Chemistry - How do you create primary amines from alcohols?

Solution 1:

In the conversion of primary alcohols to primary amines

$$\ce{R-CH2OH -> R-CH2NH2}$$

direct alkylation of ammonia normally is the last thing you want to do in the lab.

Under conditions where $\ce{OH}$ is a good leaving group, i.e. in acidic medium, the nucleophilicity of ammonia is reduced due to protonation. Moreover, there's little chance to prevent further alkylation of the initial product.

More promising strategies are:

  • Gabriel synthesis: Hydroxy-halogen-exchange, followed by reaction of the primary halide with phthalimide and subsequent hydrazinolysis

  • Mitsunobu reaction ($\ce{Ph3P, DEAD}$) of the primary alcohol using hydrazoic acid $\ce{HN3}$ as a nucleophile, followed by reduction of the alkyl azide

  • An (almost-one-pot) combination of the Appel and the Staudinger reaction

    1. Heat the primary alcohol ($\ce{R-CH2OH}$) with $\ce{Ph3P}$ and bromotrichloromethane $\ce{CBrCl3}$ in benzene, then cool down to RT (room temperature) to yield $\ce{R-CH2Hal}$

    2. Add $\ce{NaN3}$,tetrabutylammonium bromide and N,N-dimethylformamide and reflux again to obtain the azide $\ce{R-CH2N3}$, then cool down to RT, pour on water, extract with benzene and dry the organic layer

    3. Add triethylphosphite $\ce{(EtO)3P}$ to the organic layer, stir at RT to yield the iminophosphorane $\ce{R-CH2N=P(OEt)3}$

    4. Hydrolyze the iminophosphorane by refluxing with hydrochloric acid, then neutralize to release the amine

Solution 2:

For aliphatic compounds you can use alkylation

$$\ce{R-OH + NH3 -> R-NH2 + H2O}$$

For aromatic compounds like phenol

$$ \begin{matrix} \ce{C6H6O &\quad +& Zn& \ ->& C_6 H_6\\ Phenol& & (dust\ form)& \ & Benzene&} \end{matrix} $$

Zinc dust reduces the OH group in phenol

$$\begin{matrix} \ce{C6H6& + &HNO3& ->[H2SO4]& C6H5NO2 + &H_2 O&\\ Benzene& & (high\ concentration)&& Nitrobenzene& water& } \end{matrix}$$ Nitration

$$\begin{matrix} \ce{C6H5NO2& +& Sn& +& \qquad HCl_{(aq)} ->& C6H5NH2&\\ Nitrobenzene& & Tin& &Hydrochloric & Aniline&\\ &&&&acid} \end{matrix}$$ $ $
Tin and hydrochloric acid act as reducing agents

Solution 3:

In addition to the method provided by t3st you could also try the following for $$\begin{matrix} \ce{Ph-OH& +& Zn& ->& C6H6 \\ Phenol& & Zinc& & Benzene&} \end{matrix}$$ (Just like the first step of t3st 's answer.

Then you could do Electrophilic halogenation of benzene using $\small\ce{AlCl3\ or\ FeBr3}$ as catalyst. $$\begin{matrix} \ce{C6H6& ->[\ce{Cl2/AlCl3}]& Ph-Cl\\ Benzene& & Aryl\ halide&} \end{matrix}$$

Finally you could react aryl-halide with soda-amide($\small\ce{NaNH2}$) to substitute $\ce{Cl}$ with $\ce{NH2}$[citation needed] $$\begin{matrix} \ce{Ph-Cl& ->[\ce{NaNH2}]& Ph-NH2&\\ Aryl halide& & Aniline&} \end{matrix}$$