AnIntroductiontoOrganicSynthesis：有機(jī)合成簡(jiǎn)介

1、.CH221 CLASS 15CHAPTER 8: ALKYNES AN INTRODUCTION TO ORGANIC SYNTHESISSynopsis. Class 15 gives an account of the preparation, characteristics and reactions of alkynes, ending with a brief introduction to strategy in organic synthesis, based upon the chemistry of alkynes and alkenes.Centaurea cyanusI

2、ntroductionAlkynes are hydrocarbons that possess a carbon-carbon triple bond. They are not as common as alkenes in nature (but see below), but a significant number of natural products, such as some carotenoids and unsaturated fatty acids (see below), include CºC in their structures.Acetylene (C

3、HºCH, the simplest alkyne) was once the foundation of much of the organic chemical industry, based upon coal. That role has long been taken over by ethylene and propylene (based on petroleum), but acetylene is still used as starting material for acrylic polymers. It is produced by the steam-pyr

4、olysis of methane (from natural gas):Electronic Structure of AcetyleneIt has been shown in class 2 that the structure of acetylene is linear, based on sp hybridization of carbon. Its structure is summarized below.The CºC bond in acetylene is the shortest and strongest known carbon-carbon bond.N

5、aming AlkynesAlkynes take the suffix yne and the position of the triple bond is indicated by giving it the lowest possible number, except in certain cases (see below).E.g.If there is also a double bond present, and if there is a choice of numbering, then the double bond is preferred for the lowest n

6、umber.E.g.If there is a more senior group, such as a carbonyl group, then this preferentially takes the lowest number:Preparation of Alkynes: Elimination Reactions of 1,2-DihalidesTreatment of 1,2-dihalides (also called vicinal or vic-dihalides) with an excess of strong base, such as KOH, C2H5ONa or

7、 NaNH2, results in double elimination of hydrogen halide to give alkynes. 1,2-Dihalides themselves are readily prepared by the halogenation of alkenes:Alternatively, alkynes can be synthesized by hydrogen halide elimination from vinyl halides:Reactions of Alkynes: Addition of Hydrogen Halides and Ha

8、logensAlkynes react with hydrogen halides and halogens in a similar manner to alkenes, as illustrated by the example below.Note the Markovnikov orientation.Hydrohalogenation often (but not always) involves anti addition:Note that hydrohalogenation of alkenes is not generally highly stereoselective,

9、either.Halogenation, on the other hand, always appears to involve anti addition, as in the case of alkenes, as shown below.The reaction is slower than that of alkenes, possibly because of the slower formation of cyclic halonium cationic intermediates.i.eHowever, these reactions are useful for the sy

10、nthesis of polyhalogen compounds:Hydration of AlkynesMercury (ii)-Catalyzed HydrationAlkynes can be hydrated, like alkenes, but HgSO4 is usually needed as a catalyst. The products are aldehydes or ketones, as shown overleaf. Note that the initial product of hydration is an ENOL, but this is in rapid

11、 equilibrium with the generally more favorable KETO isomer. These isomers differ in the position and type of double bond and in the position of a hydrogen atom. Constitutional isomers that are in rapid equilibrium (via rearrangement) are known as TAUTOMERS and the process is called TAUTOMERISM. The

12、most common type of tautomerism is KETO-ENOL tautomerism, described above.In simple (non-conjugated cases, like those above), the keto tautomer is thermodynamically more stable, but the enol tautomer is formed more rapidly: this is an example of EQUILIBRIUM (THERMODYNAMIC) VERSUS RATE (KINETIC) CONT

13、ROL.Hydroboration/OxidationBorane adds rapidly to alkynes in the same way as it does to alkenes (with anti-Markovnikov orientation). The initial enol tautomers normally rapidly convert to the keto tautomer, giving an aldehyde or ketone as product, depending on the structure of the alkyne.Oxidative C

14、leavage of AlkynesAlkynes, like alkenes, can be cleaved by reaction with powerful oxidizing agents, such as ozone and potassium permanganate. Non-terminal alkynes give carboxylic acid fragments, whereas terminal alkynes give a carboxylic acid and CO2. Although reactions of this kind are of limited s

15、ynthetic value, they have been useful in the past in establishing the location of triple bonds in natural products, for example:Reduction of Alkynes to AlkenesThe reduction of a triple bond can be done in two major ways, giving different stereoisomers of the product. Such reactions are called STEREO

16、SELECTIVE and are of prime importance in organic synthesis. Controlled heterogeneous catalytic hydrogenation, with a Lindlar catalyst, gives mostly cis alkene, whereas Birch reduction, using alkali metals in liquid ammonia affords mainly the trans alkene.Birch reduction involves the transfer of elec

17、trons from the metal:Acid-Base Reactions of Terminal Alkynes The alkyne hydrogen of terminal alkynes, unlike the equivalents in alkenes (or alkanes), is appreciably acidic:In these equilibria, which lie well to the RIGHT, the stronger acid displaces the weaker one. Note the relative acidity: H2O >

18、; ROH > HCºCH > NH3 > RH; (see class 4 for pKA values),and the relative basicity: OH- < OR- < HCºC- < NH2- < R-The surprising acid strength of the alkyne hydrogen is best explained by the more favorable location of the lone pair electrons in a carbon sp orbital, as opp

19、osed to an sp2 or sp3 orbital:The alkyne compounds favored in the above equilibria are examples of ORGANOMETALLIC compounds and are important in organic synthesis, principally for the formation of C-C bonds, owing to the nucleophilic nature of the anionic carbon. Examples are given belowIn all the a

20、bove reactions, the alkyne C metal bond is written as ionic. In reality, it is polar covalent, with very considerable ionic character:d- d+ºC MEither way, the carbon is electron rich (nucleophilic), which enables it to react with electron poor (electrophilic) centers, such as those above. Thats

21、 what makes alkyne organometallic compounds so useful in organic synthesis.An Introduction to Organic SynthesisThis last section will use some the reactions of alkynes discussed above to illustrate the planning of some simple organic syntheses. Organic synthesis is a crucial part of chemistry. It is

22、 always better to have the simplest and most economical route to known compounds, which may be some natural product (or derivative of that natural product) that is medically valuable in the curing of certain illnesses, for example. By devising an efficient laboratory route (and eventually commercial

23、 route) to the compound, it can be obtained less expensively and hence will become more widely available. Furthermore, the abundance of a synthetic analog of a natural product leads to less environmental stress on the source of the natural product (a plant or animal). Of course, many natural products have extremely complex struc