Organic Chemistry Chapter 11 PDF

Preview

Summary

Advanced Bio-Organic Chemistry
...

Description

Organic Chemistry Chapter 11, Alkynes Alkynes are compounds that contain a carbon-carbon triple bond. Like alkenes, alkynes are nucleophiles, with easily broken pie bonds, and undergo addition reactions with electrophile reagents. 11.1, Introduction Alkynes contain a carbon-carbon triple bond - terminal alkyne has the triple bond at the end of the carbon chain, so that a hydrogen atom is directly bonded to a carbon atom of the triple bond. - Internal alkyne has a carbon atom bonded to each carbon atom of the triple bond.

An alkyne has the general molecular formula CnH2n-2, giving it four fewer hydrogens than the maximum number possible. - Because every degree of unsaturation removes two hydrogens, a triple bond introduces two degrees of unsaturation. Each carbon of a triple bond is sp hybridized and linear, and all bond angles are 180o The triple bond of an alkyne consists of one sigma bond and two pie bonds

- The sigma bond is formed by end-on overlap of the two sp hybrid orbitals. - each pie bond is formed by side-by-side overlap of two 2p orbitals - Both pie bonds of a C-C triple bond are weaker than a C-C sigma bond, making them much more easily broken. As a result, alkynes undergo many addition reactions. - Alkynes are more polarizable than alkenes because the electrons in their pie bonds are more loosely held Like trans cycloalkenes, cycloalkynes with small rings are unstable. - The carbon chain must be long enough to connect two ends of the triple bond without introducing too much strain. - Cyclooctyne is the smallest isolated cycloalkyne, though it decomposes upon standing at room temperature after a short time. - to accommodate the triple bond in a ring, bending occurs around the sp hybridized C’s, destabilizing the molecule.

11.2, Nomenclature In the IUPAC system, change the –ane ending of the parent alkane to the suffix –yne. Choose the longest carbon chain that contains both atoms of the triple bond and number the chain to give the triple bond the lower number. Compounds with two triple bonds are named as diynes, those with three are named as triynes, and so forth. Compounds with both a double and a triple bond are named as enynes. The chain is numbered to give the first site of unsaturation (either C=C or CC) the lower number. The simplest alkyne, HCCH, named in the IUPAC system as ethyne, is more often called acetylene, its common name. The two-carbon alkyl group derived from acetylene is called an ethynyl group (HCC-)

11.3, Physical properties Alkynes have low melting points and boiling points Melting points and boiling points increase as the number of carbons increases Alkynes are soluble in organic solvents and insoluble in water 11.4, Interesting Alkynes Acetylene, HCCH, is a colorless gas with an ethereal odor that burns in oxygen to form CO2 and H2O. - Because the combustion of acetylene releases more energy per mole of product formed than other hydrocarbons, it burns with a very hot flame, making it an excellent fuel for welding torches Ethynylestradiol and norethindrone are two components of oral contraceptive that contain a carbon-carbon triple bond. - Both molecules are synthetic analogues of the naturally occurring female hormones estradiol and progesterone, but are more potent so they can be administered in lower doses. Most oral contraceptives contain two of these synthetic hormones. They act by artificially elevating hormone levels in a woman, thereby preventing pregnancy. Two other synthetic hormones with alkynyl appendages are RU 486 and levonorgestrel. - RU 486 blocks the effects of progesterone, and because of this, prevents implantation of a fertilized egg. - RU 486 is used to induce abortions within the first few weeks of pregnancy. Levonorgestrl interferes with ovulation, and so it prevents pregnancy if taken within a few days of unprotected sex. Histrionicotoxin is a diyne isolated in small quantities from the skin of Dendrobates histrionicus, a colorful South American frog. This toxin, secreted by the frog as a natural defense mechanism, was used as a poison on arrow tips by the Choco tribe of South America.

