Solvent-free MW-assisted direct conversion of 3-tri-organosilyl-(germyl)-prop-2-yn-1-ols to ynimines

The direct conversion of 3-tri-organosilyl-or 3-organogermyl-prop-2-yn-1-ols into the corresponding imines using a solvent-free MW-assisted approach is reported. This highly effective methodology demonstrates the exploitation of α -silicon- or germanium-containing propynals generated in situ in a one-pot synthesis of ynimines. The efficient solvent-free MW-mediated synthesis of the corresponding silyl-or germyl-prop-2-yn-1-als has been carried out by oxidation of the starting alcohols with manganese dioxide


Introduction
Imines are widely applied as analitycal, medicinal, polymer and liquid crystalline materials, [1][2][3] and as synthons in organic synthesis. 4,5Conjugation of the triple bond and imino group in 1,3aza-enynes provides further synthetic possibilities. 6Imines with α-siliconor germaniumcontaining groups are of special interest in this series for the following reasons.The α-siliconor germanium-containing groups stabilize imines and the products of their transformations, while subsequent heterolysis of the M-Csp bond will lead to analogs with a terminal triple bond.The successful use of α,β-acetylenic silicon-containing aldimines as key compounds in the synthesis of thienomycines stimulates the search for synthetic methods and new application of organometal aza-enynes in organic synthesis. 7,β-Acetylenic aldimines are formed by the condensation of propynals with aliphatic and aromatic amines. 6,8Problems can arise, however, in the isolation of propynals owing to their volatility, toxicity or high reactivity (e.g., to polymerisation).It is known that propynal is highly mutagenic. 9Therefore the use in organic synthesis of propynals generated in situ is desirable.
Our own preliminary studies involve the one-pot synthesis of acetylenic hydroxyimines from primary-tertiary acetylenic γ-diols and primary amines by oxidation with manganese dioxide. 10his approach has been developed for some propargylic alcohols that were subjected to in situ oxidation and imine formation in high yield. 11he combination of supported reagents and microwave irradiation, as in the oxidation of benzylic alcohols using 35% MnO 2 'doped' silica 12 aroused our interest in applying this method in a solvent-free one-pot synthesis of acetylenic imines from the acetylenic alcohols 1 and 2 (both stable at room temperature) via oxidation/amination reactions.This technique can be used to carry out a wide range of reactions in short times, with high conversions and selectivity, without the need for solvents.It is also of special interest as an example of "green chemistry". 13o the best of our knowledge one-pot synthesis of imines from alcohols, as well as their acetylenic derivatives under MW conditions, has not been carried out.Our target aldehydes R 3 MC≡CCHO 3 and 4 (M = Si or Ge, respectively are representative of a class with high reactivity for application in the design of bioactive molecules, including natural analogs, 8,14a-d and the method may have advantages over the oxidation of the corresponding alcohols with activated manganese dioxide or potassium chlorochromate. 15The oxidation with MnO 2 is slow and requires a large excess of oxidant.The oxidation with pyridinium chlorochromate is more rapid, but 3-trimethylsilylprop-2-yn-1-al 1 prepared by this method is unstable and polymerizes on storage.

Scheme 1
The oxidation of the alcohols 1, 2 was carried out with five equiv. of activated MnO 2 on silica, by irradiation in a domestic microwave oven (LG MS-1904H, 700W) in an ampoule or in a screw-capped pressure vial.This method has considerable advantages over the classical one, with shortening of the reaction time by a factor of five hundred or more, increase in propynal yields (Table 1), and simplicity of isolation.It should be noted that the synthesis of ynimines by the method of ref. 11 requires 10 equiv. of MnO 2 .Our method requires no more than 5 equiv. of oxidant.
Comparison of the yields of propynals under microwave and conventional heating (oil bath) under otherwise the same conditions (vessel, reaction time, temperature) shows the specific microwave effect (non-pure thermal effect).16a,b For 3-triethylgermylprop-2-yn-1-al 4 this effect is greater than with the silicon analog 3. The oxidation of 3-triethylgermylprop-2-yn-1-ol 2 into 4 proceeds more slowly than that of the silicon analog 1 (see entries 2, 5).We have developed a very efficient method for the dry synthesis of 1,3-aza-enynes 5-12 by tandem oxidation-amination of alcohols 1, 2 with manganese dioxide on silica under MW irradiation (Scheme 2).This method leads to the target 1,3-azaenynes 5-12 in very short reaction times (2-4 min) and in high yields, without isolation of the intermediate propynals 3, 4 (Table 2).
In the reaction of aniline, a side reaction of oxidation into azobenzene 13 was observed (Scheme 3), in yields of compound 13 of 30% (entry 6) and 50% (entry 2), assessed by 1 H NMR. Compound 13 was isolated by column chromatography on Al 2 O 3 , and its structure confirmed by IR and NMR ( 1 H, 13 C) data, and its melting point matching literature data. 19ecently, the oxidation of aniline and some substituted primary aromatic amines by potassium permanganate and copper sulfate pentahydrate under solvent-free conditions was described. 20Azobenzene 13 was prepared in 75% yield using alumina as a solid support for 5 h at room temperature.The oxidation of aniline with MnO 2 /SiO 2 under our conditions (420W, 4 min) leads to 13 in 84% yield ( 1 H NMR control, 55% isolated yield).
General procedure for the microwave-assisted oxidation of acetylenic alcohols (1, 2) Method A Caution!The volume of the reaction mixture should not occupy more than 1/10-1/12 part of the ampoule volume.
A mixture of the acetylenic alcohol (1.5 mmol) and MnO 2 /SiO 2 (2.5 g) was placed in an ampoule.The ampoule was sealed and dipped into the alumina bath placed into the 20 cm 3 screw capped vial and irradiated in the domestic microwave oven, with cooling after each impulse (1 min).The temperature was measured by placing the glass thermometer in the alumina bath immediately after stopping the irradiation.The reaction mixture was extracted with CH 2 Cl 2 (3x20 ml) and the solvent removed by distillation.The residue was analyzed by 1 H NMR spectroscopy.The yields of the propynals 3, 4 are presented in Table 1.

Method B
The mixture of the acetylenic alcohol (1.5 mmol) and MnO 2 /SiO 2 (2.5 g) was placed in the ampoule.The ampoule was sealed and heated on an oil bath for some minutes at the temperature shown in Table 1.The reaction mixture was worked up as in method A and the solvent removed by distillation.The residue was analyzed by 1 H NMR spectroscopy.The yields of propynals 3, 4 are presented in Table 1.

Method C
The mixture of the acetylenic alcohol (1.5 mmol) and MnO 2 /SiO 2 (2.5 g) was placed in a closed vial, which was periodically shaken.After reaction, the mixture was extracted with CH 2 Cl 2 (3x20 ml) and the solvent removed by distillation.The residue was analyzed by 1 H NMR spectroscopy.The yields of propynals 3, 4 are presented in Table 1.

Table 1 .
Oxidation of alcohols R 3 MC≡CCH 2 OH 1, 2 to propynals R 3 MC≡CCHO 3, 4 under various conditions MW = activation by domestic microwave oven, LG MS-1904H, 700W.∆ = heating in oil bath.a Final temperature of alumina bath, according to glass thermometer immediately after stopping irradiation.b P = 420W.c P = 700W.d Yields determined by 1 H NMR.