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Chapter 9- Alkynes: Reactions and Synthesis

Ashley  Piekarski,  Ph.D.  

Alkynes

•  What  exactly  is  an  alkyne?  •  Our  study  of  alkynes  will  provide  an  introducCon  or  organic  synthesis  •  the preparation of organic molecules from

simpler organic molecules •  we are building up our toolbox of useful

organic reactions! J

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Naming Alkynes

•  General  hydrocarbon  rules  apply  with  “-­‐yne”  as  a  suffix  indicaCng  an  alkyne  

•  Numbering  of  chain  with  triple  bond  is  set  so  that  the  smallest  number  possible  for  the  first  carbon  of  the  triple  bond  

Let’s practice!

(Z)-3-methyloct-3-en-5-yne

cycloocta-1,4-diyne

5-ethyldeca-1,9-diyne

1 eq HBr

2 eq Br2

H2O, H2SO4

HgSO4

BH3, THF

H2O2, H2O, NaOH

H

O

O

(Z)-3-methyloct-3-en-5-yne

cycloocta-1,4-diyne

5-ethyldeca-1,9-diyne

1 eq HBr

2 eq Br2

H2O, H2SO4

HgSO4

BH3, THF

H2O2, H2O, NaOH

H

O

O

(Z)-3-methyloct-3-en-5-yne

cycloocta-1,4-diyne

5-ethyldeca-1,9-diyne

1 eq HBr

2 eq Br2

H2O, H2SO4

HgSO4

BH3, THF

H2O2, H2O, NaOH

H

O

O

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Preparation of Alkynes: Elimination Reactions of Dihalides

•  Treatment  of  a  1,2-­‐dihalidoalkane  with  KOH  or  NaOH  produces  a  two-­‐fold  eliminaCon  of  HX  

•  Vicinal  dihalides  are  available  from  addiCon  of  bromine  or  chlorine  to  an  alkene  

vicinal-­‐  stands  for  two  funcConal  groups  bonded  to  two  adjacent  atoms  

Reactions of Alkynes: Addition of HX and X2

•  AddiCon  reacCons  of  alkynes  are  similar  to  those  of  alkenes  

•  Intermediate  alkene  reacts  further  with  excess  reagent  

•  Regiospecificity  according  to  Markovnikov  

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Electronic Structure of Alkynes

•  Carbon-­‐carbon  triple  bond  results  from  sp  orbital  on  each  C  forming  a  sigma  bond  and  unhybridized  pX  and  py  orbitals  forming  π  bonds.  

•  The  remaining  sp  orbitals  form  bonds  to  other  atoms  at  180º  to  C-­‐C  triple  bond.  

•  The  bond  is  shorter  and  stronger  than  single  or  double  •  Breaking  a  π  bond  in  acetylene  (HCCH)  requires  318  kJ/mole  

(in  ethylene  it  is  268  kJ/mole)  

 

Addition of Bromine and Chlorine

•  IniCal  addiCon  gives  trans  intermediate  •  Product  with  excess  reagent  is  tetrahalide  

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Addition of HX to Alkynes Involves Vinylic Carbocations

•  AddiCon  of  H-­‐X  to  alkyne  should  produce  a  vinylic  carbocaCon  intermediate  

•  vinyl  groups  are  derivaCves  of  ethene,  with  one  hydrogen  atom  replaced  with  some  other  group  

Learning check

(Z)-3-methyloct-3-en-5-yne

cycloocta-1,4-diyne

5-ethyldeca-1,9-diyne

1 eq HBr

2 eq Br2

H2O, H2SO4

HgSO4

BH3, THF

H2O2, H2O, NaOH

H

O

O

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Hydration of Alkynes

•  AddiCon  of  H-­‐OH  as  in  alkenes  •  Mercury (II) catalyzes Markovinikov oriented addition •  Hydroboration-oxidation gives the non-Markovnikov

product

Mercury(II)-Catalyzed Hydration of Alkynes

•  Alkynes  do  not  react  with  aqueous  proCc  acids  

•  Mercuric  ion  is  a  Lewis  acid  catalyst  that  promotes  addiCon  of  water  in  Markovnikov  orientaCon  