11.5, Preparation of Alkynes Alkynes are prepared by elimination reactions. - A strong base removes two equivalents of HX from a vicinal or germinal dihalide to yield an alkyne by two successive E2 eliminations.

Because the vicinal dihalide are synthesized by adding halogens to alkenes, an alkene can be converted to an alkyne by the two-step process.

- This two-step process introduces one degree of unsaturation: an alkene with one pie bond is converted to an alkyne with two pie bonds. 11.6, Introduction to Alkyne reactions 11.6A, Addition reactions - Like alkenes, alkynes undergo addition reactions because they contain weak pie bonds. - Two sequential reactions take place: addition of one equivalent of reagent forms an alkene, which then adds a second equivalent of reagent to yield a product having four new bonds.

- Alkynes are electron rich. The two pie bonds form a cylinder of electron density between the two sp hybridized carbon atoms, and this exposed electron density makes a triple bond nucleophilic. As a result, alkynes react with electrophiles. 11.6B, Terminal Alkynes-Reaction as an Acid - Because sp hybridized C-H bonds are more acidic than sp2 than sp3 hybridized C – H bonds, terminal alkynes are readily deprotonated with strong base in a Bronsted-Lowry acidbase reaction. The resulting anion is called an acetylide anion. - Because an acid-base equilibrium favors the weaker acid and base, only bases having conjugate acids with pKa values higher than the terminal alkyne-that is, pKa values >25are strong enough to form a significant concentration of acetylid anion

The acetylide formed by deprotonating terminal alkynes are strong nuceophiles that can react with a variety of electrophiles.

As shown in Table 11.11, -NH2 and H- are strong enough to deprotonate a terminal alkyne, but OH and –OR are not.

11.7, Addition of Hydrogen Halides Alkynes undergo hydrohalogenation, the addition of hydrogen halides, HX (X = Cl, Br, I) - Two equivalents of HX are usually used: addition of one mole forms a vinyl halide, which then reacts with a second mole of HX to form a germinal dihalide.

Addition of HX to an alkyne is another example of electrophilic addition, because the electrophilic (H) end of the reagent is attracted to the electron-rich triple bond. - With two equivalents of HX, both the H atoms bond to the same carbon. - With a terminal alkyne, both H atoms bond to the terminal carbon; that is, the hydrohalogenation of alkynes follows Markovnikov’s rule. - With only one equivalent of HX, the reaction stops with formation of the vinyl halde. 11.8, Addition of Halogen Halogens, X2 (X = Cl or Br), add to alkynes in much the same way they add to alkenes. - Addition of one mole of X2 forms a trans dihalide, which can then react with a second mole of X2 to yield a tetrahalide.

Each addition of X2 involves a two-step process with a bridged halonium ion intermediate, reminiscent of the addition of X2 to alkenes. - A trans dihalide is formed after addition of one equivalent of X2 because the intermediate halonium ion ring is opened upon backside attack of the nuceophile. 11.9, Addition of Water Although the addition of H2O to an alkyne resembles the acid-catalyzed addition of H2O to an alkene in some ways, an important difference exists. - In the presence of strong acid or Hg2+ catalyst, the elements of H2O add to the triple bond, but the initial addition product, an enol, is unstable and rearranges to a product containing a carbonyl group- that is, a C=O. - A carbonyl compound having two alkyl groups bonded to the C = O carbon is called a ketone

Internal alkynes undergo hydration with concentrated acid, whereas terminal alkynes require the presence of an additional Hg2+ catalyst-usually HgSO4-to yield methyl ketones by Markovnikov addition of H2O.

- Tautomers are constitutional isomers that differ in the location of a double bond and a hydrogen atom. Two tautomers are in equilibrium with each other. - An enol tautomer has an O-H group bonded to a C=C - A keto tautomer has a C=O and an additional C-H bond. Equilibrium favors the keto form largely because a C=O is much stronger than a C=C. Tautomerization, the process of converting one tautomer into another, is catalyzed by both acid and base. - Under the strongly acidic conditions of hydration, tautomerization of the enol to the keto form occurs by a two-step process: protonation, followed by deprotonation.

