Cycloalkanes stability

CYCLOALKANES - STABILITY BY VANA JAGAN MOHAN RAO

1. 1 cycloalkanes BY VANA JAGAN MOHAN RAO M.S.Pharm, MED.CHEM NIPER-KOLKATA Asst.Professor, MIPER-KURNOOL Email: [email protected]

2. C y c l o a l k ane s 2 Cycloalkanes are saturated since all the carbon atoms that make up the ring are single bonded to other atoms. Because of the ring, a cycloalkane has two fewer hydrogens than an acyclic (noncyclic) alkane with the same number of carbons. The general molecular formula for cycloalkanes is C n H 2n Cycloalkanes Definition are a l k a nes which have so m e o f t h e i r carbon atoms arranged in a ring. Rings of different sizes beginning with three carbons are possible.

3. Nomenclature of Cycloalkanes 3 Cycloalkanes are commonly drawn as line structures whereby each vertex represents a carbon understood to be connected to an appropriate number of hydrogens to give carbon four bonds. Cycloalkanes are named by adding the prefix “cyclo” to the ‘alkane’ name that has the same number of carbon atoms as those in the ring. These most common cycloalkanes are represented as shown below:

4. Nomenclature of Cycloalkanes 4 Substituted Cycloalkanes The rules for naming cycloalkanes are similar to those used for straight-chain alkanes: The parent ring is the largest ring in the molecule. The parent name is generated by adding the prefix cyclo- to the name of the alkane with the same number of carbons. Identify the substituents and their location by numbering the ring from the carbon containing substi t ue n ts s o a s t o gi v e t he substi t ue n ts the l o we s t possible location numbers. iv. Alph a beti z e the substi t ue n ts i n the full n am e o f the cycloalkane.

5. Nomenclature of Cycloalkanes 5 Substituted Cycloalkanes Refer t o the cyc l o alk a n es bel o w t o i l lust r ate the nomenclature of cycloalkanes.

6. Nomenclature of Cycloalkanes 6 Substituted Cycloalkanes Larger rings take precedence over smaller rings.

7. Nomenclature of Cycloalkanes 7 Substituted Cycloalkanes If the alkyl group has a longer carbon chain than any of the rings, the straight chain system will be the parent chain.

8. Practice Questions 8 Nomenclature of Cycloalkanes Provide the IUPAC names of the following cycloalkanes

9. Conformations of Cycloalkanes 9 The bond angles in straight chain alkanes is normally 1 09 . 5 . This i s ex p e c t ed f o r a t e tr a hedr a l ar r a n ge m e n t of bonds that are not restricted. However, when the carbon atoms form part of a ring, the angle will be controlled by the requirements of the ring .

10. Stability of Cycloalkanes 10 Bayer (1885) postulated a theory of angle strain for cycloalkanes in which the difference between a tetrahedral angle (109.5 o ) and an internal angle of the appropriate polygon is used as a measure of stability. The deviation of bond angles from the tetrahedral angle causes the molecule to be strained and hence unstable compared with molecules with tetrahedral bond angles. Polygon Internal angle Polygon Internal angle 3 4 5 6 60 90 108 120 7 8 9 10 129 135 140 144

11. Stability of Cycloalkanes 11 The angles of a regular pentagon (108 o ) are very close to a n g l e ( 109 . 5 o ) and t h e r e f o r e t h e the l e a s t a n g le (B a y e r) s t ra i n is the tetrahedral cycloa l k a ne with cyclopentane. Since the angles of a regular hexagon (120 o ) are somewhat larger than the tetrahedral angle, Baeyer concluded (incorrectly) that there is a certain amount of strain in cyclohexane. Further, he suggested that as one proceeds to cycloheptane, cyclooctane etc, the deviation of the bond angles become progressively larger and the molecules would become progressively more strained.