•  The  immediate  product  is  a  vinylic  alcohol,  or  enol,  which  spontaneously  transforms  to  a  ketone  

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Mechanism of Mercury(II)-Catalyzed Hydration of Alkynes

Keto-enol Tautomerism

•  Isomeric  compounds  that  can  rapidly  interconvert  by  the  movement  of  a  proton  are  called  tautomers  and  the  phenomenon  is  called  tautomerism    

•  Enols  rearrange  to  the  isomeric  ketone  by  the  rapid  transfer  of  a  proton  from  the  hydroxyl  to  the  alkene  carbon  

•  The  keto  form  is  usually  so  stable  compared  to  the  enol  that  only  the  keto  form  can  be  observed  

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Hydration of Unsymmetrical Alkynes

•  If  the  alkyl  groups  at  either  end  of  the  C-­‐C  triple  bond  are  not  the  same,  both  products  can  form  and  this  is  not  normally  useful  

•  If  the  triple  bond  is  at  the  first  carbon  of  the  chain  (then  H  is  what  is  agached  to  one  side)  this  is  called  a  terminal  alkyne  

•  HydraCon  of  a  terminal  always  gives  the  methyl  ketone,  which  is  useful  

Hydroboration/Oxidation of Alkynes

•  BH3  (borane)  adds  to  alkynes  to  give  a  vinylic  borane  •  OxidaCon  with  H2O2  produces  an  enol  that  converts  to  the  

ketone  or  aldehyde  •  Process  converts  alkyne  to  ketone  or  aldehyde  with  

orientaCon  opposite  to  mercuric  ion  catalyzed  hydraCon  

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Comparison of Hydration of Terminal Alkynes

•  HydroboraCon/oxidaCon  converts  terminal  alkynes  to  aldehydes  because  addiCon  of  water  is  non-­‐Markovnikov  

•  The  product  from  the  mercury(II)  catalyzed  hydraCon  converts  terminal  alkynes  to  methyl  ketones  

Learning check

(Z)-3-methyloct-3-en-5-yne

cycloocta-1,4-diyne

5-ethyldeca-1,9-diyne

1 eq HBr

2 eq Br2

H2O, H2SO4

HgSO4

BH3, THF

H2O2, H2O, NaOH

H

O

O

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Learning check (Z)-3-methyloct-3-en-5-yne

cycloocta-1,4-diyne

5-ethyldeca-1,9-diyne

1 eq HBr

2 eq Br2

H2O, H2SO4

HgSO4

BH3, THF

H2O2, H2O, NaOH

H

O

O

Reduction of Alkynes

•  AddiCon  of  H2  over  a  metal  catalyst  (such  as  palladium  on  carbon,  Pd/C)  converts  alkynes  to  alkanes  (complete  reducCon)  

•  The  addiCon  of  the  first  equivalent  of  H2  produces  an  alkene,  which  is  more  reacCve  than  the  alkyne  so  the  alkene  is  not  observed  

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Conversion of Alkynes to cis-Alkenes

•  AddiCon  of  H2  using  chemically  deacCvated  palladium  on  calcium  carbonate  as  a  catalyst  (the  Lindlar  catalyst)  produces  a  cis  alkene  

•  The  two  hydrogens  add  syn  (from  the  same  side  of  the  triple  bond)  

Alkyne hydrogenation application

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Conversion of Alkynes to trans-Alkenes

•  Anhydrous  ammonia  (NH3)  is  a  liquid  below      -­‐33  ºC  •  Alkali metals dissolve in liquid ammonia and function

as reducing agents •  Alkynes  are  reduced  to  trans  alkenes  with  sodium  or  

lithium  in  liquid  ammonia  •  The  reacCon  involves  a  radical  anion  intermediate  

