通过叠氮还原也是制备烷基伯胺的一个较为常用的方法，一般烷基叠氮主要通过烷基卤代物用叠氮基取代而来；烷基醇也可通过DPPA直接得到转化为烷基叠氮（好象一般为伯醇）。虽然许多文献使用叠氮酸通过与醇的MItsunobu很高的收率得到烷基叠氮，但由于叠氮酸有挥发性且剧毒，因而不建议在实验室使用。对于叔醇其也可通过TMSN3在Lewis 酸存在下转化为叔烷基叠氮。

    1、叠氮的合成

通过烷基卤代物的取代合成烷基叠氮示例

      对于烷基卤代物的取代反应，由于原料与产品一般极性相差不大，TLC跟踪时一定要仔细。

     A solution of 19.1 g. (0.047 mole) of the starting material in 500 mL of acetone and 50 mL of water was treated with 3.05 g (0.047 mole) of sodium azide and the mixture heated under reflux for about eighteen hours and then taken to dryness in vacuo. The residue was partitioned between ethyl acetate and water, and the organic layer separated, washed with brine, taken to dryness and the residue recrystallized from isopropanol to give 10.3 g (60%yield) of the desired product.

通过磺酸酯的取代合成烷基叠氮示例

     Sodium azide (1.73 g, 26.61 mmol) was added to a solution of the starting material (5.24 g,15.95 mmol) in N,N-dimethylformamide (50 ml). The mixture was stirred at 100.deg. C. for 1 hour, water (40 ml) was added to the reaction mixture. The mixture was extracted with ethyl ether and dried over magnesium sulfate. After evaporation of the solvent, the residue was purified by column chromatography on silica gel eluding with n-hexane/ethyl acetate(=20/1) to give the desired product (4.30 g, yield 98%).

通过 DPPA 直接将醇转变为烷基叠氮示例

   A mixture of the starting material (213 mg, 0. 257 mmol), diethyldiazodicarboxylate (250uL,159 mmol, 2 eq), diphenylphosphoryl azide (343 uL, 1.59 mmol, 2 eq) and triphenylphosphine (417 mg, 1. 59 mmol, 2 eq) was stirred at 21.deg. until all starting alcohol was consumed.The reaction was evaporated to dryness and the crude residue purified on column with 5%EtOAc/hexane followed by 100% toluene as eluent. The desired product was isolated as a solid (181 mg, 78% yield).

通过 TMSN3 在Lewis 酸存在下转化叔醇为叔烷基叠氮示例

   A stirred solution of the material (44.3 g, 364.89 mmole) and azidotrimethylsilane (63.06 g,547.34 mmole) in dry CH2Cl2 (2.2 L) at room temperature under argon was treated with boron trifluoride diethyl etherate (67.32 g, 474.36 mmole). After being stirred for 5 days,

the resulting solution was quenched with water (1.5 L). The organic layer was separated,washed with saturated NaHCO3 solution, water and brine, dried over anhydrous MgSO4 and evaporated in vacuo. The residue was chromatographed on a column of silica gel (E. Merck, 230-400 mesh, 700 g) eluting with EtOAc-hexane (1:3) to afford the title compound (124.9 g) as a light yellow oil in 81.3percent yield.

2、叠氮的还原

    催化加氢和化学还原法均可用于叠氮的还原，常用的催化加氢催化剂为Pd/C, RaneyNi, 当分子内有对氢化敏感的卤素时，可用PtO2作催化剂。化学还原最温和的条件是使用三苯基膦在湿的四氢呋喃中还原，当然LAH也可用于该还原。

通过 Pd/C 催化剂催化加氢还原烷基叠氮示例

      A solution of the material (6.42 g, 19.6 mmoles) dissolved in ethanol (128 mL) was stirred for 1 hour in the presence of 10 percent w/w palladium-on-charcoal (1.67 g) in an atmosphere of hydrogen under atmospheric pressure. At the end of this time, the rection mixture was filtered and the filtrate was concentrated by evaporation under reduced pressure.The resulting crystalline residue was recrystallized from diethyl ether, to afford 4.90g of the title compound, melting at 104~105 °C.

通过 Pd/BaSO4 催化剂催化加氢还原烷基叠氮示例

     Palladium/barium sulfate catalyst (0.3 g) was added to a solution of the starting material (6.0g, 32.8 mmols) in ethanol (40 mL) and 0.5N hydrochloric acid (40 mL). Hydrogenation takes place at about 60 psi for 2 hours. After filtration, the volume is concentrated to about 30 mL. When the PH is brought to 6.5 with ammonia, the amino acid separates as a white powder. After washing with ethanol/water and drying, 3.5 g of the productwas obtained. melting at 283~285 °C.

通过 PtO2 催化剂催化加氢还原烷基叠氮示例

   Platinum oxide (14 mg, 0.062 mmol) was added to a solution of the starting material (138 mg,0.5 mmol) in MeOH (4 mL). This mixture was hydrogenated in an atmosphere of hydrogen using a hydrogen filled balloon for 3 h at room temperature. The catalyst was filtered through

a bed of CELITE diatomaceous earth and washed with MeOH. The filtrate was concentrated to give the title compound as oil.

通过 Raney Ni 催化剂催化加氢还原烷基叠氮示例

    The material (21.7 g, 74.5 mmols) was dissolved in methanol (325 mL). Triethyl- amine (9.5 mL) and subsequently hydrazine hydrate (13.5 mL) was added. Then 10 g of raney-nickel was added portionwise to the reaction solution under agitation at room temperature. After three hours, the addition of raney-nickel is completed, the reaction mixture is agitated for another one hour, then the raney-nickel is filtered off. The filtrate was evaporated under vacuum, the residue was dissolved in methylene chloride and the solution is washed with water and sodium chloride solution (10%). Subsequently, the organic phase was dried over sodium sulfate, filtered and evaporated. 17.1 g of the product was obtained. Its dihydrochloride has a melting point of 209~213 °C.

通过 PPh3-THF-H2O 体系还原烷基叠氮示例

      To a solution of 1.1 g (5.9 mmol) 8-azidomethyl-1,6-napthyridine in 20 mL THF was added 2mL H2O and 3 g PPh3. The resulting solution was allowed to stir overnight at room temperature, then concentrated in vacuo. Purification by flash chromatography (50×140 mm silica gel, linear gradient 5-20percent (10 percent NH4OH in MeOH:CH2Cl2) yielded the desired product.

通过 LAH 还原烷基叠氮示例

      A solution of the material (10 g, 32.9 mmols) in dry tetrahydrofuran (100 mL) was added dropwise to a stirred suspension of lithium aluminium hydride (4 g, 0.1 mol) in tetrahydrofuran (200 mL) under nitrogen. The resulting mixture was stirred at room temperature for 1 h and quenched with water (4 mL), followed by 15 percent sodium hydroxide (4 mL) and water (12 mL). The mixture was then filtered and the residue washed with tetrahydrofuran (50 mL). The combined filtrate was evaporated to give the title compound (7.5 g, 82% yield) as a pale pink oil.