Alkynes halogen atoms

The reaction time between 4-iodopyrazoles and 1-alkynes varies from 5 to 25 h and the yield of products is 55-95%. It is noteworthy that the nature of the terminal acetylene has a greater effect on the rate of halogen atom substitution for low-reactive 4-iodopyrazoles. Thus, the reaction time for ethynylarenes is 5-6 h, and for less acidic aliphatic 1-alkynes is 10-25 h (Table XTT). 

In this section, you reviewed how to name and draw alkanes, alkenes, and alkynes. You also learned how to name aromatic hydrocarbons. The names of all the other organic compounds you will encounter in this unit are based on the names of hydrocarbons. In the next section, you will learn about organic compounds that have single bonds to halogen atoms, oxygen atoms, and nitrogen atoms. 

Halogen atoms. The introduction of side-chains on 9-trifluoromethyl-paullone 409 can be accomplished applying a Stille coupling (Scheme 86, Section 5.2.1.1 (2005EJM655)). Similarly, a Heck reaction of iodo 409 with terminal alkenes under standard conditions affords 2-substituted paullones 413 exclusively as E-isomers. The reaction of terminal alkynes with 409 in the presence of cuprous iodide and a palladium catalyst in triethylamine furnishes the 2-alkynyl-paullones 412 (2000BMCL567). 

Some examples of these addition reactions are provided in the following equations. Note that each proceeds with anti addition of the two halogen atoms. In the last example, starting with an alkyne, the two bromines end up trans. 

The reactivity of halogen atoms in position 2 of oxazoles is considerably enhanced by quaternization. This is best illustrated by the synthetic utility of the salt (141) which, like other Ar-alkyl-2-halogeno-azolium and -azinium salts, effects a number of condensation reactions but it far surpasses these other salts in activity (79AG(E)707). Thus it activates carboxylic acids and it dehydrates formamides to isocyanides (Scheme 6). Amides are similarly converted into cyanides, ketones (RCH2COAr) into alkynes (RC=CAr), and cyanohydrins (RCH(OH)CN) are transformed into the corresponding chloro compounds <79CL1117>. 

Similarly, Takahashi and coworkers reported that treatment of alkynes with zirconocene-ethylene complex (9) and homoallylic bromides gave allylcyclo-propane derivatives [21]. Therefore, the possibility of y-elimination of the halogen atom in zirconacyclopentene intermediates appeared to be more general as expected. The plausible mechanism is shown in Scheme 13. Carbozirconation... 

Elimination of two halogen atoms is a frequently used process in the synthesis of alkenes and alkynes, using a variety of conditions, and examples will be given later (see Chapter 7). Normally, fluorine is not easily removed by this process, although there are a number of cases where defluorination has been achieved, for instance in the preparation of fluoroaromatic compounds (Chapter 9). 

The catalytic replacement of halogen atoms by alkynic groups is reported to take place more readily with 2- than with 4-iodoimidazoles (b-76MI40701). Again, this observation must be treated with suspicion. 

Cyclopropyl-l,l-dihaloethenes with or without an additional halogen atom attached to C2, are generally converted to alkynes by treatment with butyllithium. The yields were generally good. The structure of the products depended on the amount of butyllithium as well as how the reaction mixture was quenched. When more than 2 equivalents of base were employed and quenching was performed with water or alcohol, the corresponding acetylenylcyclopropane was formed. ° 1 s 16,1 s 19,1820 However, when more than 2 equivalents... 

Et3B is an effective tool for halogen atom transfer radical reactions (see also Chap. 1.5). Perfluoroalkyl iodide [29], a-halo nitrile and a-halo ester [30] added to alkenes and alkynes at low temperature. Not only terminal alkenes but also internal alkenes can be employed to furnish iodine atom transfer adducts (Scheme 23). Furthermore, addition of perfluoroalkyl iodide to silyl and germyl enolate provided a-perfluoroalkyl ketones [31]. The reaction would involve the elimination of a tri-... 

Elimination reactions can also be used to prepare alkynes. Dihalides can be converted into alkynes by treatment with base, provided that the two halogen atoms are on the same, or adjacent, carbon atoms. In general, alkyne formation requires more drastic reaction conditions than alkene formation, and a strong base, such as sodium amide, is usually employed (Reactions 5.4 and 5.5). The product of Reaction 5.5, phenylethyne, is shown in Figure 5.1 as a ball and stick model. 

Nickel(0)-catalyzed [2 + 2 + 2] cocyclization of the precursor (177) in the presence of several chiral ligands afforded the chiral tetrahydroisoquinoline (178) in a novel asymmetric cycloaddition. Compound (178) could be transformed into the benzo[a]quinolizidine (180), albeit in modest enantiomeric excess, through a multistep route involving extension of the alkynic side chain at C-1 to yield (179), introduction of a cu halogen atom, reduction of the triple bond, A(-deprotection and final eyelization (Scheme 29) <94J0C6133>. 

The presence of halogen atoms in a molecule is compatible with formation of an ylid and subsequent Wittig reaction. Carbon tetrabromide and triphenylphosphine have been used to give vinyl dibromide products, which are rapidly converted to the corresponding alkyne. Indeed, this is an important synthetic route to alkynes called the Corey-Fuchs procedure. The reaction of 511 with this reagent gave vinyl dibromide 512 in 77% yield as part of Marshall s synthesis of callystatin When 512 was treated with butyllithium... 

Aniline, acetanilide, benzyl alcohol or methyl benzoate containing a halogen atom in the or /zo-position react with 1 -alkynes in the presence of bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide to give the corresponding o-alkynylbenzenes (e.g. equation 6). Some of the products can be cyclized the aniline derivative 53, for instance, is converted into 2-phenylindole in 99% yield on treatment with a catalytic amount of copper(I) iodide. ... 

Other metals like rhodium(I) have also been used for the direct cyclization of iminoaryls with alkynes without the prior existence of halogen atom on the aryl ring to produce highly substituted isoquinolines in good yields. 

A geminal dihalide (abbreviated gem-diAiaAiAf has two halogen atoms bonded to the same carbon geminus, Latin twins). Ketones can be converted to m-dichlorides by reaction with phosphorus pentachloride, and the jf wj-dichlorides can be used to synthesize alkynes. 

Compounds containing halogen atoms directly joined to triply bonded carbon (haloalkynes) are formed either by (1) reaction between molecular halogen and a metallic derivative of the alkyne. 

In the next chapter, we will learn a method for preparing alkynes (compounds containing C C triple bonds). In the following reaction, a dihalide (a compound with two halogen atoms) is treated with an excess of strong base (sodium amide), resulting in two successive E2 reactions. Draw the mechanism for this transformation. 

---