Synthesis of Alkynes by Elimination Reactions

A vicinal dihalide (abbreviated vic-dihalide) is a compound bearing the halogens on adjacent carbons (vicinus, Latin adjacent). A vicinal dibromide, for example, can be synthesized by addition of bromine to an alkene (Section 8.1). The vtc-dibromide can then be subjected to a double dehydrohalogenation reaction with a strong base to yield an alkyne. 

The dehydrohalogenations occur in two steps, the first yielding a bromoalkene, and the second, the alkyne. 

The two dehydrohalogenations may be carried out as separate reactions, or they may be carried out consecutively in a single mixture. Sodium amide (NaNH2), a very strong base, can be used to cause both reactions in a single mixture. At least two molar equivalents of sodium amide per mole of the dihalide must be used. For example (see below) adding bromine to 1,2-diphenylethene provides the starting material for a synthesis of 1,2-diphenylethyne. 

The strongly basic amide ion brings about an E2 reaction. 

Bromoalkene Amide ion A second E2 reaction produces the alkyne. 

We need to add two groups to acetylene an ethyl group and a six-carbon aldehyde (to form the secondary alcohol). If we formed the alcohol group first, the weakly acidic —OH group would interfere with the alkylation by the ethyl group. Therefore, we should add the less reactive ethyl group first, and add the alcohol group later in the synthesis. 

The ethyl group is not acidic, and it does not interfere with the addition of the second group  

Show how you would synthesize each compound, beginning with acetylene and any necessary additional reagents. 

If a synthesis requires both alkylation of an acetylide and addition to a carbonyl, add the less reactive group first alkylate, then add to a carbonyl. In general, you should add reactive functional groups late in a synthesis. 

In some cases, we can generate a carbon-carbon triple bond by eliminating two molecules of HX from a dihalide. Dehydrohalogenation of a geminal or vicinal dihalide gives a vinyl halide. Under strongly basic conditions, a second dehydrohalogenation may occur to form an alkyne. 

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Introduction 392 9-2 Nomenclature of Alkynes 393 9-3 Physical Properties of Alkynes 394 9-4 Commercial Importance of Alkynes 395 9-5 Electronic Structure of Alkynes 396 9-6 Acidity of Alkynes Formation of Acetylide Ions 397 9-7 Synthesis of Alkynes from Acetylides 399 9-8 Synthesis of Alkynes by Elimination Reactions 403 Summary Syntheses of Alkynes 404 9-9 Addition Reactions of Alkynes 405... 

Synthesis of Alkynes by Elimination Reaotions 314 [ A MECHANISM FOR THE REACTION ] Dehydrohalogenation of w c-Dibromides to Form Alkynes 315... 

The methods for the synthesis of alkynes have been extensively reviewed in the past 20 years two books, which deal particularly with the preparative aspects of alkyne chemistry, have been published. Except for the syntheses of acetylene and propyne, which are prepared in technical processes from carbides, from methane by oxidation, or by electric arc processes, all carbon-carbon triple bonds must be generated by an elimination reaction. Again, as in the synthesis of alkenes, the most important is the de-hydrohalogenation. 

A synthesis of alkynes from esters via a one-carbon homologation is by reaction with 1-lithiomethylbenzotriazole, followed by elimination of the derived benzotriazol-1-ylmethyl ketone tosylhydrazones. ... 

Alkynylsilanes—reactive precursors and versatile synthons for various reactions—can be obtained mainly by silylation techniques of metallated alkynes (including Grignard derivatives), or by elimination reactions of halogenated alkanes and alkenes in the presence of a silylating agent. The main classes of alkynylsilanes will be discussed as well as some derivatives which may be of further interest to organic synthesis. 

The E2 reaction can also be applied to the synthesis of alkynes. When a vinyl halide is treated with a strong base, loss of HX by what is essentially an E2 process leads to formation of a triple bond. In a simple example, 12-methyltridec-l-ene was treated with bromine in dichloromethane to give dibromide 193. When this was treated with potassium tert-butoxide in petroleum ether, in the presence of 18-crown-6, initial elimination gave vinyl bromide 194 but this reacted again with the base, and an E2 reaction gave alkyne 195 in 72% yield for both chemical steps. Alkyne 195 was used in Mori s synthesis of the sphingosine derivative sulfobacin... 

Catalysis of the [2+2+2] cycloaddition of alkynes by transition metal complexes has been extensively exploited for the synthesis of complex organic molecules [30-34]. The accepted mechanism for this transformation, shown in Scheme 10, involves coordination of two alkyne molecules to the metal centre followed by oxidative coupling to form the coordinatively unsaturated metallocyclo-pentadiene 49, which can coordinate a third molecule of alkyne to afford 50. Insertion of the alkyne in a metal-carbon bond of this complex leads to met-allocycloheptadiene 51, and reductive elimination then affords cyclotrimer 52 and regenerates the catalytic species. Alternatively, the transformation of 49 into 52 might involve a Diels-Alder reaction giving intermediate 53, followed by reductive elimination [35]. 

Hydrazoyl halides are useful reagents for the synthesis of pyrazolines and pyrazoles (80JHC833). The elimination of HX, usually with triethylamine, is now the preferred method for the generation of the nitrilimine (621) in situ. Although in some cases it is not clear if the mechanism involves a nitrilimine (621) (as for example in the Fusco method in which sodium salts of /3-diketones are used), in other reactions it is the most reasonable possibility. For example, the synthesis of pyrazolobenzoxazine (633) from the hydrazoyl halide (631) probably occurs via the nitrilimine (632). Trifluoromethylpyrazoles (634) have been prepared by the reaction of a hydrazoyl halide and an alkynic compound in the presence of triethylamine (82H(19)179). 

The ring system can be generated by D-A addition of a substituted cyclopentadienone and an alkyne. A reaction sequence involving addition followed by CO elimination can be used for the synthesis of highly substituted benzene rings.308... 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Otera and coworkers developed an alternative procedure to the Julia method for generating dienes or alkynes in the same reaction by the double elimination of /J-acetoxy or /1-alkoxy sulphones with potassium /-butoxide (equation 58)98,99. The reaction pathway leading to the diene or an alkyne depends on the substrate structure and the reaction conditions. If an allylic hydrogen is present in the substrate then diene is formed, otherwise, the alkyne is the product of the reaction. This modified Julia methodology has een applied to the synthesis of vitamin A (equation 59)100, alkaloids piperine (equation and trichonine (equation 61)102. 

The reaction of 77 with alkynes has further been elaborated for the synthesis of substituted phthalonitriles 81. An alternative for the synthesis of these compounds is the cycloaddition reaction of 77 with enamines followed by a retro-Diels-Alder loss of N2 and elimination of the amine (Scheme 16). Generally, more forcing reaction conditions are required and lower yields are obtained in reactions with alkynes than in reactions with enamines, for example, 4-ethyl-5-methylphthalonitrile is obtained in 51% yield from 2-pentyne (xylene, 150°C, 18 days) and in 73% yield from 4-(l-ethylprop-l-en-l-yl)morpholine (CHCI3, 70°C, 7 days) <1998T1809>. The mechanism of the reaction with enamines has been studied in detail. This revealed a [1,5] sigmatropic rearrangement in the cyclohexa-2,4-dien-1-amine intermediates formed after the loss of N2 <1998T10851>. 

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