Alcohols addition-elimination

As regards reaetions other than nitration brought about by some of these systems, especially noteworthy are the addition processes undergone by eertain indole derivatives when treated with solutions of nitrie aeid in aeetie aeid. Produets inelude glycols, nitro-alcohols, and nitro-alcohol acetates. Such additions might well be encountered with some polynuclear aromatie eompounds, and with sueh eompounds the possibility of nitration by addition-elimination must always be borne in mind. 

Hydrolysis. Esters are cleaved (hydroly2ed) into an acid and an alcohol through the action of water. This hydrolysis is cataly2ed by acids or bases. The mechanistic aspects of ester hydrolysis have received considerable attention and have been reviewed (16). For most esters only two reaction pathways are important. Both mechanisms involve a tetrahedral intermediate and addition-elimination reactions i7i7... 

Addition and elimination processes are the reverse of one another in a formal sense. There is also a close mechanistic relationship between the two reactions, and in many systems reaction can occur in either direction. For example, hydration of alkenes and dehydration of alcohols are both familiar reactions that are related as an addition-elimination pair. 

The mechanistic pattern established by study of hydration and alcohol addition reactions of ketones and aldehydes is followed in a number of other reactions of carbonyl compounds. Reactions at carbonyl centers usually involve a series of addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid-catalyzed or base-catalyzed. The rate and products of the reaction are determined by the reactivity of these tetrahedral intermediates. 

There are alternatives to the addition-elimination mechanism for nucleophilic substitution of acyl chlorides. Certain acyl chlorides are known to react with alcohols by a dissociative mechanism in which acylium ions are intermediates. This mechanism is observed with aroyl halides having electron-releasing substituents. Other acyl halides show reactivity indicative of mixed or borderline mechanisms. The existence of the SnI-like dissociative mechanism reflects the relative stability of acylium ions. 

During the course of base-catalyzed exchange in O-deuterated alcohols, the vinylic hydrogen in the a position to the ketone is replaced by deuterium, in addition to the hydrogens activated by enolization. Thus, under these conditions the exchange of androst-l-en-3-one (16, R = H) gives a trideuterio derivative (18) instead of the expected 4,4-d2 analog (16, R = D). " (For other examples see compounds 13, 19, 21, 23, 26 and 27.) Incorporation of this deuterium is due to rapidly reversible alcohol addition (16 -+17) and elimination (17 18) which competes with the enolization step. " ... 

Because of thetr electron deficient nature, fluoroolefms are often nucleophihcally attacked by alcohols and alkoxides Ethers are commonly produced by these addition and addition-elimination reactions The wide availability of alcohols and fliioroolefins has established the generality of the nucleophilic addition reactions The mechanism of the addition reaction is generally believed to proceed by attack at a vinylic carbon to produce an intermediate fluorocarbanion as the rate-determining slow step The intermediate carbanion may react with a proton source to yield the saturated addition product Alternatively, the intermediate carbanion may, by elimination of P-halogen, lead to an unsaturated ether, often an enol or vinylic ether These addition and addition-elimination reactions have been previously reviewed [1, 2] The intermediate carbanions resulting from nucleophilic attack on fluoroolefins have also been trapped in situ with carbon dioxide, carbonates, and esters of fluorinated acids [3, 4, 5] (equations 1 and 2)... 

Rase-catalyzed reaction of alcohol favors addition, whereas increasing amounts of alkoxide favor addition-elimination reactions. Perfluoro-2-methyl-2-pentene and methanol form the saturated ether, whereas two equivalents of sodium methoxide form the vinylic ether [S] (equation 4). 

The addition of nucleophiles to cyclic fluoroolefins has been reviewed by Park et al. [2 ]. The reaction with alcohols proceeds by addition-elimination to yield the cyclic vinylic ether, as illustrated by tlie reaction of l,2-dichloro-3,3-di-fluorocyclopropene Further reaction results in cyclopropane ring opening at the bond opposite the difluoromethylene carbon to give preferentially the methyl and ortho esters of (Z)-3-chloro-2-fluoroacrylic acid and a small amount of dimethyl malonate [29] (equation 8). 

The nucleophilic attack of nitrogen bases leads to a variety of products as the result of addition or addition-elimination reactions The regioselectivity resembles that of attack by alcohols and alkoxides an intermediate carbanion is believed to be involved In the absence of protic reagents, the fluorocarbanion generated by the addition of sodium azide to polyfluonnated olefins can be captured by carbon dioxide or esters of fluonnated acids [J 2, 3] (equation I)... 

