CONFORMATIONAL

 ANALYSIS  OF  
ACYCLIC  AND  CYCLIC  COMPOUNDS  
 CONFORMATIONAL  ANALYSIS    

•  I f   t w o   d i f f e r e n t   t h r e e -­‐ d i m e n s i o n a l  
arrangements   in   space   of   the   atoms   in   a  
molecule  are  interconvertible  merely  by  free  
rotation   about   bonds,   they   are   called  
conformations  (if  not,  con<igurations)  
 
•  Con<igurations   represent   isomers   that   can   be  
separated    
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•  Conformations   represent   conformers,   which  
are   rapidly   interconvertible   and   thus   non  
separable  
•  The   terms   conformational   isomer   or   rotamer  
are  sometimes  used  instead  of  conformers  
•  The   conformation   of   a   molecule   in   solid   state  
is  not  necessarily  the  same  as  in  solution  

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 STRAIN    

•  Strain   exists   in   a   molecule   when   bonds   are  

forced  to  make  abnormal  angles,  resulting  in  
higher   energy   than   would   be   the   case   in   the  
absence  of  angle  of  distortion  
•  Strained  molecules  contain  strain  energy,  i.e.  
their  potential  energies  are  higher  than  they  
would  be  if  strain  were  absent  

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•  There  are  three    types  of  strain  in  rings:    
–  angle  strain,  torsional  strain,  transannular  strain  
•  Angle   strain   -­‐   expansion   or   compression   of  
bond  angles  away  from  the  most  stable  
•  Torsional   (or   Pitzer)   strain   -­‐   eclipsing   of  
bonds   on   neighboring   atoms   or   occurs   during  
rotation   (torsion)   about   carbon-­‐carbon   single  
bond  
•  Steric   strain   -­‐   repulsive   interactions   between  
nonbonded  atoms  in  close  proximity  
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 CONFORMATION  ANALYSIS  IN    
OPEN  CHAIN  SYSTEM  

•  For  any  open  chain  single  bond  that  connects  

two   sp3   carbon   atoms,   an   in<inite   number   of  
conformations  are  possible  each  of  which  has  
a  certain  energy  associated  with  it  
•  For   ethane   there   are   two   extremes,   a  
conformation  of  highest  and  one  with  lowest  
potential   energy,   depicted   in   two   ways   as  
follows:  
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 H H

H H

H H H H

H H

H H
Staggered conformation Eclipsed conformation

Andiron/Sawhorse formulas for Ethane

H
H H
H H
H
H H H H
H H
Staggered conformation Eclipsed conformation

Newman Projections for Ethane

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•  The   st a ggered   conforma t ion   is   t he  
conformation   of   lowest   potential   energy   of  
ethane  
•  As   the   bond   rotates,   the   energy   gradually  
increases   until   the   eclipse   conformation   is  
reached,   when   the   energy   is   maximum   as  
depicted  in  the  next  slides  
•  The   angle   of   torsion,   which   is   a   dihedral  
angle,   is   the   angle   between   the   XCC   and   the  
CCY  planes  
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9
•  For   ethane   the   difference   in   energy   is   about  
2.9  kcal/mol  (12  kJ/mol)  
•  The   difference   is   known   as   the   energy  
barrier,   since   in   free   rotation   about   a   single  
bond  there  must  be  enough  rotational  energy  
to   cross   the   barrier   every   time   two   hydrogen  
atoms  are  opposite  to  each  other  
 
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•  It  can  be  concluded  that:  
–  The   ethane   molecule   has   its   lowest   energy   in  
staggered   conformation   because   in   this  
conformation   the   orbitals   of   C-­‐H   bonds   have   the  
least   amount   of   overlap   with   the   C-­‐H   orbitals   of  
the  adjacent  carbon  
–  At   ordinary   temperatures   enough   rotational  
energy   is   present   for   the   ethane   molecule   rapidly  
to  rotate  

