Chapter 8: Alkynes: an introduction to organic synthesis 8.2 Preparation of alkynes: elimination of dihalides

Alkynes contain a C ≡C triple bond Recall from 7.1 that an alkene can be prepared by elimination of H and Br from an alkyl bromide using KOH. ≡ Acetylene: H-C C-H is the common name for ethyne, The same can be done (twice) to make an alkyne. used as a torch fuel This is useful in making an alkyne (triple bond) from an Alkyne nomenclature follows normal hydrocarbon alkene (double bond). naming rules: 1. Number from the end closest to the triple bond 2. If it's a tie between the ends to two triple bonds, use branching 3. Double bonds take priority over triple bonds when they are equal distance to the end of a chain. 4. Triple bonds are linear so there is no cis/trans or E/Z, although any double bonds in the molecule can still have stereochemical designators.

As we'll see later, an alkyne can be reduced selectively to either a cis or trans alkene, so this can be a way of converting between cis and trans alkenes.

ch8 Page 1 ch8 Page 2 8.3 Reactions of alkynes: addition of HX Addition of HX and X 2 Alkynes contain linear (180 o bond angle), sp -hybridized Two equivalents of HBr or HCl can add to an alkyne - carbons. both with Markovnikov regiochemistry. H and X usually have trans stereochemistry. The triple bond is made of one σ and two perpendicular π bonds. Those π bonds can react very similarly to the π bond in an alkene.

Addition of HX to an alkyne takes place via a vinylic carbocation (+ is on a double-bonded C)

Halogens can also add twice:

ch8 Page 3 ch8 Page 4 8.4 Hydration of alkynes and tautomerism Mechanism of mercury(II)-catalyzed hydration Hydration of alkynes has many ideas in common with 1. Electrophilic addition of Hg 2+ to make vinylic cation. hydration of alkenes, but there are some very important 2. Nucleophilic addition of H 2O with loss of proton. differences. 3. Proton from aqueous acid replaces Hg + 4. Proton transfer from O to C in 2 steps converts enol Aqueous acid alone will allow Markovnikov hydration of to more stable keto tautomer. alkenes, but will not react with alkynes .

Aqueous acid + catalytic HgSO 4 will readily hydrate alkenes, but the enol produced will rapidly isomerize to a more stable ketone.

(enol intermediate)

Tautomerism : rapid isomerization between enol and keto isomers by proton transfer. Hydration is most useful on terminal alkynes (R-C≡C-H) and symmetrical alkynes because it produces only one product. Unsymmetrical internall alkynes make mixtures.

ch8 Page 5 ch8 Page 6 Hydroboration/oxidation of alkynes 8.5 Reduction of alkynes

BH 3 adds to alkynes in a non -Markovnikov orientation to Catalytic hydrogenation with Pd/C gives complete give a vinylic borane. Oxidation makes an enol that reduction to an alkane just like hydrogenation of alkenes. tautomerizes to a more stable ketone.

Again, unsymmetrical internal alkynes produce a mixture Reduction with a deactivated catalyst (Lindlar catalyst = of products. "poisoned" Pd on CaCO 3) occurs by a syn addition to give a cis alkene. Terminal alkynes produce an aldehyde because addition is non-Markovnikov, opposite of Hg(II)-catalyzed hydration.

A trans alkene can be formed with a dissolving -metal reduction. Addition of H's is stepwise so the more stable trans alkene is formed.

ch8 Page 7 ch8 Page 8 8.6 Oxidative cleavage of alkynes 8.7 Alkyne acidity: formation of acetylide anions

Alkynes can be cleaved by KMnO 4 or O 3 to make Terminal alkynes are weak acids (p Ka ~25). carboxylic acids. This is not so useful synthetically, but can be used to determine the position of triple bonds in Which direction will the following equilibria lie? alkynes. - - Molecule pKa HC ≡CH + OH ⇌ HC ≡C: + H 2O Ozonolysis of an unknown alkyne gives one 6 -carbon CH 4 60 dicarboxylic acid HOOC-(CH 2)4-COOH and 2 equivalents CH 2=CH 2 44 of acetic acid, CH 3COOH. What is the structure of the NH 3 35 unknown alkyne? - - ≡ HC ≡CH + NH 2 ⇌ HC ≡C: + NH 3 HC CH 25

H2O 16

+ - NaNH 2 is Na NH 2 (sodium amide) - a base strong enough to deprotonate terminal alkynes. The conjugate base of an alkyne is called an acetylide ion .

(Hydrogens attached to sp carbons are more acidic than sp 2 or sp 3 because the sp carbon anion is more stable)

ch8 Page 9 ch8 Page 10 8.8 Alkylation of acetylide anions 8.9 An introduction to multistep organic synthesis Our first carbon -carbon bond forming reaction is the Organic synthesis is the process of building complex alkylation of acetylide ions . molecules from simpler ones, one reaction at a time, through a multistep sequence. The acetylide ion is a very strong nucleophile. It can add to electrophilic carbons, displacing one of the other
Synthesis of isolated natural products bonds on the carbon. This works best with a 1 o alkyl
Synthesis of modified natural products bromide or iodide.
Synthesis of new molecules
For drug/material design
To better understand chemsitry

To be successful in mulitstep organic synthesis, you must know the reactions!

Starting functional group
Functional group produced (regiochemistry, stereochemistry)
Reagents used
Limitations

Careful, this does not work with 2 o or 3 o alkyl halides!

ch8 Page 11 ch8 Page 12 Retrosynthetic analysis Synthesis practice Retrosynthetic analysis is the best strategy for planning Plan a retrosynthesis for the following synthesis problem, syntheses: it's working backwards - first looking at the then write the full forward sequence of synthetic complex final product you need to make, and considering reactions with reagents. what reactions could make that product.

The retrosynthetic analysis uses a two -bar arrow. Carbon-carbon bonds that are "broken" in the retrosynthetic direction are actual carbon -carbon bond forming reactions in the forward direction.

Retrosynthetic direction :

Forward direction:

ch8 Page 13 ch8 Page 14 Synthesis practice Synthesis practice Plan a retrosynthesis for the following synthesis problem, Plan a retrosynthesis for the following compound, then write the full forward sequence of synthetic starting with compounds with no more than five reactions with reagents. carbons, then write the full forward sequence of synthetic reactions with reagents.

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