CHEM 3013 ORGANIC CHEMISTRY I LECTURE NOTES CHAPTER 8

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1 EM 3013 GANI EMISTY I LETUE NTES 1 1. The Alkyne Functional Group APTE 8 Alkynes are compounds with carbon-carbon triple bonds. ecall that alkanes use sp 3 hybrid orbitals and that alkenes use sp 2 hybrid orbitals. The alkynes form bonds using a third type of hybrid orbital, the sp orbital. The consequence of this kind of bonding are two fold: (1) Because of the extra "electron glue" provided by the two sets of π- electrons, t he alkyne bond is the shortest - bond known (about 1.2Å, as compared with 1.33Å for alkenes and 1.54Å for alkanes). and (2) Alkynes are incapable of is/trans geometric isomerism because of the resulting linear configuration of the substituents. Acetylene (an alkyne) E N E G Y 2p 2s mix 2s and 2p orbitals 2p 2sp 1s Elemental arbon 1s sp ybridized arbon in Alkynes π-bonds (two 2p orbitals on carbon σ-bond (1s orbital on hydrogen and sp orbital on carbon) σ-bond (two sp orbitals on the carbons Bonding in Alkenes 2. Nomenclature of Alkynes The simplest possible alkyne is 2 2 is known by the common name of acetylene. Another name for alkynes as a class is acetylenes. a. IUPA Nomenclature The systematic nomenclature of alkynes is similar to alkenes.

2 1. Name the longest chain containing the triple bond 2. The suffix -ane is replaced by -yne and the triple bond is given the lowest possible number. 3. When double and triple bonds are present in the same molecule, the principal chain is the carbon chain containing the greatest number of double and triple bonds. 4. The compound still ends with the suffix -yne 5. Precedence is given to the naming scheme which gives the lowest number for the first multiple bond regardless whether it is double or triple. 6. In naming the compounds, the double bond is named first...dropping the last e of the -ene suffix. 2 2,6-dimethyl-hept-2-yne The eight membered ring is the smallest stable cyclic alkene 3,6,8-trimethyl-4-isopropylcyclooctyne trans- 5-nonen-3-yne (Z)-3-ethyl-2-nonen-6-yne ompounds that contain both double and triple bonds are named as alkynes. Precedence is given to the naming scheme which gives the lowest number for the first multiple bond regardless if it is a double or triple. In naming, the double bond is cited first. If both double and triple bonds are at equivalent the double bond takes precedence. Alkyne Nomenclature b. Alkynes as Substituents Side-chain groups containing a triple bond are called alkynyl groups and are named by replacing the final -e and adding the suffix -yl.. The alkynyl group is numbered outward from the point of attachment to the principal chain trans-3-(2-butynl)-6-methyl-cyclohexene 3 4' 3 3' 2' Named as a substituent; Fewer carbons than ring 2 1' c. Properties of Alkynes Naming Alkynes as substituent groups

3 Terminal alkynes (those that have a - bond) are less stable than internal alkynes. The situation is similar to alkenes (recall that alkene stability increases with alkyl substitution), and for the same reason: yperconjugation. verlap of π-type orbitals with SP 3 ybridized orbitals on adjacent alkyl groups leads to a stabilizing interaction. 3 Structural Isomers Pentyne 2-Pentyne Terminal Alkyne Internal Alkyne eats of ydrogenation = Kcal/mole E N E G Y 1-pentyne 2-pentyne 3.3 Kcal mole = Kcal/mole pentane Internal alkynes are more stable than terminal alkynes because of yperconjugation. Energy Differences in Alkynes 3. Synthesis of Alkynes There are relatively few general methods of alkyne syntheses, the best two are: (1) alkylation of acetylene (to be discussed somewhat later), and (2) Twofold elimination of X from dihalides. Acetylene itself can be made by a simple process of hydrolysis of calcium carbide as described by the following reaction: a a()2. Acetylene is a gas, and was one of the first illuminating gases used in gas lights. The reaction described above is also the source of acetylene used in "carbide cannons" which are often fired off when a touchdown is scored during a football game. A small amount of a2 is added to water, acetylene is generated and then ignited in an enclosed space. Thus creating the BM. ecall that the elimination of X from an alkyl halide (upon treatment with a base) will result in the formation of alkenes. The π-bond systems of alkynes can be prepared in much the same manner. Since an alkyne has two π-bonds however, we have to eliminate two molecules of X. This is usually done by treatment of a vicinal dihalide with an excess of strong base. Vicinal dihalides are the starting material of choice because they are readily available by the addition of bromine or chlorine to an alkene. Thus the overall method of halogenation-dehalogentaion provides an excellent route for going from an alkene to an alkyne. Although different bases can be used for this double elimination of 2X from dihalides, salts of the amide anion (N2 - ) are usually preferred because it's strongly basic nature gives higher yields of products. The twofold elimination process occurs in two discrete steps, passing through a vinyl halide intermediate.