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•  Larger   groups   than   hydrogen   cause   larger  
barriers    
•  When   the   barriers   are   large   enough,   as   in  
case   of   suitably   substituted   biphenyls,  
rotation   at   room   temperature   is   completely  
prevented,   this   leads   to   con<igurations   not  
conformations  
•  Even   for   compounds   with   small   barriers,  
cooling   to   low   temperatures   may   remove  
enough   rotational   energy   for   what   would  
otherwise   be   conformational   isomers   to  
become  con<igurational  isomers   12
•  Consider   a   1,2-­‐disubstituted   ethane   (YCH2-­‐
CH2Y   or   YCH2-­‐CH2X),   such   as   n-­‐butane,   for  
which  there  are  four  extremes:  
–  A  fully  staggered  conformation,  called  anti,  trans  
or  antiperiplanar  
–  Another   staggered   conformation,   called   gauche  
or  synclinal  
–  Eclipsed   conformations   called   the   synperiplanar  
and  anticlinal  

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•  For  butane  and  other  molecules  of  the  forms  
YCH 2 -­‐CH 2 Y   and   YCH 2 -­‐CH 2 X,   the   anti  
conformer  is  the  most  stable,  but  exceptions  
f o r   m o l e c u l e s   c o n t a i n i n g   s m a l l  
electronegative   atoms,   especially   <luorine  
and  oxygen  
•  2-­‐<luoroethanol,   1,2-­‐di<luroethane   and   2-­‐
< l u o r o e t h y l   t r i c h l o r o a c e t a t e   e x i s t  
predominantly  in  the  gauche  form    

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Main  conformation  energy  pro<iles  of  acyclic  sp3-­‐
based  compounds  correlate  with  the  pro<ile  of  n-­‐
butane:  
 

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16
 Synperiplanar  

Anticlinal   Anticlinal  

Antiperiplanar   Synclinal   Synclinal  

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CONFORMATIONS  OF  CYCLOALKANES

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 CYCLOBUTANE
•  P u c k e r e d   ( w r i n k l e d )   c o n f o r m a t i o n  ,
substituents   in   axial-­‐like   (equatorial-­‐like)  
positions  
•  1 , 3 -­‐ S u b s t i t u t e d   c y c l o b u t a n e s :   s m a l l  
preference   for   cis-­‐   isomer   with   equatorial-­‐
like  positions  over  trans-­‐isomer  

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 CYCLOPENTANE

•  Two  main  conformations:  envelope  and  half-­‐

chair   (low   difference   in   energy=rapid  
interconversion)  

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 CYCLOHEPTANE

•  Has   four   main   conformations   identi<ied:  

twist-­‐chair,  chair,  boat,  twist-­‐boat  

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 CONFORMATION  IN  SIX-­‐  MEMBERED  RINGS  
•  For   cyclohexane   there   are   two   extreme  
conformations   in   which   all   the   angles   are  
tetrahedral  
•  T h e s e   a r e   c a l l e d   b o a t   a n d   c h a i r  
conformations  and  in  each  the  ring  is  said  to  
be  puckered  or  wrinkled  
•  The   chair   conformation   is   rigid   but   the   boat  
conformation   is   <lexible   and   can   easily   pass  
over  to  a  somewhat  more  stable  form  known  
as  the  twist  conformation    
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•  The   most   stable   conformation   for  
cyclohexane  ring  is  the  chair  conformation  
•  The   C-­‐C   bond   angles   are   all   109.5˚,   hence  
free   of   angle   strain   as   well   as   free   of  
torsional  strain  
•  Appear  to  be  perfectly  staggered  
•  Partial  rotation  at  C-­‐C  bond  single  bond  of  
the   ring,   the   chair   con<irmation   assume  
the   boat   conformation   (refer   energy  
diagram  next  slide)  
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24
 CONFORMATION  IN  SIX-­‐MEMBERED  
RING  CONTAINING  HETERO  ATOMS  

