RADICAL INDUCED DEAMINATION OF PRIMARY & SECONDARY AMINES BY TRIBUTYLTIN TRITIDE

伯、仲和叔脂肪族或脂环族 异氰化物、异硫氰酸酯和异硒代氰酸酯是平滑的， 在自由基反应条件下选择性地还原为 使用TBTH作为还原剂制备相应的烃。 这些 自由基反应可以在中性条件下进行， 结构重组的可能性。 反应 在概念上类似于初级和次级的脱氧 醇（巴顿反应），和选择性取代伯 通过氢原子的氨基官能化是用于合成氨基的期望反应。 许多天然产品的标签。 由于自由基诱导的脱氨基作用 异腈的TBTH反应是一个很有价值的通用反应， 高标记TBTT的可用性意味着该方法可以 作为氚标记技术开发。 合成 用于自由基氚化反应的异氰化物底物需要 - 使用乙酸甲酸酐使氨基官能团脱附，或 甲酸对硝基苯酯，然后用磷脱水 氯氧化物/三乙胺在二氯甲烷中的混合物，以提供 前体产率良好。 对于羟基化化合物， 氨基之后用乙酸酐进行O-过乙酰化。 据悉，异硫氰酸酯首先被还原成异氰化物 在脱氨基之前，与异氰化物相比几乎没有优势， 路线 然而，异硫氰酸酯以更高的化学产率形成 仲和叔异氰化物，因此可以是 在有限的情况下是有利的。 异氰化物与TBTH的反应 需要存在AIBN作为引发剂，和热，以及相对的 减少的难易程度为第三教育>第二教育>第一教育。 芳族 异氰化物在这些反应条件下不被还原。 我们有 将该方法应用于2-脱氧葡萄糖的合成，并使用 以葡萄糖胺为起始原料。 葡萄糖胺被释放 从盐酸盐中分离，然后N-甲酰化。 的 将N-甲酰葡萄糖胺进行过乙酰化， 得到2-葡糖胺异氰化物，然后将其分离， 纯化用于标记反应。 实现了氰化物提取 与新制的三丁基氘化锡在苯中于80 ℃下反应2小时 在催化量的AIBN的存在下。 产品 用1H/2 H NMR分析四-O-乙酰基-[2- 2 H]-脱氧葡萄糖 在1.5和2 ppm处显示氘峰。 后续 最后一步中的脱乙酰化产生[2- 2 H]-脱氧葡萄糖。 一个 正三丁基氚化锡（25%氚）的类似应用 2-三硫代-2-脱氧葡萄糖的合成没有得到产物， 回收原料。 该反应在进一步的 氚重复测定前的氘研究 标记实验。

Primary, secondary, and tertiary aliphatic or alicyclic isocyanides, isothiocyanates and isoselenocyanates are smoothly and selectively reduced under free radical reaction conditions to the corresponding hydrocarbons using TBTH as a reducing agent. These radical reactions can be performed under neutral conditions without the possibility of structural rearrangements. The reaction is conceptually similar to the deoxygenation of primary and secondary alcohols (Barton reaction), and the selective replacement of a primary amino function by a hydrogen atom is a desirable reaction for the labelling of many natural products. Since radical-induced deamination of isocyanides by TBTH is a general reaction of considerable value, the availability of highly labelled TBTT means that this procedure can be developed as a tritium labelling technique. Synthesis of isocyanide substrates for the radical tritiation reaction requires formylation of the amino function using acetic formic anhydride or p-nitrophenyl formate followed by dehydration with phosphorus oxychloride/triethylamine in methylene dichloride to provide the precursor in good yield. For hydroxylated compounds, formylation of the amino group is followed by O-peracetylation with acetic anhydride. It is reported that isothiocyanates are first reduced to isocyanides before deamination, and have little advantage over the isocyanide route. However, isothiocyanates are formed at higher chemical yields than secondary and tertiary isocyanides, and may therefore be advantageous in limited cases. Reaction of isocyanides with TBTH requires the presence of AIBN as initiator, and heat, and the relative ease of reduction is tertiary > secondary > primary. Aromatic isocyanides are not reduced under these reaction conditions. We have applied this approach to the synthesis of 2-deoxyglucose and used glucoseamine as the starting material. Glucoseamine was liberated from the hydrochride salt and then was N-formylated. The N-formylglucoseamine was peracetylated, and the product was dehydrated to give 2-glucoseamine isocyanide, which was then isolated and purified for the labelling reaction. Cyanide abstraction was achieved with freshly made tributyltin deuteride in benzene at 80oC for 2 hours in the presence of a catalytic amount of AIBN. The product tetra-O-acetyl-[2-2H]-deoxyglucose was analysed with 1H/2H NMR spectroscopy to show deuterium peaks at 1.5 and 2 ppm. Subsequent deacetylation in the final step generated [2-2H]-deoxyglucose. An analogous application of n-tributyltin tritide (25% tritium) to the synthesis of 2-tritio-2-deoxyglucose did not give the product, and the starting material was recovered. The reaction is under further investigation with deuterium before repetition of the tritium labelling experiment.