4 Alkynes via gem-dihalides l l 2 eq. strong base 3 Alkynes via vicinal dihalides 3 l 3 l 2 eq. strong base 3 3 N 2 - = Amide anion...conjugate base of ammonia (N3 ) pk a (N 3 ) = 35 Mechanism 3 l 3 l + N N 2 l Alkynes are formed via two consecutive elimination reactions. 3 3 Alkynes via Elimination eactions of Dihalides 4. Electrophilic eactions of Alkynes a. Addition of X and X 2 The chemistry of alkynes is dominated by electrophilic addition reactions similar to that of alkenes. For example, X can be added to alkynes to give vinylic halides as products. owever, X will also react with the alkene product ( alkynes are somewhat less reactive than alkenes to electrophilic addition) to result in formation of a geminal dihalide (both halogens on the same carbon). Thus every addition reactions to alkynes will result in some formation of dihalide. The reaction leading to vinyl halide can be maximized by avoiding an excess of X. The initial addition process follows Markovnikov's rule where applicable. That is, when terminal alkynes react, the vinyl halide produced will be the one in which the + (electrophile) has added to the terminal carbon. The reason for this alkyne regioselectivity is directly analogous to that described for alkenes. The electrophile will add so as to form the more stable vinyl cation intermediate. As for simple carbocations, the vinyl cation with the greater amount of alkyl substitution at the carbon bearing the + charge will be more stabilized through hyperconjugation. While regioselectivity is not observed in electrophilic addition to internal alkynes ( the two possible vinyl cations in this case are of equal stability), the reaction often shows stereoselectivity. The vinyl halide produced by addition of X to an internal alkyne very often (but not always) shows a trans relationship of the and X.

5 The electrophilic addition of X2 to alkynes leads to vinylic dihalides (alkenes with halogens on each carbon of the double bond). The stereoselectivity of this reaction again leads to trans products l 3 2 l Additions follow Markovnikov's ule l l l 3 Additions usually (not always) give trans stereochemistry of and X l (XS) 3 3 l Excess of acid leads to a dihalide product through two consecutive additions Br 2 l 4 Br Br Addition of X and X 2 to Alkynes alogens add to alkynes to give addition products with trans stereochemistry... Watch out for further addition when XS reagent is present!

