Sect 4.6: Monosubstituted cyclohexane rings

Methylcyclohexane conformations Equitorial methyl Axial methyl

1.7 kcal/mol 0 kcal/mol ENERGYENERGYENERGYENERGY Energy difference between an axial and an equitorial methyl group

1,3-diaxial interactions 1,3-Diaxial interactions on the top of the ring STERIC REPULSION RAISES THE ENERGY OF THE AXIAL CONFORMATION

H H H H CH 3 H H H H 1,3-diaxial interactions CH 1,3-Diaxial interactions: Newman projection view 1,3-Diaxial interactions

CH 3 CH 2 gauche steric nteractions GAUCHE STERIC INTERACTIONS (like gauche butane) CH 3 CH 2 Axial Equitorial No gauche steric problem when the group is equitorial Monosubstituted cyclohexanes: gauche steric interactions CH 3 60 o 180 o

Large groups will generally prefer to occupy an equatorial position where there is an absence of 1,3-diaxial (steric) interactions Keep in mind, however, that the axial conformation will also be present, but in smaller amount. General rule axial conformation equatorial conformation

 G o for group in the axial position CH 3 - CH 3 CH 2 - CH 3 -CH- CH 3 CH 3 -C- CH > >21 Group Xkcal/molkJ/molGroupkcal/molkJ/mol Cl- Br- HO C6H5-C6H5-3.1 CH 3 -C-O- O Table 4.5: Conformational energy differences for substituents attached to a cyclohexane ring Equitorial preferred

C C C C H H H H H H H H H t -BUTYLCYCLOHEXANE Basically “locks” the ring in a chair with the tert -butyl group in the equatorial position. Too big a group to go into the axial position - must go equatorial. The axial value for this group in Table 4-5 ( >5 Kcal/mole) indicates a minimum value because there is so little axial that it is difficult to measure any real value.

tert-Butylcyclohexane with the group axial HUGE steric strain

Molecules viewed with Chime Click on START, Click on PROGRAMS Click on Netscape Communicator (4.7), then launch Netscape Navigator Using Google, type in the address for the Dept. of Chemistry, WWU: Select, course materials, select “WWU virtual molecular model set” You may need the free program, Chime, to run this program. Note: Internet Explorer and Netscape 7.1 won’t work!

Sect 4.7: cis and trans isomerization in cycloalkanes

cis-trans isomerism Different spatial arrangements The arrangements cannot be converted into one another by rotation cis Both substituents on same side of plane trans Substituents on opposite sides of plane

cis and trans isomers cistrans applies to substituents on a ring or (later) double bond both substituents are on the same side of the ring the substituents are on opposite sides of the ring These two compounds are geometric isomers Cl

Naming cis /trans isomers cis-1,2-dichlorocyclopropane trans-1,2-dichlorocyclopropane notice italics place designation in front of name Cl

How many different dimethylcyclobutanes are there? 1,1 - 1,2-1,3- Constitutional isomers cis /trans isomers (geometric) no cis or trans cistranscistrans no cis/trans here

Notice that it is OK to use planar rings when figuring out cis / trans isomers. Planar ring approximation You only need to use puckered rings when you are dealing with conformations. Use planar structures on tests!

Sect 4.8: disubstituted cyclohexanes: cis/trans isomerism Use chair structures!!

trans - 1,2-dimethylcyclohexane trans-1,2-dimethylcyclohexane trans-1,2-dimethylcyclohexane has two possible conformers has two possible conformers CHAIR-1CHAIR-2 e,ea,a Which conformer is more stable? The trans e,e one! Methyl below Methyl above

 G o = ( 2)(1.7) – 0 = 3.4 kcal/mol CH CH- CH 3 3 -C- CH > >21 Groupkcal/molkJ/molGroupkcal/molkJ/mol Cl- Br- HO C 6 H CH 3 -C-O- O trans -(a,a)- 1,2-dimethylcyclohexane Reference = 0 kcal/mol 2 x 1.7 kcal 3.4 kcal/mol higher trans -(e,e)- 1,2-dimethylcyclohexane (two axial methyls) Calculating the energy difference using values from Table 4.5

1,3-Diaxial interactions (steric) on top and bottom of ring Two axial-axial 1.7 kcal/mol each Equatorial groups are assumed to be 0 kcal/mol No diaxial interactions lots of room

What about cis-1,2-dimethylcyclohexane? Class exercise!!