Condensation of piperazine with 2-methoxytropone gives the addition-elimination product 12 [2]. Alkylation of the remaining secondary amino group with bromoketone 13, itself the product from acylation of dimethyl catechol, gives aminoketone 14. Reduction of the carbonyl group with sodium borohydride leads to secondaiy alcohols 15 and 16. Resolution of these two enantiomers was achieved by recrystallization of their tartrate salts to give ciladopa (16) [3],... 

Simpson and Burt have studied the same reactions in the presence of various amounts of ethanol and have plotted graphs of phosphonate (81 R = Ph) and phenyl acetylene produced against moles of alcohol added. Acetylene in the product reached a maximum (around 60%) when two moles of ethanol were added and stayed fairly constant beyond this, which suggests that the attack-on-halogen contribution to the mechanism is approximately 60%. The rest of the reaction presumably follows some other mechanism and the authors suggest the addition-elimination route (79) in view of the isolation of the phosphonate (83) from the reaction of tri(isopropyl) phosphite with the bromoacetylene (84). 

RajanBabu et al. have described an addition-elimination sequence employing vinyl stannanes for the preparation of homoallylic alcohols containing 5-membered rings [104],... 

Although the high reactivity of metal-chalcogen double bonds of isolated heavy ketones is somewhat suppressed by the steric protecting groups, Tbt-substituted heavy ketones allow the examination of their intermolecular reactions with relatively small substrates. The most important feature in the reactivity of a carbonyl functionality is reversibility in reactions across its carbon-oxygen double bond (addition-elimination mechanism via a tetracoordinate intermediate) as is observed, for example, in reactions with water and alcohols. The energetic basis... 

In the reduction of acids there is a tendency for the lithium salt, RCO20Li to separate from the ethereal solution, and thus bring reduction to a halt this can be avoided by first converting the acid to a simple, e.g. Me or Et, ester. In the reduction of the latter, the initial nucleophilic attack by AIH4 results in an addition/elimination reaction—OR is a good leaving group in (40)—followed by normal attack, as above, on the resultant carbonyl compound (41) to yield the primary alcohol (42) ... 

Electrophilic metals or metal complexes, when incorporated into either the acyl or alcohol functions of the ester, might be expected to increase the rate of addition of amine. This might occur through direct carbonyl-0 or alcohol-0 coordination (21 or 22, Scheme 21) or by being positioned at a discrete distance from these (cf. 23 and 24). When the metal is attached to the alcohol function loss of this group might also be accelerated (in a stepwise addition-elimination reaction), but with acyl activation loss of alcohol might be expected to be retarded. 

For neutral nucleophiles (e.g. amines, alcohols, water) there is much evidence that the addition-elimination mechanism depicted in equation 1 fits very well most of the intermolecular and intramolecular nucleophilic displacements involving nitro-activated aromatic substrates1. 

The first mechanism appears to be the better basis for describing most of the results referred to by Cramer (56). It will, however, be noted that the addition-elimination mechanism requires that the metal catalyst be supplied as a metal hydride. Where the catalyst has not been supplied in this form, the reaction has usually been carried out in the presence of reagents known to convert transition metal compounds to hydrides (e.g. protonic acids, alcohols or hydrogen). These substances are known as co-catalysts and, where they have been used, induction periods have been encountered which are consistent with hydride formation as required in mechanism (a), but which would not be expected for (b). 

Hydride reduction of esters to alcohols involves elimination steps, in addition to hydride transfer. 

Synthesis of the polymer-bound allyl sulfoximine 60 was accomplished by the addition-elimination-isomerization route starting from the enantiomerically pure polymer-bound N-methyl-S-phenylsulfoximine 59, which was prepared as previously described from Merrifield resin and sulfoximine 12 with a loading of 84% (Scheme 1.3.23) [42]. The successive treatment of resin 59 with n-BuLi in THF and with isovaleraldehyde furnished the corresponding polymer-bound lithium alcoholate, which upon reaction with ClC02Me and DBU afforded the corresponding polymer-bound vinylic sulfoximine (not shown in Scheme 1.3.23), the isomerization of which with DBU in MeCN afforded sulfoximine 60. 

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