•  The   basic   principles   are   the   same,   i.e.   there  

are   chair,   twist   and   boat   forms,   axial   and  
equatorial  groups,  but  in  certain  compounds  
a  number  of  new  factors  enter  the  picture  
•  In   5-­‐alkyl-­‐substituted   1,3-­‐dioxanes,   the  
substituent   has   a   much   smaller   preference  
for   the   equatorial   position   than   in  
cyclohexane   derivatives,   the   energy   values  
are  much  lower   25
•  An   alkyl   group   located   on   a   carbon   α to   a  
hetero   atom   prefers   the   equatorial   position,  
which   of   course   the   normal   expected  
behaviour  
•  But   a   polar   group   in   such   a   location   prefers  
the  axial  position,  this  phenomenon  is  known  
as   anomeric   effect,   is   the   greater   stability   of  
α-­‐glucosides  over  β-­‐glucosides  

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•  This   is   due   to   the   fact   that   one   of   the   lone  
pairs   of   the   polar   atom   connected   to   carbon  
can   be   stabilized   by   the   overlapping   with  
antibonding   orbital   of   the   bond   between  
carbon  and  the  other  polar  atom  

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 PHYSICAL  PROPERTIES  OF  ALKANES  
AND  CYCLOALKANES  
•  Examining  un-­‐branched  alkanes,  each  alkane  
differs   from   preceding   one   by   a   -­‐CH2-­‐,   these  
are  known  as  homologs  
•  At  STP:    
–  the   <irst   FOUR   members   of   the   homologous  
series  of  unbranched  alkanes  are  gases    
–  C5-­‐C17  (pentane  to  heptadecane)  are  liquids    
–  unbranched   alkanes   with   18   and   more   carbon  
atoms  are  solids    
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 PHYSICAL  PROPERTIES  OF  UNBRANCHED  
ALKANES  
C  atoms   Name   Bp  (˚C)   Mp  (˚C)   Density  (g/mL)  
1   Methane   -­‐161.5   -­‐182  
2   Ethane   -­‐88.6   -­‐183  
3   Propane   -­‐42.1   -­‐188  
4   Butane   -­‐0.5   -­‐138  
5   Pentane   36.1   -­‐130   0.626  
6   Hexane   68.7   -­‐95   0.659  
7   Heptane   98.4   -­‐91   0.684  
8   Octane   125.7   -­‐57   0.703  
9   Nonane   150.8   -­‐54   0.718  
10   Decane   174.1   -­‐30   0.730  
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PHYSICAL  PROPERTIES  OF  UNBRANCHED  
ALKANES  
C  atoms   Name   Bp    (˚C)   Mp  (˚C)   Density  (g/mL)  
11   Undecane   195.9   -­‐26   0.740  
12   Dodecane   216.3   -­‐10   0.749  
13   Tridecane   235.4   -­‐5.5   0.756  
14   Tetradecane   253.5   6   0.756  
15   Pentadecane   270.5   10   0.763  
16   Hexadecane   287   18   0.773  
17   Heptadecane   303   22   0.778  
18   Octadecane   316.7   32   0.777  
19   Nonadecane   330   32   0.777  
20   Eicosane   343   36.8   0.789  

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 PHYSICAL  PROPERTIES  OF  CYCLOALKANES  

C  atoms   Name   Bp  (˚C)   Mp  (˚C)   Density  (g/ Refractive  

mL)   index  
3   Cyclopropane   -­‐33   -­‐126.6  

4   Cyclobutane   13   -­‐90  

5   Cyclopentane   49   -­‐94   0.751   1.4260  

6   Cyclohexane   81   6.5   0.779   1.4064  

7   Cycloheptane   118.5   -­‐12   0.811   1.4266  

8   Cyclootane   149   13.5   0.834   1.4449  

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 REACTIONS  OF  ALKANES  

•  Alkanes   as   a   class   are   characterized   by   a  

general  inertness  to  many  chemical  reagents  
•  The  C-­‐C  and  C-­‐H  bonds  are  very  strong,  they  
do   not   break   unless   heated   to   very   high  
temperatures  
•  Due   to   the   fact   that   C   and   H   have   nearly  
same   electronegativity,   the   C-­‐H   bond   is  
slightly   polarized,   as   a   result   they   are  
generally  unaffected  by  most  bases  
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 1.  Halogenation  (Substitution  Reaction):  