What about cis / trans isomers in disubstituted rings other than 1,2-dimethylcyclohexane? 1,3-dimethylcyclohexane: 4 chair structures 1,4-dimethylcyclohexane: 4 chair structures 1,1-dimethylcyclohexane: no cis/ trans isomers

Which conformer has the higher energy? CH 3 OH axial = 1.7 kcal/mol axial = 0.7 kcal/molequatorial = 0 kcal/mol 1.7 kcal/mol 0.7 kcal/mol  G = ( ) = 1.0 kcal/mol This one! Both are trans!

Guideline In substituted cyclohexane rings, the best (lowest energy) conformation will have the largest groups in equatorial positions whenever possible.

Sect 4.9: decalin skip this section, winter 07

trans-ring fusioncis-ring fusion bonds are trans bonds are cis cis and trans ring fusions cis-decalin: less stable trans-decalin

other representations solid wedge = towards you dashed wedge = away from you A dot implies the hydrogen is towards you (on top). trans cis Drawing Conventions top bottom

Sect 4.10: read this section; no lectures Skip this section, winter 07

Sect 4.11: cis/trans isomerism in alkenes

Alkene geometry: planar Alkene geometry: planar  bond  bond  bond  bond sp 2 SIDE VIEW END VIEW planar

ROTATION BREAKS THE  BOND Unlike  bonds,  bonds do not rotate. It requires about kcal/mole ( ~ 240 kJ/mole ) to break the  bond - this does not happen at reasonable temperatures. NO!

cis / trans isomers (geometric isomers) cis / trans isomers (geometric isomers) Because there is no rotation about a carbon-carbon bond, isomers are possible. cis trans substituents on the same side of main chain substituents on opposite sides of main chain

Compare cis / trans isomers in ring compounds to alkenes cistrans cis / trans isomers are also called geometric isomers

If an alkene has two identical substituents on one of the double bond carbons, cis / trans isomers are not possible. all of these compounds are identical Two identical substituents Two identical substituents no cis / trans isomers

Some other compounds with no cis / trans isomers

cis-3-hexene trans-3-hexene Naming cis / trans isomers of alkenes Naming cis / trans isomers of alkenes notice that these prefixes are in italics main chain stays on same side of double bond = cis main chain crosses to other side of double bond = trans

if C<8 then the chain is too short to join together Rings with double bonds trans double bonds are not possible until the ring has at least eight carbon atoms cis trans smallest ring that can have a trans double bond C = 5 C = 6 C = 8 Note that both cis and trans exist for C8. trans

cis-3-methyl-2-pentenetrans-3-methyl-2-pentene Be Careful !!! This compound is cis but the two methyl groups are ….trans to each other. This compound is trans but the two methyl groups are ….cis to each other. The main chain determines cis / trans in the IUPAC name but the terms cis and trans are also used to designate the relative position of two groups: a new system is needed!

Sect 4.12: E/Z nomenclature

To avoid the confusion between what the main chain is doing and the relationship of two similar groups ….. the IUPAC invented the E/Z system. E/Z system of nomenclature E/Z system of nomenclature FCl I H This system also allows alkenes like the one above to be classified ….. an impossibility with cis / trans. cis ? trans ?

In this system the two groups attached to each carbon are assigned a priority ( 1 or 2 ). If priority 1 groups are both on same side of double bond: E / Z Nomenclature E / Z Nomenclature ZE If priority 1 groups on opposite sides of double bond: E isomer = entgegen = opposite (in German) Z isomer = zusammen = together (in German) same side opposite sides

Assigning priorities Assigning priorities 1. Look at the atoms attached to each carbon of the double bond. 2. The atom of higher atomic number has higher (1) priority. example F > H I > Br Since the 1’s are on the same side, this compound is Z (Z)-1-bromo-2-fluoro-1-iodoethene notice use of parentheses

