Hydration, of alkynes

In the presence of excess hydrogen halide, geminal dihalides are formed by sequential addition of two molecules of hydrogen halide to the carbon-carbon triple bond. 

The second mole of hydrogen halide adds to the initially formed alkenyl halide in accordance with Markovnikov s rule. Overall, both protons become bonded to the same carbon and both halogens to the adjacent carbon. 

Design a synthesis of 1,1-dichloroethane from each of the following. Write a series of equations, showing reactants and products, as illustrated in the Sample Solution. 

Sample Solution (a) Reasoning backward, we recognize 1,1-dichloroethane as the product of addition of two molecules of hydrogen chloride to acetylene. Thus, the synthesis requires converting ethylene to acetylene as a key feature. As described in Section 9.7, this may be accomplished by conversion of ethylene to a vicinal dihalide, followed by double dehydrohalogenation. A suitable synthesis based on this analysis is as shown  

Hydrogen bromide (but not hydrogen chloride or hydrogen iodide) adds to alkynes by a free-radical mechanism when peroxides are present in the reaction mixture. As in the free-radical addition of hydrogen bromide to alkenes (Section 6.18), a regioselectivity opposite to Markovnikov s rule is observed. 

Water adds to one of the n bonds of a triple bond in aqueous sulfuric acid in the presence of mercuric sulfate catalyst. The reaction is regiospecific and occurs by Markovnikov addition. However, the alcohol that forms has its —OH group bonded to the double-bonded carbon atom of an alkene. This type of compound is called an enol, a name that includes both the -me suffix of a double bond and the alcohol suffix -ol. 

Enols are unstable compounds that rapidly rearrange to carbonyl compounds. The conversion of the enol intermediate to a ketone is a rapid, reversible reaction whose equilibrium lies very far on the side of the more stable carbonyl compound. It occurs by a concerted 1,3-proton shift. We will discuss this reaction in much greater detail when we discuss the chemistry of carbonyl compounds. 

Thus the product of the hydration of an alkyne is a ketone. The more substituted carbon atom of the alkyne is converted into a carbonyl carbon atom. 

Problem 7.9 Consider the regioselectivity of the hydration of 2-decyne. Write the products of the reaction. Predict the percentage of each compound in the product mixture. 

The initial hydration of an alkyne places the hydroxyl group on the more substituted carbon atom. This carbon atom is the eventual site of the carbonyl group. In 2-decyne, both C-2 and C-3 are substituted to the same degree. C-2 is bonded to a methyl group C-3 is bonded to a heptyl group. As a consequence, hydration can occur either of two ways, and two products, 2-decanone and 3-decanone, are formed. 

By analogy to the hydration of alkenes, hydration of an alkyne is expected to yield an alcohol. The kind of alcohol, however, wonld be of a special kind, one in which the hydroxyl group is a substituent on a carbon-carbon donble bond. This type of alcohol is called an enol (the double bond snftix -ene pins the alcohol snftix -ol). An important property of enols is their rapid isomerization to aldehydes or ketones under the conditions of their formation. 

Step 2 The carbocation transfers a proton from oxygen to a water molecule, yielding a ketone 

FIGURE 9.6 Conversion of an enol to a ketone takes place by way of two solvent-mediated proton transfers. A proton is transferred to carbon in the first step, then removed from oxygen in the second. 

Mercury(ll) sulfate and mer-cury(ll) oxide are also known as mercuric sulfate and oxide, respectively. 

Delocalization of an oxygen lone pair stabilizes the cation. All the atoms in B have octets of electrons, making it a more stable structure than A. Only six electrons are associated with the positively charged carbon in A. 

Step 1 The enol is formed in aqueous acidic solution. The first step of its transformation to a ketone is proton transfer to the carbon-carbon double bond. 