12. Baeyer Theory vs Experimental Facts 12 Hea t s o f co m bus t ion c a n o ft e n fu r nish v al u able information on the relative stabilities of compounds. Apparentl y , cyc l o h exanes are j u s t as st a b le as st r a i g h t c h ain alkanes. Ring size Heat of combustion per CH 2 (kcal/mol) Ring size Heat of combustion per CH 2 (kcal/mol) 3 4 5 6 166.6 164.0 158.7 157.4 7 8 9 10 158.3 158.6 158.8 157.4 Heat of combustion for an open chain alkane per –CH 2 - is 157.4 kcal/mol

13. Baeyer Strain vs Heats of Combustion 13 When the heats of combustion is extended to other larger cycloalkanes, a clearer picture emerges. The Bayer theory appears to apply to cycloalkanes from three carbons (cyclopropane) to five carbons (cyclopentane), but fails for larger ring sizes.

14. Where Does the Baeyer Theory Fail? 14 The Baeyer theory fails for larger rings because: The angles that Baeyer used for each ring were based on the assumption that the rings were flat. I n f a c t , al l cyc l oalk a nes exc e pt cyc l opr o p a ne a r e not planar (flat). The reality is that cycloalkanes tend to adopt puckered three dimensional conformations that allow all the bond angles to be nearly tetrahedral.

15. Conformations of Cycloalkanes 15 The stability of cycloalkanes are influenced by a combination of three factors: Baeyer strain or angle strain: The strain due to expansion or compression of bond angles. There is increase in energy when bonds deviate from the optimum tetrahedral bond angle of 109.5 o . Torsional strain or bond strain: The strain due to the eclipsing of bonds on neighbouring atoms. There is increase in energy when there are eclipsing interactions. iii. Steric strain: The strain due to the repulsive interactions when atoms approach each other too closely. There is increase in energy when atoms are forced too close to one another.

16. Conformations of Cycloalkanes 16 The ring strain of a cycloalkane is a combination of the effects of angle strain, torsional strain and steric strain. The various arrangements in space that are available to a molecule by rotation about single bonds is its conformations. The investigations of various conformations of a molecule and their relative stabilities is known as conformational analysis. We will look at the conformational analysis of cyclopropanes, cyclobutanes, cyclopentanes and cyclohexanes to identify the lowest energy conformers.

17. Cyclopropanes 17 Structure and Bonding The s e are three m ember e d rin g c a r b o c ycles o f for m u l ar C 3 H 6 and a ring bond angle of 60 o . T h is s i g n if i c a nt an g le co m p r e s s i on re l a t ive t o t he tetrahedral bond angle leads to strain in the cyclopropane. H H H H H H

18. Cyclopropanes 18 Bonding The bonds in cyclopropane rather than being straight are curved like a banana. Since the orbitals in cyclopropane are at wrong angles for good overlap, there is a significant angle strain (Baeyer strain) in the ring. H H H H H H "Banana bonds"

19. Cyclopropanes 19 Bonding Since all 6 C-H bonds in cyclopropane are eclipsed, this leads to bond strain (torsional strain) in the cyclopropane. As a result of angle strain and torsional strain, cyclopropane is very unstable and therefore more reactive than straight chain alkanes. The ring opening reactions of cyclopropane serve to relieve this strains.

20. Cyclobutanes 20 Bonding Cyclobutane is a four membered carbocycle of formula C 4 H 8 . Just like cyclopropane, the bond angles in cyclobutane are strained as a result of angle compression compared to related linear or unstrained hydrocarbons. As a result of angle strain, cyclobutane is unstable above 500 o C. But u n l i ke cyc l op r opan e , c y c l obutane has slighltly greater freedom of rotation.

21. C y c l o bu t an e s 21 The planar cyclobutane has all its 8 C-Hs in an eclipsed arrangement with bond angles of 90 o , while the puckered conformation has a bond angle of 88 o . Although the puckered conformation increases the angle strain, it significantly reduces the torsional strain. Conformations O n e ca n e n v i s a g e t w o extr em e for m s o f c ycl o b u t a n e : A planar form and a bent form (referred to as the puckered form). 25º

22. C y c l o bu t an e s 22 Conformations C y cl i c m o l e cules m in i m i z e the an g le s t rain and torsional strain in them by ring puckering (bending). Cyclobutane consists of two puckered conformations which are in rapid equilibrium. H H H H H H H H H H H H H H H H

23. Cyclobutanes 23 Conformations Note how in the puckered con f or m ation of cyclobutane there are two different kinds of C–H bonds and hence two different kinds of H atoms. There are those C–H bonds that are nearly anti to other C–H bonds , and there are those C–H bonds that are nearly anti to C–C bonds . When we will look at cyclohexanes, we will see that this has great significance in the stability of the cyclohexane rings.