Priorities in the E-Z Nomenclature system

3. If you can’t decide using the first atoms attached, go out to the next atoms attached. If there are non-equivalent paths, always follow the path with atoms of higher atomic number. Once you find a difference, you can stop This molecule has Z configuration. comparison stops here path goes to F not to H path goes to C not to H

CH 2 FCH 3 H CH 2 CH 3 Let’s give this compound a cis/trans name and an E/Z name trans-3-fluoromethyl-2-pentene (longest chain) (Z)-3-fluoromethyl-2-pentene (priorities)

CHCH 2 CO H 4. C=C double bond: equivalent to having two carbons. C=O double bond: equivalent to having two oxygens. CH CH 2 C CO H CO 1 2 C

(E)

(Z)

More than one double bond: dienes

trans, transtrans, cis cis, cis cis, trans DIENES AND POLYENES E,EE,Z Z,ZZ,E (2E,4E)-2,4-hexadiene identical (2E,4Z)-2,4-hexadiene (2Z,4Z)-2,4-hexadiene(2Z,4E)-2,4-hexadiene Hexadiene

(E)-1,3-hexadiene no E/Z (E) structure

CH 2 OH bonds in the ring are cis 12 cis and Z are not always the same for a given ring but this compound is E 12 H

Sect 4.13: Relative stabilities of alkenes: hydrogenation

Hydrogenation of Alkenes + CCHH CC HH catalyst The catalyst is Pt, PtO 2, Pd, or Ni an addition reaction

Examples

CH 3 H H H H syn addition anti addition X not observed Both hydrogen atoms add to the same side of the double bond stereospecific H 2 / Pt

Hydrogenation is exothermic Hydrogenation is exothermic  H = approx. -30 kcal/mol Exothermic reaction!

HH CH 3 CH 2 CH 2 CH 3 +H 2 kcal/mol Butene isomers --- Heats of hydrogenation Butene isomers --- Heats of hydrogenation All are hydrogenated to the same product (butane) therefore their energies may be compared. Higher energy Lower energy (more stable) (less stable)

H H R H H H R R R H R H H R R H R H R R monosubstitutedtrisubstituted disubstituted tetrasubstituted increasing substitution R R R R stability Alkene isomers different positions of the double bond cis trans 1,1- 1,2- less stable more stable

steric repulsion steric repulsion 1,1- cis-1,2- trans-1,2- Steric repulsion is responsible for energy differences among the disubstituted alkenes among the disubstituted alkenes (Z) (E)

Some examples of stabilities of isomers EXAMPLE ONE has lower energy than (more stable) EXAMPLE TWO ISOMERS has lower energy than (more stable) ISOMERS disubstitutedmonosubstituted trisubstituteddisubstituted

Sect 4.14, 4.15, 4.16 Bicyclic compounds and spiro compounds

bicyclo[3.2.1]octane number of rings total number of carbon atoms sizes of bridges, largest first 3 carbons 2 carbons 1 carbon bridgeheads Naming a bicyclic compound Naming a bicyclic compound

Bicyclic ring compounds bicyclo[2.2.1]heptane bicyclo[1.1.0]butane bicyclo[1.1.1]pentane bicyclo[2.1.1]hexane bicyclo[2.2.2]octane bicyclo[3.1.1]heptane bicyclo[4.4.1]undecane

Many examples of the trans ring fusion are found in nature. The cis ring fusion is not found nearly as often as trans. cholestanol trans eq (a close relative of cholesterol) Rings in nature Rings in nature NATURAL PRODUCTS : compounds that occur in living sytems, such as plants and animals.

CH 3 CH 3 OH O TESTOSTERONE

PROGESTERONE CH 3 O CH 3 O CH 3 ESTROGEN

Some bicyclic natural products camphor  -pinene  -pinene cineole EUCALYPTUS TURPENTINE CAMPHOR TREE

spiro[2.4]heptane Spiranes Spiranes Here the smaller ring comes first in the name. Spiro ring junctions always involve two rings, so bi- and tricyclo, etc. are not needed. The prefix “spiro” is used instead.

Polycyclic compounds Polycyclic compounds These have been made synthetically. cubane “bucky ball” basketane adamantane buckminsterfullerene propellane