differs as a result of the degree of rotation around a C-C single bond Classification of Isomers: A. Stereoisomers ◦ Isomers with the same bonding attachment of atoms but different spatial orientation 3. Geometric Isomers - isomers where groups or atoms display orientation differences around a double bond or ring. Conformational Isomers: ❑ Rotation is a consequence of the cylindrical symmetry of sigma bonds ❑ It is possible to describe forms of molecule that differs in the arrangement of atoms due to rotation around a C-C single bond (CONFORMATIONAL ISOMERS/ CONFORMERS) ❑ There are conformations of low energy or high energy ❑ Rotation does not result to isolable forms (interconversion is very rapid) Conformational Isomers: ETHANE MOLECULE  Representation of Conformational Isomers: 1. Sawhorse Projection ❑ views C-C bond from an oblique angle and indicates spatial orientation by showing all C-H bonds ETHANE  Representation of Conformational Isomers: 1. Newman Projection ❑ views C-C bond directly end-on and represents the 2 C atoms by a circle. Bonds attached to the front C are represented by lines to the center of the circle, and bonds attached to the rear C are represented by lines to the edge of the circle. ETHANE  Representation of Conformational Isomers: ACTIVITY 1: Sight along C1-C2 bond of 1- chloropropane and draw the structure of propane using the sawhorse and Newman projection.  Conformational Isomers: Rotation around a C-C single bond is not really free Experiments show that there is a small barrier to rotate and that some conformations are more stable than the others Low energy conformation is the preferred conformation At equilibrium, greater population of molecules of a compound assume the preferred conformation (equilibrium conformation) Conformational Isomers: 6 C-H bonds are as far away from 6 C-H bonds are as close as one another as possible possible (lowest energy conformer, 99%) (highest energy conformer, 1%)  Conformational Isomers: ▪ Staggered : 60o, 180o , 300o Eclipsed : 0o, 120o, 240o ▪ 12 KJ/mol torsional strain due to H-H eclipsing interaction (4.0 KJ/mol or 1 Kcal/mol for every H-H eclipsing) Conformational Isomers:  Conformational Isomers of other Alkanes: 1. Propane  Conformational Isomers of other Alkanes: 2. Butane not all staggered or eclipsed have the same energy Anti conformation (lowest energy); occurs if the methyl groups are 180o away from each other eclipsed: 2 CH3-H, 1 H-H  Conformational Isomers of other Alkanes: 2. Butane Gauche conformation; no eclipsing; occurs if the methyl groups are 60o away from each other Steric strain - repulsive interaction that occurs when atoms are forced close together than their atomic radii allow  Conformational Isomers of other Alkanes: 2. Butane Eclipsed: torsional strain and steric strain are present Conformational Isomers of other Alkanes: Conformational Isomers of other Alkanes: Conformational Isomers of other Alkanes: 3. Ethylene glycol (HOCH2CH2OH) OH H-bond OH OH OH OH OH Gauche (most stable) eclipsed anti Allows interaction of H and –OH (H- bonding)  Conformational Isomers of other Alkanes: 3. dichloroethane Cl anti (most stable) If gauche, C-Cl polar bonds are in close proximity Cl − ( ; higher energy) 𝜹 𝐞 𝐧 𝐝 𝐬 𝐚 𝐫 𝐞 𝐜 𝐥 𝐨 𝐬 𝐞 𝐠 𝐫 𝐞 𝐚 𝐭 𝐞 𝐫 𝐫 𝐞 𝐩 𝐮 𝐥 𝐬 𝐢 𝐨 𝐧  Conformational Isomers of other Alkanes: 3. n-propylchloride or 1-chloropropane − Cl + Cl gauche (most stable) CH3 dipole attraction between C-Cl and C-CH3 𝜹 𝜹  Conformational Isomers: Barrier to rotation of C-C single bond of the sp2-sp2 type: e.g. 1,3- butadiene = − = CH=2 CH2 CH2 = − = − = CH2 S-cis-1,3-butadiene S-trans-1,3-butadiene (more stable) (unfavourable arrangement of pi electron clouds; repulsion) 𝟐 𝟐 𝑪 𝑪 𝑯 𝑯 𝑪 𝑪 𝑯 𝑯 𝑪 𝑯 𝑪 𝑯 𝑪 𝑯 𝑪 𝑯  CONFORMATIONS OF RING COMPOUNDS ✓ (1800’s) cyclic molecules existed but limitation on ring size were unclear; 5-,6 – ringed were numerous but smaller and larger rings had not been prepared ✓ According to Adolf Baeyer, small and large rings are unstable due to angular strain (strain in a molecule when bond angles are forced to deviate from the ideal 109.5o)  CONFORMATIONS OF RING COMPOUNDS FACTS:  CONFORMATIONS OF RING COMPOUNDS BAEYER is ONLY PARTIALLY CORRECT!!! - cycloalkanes are not flat. They adopt puckered 3-D conformation that allow bond angle to be nearly 109o C7-C11 cycloalkanes – torsional strain due to H-H eclipsing and steric strain due to repulsion between bonded atoms that approach too closely C14 up – strain free  CONFORMATIONS OF RING COMPOUNDS Three kinds of strain that contributes to cycloalkanes: 1. Angle strain—the strain due to expansion or compression of bond angles. 2. Torsional strain—the strain due to eclipsing of bonds on neighboring atoms. 3. Steric strain—the strain due to repulsive interactions when atoms approach each other too closely.  CONFORMATIONS OF CYCLOALKANES: CYCLOPROPANE ✓ most strained among cycloalkanes (60o C-C-C bond angles) ✓has considerable torsional strain (C-H bonds on C atoms are eclipsed)  CONFORMATIONS OF CYCLOALKANES: CYCLOPROPANE ✓ has bent bonds ✓ cyclopropane bonds are weaker and more reactive than typical alkane bonds  CONFORMATIONS OF CYCLOALKANES: CYCLOBUTANE ✓ has less angular strain than cyclopropane but has more torsional strains because of larger number ring hydrogens ✓ not quite flat but is slightly bent (increase angular strain and decrease in torsional strain until minimum energy balance between the 2 opposing effects is achieved)  CONFORMATIONS OF CYCLOALKANES: CYCLOBUTANE  CONFORMATIONS OF CYCLOALKANES: CYCLOPENTANE ✓ predicted by Baeyer to be strain free (wrong!) ✓ Planar is strain-free but has large amount of torsional strain (26 KJ/mol) ✓ Twists to adopt puckered nonplanar conformation ✓ 4 C’s are in the same plane; 5th C atom bent out of plane  CONFORMATIONS OF CYCLOALKANES: CYCLOPENTANE  CONFORMATIONS OF CYCLOALKANES: CYCLOHEXANE ▪ Occur in nature widely (steroids and other pharmaceutical agents) ▪ cyclohexane adopts a strain-free 3D conformation called CHAIR CONFORMATION  CONFORMATIONS OF CYCLOALKANES: CYCLOHEXANE  CONFORMATIONS OF CYCLOALKANES: CYCLOHEXANE TWIST-BOAT CONFORMATION (has torsional and steric strain: 23 KJ/mol higher in energy than chair conformation) AXIAL AND EQUATORIAL BONDS IN CYCLOHEXANE  AXIAL AND EQUATORIAL BONDS IN CYCLOHEXANE Kinds of positions for substituents in cyclohexane: 1. Axial position - perpendicular to the ring, parallel to the ring axis 2. Equatorial position - in the rough plane of the ring, around the ring equator. AXIAL AND EQUATORIAL BONDS IN CYCLOHEXANE AXIAL AND EQUATORIAL BONDS IN CYCLOHEXANE AXIAL AND EQUATORIAL BONDS IN CYCLOHEXANE  CONFORMATIONS OF MONOSUBSTITUTED CYCLOHEXANE 1a-bromocyclohexane (less stable) 1e-bromocyclohexane (more stable)  CONFORMATIONS OF MONOSUBSTITUTED CYCLOHEXANE  CONFORMATIONS OF DISUBSTITUTED CYCLOHEXANE  CONFORMATIONS OF DISUBSTITUTED CYCLOHEXANE Optical Isomers Understanding the causes and consequences of molecular handedness is crucial to understanding organic and biological chemistry. Optical Isomers Handedness is important in organic chemistry and biological chemistry. Many drugs and almost all molecules in