In the previous chapter, we saw that alkenes will undergo acid-cataly2ed hydration when treated with aqueous acid (H3O ). The reaction proceeds via a Markovnikov addition, thereby installing a hydroxyl group at the more substituted position  

Alkynes are also observed to undergo acid-catalyzed hydration, but the reaction is slower than the corresponding reaction with alkenes. As noted earlier in this chapter, the difference in rate is attributed to the high-energy, vinylic carbocation intermediate that is formed when an alkyne is protonated. The rate of alkyne hydration is markedly enhanced in the presence of mercuric sulfate (HgS04), which catalyzes the reaction  

The initial product of this reaction has a double bond (en) and an OH group ( /) and is therefore called an enol. But the enol cannot be isolated because it is rapidly converted into a ketone. The conversion of an enol into a ketone will appear again in many subsequent chapters and therefore warrants further discussion. Acid-catalyzed conversion of an enol to a ketone occurs via two steps (Mechanism 10.2). 

The It bond of the enol is Enol protonated, generating a resonance-stabilized intermediate 

The Tt bond of the enol is first protonated, generating a resonance-stabilized intermediate, which is then deprotonated to give the ketone. Notice that both steps of this mechanism are proton transfers. The result of this process is the migration of a proton from one location to another, accompanied by a change in location of the it bond  

An anti-Markovnikov hydration of terminal alkynes could be a convenient way of preparing aldehydes, but so far only a few ruthenium-complexes have been identified that catalyze this unusual hydration mode ]16]. The presence of bidentate phosphine ligands ]16b], the coordination of a water molecule stabilized by hydrogen bonding ]16e] and the use of phosphinopyridine ligands ]16f] seem to be of major importance in these processes. 

Furthermore, a small 3x3 ligand library with electron donating (p-anisyl) and electron withdrawing (4-F-C6H4) aryl substituents at the phosphine donor were studied, but none of these combinations proved superior to the parent 6-DPPAP (10a)/3-DPICon (Ila) system (Table 2.6). 

Single crystals, suitable for X-ray diffraction were obtained from slow diffusion of cyclohexane into a concentrated solution of 13e in dichloromethane. As proposed, the 

6-diphenylphosphino-2-pyridone, 6-DPPAP (10a) 6-diphenylphosphino-N-pivaloyl-2-aminopyridine, 3-DPICon (Ila) 3-diphenylphosphinoisoquinolone. 

Aield calculated from GC response factors relative to internal hexadecane standard. A -Pril -PrN coordination ofthe phosphinopyridine with replacement of the acetonitrile ligand. 

Like alkenes (Sections 7.4 and 7.5), alkynes can be hydrated by either of two methods. Direct addition of water catalyzed by mercury(II) ion yield the Markovnikov product, and indirect addition of water by a hydrobora-1 tion/oxidation sequence yields the non-Markovnikov product. 1 

Alkynes don t react directly with aqueous acid but will undergo hydration readily in the presence of mercury(II) sulfate catalyst. The reaction occurs with Markovnikov regiochemistry The -OH group adds to the more highly substituted carbon, and the -H attaches to the less highly substituted one. 

Interestingly, the product actually isolated from alkyne hydration is not the vinylic alcohol, or enol iene + ol), but is instead a ketone. Although the. enol is an intermediate in the reaction, it immediately rearranges to a ketone by a process called keto-enol tautomerism. The individual keto an( enol forms are said to be tautomers, a word used to describe constitutional isomers that interconvert rapidly. With few exceptions, the keto-enol tautomeric equilibrium lies on the side of the ketone enols are almost nevei isolated. Well look more closely at this equilibrium in Section 22.1, 

A mixture of both possible ketones results when an unsymmetrically substituted internal alkyne (RC=CR ) is hydrated. The reaction is therefoi 

Methanisfti of the mercury(l1)-catalyzed hydration of an alkyne to yield a ketone. The reaction yields an intermediate enol, which rapidly tautomerizes to give a ketone. 

Thomsont Click Organic Interactive to learn to interconvert enol and carbonyl tautomers. 

O The alkyne uses a pair of electrons to attack the electrophilic mercury(II) ion, yielding a mercury-containing vinylic carbocation intermediate. 