24. Cyclopentanes 24 Cyclopentane is a five membered carbocycle of formula C 5 H 10 . There are two extreme conformations of cyclopentane (the planar and envelope conformations). In the planar conformation, postulated in the Baeyer theory, the bond angle in the ring is 108 o and all 10 C-H bonds are eclipsed. H H H H H H H H H H H H H H H H H P u cker i ng H H No TS TS Envelope conformer Planar conformer

25. Cyclopentane 25 In the envelope conformation, four carbons are on the plane, while the fifth carbon is out of plane, sort of like the flap of an envelope. The number of eclipsed hydrogens is reduced at the expense of angle strain, the bond angle is 105º. (The Envelope Confomer) H H H H H H H H H H

26. Cyclopentane 26 (The Envelope Confomation) conformation undergoes The envelop c o nf o r m a t ion a l cha n ge i n w h i ch the c a r b on a rapid a t the envelope alternates. Suppose the different C atoms in the ring are non- identical, i.e. have different substituents. How do we know which C atom in cyclopentane will pucker? H H H H H H H H H H H H H H H H H H H H

27. Substitued Cyclopentanes (The prefered Envelope Confomation) 27 W h e n we h a ve s ubs t i t uted c ycl o p e nta n e s , occurs preferably involving the substituted p u cke r ing c a r bon to g e ner a te t h e e n vel o pe c o nfo rm er with r e d u c e d t o r t ion a l strain. F o r 1 , 2 - diisop r opyl c y c lo p e nta n e, the p r ef e r ed c onfor m er of lowest energy is the staggered envelope.

28. Cyclohexanes 28 C y c l oh e x a ne i s a s i x m e m bered c a r b o c yc l e o f for m u l a C 6 H 12 . There are two extreme conformations of cyclohexane (the planar and chair conformations) that can be envisaged. In the planar conformation postulated in the Baeyer theory, the bond angle in the ring is 120 o , all 12 C-H bonds are eclipsed and as a result very unstable. Recall that the combustion data of cyclohexane suggests that it is free from ring strain and torsional strain. H H H H H H H Planar conformer Chair conformer H H H H H H H H H H H H H H H H puckering

29. Cyclohexanes In the chair conformation of cyclohexane, all 12 C-H bonds are staggered and the bond angle is 109.5º (tetrahedral bond angle) . With no angle strain and no torsional strain, the chair conformer of cyclohexane is very stable and is the preferred conformation in which cyclohexane systems exist in. 29 Chair conformer H H H H H H H Planar conformer H H H H H Conformations H H H H H H H H H H H puckering

30. Cyclohexanes Chair Conformers 30 Looki n g a t the chair co n f orm a t i o n , one c an identify a back-rest, a seat and a leg-rest like that of a chair. r Chair conforme

31. Cyclohexanes 31 Boat Conformations Boat conformations are also possible with cyclohexane systems, but they are of higher energy than the chair conformations.

32. Cyclohexanes Conformational Energy 32 Of al l c o nf o r m a t io n s o f cycl o h e x a n e , the c hair conformations are of least energy and thus most stable. C h a i r c onfor m a t io n s are th e r e fore t he m ost re a list i c representations of cyclohexanes.