our bodies are handed. Molecular handedness makes possible the precise interactions between enzymes and their substrates that are involved in the hundreds of thousands of chemical reactions on which life is based. Enantiomers and the Tetrahedral Carbon What causes molecular handedness? Enantiomers and the Tetrahedral Carbon What causes molecular handedness? ❑ ENANTIOMERS (Greek enantio, meaning “opposite”) ✓ Molecules that are not identical to their mirror images. ✓ result whenever a tetrahedral carbon is bonded to four different substituents Enantiomers and the Tetrahedral Carbon What causes molecular handedness? Enantiomers and the Tetrahedral Carbon What causes molecular handedness? Reason for Handedness in Molecule: CHIRALITY CHIRAL ✓ a molecule that is not identical to its mirror image (ky-ral, from the Greek cheir, meaning “hand”). How can you predict whether a given molecule is or is not chiral? ✓ A molecule is not chiral if it has a plane of symmetry. PLANE OF SYMMETRY ✓ plane that cuts through the middle of a molecule (or any object) in such a way that one half of the molecule or object is a mirror image of the other half. Reason for Handedness in Molecule: CHIRALITY Reason for Handedness in Molecule: CHIRALITY NONCHIRAL or ACHIRAL ✓ molecule that has a plane of symmetry in any conformation (identical molecules). Reason for Handedness in Molecule: CHIRALITY CHIRALITY CENTERS, STEREOCENTER, ASSYMNETRIC CENTER, or STEREOGENIC CENTER. ✓ tetrahedral carbon atom bonded to four different groups ✓ most common, although not the only, cause of chirality in an organic molecule ✓ CHIRALITY is a property of the entire molecule, whereas a CHIRALITY CENTER is the cause of chirality. Reason for Handedness in Molecule: CHIRALITY CHIRALITY or ASSYMETRIC CENTER Reason for Handedness in Molecule: CHIRALITY CHIRALITY or ASSYMETRIC CENTER Reason for Handedness in Molecule: CHIRALITY CHIRALITY or ASSYMETRIC CENTER Carbons in =CH2, -CH3, C=O, C=C, and C=C groups can’t be chirality centers. Reason for Handedness in Molecule: CHIRALITY CHIRALITY or ASSYMETRIC CENTER Reason for Handedness in Molecule: CHIRALITY CHIRALITY or ASSYMETRIC CENTER  Optical Activity ✓ Jean Baptiste Biot studied plane polarized light ✓ A beam of ordinary light consists of electromagnetic waves that oscillate in an infinite number of planes at right angles to the direction of light travel. ✓ When a beam of ordinary light passes through a device called a polarizer, however, only the light waves oscillating in a single plane pass through and the light is said to be plane-polarized. Light waves in all other planes are blocked out. Optical Activity  Optical Activity A. Angle of Rotation ✓ Optically Active Molecules causes rotation of the plane of polarization at a certain angle (∝) B. Direction of Rotation b.1 levorotatory – molecules that rotate plane polarized light to the left or counterclockwise [e.g. (-)-morphine] b.2 dextrorotatory- molecules that rotate plane polarized light to the right or clockwise [e.g. (+)-sucrose] Optical Activity [∝]D = +13.82 [∝]D = -23.82. Pasteur’s Discovery of Enantiomers Enantiomers (a.k.a optical isomers) have identical physical properties, such as melting point and boiling point, but differ in the direction in which their solutions rotate plane-polarized light. Sequence Rules for Specifying Configuration ❑ Structural drawings provide a visual representation of stereochemistry, but a written method for indicating the three-dimensional arrangement, or configuration, of substituents at a chirality center is also needed. ❑ The