6 Br Br - 1st Step: Electrophilic addition VINYL ATIN of + to Alkyne 2nd Step: π-bond. Nucleophilic attack of Br - to vinyl cation Br 6 Markovnikov Addition Br Br - Br - Br Br Alkynes will add the electrophile so as to give the most stable vinyl cation bserved Product Mechanism of Electrophilic Addition to Alkynes Most Stable > > ~ > ~ STABILITY Least Stable Vinyl ations are less stable than similarly substituted alkyl carbocations. This accounts for the somewhat lower reactivity of alkynes towards electrophilic reagents (ammonds Postulate) Vinyl ation Stability b. ydration of Alkynes Like the acid-catalyzed addition of water to alkenes, water can be added to alkynes. owever, because of the somewhat lower reactivity of the alkyne, the reaction must be carried out with the use of the extremely electrophilic g(ii) to initially activate the alkyne (see oxymercuration-demercuation of alkenes). The reaction follows a Markovnikov process, with initial production of a vinyl cation which is subsequently trapped by water (acting as a nucleophile) to give an enol (vinyl alcohol). This enol is unstable and undergoes a TAUTMEIZATIN (rearrangement in which a new structural isomer is formed by shift of a hydrogen atom and a π-bond) to form a ketone. Since the reaction follows a Markovnikov regiochemistry, a methyl ketone is produced from the reaction of a terminal alkyne.

7 gs 4 + / 2 gs / The acid catalyzed hydration of alkynes results in the formation of ketones... Terminal alkynes methyl ketones Internal alkynes ketone mixture MEANISM + g +2 S4-2 Markovnikov type addition of mercuric ion to alkyne, resulting in formation of most stable vinylic cation g 2 g KET Tautomer ydration of Alkynes apid earrangement K eq = 10 8 ENL Tautomer g Tautomers are special kinds of constitutional isomers which can rapidly interconvert. c. ydroboration of Alkynes ydroboration of terminal alkynes is an important reaction for the synthesis of aldehydes. It should be noted that this reaction is complimentary to the mercury catalyzed hydration described just previously. The reagent based specificity allows complete regiochemical (and product) control.

8 1 2 B TF Na, 2 B 2 TF 2 2 Na, The hydroboration of alkynes results in the formation of: Terminal alkynes aldehydes Internal alkynes ketone mixture MEANISM + B 2 B 2 = disiamylborane A sterically large hydroborating agent; can stop at the mono adduct B Na, 2 K eq = 10 6 ENL Tautomer B KET Tautomer ydroboration of Alkynes gs Methyl Ketone B TF Na, 2 omplimentary eactions of Terminal Alkynes Aldehyde 5. atalytic ydrogenation of Alkynes Alkynes can be catalytically hydrogenated (reduced) to yield alkenes or alkynes. Because the reductions of alkenes and alkynes occur with almost equal facility ( actually, alkynes can be reduced slightly easier), it is often difficult to stop the reduction of an alkyne at the alkene stage when using standard catalysts. omplete hydrogenation of the triple bond to yield an alkane is done through the use of two equivalents of 2 and a standard catalyst. Partial reduction of the alkyne (stopping at the alkene stage) can be carried out through the use of a Lindlar atalyst. In the Lindlar catalyst, a "poison" (usually an aromatic amine such as pyridine or quinoline) has been added to the catalyst to lower its activity, further reduction is prevented. The stereoselectivity of this reaction is determined by SYN addition of the complexed hydrogen to the sme face of the alkyne π-bond. is alkenes are formed.

9 2, Pd/ Et 3 + UNEATED ALKYNE The catalytic reduction of alkynes, using standard hydrogenation catalysts gives a mixture of products: alkenes (from one equivalent of 2 uptake), alkanes (from two equivalents of 2 uptake) and unreacted alkyne (all 2 used up). 9 The use of two equivalents of 2 will give only alkanes 2 2, Pd/ 2 Et 3 atalytic hydrogenation of alkynes can be stoped at the alkene stage through the use of Lindlar atalysts (Deactivated atalyst) 2 Lindlar 2 2 catalyst atalytic ydrogenation of Alkynes Lindlar catalyst : Pd/aso 4 deactivated by addition of poison (quinoline) Lndlar catalyst 1 2 SYN addition leads to cis stereochemistry Metal surface attraction weakens - bond Activated 2 adds to alkyne π-system atalyst regenerated SYN Addition of Alkynes 6. Dissolving Metal eductions of Alkynes In contrast to the catalytic hydrogenation method, which yields cis-alkenes from alkynes, the reaction of alkynes with sodium or lithium metal in liquid ammonia produces the complimentary trans-alkene. The mechanism of this reaction involves the addition of electrons (given up by the electropositive metal) to the π-system of the alkyne to from an intermediate radical-anion which reacts with the ammonia solvent by pulling off a proton. The resulting radical, in turn, undergoes further reduction to form a vinyl anion. Which again reacts with ammonia, by pulling off a proton, to give the final trans-alkene.

