Haloalkane Reactions

Haloalkanes or alkyl halides are compounds derived from alkanes (C_nH_n) that have one or more halogen functional groups (F, Cl, Br, I) in the carbon chain.

The most characteristic reactions are listed below.

Reduction to alkanes

Reaction of alkyl halides with Zn^o in an acid medium

Treatment with metallic Zn with an aqueous acid of an alkyl halide leads to the formation of an alkane and the corresponding zinc halide. It is a general process for the substitution of a halogen atom by hydrogen.

Reaction of alkyl halides with LiAlH₄

Primary and secondary alkyl halides react with good yields with LiAlH₄ in diethyl ether to give alkanes. The result is the substitution of a halogen atom for hydrogen.

LiAlH₄ reacts violently with water and alcohols, being incompatible with a number of functional groups present in the molecule, for example:

Table 1: LiAlH₄ reactivity summarized.

Functional group	Final product
Nitro-compound	Amine
Amide
Azide
Nitrile
Aldehyde	Primary alcohol
Acyl chloride
Carboxylic acid
Ester
Ketone	Secondary alcohol
Epoxide	Alcohol
Sulfonate	Alkane

Radical dehalogenation

Alkyl iodides and bromides are reduced with good yields to alkanes by radical dehalogenation with tri-n-butyltin hydride. Fluorides hardly react at all, whereas chlorides react with more difficulty. The order of reactivity for the halides is:

tertiary > secondary > primary

The reaction requires the presence of a radical initiator such as AIBN or peroxides. The reaction conditions are quite mild and compatible with a multitude of functions such as alkenes, carbonyl compounds, acids, lactones, etc.).

Its disadvantage is the toxicity of the reagent and the by-products generated.

Dehalogenation of vicinal halides

Because vicinal dihalides are obtained by addition of halogens to alkenes, this reaction is of relative interest.

Wurtz synthesis (obtaining alkanes)

It consists of the formation of an alkane from two alkyl halides, by treatment with metallic sodium. In the latter case, the product mixtures are very significant.

Wurtz synthesis is one of the oldest organic reactions and is of historical interest today, due to its low yields and formation of by-products.

Corey-House synthesis (obtaining alkanes)

In the 1980s, Corey and House developed an alternative method to the Wurtz synthesis for the synthesis of alkanes, starting from an alkyl halide, which is reacted with Li^o. The organolithium obtained is treated with CuI to give a lithium dialkylcuprate (Gilman‘s reagent), which is reacted with an alkyl halide.

Unlike the Wurtz synthesis, much greater control is exercised over the products obtained, avoiding the formation of by-products and yields are substantially improved. The alkyl halide used in the last step cannot be tertiary, obtaining higher yields when it is primary or methyl.

Nucleophilic substitution

Elimination

Summary of substitution and elimination reactions

Table 2: Summary of Substitution Reactions (S_N2, S_N1) and Elimination (E2, E1).

	Methyl / alkyl 1º	Alkyl 2º, 1º (or 2º stabilized by resonance)	Alkyl 3º
SN2	Strong nucleophiles		Never
SN1	Never	Weak nucleophiles
E2	Only when using strong non-nucleophilic bases		Any strong base
E1	Never	Weak base
SN2 / E2	Methyl halide does not give elimination. Halide 1º favors SN2	Nucleophilic based mixtures	Only E2
SN1 / E1	Never	Mixtures even if H is not present at β

 

Table 3: Summary of Substitution Reactions (S_N2, S_N1) and Elimination (E2, E1).

	Regiochemistry	Stereochemistry
SN2	–	Inversion of configuration
SN1	Possibility of transpositions	Racemic mixtures
E2	(Zaitsev’s rule) except with bulky bases.	Leaving group and antiperiplanar H. trans Alkene is formed if possible
E1	(regla de Zaitsev)	Favored trans alkene

Organometallic compounds

Alkyl, aryl and vinyl halides react with metals to give organometallic compounds. When the metal is Mg, the compound is called magnesian or Grignard reagent. Other metals used are Li, Cu or Zn. Organometallic compounds are good nucleophiles and have a strong basic character.

Grignard reagents undergo hydrolysis easily, being reduced to the corresponding hydrocarbon:

or added to carbonyl compounds to produce, after subsequent hydrolysis, alcohols:

Back to the Synthesis and Reactivity of Organic Compounds.