method used employs a set of sequence rules to rank the four groups attached to the chirality center and then looks at the handedness with which those groups are attached. Sequence Rules for Specifying Configuration CAHN-INGOLD PRELOG RULES: CAHN-INGOLD PRELOG RULES: CAHN-INGOLD PRELOG RULES: R,S Configuration ❑ Having ranked the four groups attached to a chiral carbon, we describe the stereochemical configuration around the carbon by orienting the molecule so that the group with the lowest ranking (4) points directly back, away from us. ❑ Then look at the three remaining substituents, which now appear to radiate toward us like the spokes on a steering wheel R,S Configuration ❑ If a curved arrow drawn from the highest to second-highest to third-highest ranked substituent (1 -> 2 -> 3) is clockwise, we say that the chirality center has the R configuration (Latin rectus, mean- ing “right”). ❑ If an arrow from 1 -> 2 -> 3 is counterclockwise, the chirality center has the S configuration (Latin sinister, meaning “left”). R,S Configuration R,S Configuration R,S Configuration (S)-Glyceraldehyde [(S)-(–)-2,3-Dihydroxypropanal (S)-Alanine [(S)-(+)-2-Aminopropanoic acid] Diastereomers # stereoisomers = 2n n=# chirality center Lactic acid: 2 stereoisomers Diastereomers Diastereomers Stereoisomers NOT enantiomers Diastereomers ✓ Stereoisomers that are not mirror images  Diastereomers vs Enantiomers Enantiomers have opposite configurations at all chirality centers, whereas diastereomers have opposite configurations at some (one or more) chirality centers but the same configuration at others. In the special case where two diastereomers differ at only one chirality center but are the same at all others, we say that the compounds are epimers. Epimers Epimers Meso Compounds The 2R,3R and 2S,3S structures are enantiomers. Meso Compounds The 2R,3S and 2S,3R structures are identical. Meso Compounds 2R,3S and 2S,3R structures are superimposable as can be seen by rotating one structure 180°. They are identical because the molecule has a plane of symmetry The molecule is ACHIRAL Meso Compounds Meso Compounds MESO COMPOUNDS Compounds that are achiral, yet contain chirality centers. Racemic Mixture ❑ 50:50 mixture of the two chiral tartaric acid enantiomers. denoted by either the symbol (±) or the prefix d,l to indicate an equal mixture of dextrorotatory and levorotatory forms. ❑ show no optical rotation because the (+) rotation from one enantiomer exactly cancels the (-) rotation from the other. Chirality in Nature Chirality in Nature Chirality in Nature GEOMETRIC ISOMERS ❑ result of restricted rotation around a double bond (due to pi bond hindrance) ❑ Isolable ❑ Assume preferred spatial arrangement of groups around a double bond or ring ❑ Occurs if the two doubly bonded carbon atoms contain two different substituent GEOMETRIC ISOMERS A. CIS/TRANS cis – used when two identical groups are on the same side of the plane trans – used when identical groups are on the opposite sides of the plane GEOMETRIC ISOMERS A. CIS/TRANS CH3CH=CHCH3 (2-butane) CH3 H CH3 CH3 C=C CH3 H C=C H H cis – 2-butene trans – 2-butene GEOMETRIC ISOMERS A. CIS/TRANS GEOMETRIC ISOMERS A. CIS/TRANS (Activity) CH3CH=CHCH=CHCH2CH3 (2,4- heptadiene) GEOMETRIC ISOMERS B. Z/E Zusamen (Z) – used if the two high priority groups are on the same side of the plane Entgegen (E) – used if the two high priority groups are on the opposite side of the plane  GEOMETRIC ISOMERS B. Z/E Br F Cl F C=C C=C Cl I Br I Z-1-bromo-1-chloro-2-fluoro-2-iodoethene E-1-bromo-1-chloro-2-fluoro-2-iodoethene