Amine azide synthesis

Atorvastatin, structure of, 105. 516 ATP (see Adenosine triphosphate) ATZ, see Anilinothiazolinone, 1031-1032 Aufbau principle. 6 Axial bonds (cyclohexane), 119 drawing, 120 Azide, amines from, 929 reduction of, 929 Azide synthesis, 929 Azo compound, 944 synthesis of, 944-945 uses of. 945... 

Reduction of azides is a classical approach to primary amine synthesis. Treatment of 17 with sodium azide in DMF or in THF/H2O mixtures in the presence of phase transfer catalysts effects a quantitative conversion to the corresponding polymeric azide, 27. Recently the reduction of azides to primary amines via hydrolysis of iminophosphoranes produced by interaction of the azide with triethyl phosphite was reported.30 Application of this technique to the azidomethyl polymer, 27, as shown below, failed to produce a soluble polyamine. 

The use of acyl azides in the preparation of amines by the Curtius rearrangement has been discussed previously (Section 23-12E). Alkyl azides can be reduced readily by lithium aluminum hydride to amines and, if a pure primary amine is desired, the sequence halide — azide — amine may give as good or better results than does the Gabriel synthesis (Section 23-9D). 

The isocyanate can he isolated if the Curtius degradation is carried out in an inert solvent. The isocyanate also can be reacted with a heteroatom-nucleophile either subsequently or in situ. The heteroatom nucleophile adds to the C=N double bond of the isocyanate via the mechanism of Figure 8.12. In this way, the addition of water initially results in a carbamic acid. However, all carbamic acids are unstable and immediately decarboxylate to give amines (see Figure 8.5). Because of this consecutive reaction, the Curtius rearrangement represents a valuable amine synthesis. The amines formed contain one C atom less than the acyl azide substrates. It is due to this feature that one almost often refers to this reaction as Curtius degradation, not as Curtius rearrangement. 

An alternative to the azide synthesis is the Gabriel amine synthesis, which uses a phthalimide alkylation for preparing a primary amine from an alkyl halide. Imides (-CONHCO-) are similar to ethyl acetoacetate in that... 

The yield of a 1-adamantamine decreases in the presence of a more polar compound, such as cyclohexanol, which adsorbs more readily onto TiOj particles than 1-azidoadamantane. Because azides can be produced readily from alkyl halides, photoreduction of azides on SC provides an easier alternative to amine synthesis [151]. 

Sigurdsson et al. developed the synthesis of isocyanates from aliphatic amines [21]. Thus, the reaction of an aliphatic amine with trichloromethyl chloroformate (diphosgene) in the presence of Proton Sponge (1) (2 equiv.) at 0°C gave isocyanate in 81% yield. Azide isocyanate was synthesized from azide amine by means of a similar procedure by Keyes et al. [22] (Scheme 8.8). 

An analogous reaction is the conversion of olefins into primary amines by the consecutive action of BH3. THF and trimethylsilyl azide. The observation that organoboranes and chloramine give primary amines is the basis of an amine synthesis in which olefins are treated with the complex BH3 THF, followed by aqueous ammonia and aqueous sodium hypochlorite. Imines are reduced by the chiral dioxaborolidine 162 to yield optically active amines. 1-Imino-l-phenylpropane, for instance, affords 1-phenylpropylamine in 73% enantiomeric excess (equation 59). ... 

NO N3 nitrite, azide NaN02, NaNs (useful for amine synthesis)... 

Arylamines are prepared by nitration of an aromatic ring followed by reduction. Alkylamines are prepared by Sn2 reaction of ammonia or an amine with an alkyl halide or by the Gabriel amine synthesis. Amines can also be prepared by a number of reductive methods, including UAIH4 reduction of amides, nitriles, and azides. Also important is the reductive amination reaction in which a ketone or an aldehyde is treated with an amine in the presence of a reducing agent such as NaBH4. In addition, amines result from the Hofmann... 

Azide ion, hexamethyienetetramine, or phthaiimide can be used as synthons for ammonia in amine synthesis by nucieophiiic substitution. The cyanide ion is a synthon for [HjNCHj] . Amines may be synthesized by reduction or Hofmann degradation of amides. 

The intermediates in making amines are isocyanates (0==C==N) just like the Hofmann Rearrangement. The isocyanates are decomposed with water, just like the Hofmann. In fact, there is a lot of similarity between the Hofmann and the Schmidt reactions. Before I detail the synthesis steps, I should note that if you wish to generate the Hydrazoic Acid in the flask by adding Sodium Azide, you might need a powder addition funnel. This bit of equipment is quite pricey and it s likely you won t have one, so the first part of the synthesis details how to make the Hydrazoic Acid separately. 

The preparation of amines by the methods described m this section involves the prior synthesis and isolation of some reducible material that has a carbon-nitrogen bond an azide a nitrile a nitro substituted arene or an amide The following section describes a method that combines the two steps of carbon-nitrogen bond formation and reduction into a single operation Like the reduction of amides it offers the possibility of prepar mg primary secondary or tertiary amines by proper choice of starting materials... 

---