Why am I learning this, Dr. P?

Transcription

1 Chapter 4- Organic Compounds: Cycloalkanes and their Stereochemistry Ashley Piekarski, Ph.D. Why am I learning this, Dr. P? Cyclic compounds are commonly encountered in all classes of biomolecules: Proteins Lipids Carbohydrates Nucleic acids 1

2 Naming Cycloalkanes Cycloalkanes are saturated cyclic hydrocarbons Have the general formula (C n H 2n ) Naming Cycloalkanes Find the parent number of carbons in the ring Number the subshtuents When 2 or more different alkyl groups that could potentially receive the same numbers are present, number them by alphabetical priority If halogens are present, treat them just like alkyl groups 2

3 Learning check Give IUPAC names for the following cycloalkanes: Br Br Cis-Trans Isomerism in Cycloalkanes Cycloalkanes are less flexible than open- chain alkanes- build cyclopropane Much less conformahonal freedom in cycloalkanes 3

4 Cis-Trans Isomerism Because of their cyclic structure, cycloalkanes have 2 faces as viewed edge- on Therefore, isomerism is possible in subshtuted cycloalkanes Stereoisomerism Compounds which have their atoms connected in the same order but differ in 3- D orientahon 4

5 Learning check Name the following compounds, including the cis- and trans- prefix: H 3 C H CH 3 H Cl H H (1R,3R)-1,3- Stability of cycloalkanes: Ring strain Rings larger than 3 atoms are not flat Cyclic molecules can assume non- planar conformahons to minimize angle strain and torsional strain by ring- puckering Larger rings have many more possible conformahons than smaller rings and are more difficult to analyze 5

6 Stability of cycloalkanes: The Baeyer Strain Theory Since carbon prefers to have bond angles of approximately 109 degrees, ring sizes other than five and six may be too strained to exist Rings from 3-30 carbons do exist, but are strained due to bond bending distorhons and steric interachons Summary: Types of Strain Angle strain: expansion or compression of bond angles away from most stable Torsional strain: eclipsing of bonds on neighboring atoms Steric strain: repulsive interactions between nonbonded atoms in close proximity 6

7 Conformations of Cycloalkanes Cyclopropane 3-membered ring must have planar structure Symmetrical with C-C-C bond angles of 60 degrees Requires that sp 3 based bonds are bent All C-H bonds are eclipsed Bent Bonds of Cyclopropane The C- C bond is displaced outward from internuclear axis 7

8 Cyclobutane Cyclobutane has less angle strain than cyclopropane but more torsional strain because of its larger number of ring hydrogens Cyclobutane is slightly bent out of plane- one carbon atom is about 25 degrees above The bend increases angle strain but decreases torsional strain Cyclopentane Planar cyclopentane would have no angle strain but very high torsional strain Actual conformahons of cyclopentane are nonplanar, reducing torsional strain Four carbon atoms are in a plane The fifth carbon atom is above or below the plane- looks like an envelope 8

9 Conformations of Cyclohexane SubsHtuted cyclohexanes occur widely in nature The cyclohexane ring is free of angle strain and torsional strain The conformahon has alternahng atoms in a common plane and tetrahedral angles between all carbons This is called a chair conformahon Chair conformation 9

10 Axial and Equatorial Bonds in Cyclohexane The chair conformahon has two kinds of posihons for subshtuents on the ring: axial posihons and equatorial posihons Chair cyclohexane has six axial hydrogens perpendicular to the ring and six equatorial hydrogens near the plane of the ring Axial and Equatorial Positions Each carbon atom in cyclohexane has one axial and one equatorial hydrogen Each face of the ring has three axial and three equatorial hydrogens in an alternahng arrangement 10

11 Drawing the Axial and Equatorial Hydrogens Conformational Mobility of Cyclohexane Chair conformahons readily interconvert, resulhng in the exchange of axial and equatorial posihons by a ring- flip 11

12 Learning check Draw two different chair conformahons of trans- 1,4- dimethylcyclohexane (label all posihons as axial or equatorial) Conformations of Monosubstituted Cyclohexanes Cyclohexane ring rapidly flips between chair conformahons at room temperature Two conformahons of monosubshtuted cyclohexane are not equally stable The equatorial conformer of methyl cyclohexane is more stable than the axial conformer 12

13 1,3-Diaxial Interactions Difference between axial and equatorial conformers is due to steric strain caused by 1,3- diaxial interachons Hydrogen atoms of the axial methyl group on C1 are too close to the axial hydrogens three carbons away on C3 and C5 Relationship to Gauche Butane Interactions Gauche butane is less stable than anh butane by 3.8 kj/mol because of steric interference between hydrogen atoms on the two methyl groups The four- carbon fragment of axial methylcyclohexane and gauche butane have the same steric interachon In general, equatorial posihons give more stable isomers 13

14 Conformational Analysis of Disubstituted Cyclohexanes In disubshtuted cyclohexanes the steric effects of both subshtuents must be taken into account in both conformahons There are two isomers of 1,2- dimethylcyclohexane: cis and trans In the cis isomer, both methyl groups are on the same face of the ring, and the compound can exist in two chair conformahons Consider the sum of all interachons In cis- 1,2, both conformahons are equal in energy Trans-1,2-Dimethylcyclohexane Methyl groups are on opposite faces of the ring One trans conformahon has both methyl groups equatorial and only a gauche butane interachon between methyls (3.8 kj/mol) and no 1,3- diaxial interachons The ring- flipped conformahon has both methyl groups axial with four 1,3- diaxial interachons Steric strain of 4 x 3.8 kj/mol = 15.2 kj/mol makes the diaxial conformahon 11.4 kj/mol less favorable than the diequatorial conformahon trans- 1,2- dimethylcyclohexane will exist almost exclusively (>99%) in the diequatorial conformahon 14

15 Learning check Draw the most stable chair conformahon of the following molecules and eshmate the amount of strain in each: trans-1-chloro-3-methylcyclohexane cis-1-tert-butyl-4-ethylcyclohexane Conformations of Polycyclic Molecules Decalin consists of two cyclohexane rings joined to share two carbon atoms (the bridgehead carbons, C1 and C6) and a common bond Two isomeric forms of decalin: trans fused or cis fused In cis- decalin hydrogen atoms at the bridgehead carbons are on the same face of the rings In trans- decalin, the bridgehead hydrogens are on opposite faces Both compounds can be represented using chair cyclohexane conformahons Flips and rotahons do not interconvert cis and trans 15

16 Applications Molecular mechanics Computer program based on work by N.L. Allinger of the University of Georgia E total = E bond stretching + E angle strain + E torsional strain + E van der Waals Through hundreds of iterations, the program automatically changes the geometry slightly in an attempt to lower strain Pharmaceu0cal research Molecular mechanics can be used to design new pharmaceutical agents that will fit with a receptor molecule in the body 16