Post on 21-Dec-2015
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Alkynes
Structure
sp hybridization
Acidity of Terminal Alkynes
Other strong bases that will ionize the terminal alkyne:
Not KOH
Stronger base
Weaker base
Important Synthetic Method: Dehydrohalogenation
1. Dehydrohalogenation…
An alkyl halide can eliminate a hydrogen halide molecule, HX, to produce a pi bond.
RCH=CHR + HX RCHXCH2RStrong base
Also, if we start with a vinyl halide and a very strong base (vinyl halides are not very reactive).
RCH=CHBr RCCHNaH
Or rewriting
RCHBrCH2R RCH=CHRbase
Recall that HX can be added to a double bond to make an alkyl halide. HX can also be removed by strong base, called dehydrohalogenation.
Preparation of alkene
Synthetic planning (Retrosynthesis)
CH3
prop-1-yne
Target molecule.
Br
H
CH3
NaNH2NaNH2
CH3
Br
H
H H
BrCH3
Br2
Trace the reactions sequence from the desired product back to ultimate reactants.
H
HH
H
CBut typical of synthetic problems side reaction occurs to some extent and must be taken into account.
Overall Sequence converts alkene alkyne
Work Backwards…..
Starting reactant
More Sythesis: Nucleophilic Substitution
Use the acidity of a terminal alkyne to create a nucleophile which then initiates a substitution reaction.
Note that we still have an acidic hydrogen and, thus, can react with another alkyl group in this way to make RCCR’
Alkyl halides can be obtained from alcohols
ROH + PX3 RX
Reactions: alkyne with halogen
No regioselectivity with Br2.
Stereoselective for trans addition.
RCCR + Br2 RBrC=CBrR
Reactions: Addition of HX
The expected reaction sequence occurs, formation of the more stable carbocation.
Markovnikov orientation for both additions.
Now for the mechanism….
MechanismThe expected reaction sequence occurs, formation of the more stable carbocation.
Addition of the second mole, another example of resonance.
Reactions: Acid catalyzed Hydration (Markovnikov).
Markovnikov addition, followed by tautomerism to yield, usually, a carbonyl compound.
Reactions: Anti Markovnikov Hydration of Alkynes, Regioselectivity
Similar to formation of an anti-Markovnikov alcohol from an alkeneStep 1, Internal Alkyne: addition to the alkyne with little or no regioselectivity issue.
Alternatively Asymmetric, terminal, alkyne if you want to have strong regioselectivity then use a borane with stronger selectivity for more open site of attack.
sia2BH
Less exposed site.
More exposed site.
overall: R R'
BH3 H2O2, NaOHRCH2CR'
o
R R'
H BStep 1 Step 2
Aldehyde not ketone.
Tautomerism, enol carbonyl
Overall…
Step 2, Reaction of the alkenyl borane with H2O2, NaOH would yield an enol. Enols are unstable and rearrange (tautomerize) to yield either an aldehyde or ketone.
H
OH
enol
H
B
H2O2
NaOHH
O
Hcatalyzed bybase or acid
either an aldehyde or a ketone
internal alkyne ketone (possibly a mixture, next slide)
Terminal alkyne aldehyde
ExamplesAs before, for a terminal alkyne.
Used to insure regioselectivity.
Get mixture of alkenyl boranes due to low regioselectivity.
But for a non-terminal alkyne frequently will get two different ketones
Reduction, Alkyne Alkene
You can use a reduced activity catalyst (Lindlar), Pd and Pb, which stops at the alkene. You obtain a cis alkene.
1. Catalytic Hydrogenation
Syn addition
If you use catalysts which are also effective for alkene hydrogenation you will get alkane.
Reduction - 2
2. Treatment of alkenyl borane with a carboxylic acid to yield cis alkene.
BH3
H B
hex-3-yne
CH3CO2H
3. Reduction by sodium or lithium in liquid ammonia to yield the trans alkene.
Instead of H2O2 / NaOH
Alkenyl borane
Plan a Synthetic SequenceRetrosynthesis
Synthesize butan-1-ol from ethyne. Work backward from the target molecule.
OH
butan-1-ol
Target molecule
Is read as “comes from”.
A big alkyne can be formed via nucleophilic substitution. This is the chance to make the C-C bond we need.
Do a “disconnect” here.
Br
bromoethane
ethyne
Catalytic Lindlar reduction
Catalytic reduction Lindlar
Addition of HBr.
Convert ethyne to anion and react with EtBr.
1. BH3
2. H2O2, NaOH
Now, fill in the “forward reaction” details
Major problem: make big from small. Be alert for when the “disconnect” can be done.
Ask yourself! Do we know how to join any two molecules together to yield an alcohol?
Not yet! So how can we get it?How about joining molecules to get an alkene? Not yet!! So how can we get an alkene?
Can we get an alkyne from smaller molecules?
YES!