Mechanism- Conversion of Alkynes to trans-Alkenes

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Learning check

(Z)-3-methyloct-3-en-5-yne

cycloocta-1,4-diyne

5-ethyldeca-1,9-diyne

1 eq HBr

2 eq Br2

H2O, H2SO4

HgSO4

BH3, THF

H2O2, H2O, NaOH

H

O

O

Oxidative Cleavage of Alkynes

•  Strong  oxidizing  reagents  (O3  or  KMnO4)  cleave  internal  alkynes,  producing  two  carboxylic  acids  

•  Terminal  alkynes  are  oxidized  to  a  carboxylic  acid  and  carbon  dioxide  

•  Neither  process  is  useful  in  modern  synthesis  –  were  used  to  elucidate  structures  because  the  products  indicate  the  structure  of  the  alkyne  precursor  

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Alkyne Acidity: Formation of Acetylide Anions

•  Terminal  alkynes  are  weak  Brønsted  acids  (alkenes  and  alkanes  are  much  less  acidic    

Alkyne Acidity: Formation of Acetylide Anions

•  Terminal  alkynes  are  weak  Brønsted  acids  (alkenes  and  alkanes  are  much  less  acidic  (pKa  ~  25.  See  Table  8.1  for  comparisons))  

•  ReacCon  of  strong  anhydrous  bases  with  a  terminal  acetylene  produces  an  acetylide  ion  

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Alkyne Acidity: Formation of Acetylide Anions

•  The  sp-­‐hydbridizaCon  at  carbon  holds  negaCve  charge  relaCvely  close  to  the  posiCve  nucleus  

Alkylation of Acetylide Anions

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Alkylation of Acetylide Anions

•  Acetylide  ions  can  react  as  nucleophiles  as  well  as  bases  

•  ReacCon  with  a  primary  alkyl  halide  produces  a  hydrocarbon  that  contains  carbons  from  both  partners,  providing  a  general  route  to  larger  alkynes  

Limitations of Alkyation of Acetylide Ions

•  ReacCons  only  are  efficient  with  1º  alkyl  bromides  and  alkyl  iodides  

•  Acetylide  anions  can  behave  as  bases  as  well  as  nucleophiles  

•  ReacCons  with  2º  and  3º  alkyl  halides  gives  dehydrohalogenaCon,  converCng  alkyl  halide  to  alkene  

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Learning check

(Z)-3-methyloct-3-en-5-yne

cycloocta-1,4-diyne

5-ethyldeca-1,9-diyne

1 eq HBr

2 eq Br2

H2O, H2SO4

HgSO4

BH3, THF

H2O2, H2O, NaOH

H

O

O

An Introduction to Organic Synthesis

•  Organic  synthesis  creates  molecules  by  design  •  Synthesis  can  produce  new  molecules  that  are  needed  as  

drugs  or  materials  •  Syntheses  can  be  designed  and  tested  to  improve  efficiency  

and  safety  for  making  known  molecules  •  Highly  advanced  synthesis  is  used  to  test  ideas  and  methods,  

answering  challenges  •  Chemists  who  engage  in  synthesis  may  see  some  work  as  

elegant  or  beau3ful  when  it  uses  novel  ideas  or  combinaCons  of  steps  –  this  is  very  subjecCve  and  not  part  of  an  introductory  course  

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Synthesis as a Tool for Learning Organic Chemistry

•  In  order  to  propose  a  synthesis  you  must  be  familiar  with  reacCons  •  What they begin with •  What they lead to •  How they are accomplished •  What the limitations are

•  A  synthesis  combines  a  series  of  proposed  steps  to  go  from  a  defined  set  of  reactants  to  a  specified  product  •  Questions related to synthesis can include partial

information about a reaction of series that the student completes

Strategies for Synthesis

•  Compare  the  target  and  the  starCng  material  •  Consider  reacCons  that  efficiently  produce  the  outcome.  

Look  at  the  product  and  think  of  what  can  lead  to  it  Example  •  Problem: prepare octane from 1-pentyne •  Strategy: use acetylide coupling

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Learning check

•  Synthesize  2-­‐bromopentane  from  acetylene  

Learning check

•  Synthesize  butanal  from  4-­‐octyne  

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Learning check

•  Synthesize  2-­‐heptanone  from  acetylene