10 The trans nature of the reaction occurs because in the radical anion intermediate, the orbital with the lone-pair and the orbital with the single electron want to be as far apart as possible (in order to minimize repulsions). Thus they take on a trans arrangement. 10 1) Li, N ) 2 1 Trans only "Dissolving Metal" Li + N 3 Li + + e - (N 3 ) n Electropositive metals such as Li, Na will ionize in a liquid ammonia solution, giving up an electron which becomes "solvated " by ammonia molecules Mechanism 1 2 solvated electrons N adical Anion The radical and lone-pair get as far apart as possible 2 1 N N as an acid 2 N 3 as an acid 1 2 solvated electrons reduction of radical to anion 2 Dissolving Metal eduction of Alkynes to trans Alkenes 7. xidative leavage of Alkynes Powerful oxidizing agents such as ozone or acidic KMn4 will cleave the triple bonds of alkynes. The triple bond is generally less reactive than is the double bond so yields of this reaction may be low. If a terminal alkyne is utilized in this reaction, a carboxylic acid and 2 is produced or KMn 4 3 or KMn 4 1 xidative leavage of Alkynes Alkynes undergo oxidativecleavage just like alkenes... owever, they are somewhat less reactive and the yields of cleavage products can be low. 8. Alkylation of Alkynes a. Acidity of Alkynes ne of the striking differences in the chemical behavior of alkenes and alkynes is their differences in acidities. Terminal alkynes have hydrogens which are many times more acidic than the hydrogens of alkanes or alkenes. This is a result of the increased s character in the sp bond between

11 the carbon and hydrogen of terminal alkynes. The anion ( which is the conjugate base of a terminal alkyne) is more stable because the electron pair is closer to the positive charged carbon nucleus. Thus, the acidic hydrogen of terminal alkynes can be removed by a strong base (such as N2-) to form the acetylide anion : - : - 11 ydrocarbon K a pk a Stronger Acid onjugate Base More Stable Weaker Acid 3 2 Less Stable arbon centers with increasing s orbital character will best stabilize carbanions because the negative anion is closer to the positive nucleus. Acetylide Formation: A strong base is able to remove a terminal hydrogen from an alkyne resulting in formation of the conjugate base called acetylide anion. NaN 2 Na + + N 3 N 3 N 2 - = Amide Anion... A very strong base (about x stronger than - ) Acidity of Alkynes N 3 pk a = 35 b. Alkylation of Acetylides By using the parent acetylene or a terminal alkyne, it is possible to introduce one, or two alkyl groups and thus form an entirely new alkyne. The presence of an unshaired pair of electrons on an acetylide anion makes the carbon strongly nucleophilic. Thus acetylide anions ( - : - ) can react with alkyl halides such a bromomethane (3-Br) to substitute for the halogen a yield a new alkyne product ( - -3). Amide anion abstracts proton...forms the acetylide anion. A second alkylation step leads to a new carbon carbon bond. Alkylation of Alkynes 3 Br KN N Br - Acetylide acts as a KN 2 nucleophile...forms N 3 a new carbon-carbon bond (Alkylation) 3 3 Br Amide again abstracts a proton 3

12 12 l Pl l Br Br 2 l 2 Br 3 2 Br Br u(n 3 ) 4 NaN NaN 2 u gs S 4 1-propyne (1) 3 (2) Zn / 2 NaN 2 liq N Br Na Ag(N 3 ) 2 Br Br Ag Li in liq N 3 2, Ni 2 B or Pd/a 3 2, Quinoline Alkyne eaction Summary