250-400 ˚C, or Light

C H + X2 C X + HX

Usually a mixture
Reactivity X2: Cl2 > Br2
H2: 3 ˚> 2˚ > 1˚ > CH3-H

Example:

CH3 CH3 CH3

Cl2
H3C C CH3 H3C C CH2Cl + H3C C CH3
H 250-400 ˚C H
Cl

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HALOGENATION   OF   ALKANES:     CHAIN  
REACTION  

Step  1:    Initiation  

•  Heat  or  uv  light  cause  the  weak  halogen  bond  
to   undergo   homolytic   cleavage   to   generate  
two   chlorine   radicals   and   starting   the   chain  
process      
  heat or light
Cl Cl Cl Cl

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Step  2:    Propagation  

•  A  chloride  radical  abstracts  a  hydrogen  to  form  HCl  

and  a  methyl  radical  
•  The   methyl   radical   abstracts   a   chlorine   atom   from  
another   molecule   of   Cl2   to   form   the   methyl   chloride  
product   and   another   chloride   radical,     which   can  
then  itself  reacts  creating  a  cycle  that  can  repeat      

Cl H CH3 H Cl + CH3

Cl Cl CH3 H3C Cl + Cl

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Step  3:      Termination  
 •  Various   reactions   between   the   possible   pairs   of  
radicals  allow  for  the  formation  of  ethane,  Cl2  or  the  
product,  methyl  chloride    
•  These   reactions   remove   radicals   and   do   not  
perpetuate  the  cycle      

Cl + Cl Cl Cl
or
CH3 + CH3 H3C CH3
or
CH3 + Cl H3C Cl 36
 2.  Combustion  
Example:
flame
CnH2n+2 + excess O2 nCO2 + (n+1)H2O

flame
n-C5H12 + 8O2 5CO2 + 6H2O

3.  Pyrolysis  (Cracking)  
400-600 ˚C
Alkane H2 + smaller alkanes + alkenes
with or without catalysis

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 PREPARATION  OF  ALKANES  

1.  Hydrogenation  of  alkenes  

H2/Pt, Pd or Ni
CnH2n CnH2n + 2

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 2.  Reduction  of  Alkyl  Halides  

a:  Hydrolysis  of  Grignard  reagent  

H2O
R-X + Mg R-MgX R-H

Example:
H2O
CH3CH2CHCH3 CH3CH2CHCH3 CH3CH2CH2CH3

Br MgBr n-Butane
sec-Butylbromide sec-Butyl magnesium bromide

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b:  Reduction  by  metal  and  acid  

R-X + Zn + H+ R-H + Zn2+ + X-

Example:
Zn/H+
CH3CH2CHCH3 CH3CH2CH2CH3

Br n-Butane
sec-Butylbromide

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3 .   C o u p l i n g   o f   a l k y l   h a l i d e s   w i t h  
organometallic  compounds  
R
Li CuX
R X R Li R CuLi
May be Lithium dialkylcopper
1˚, 2˚, 3˚ Alkyllithium
R R'

R'-X
Should be
Example 1: 1˚

CH2CH3
Li CuI
CH3CH2 Cl CH3CH2 Li CH3CH2 CuLi

CH3CH2CH2(CH2)5CH3
n-Nonane
CH3(CH2)5CH2Br
n-Heptyl bromide

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 Example 2:

CH3 CH3 t-C4H9

Li CuI
H3C CH3 t-C4H9 CuLi CH3
H3C CH3

Cl Li H3C CH2(CH2)3CH3
tert-Butyl chloride
CH3(CH2)3CH2Br CH3
n-Pentyl bromide 2,2-Dimethylheptane

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