0 Nucleophilic attack of water on the carbocation forms a C-0 bond and yields a protonated mercury-containing enol. 

Mechanism of the mercury(ll)-catalyzed hydration of an alkyne to yield a ketone. 

The reaction occurs through initial formation of an intermediate enol, which tautomerizes to the ketone. 

The aldehyde or ketone is called the keto form, and the keto enol equilibration is referred to as keto-enol isomerism or keto-enol tautomerism. Tautomers are constitutional isomers that equilibrate by migration of an atom or group, and their equilibration is called tautomerism. Keto-enol isomerism involves the sequence of proton transfers shown in Mechanism 9.2. 

Like alkenes, alkynes can be hydrated. The reaction is generally catalyzed hy mercuric ions in an oxymercuration process (Fig. 10.71), although simple acid catalysis is also known. In contrast to the oxymercuration of alkenes, no second, reduction step is required in this alkyne hydration. By strict analogy to the oxymercuration of alkenes, the product should be a hydroxy mercury compound, hut the second double bond exerts its influence and further reaction takes place. The double hond is protonated and mercury is lost to generate a species called an enol. An enol is part alkene and part alcoho/, hence the name. 

FIGURE 10.71 The oxymercuration of alkynes resembles the oxymercuration of alkenes. In the alkyne case, the product is an enol, which can react further. 

Enols are extraordinarily important compounds, and more than one chapter will mention their chemistry. Here their versatility is exemplified by their conversion into ketones. We have already seen a synthesis of ketones in this chapter 

FIGURE 10.72 Protonation of carbon, followed by deprotonation at oxygen, generates the carbonyl compound. This sequence is a general reaction of enols. 

Nearly all ketones and aldehydes containing a hydrogen on the carbon adjacent to the carbonyl carbon are in equilibrium with the related enol forms. How much enol is present at equilibrium is a function of the detailed structure of the molecule, but there is almost always some enol present. In simple compounds, the ketone form is greatly favored. This interconversion is called keto-enol tautomerization. 

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Addition of a hydroxy group to alkynes to form enol ethers is possible with Pd(II). Enol ether formation and its hydrolysis mean the hydration of alkynes to ketones. The 5-hydroxyalkyne 249 was converted into the cyclic enol ether 250[124], Stereoselective enol ether formation was applied to the synthesis of prostacyclin[131]. Treatment of the 4-alkynol 251 with a stoichiometric amount of PdCl2, followed by hydrogenolysis with formic acid, gives the cyclic enol ether 253. Alkoxypalladation to give 252 is trans addition, because the Z E ratio of the alkene 253 was 33 1. 

Hydration of alkynes follows Markovmkov s rule terminal alkynes yield methyl substituted ketones... 

You have had earlier experience with enols m their role as intermediates m the hydration of alkynes (Section 9 12) The mechanism of enolization of aldehydes and ketones is precisely the reverse of the mechanism by which an enol is converted to a carbonyl compound... 

Hydration of alkynes (Section 9.12) Reaction occurs by way of an enol intermediate formed by Markovnikov addition of water to the triple bond. 

Table 10.6 [AuCl(IPr)]/AgSbF catalysed hydration of alkynes [38] ...

Enzyme-like Acceleration in Catalytic Anti-Markovnikov Hydration of Alkynes to... 

The hydration of alkynes represents a prime example in which simple coordinative activation by transition metal complexation greatly facilitates an otherwise very slow chemical process (Equation (107)). This reaction has been a long-studied problem, but only recently have alternatives to the classical use of catalysts such as Hg(n) salts been sought. These new catalyst systems typically display much enhanced reactivity, and some can mediate an anti-Markovnikov hydration through a novel mechanism (Table 1). 

Scheme 10.7 A mechanism proposed for the anti-Markovnikov hydration of alkynes.

Recently, a new class of supramolecular CpRu-containing catalysts for hydration of alkynes has emerged. These catalysts are based on the supramolecular self-assembly of monodentate ligands through hydrogen bonding association, as shown in Scheme 10.9 [41-43]. The remarkable activity of catalytic systems such as 15-17... 

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