11.10, Hydroboration-Oxidation Hydroboration-oxidation is a two-step reaction sequence that converts an alkyne to a carbonyl compound.

- Addition of borane forms an organoborane - Oxidation with basic H2O2 forms an enol. - Tautomerization of the nol forms a carbonyl compound. - The overall result is addition of H2O to a triple bond. Hydroboration-oxidation of an internal alkyne forms a ketone. - Hydroboration of a terminal alkyne adds BH2 to the less substituted, terminal carbon. - After oxidation to the enol, tautomerization yields an aldehyde, a carbon compound having a hydrogen atom bonded to the carbonyl carbon.

Hydration (H2O, H2SO4, and HgSO4) and hydroboration-oxidation (BH3 followed by H2O2, HO-) both add the elements of H2O across a triple bond. 11.11, Reaction of Acetylide Anions Terminal alkynes are readily converted to acetylide anions with strong bases such as NaNH2 and NaH. These anions are strong nucleophiles, capable of reacting with electrophiles such as alkyl halides and epoxides

- 11.11A, Reaction of Acetylide Anions with Alkyl Halides Acetylide anions react with unhindered alkyl halides to yield products of nucleophilic substitution. Because acetylide anions are strong nucleophiles, the mechanism of nucleophilic substituion is SN2, and thusreactions is fastest with CH3X and 1o alkyl halides.

- Nucleophilic substitution with acetylide anions forms new carbon-carbon bonds Although nucleophilic substitution with acetylide anions is a very valuable carbon-carbon bond forming reaction, it has the same limitations as any SN2 reaction. - Steric hindrance around the leaving group causes 2o and 3o alkyl halides to undergo elimination by an E2 mechanism,.

- 11.11B, reaction of acetylide anions with epoxides Acetylide anions are strong nucleophiles that open epoxide rings by an SN2 mechanism. - This reaction also results in formation of a new carbon-carbon bond. Backside attack occurs at the less substituted end of the epoxide.

11.12, Synthesis - 11.12A, General Terminology and Conventions To plan a synthesis of more than one step, we use the process of retrosynthetic analysisthat is, working backwards from the desired product to determine the starting materials from which it is made. - To write a synthesis working backwards from the product to the starting material, an open arrow is used to indicate the product is drawn on the left and the starting material on the right.

The product of a synthesis is often called the target compound. - Using retrosynthetic analysis, we must determine what compound can be converted to the target compound by a single reaction. That is, what is the immediate precursor of the target compound? In designing a synthesis, reactions are often divided into two categories: - Those that form new carbon-carbon bonds. - Those that convert one functional group into another-that is, functional group interconversions. Carbon-carbon bond forming reactions are central to organic synthesis because simpler and less valuable starting materials can be converted to more complex products. Keep in mind that whenever the product of a synthesis has more carbon-carbon bonds than the starting material, the synthesis must contain at least one of these reactions. Key Concepts Alkynes General facts about alkynes - Alkynes contain a carbon-carbon triple bond consisting of a strong sigma bond and two weak pie bonds. Each carbon is sp hybridized and linear. - Alkynes are named using the suffix –yne - Alkynes have weak intermolecular forces, giving them low mp’s and low bp’s, making them water insoluble. - Because its weaker pie bonds make an alkyne electron rich, alkynes undergo addition reactions with electrophiles Addition reactions of alkynes

[1] Markovnikov’s rule is followed. H bonds to the less substituted C to form the more stable carbocation. [2] Bridged halonium ions are formed as intermediates. - Anti addition of X2 occurs

[3] Markovnikov’s rule is followed. H bonds to the less substituted C to form the more stable carbocation. - An unstable enol is first formed, which rearranges to a carbonyl group. [4] The unstable enol, first formed after oxidation, rearranges to a carbonyl group....