33. Cyclohexanes Chair Conformation: Axial and Equitorial Bonds 33 There are two types of bonds in cyclohexanes: Equitorial bonds are oriented towards the rings equator, while axial bonds are on the rings axis. a x a x a x e q e q a x e q e q e q 1 2 3 5 6 Ring axis ax 4 a x e q Ring equator

34. Substituted Cyclohexanes 34 To ring flip, identify where the substituents are. I n one c o nfo rm e r , p u sh u p a t C - 4 a n d do w n a t C - 1 to obtain the 4 C 1 conformer. The other conformer is obtained by pushing up at C-1 and down at C-1 to provide the 1 C 4 conformer. ring flip push this carbon up Ring flipping pull this carbon down

35. 35 Drawing Chair Conformations of Cyclohexanes Draw two parallel lines, slanted down ward and slightly offset from each other. Locate the topmost carbon atom above and to the right of the plane and connect the bonds. Locate the bottom-most carbon atom below and to the left of the plane of the middle four carbons and connect the bonds. Note that the bonds to the bottom-most carbon are parallel to the bonds to the top-most carbon.

36. Substituted Cyclohexanes Drawing Chair Conformations of Cyclohexanes 36 Draw the six axial bonds on each carbon parallel to the ring axis and alternating up- down. Now add the six equatorial bonds on each carbon in three sets of two parallel lines. Each set is also parallel to two ring bonds.

37. Substituted Cyclohexanes Chair Conformation: Axial and Equitorial Bonds 37 I n m e t h y l cyc l oh e x a n e , t he m eth y l g r oup ca n be i n an equatorial or axial position. W e m ig h t, ther e f ore, e x pect t o find t w o c o nf o r m ers of methylcyclohexane.

38. 39 Stability of Cyclohexane Conformers Although cyclohexane rings rapidly flip between conformations at room temperature, the two conformers of a monosubstituted cyclohexane are not of equal stability. H C H H H H H H H H H H H H 1 H 2 3 4 5 6 ring flip H H H H H H H H H C H 1 2 H H 3 H 4 H 5 6 1 C 4 conformer = 5% 1 4 C conformer = 95% 1 C 4 I n the co n f orm e r , there i s van der W a a ls s t r a i n between hydrogens of the axial CH 3 and hydrogens at C-3 and C-5, while in the 4 C 1 conformer, there is a smaller van der Waals strain between hydrogens at C-1 and hydrogens at C-3 and C-5.

39. Substituted Cyclohexanes Conformational Free Energy of Methylcyclohexane 41 T h e i nv es t igation o f m olecul a r c o nf o r m a t io n s a nd t h e i r relative energies is called conformational analysis . As a generalization, for other monosubstituted cycloalkanes: “ a substituent is almost always stable in an equatorial position that in an axial position ” .  G 7.6 kJ/mol H H H H H CH 3 H H H H H H H H H H H H H CH 3 H H H H

40. 42 Stability of Conformers The exact amount of 1,3-diaxial steric strain for axial groups depends, on the nature and size of the axial group. The steric strain increases through the series CH 3 - < CH 3 CH 2 - < (CH 3 ) 2 CH- < (CH 3 ) 3 C- in parallel with increasing bulk of the successively larger alkyl groups. H C H H H H H H H H 3 C CH 3 C H 3 H 1 H 2 3 4 5 H 6 ring flip H H H H H H C H H H H CH 3 C H 3 CH 3 1 2 H 3 4 5 6 < 0.01% 99.99% There is severe 1,3-diaxial interaction involving the t - butyl group in 1 C 4 , while decreased van der Waals strain in 4 C 1 .

41. 43 Stability of Conformers The exact amount of 1,3-diaxial steric strain for axial groups depends, on the nature and size of the axial group. The steric strain increases through the series CH 3 - < CH 3 CH 2 - < (CH 3 ) 2 CH- < (CH 3 ) 3 C- in parallel with increasing bulk of the successively larger alkyl groups. H C H H H H H H H H 3 C CH 3 C H 3 H 1 H 2 3 4 5 H 6 ring flip H H H H H H C H H H H CH 3 C H 3 CH 3 1 2 H 3 4 5 6 < 0.01% 99.99% There is severe 1,3-diaxial interaction involving the t - butyl group in 1 C 4 , while decreased van der Waals strain in 4 C 1 .

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