CN105481624B - The catalysis oxidation synthetic method of Arneel SD - Google Patents

Abstract

The invention discloses a method for synthesizing fatty nitriles by catalytic oxidation, using fatty aldehydes as reaction substrates, 2,2,6,6-tetramethylpiperidine-1-oxygen free radicals (TEMPO), alkali metal salts, nitrous acid Tert-butyl ester (TBN) is used as a catalyst, hexamethyldisilazane (HMDS) is used as a nitrogen source, oxygen is used as an oxidant, and the reaction substrate is reacted in an organic solvent under normal pressure and a temperature of 25-50°C. After the reaction is finished, the fatty nitrile is obtained through post-treatment. The method is simple and safe to operate and reduces environmental costs.

Description

Catalytic oxidation synthesis method of fatty nitrile

technical field

The invention belongs to the technical field of chemistry, in particular to a catalytic oxidation synthesis method of fatty nitriles.

Background technique

Nitrile compounds are important synthetic building blocks in organic synthesis and are key structural units of many dyes, medicines, pesticides and electronic materials. Nitrile compounds are also important intermediates in organic synthesis because the cyano groups contained in them have the ability to transform into other important functional groups such as amino groups, amido groups, aldehyde groups, carboxyl groups, and ester groups. The most traditional synthesis method of nitrile compounds is by Sandmeyer reaction or Rosenmund–von Braun reaction, but these two methods have serious defects, both require the use of stoichiometric CuCN, and the reaction conditions are relatively severe. Since then, a transition metal-catalyzed cyanation reaction route of aromatic halides has been developed to synthesize aromatic nitriles. KCN, NaCN, Zn(CN) ₂ , TMSCN, K ₄ [Fe(CN) ₆ ] and other cyanide sources are used in the reaction. The disadvantages of this type of synthesis method are: (1) the cyanogen sources used are generally poisonous, and care must be taken during use to avoid the generation of toxic HCN; (2) stoichiometric metal wastes are inevitably produced, resulting in (3) The control requirements of the reaction process are relatively strict. Amide dehydration is another way to synthesize aromatic nitriles, but the reaction must use dehydrating agents such as P ₂ O ₅ , POCl ₃ , SOCl ₂ and PCl ₅ , and the reaction temperature is relatively high. Nitrile compounds can also be synthesized from aldoxime, but often have the disadvantages of low product yield and excessive use of toxic reagents. Considering the convenience of the source of raw materials, people pay more and more attention to the synthesis methods using aldehydes, alcohols or acids as raw materials, and urea, ammonia or hydroxylamine as nitrogen sources. However, in most of these reported methods, the use of transition metals And toxic reagents are still unavoidable.

In recent years, the green catalytic oxidation technology using molecular oxygen as a clean oxygen source has attracted more and more attention. Molecular oxygen is a sustainable natural resource with low cost and high atom economy, and the by-product of oxidation reaction is only water without pollution. Jinho Kim (J. Org. Chem. 2015, 80, 11624) reported a aldehyde compound as raw material, ammonium acetate as nitrogen source, and 4-acetamido-2,2,6,6-tetramethyl Piperidine nitroxide radicals are used as catalysts, and oxygen is used as an oxidant to synthesize nitrile compounds, but this method has limitations in use, and aliphatic aldehydes are not suitable as substrates.

Contents of the invention

The purpose of the present invention is to provide a kind of with fatty aldehyde as raw material, take hexamethyldisilazine as nitrogen source, prepare the method for fatty nitrile by catalytic oxidation reaction.

In order to achieve the above-mentioned purpose, the present invention adopts the following technical scheme: using aliphatic aldehyde as the reaction substrate, using 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO), alkali metal salt, nitrous acid Tert-butyl ester (TBN) is used as a catalyst, hexamethyldisilazane (HMDS) is used as a nitrogen source, oxygen is used as an oxidant, and the reaction substrate is reacted in an organic solvent under normal pressure and a temperature of 25-50°C. , after the reaction is completed, the fatty nitrile is obtained through separation and treatment.

In the present invention, the fatty aldehydes are saturated chain fatty aldehydes (such as C1~C20 fatty aldehydes), unsaturated chain fatty aldehydes (such as C1~C20 unsaturated fatty aldehydes), alicyclic aldehydes (such as 3~C20 Alicyclic aldehydes with 8-membered ring structure), substituted saturated heterocyclic aldehydes or aldehydes with other functional groups; the substituted saturated heterocyclic aldehydes refer to the heterocycles of saturated heterocyclic aldehydes containing N, O and other heteroatoms is substituted by one or more substituents, each of which is independently selected from one of the following: C1-C4 alkyl, halogen, C1-C4 alkoxy, tert-butoxycarbonyl; Aldehydes of other functional groups refer to substituted saturated chain fatty aldehydes and substituted unsaturated chain fatty aldehydes, and the substituted saturated chain fatty aldehydes and substituted unsaturated chain fatty aldehydes refer to saturated chain fatty aldehydes or The hydrocarbon group of the unsaturated chain aliphatic aldehyde is substituted by one or more substituents, each of which is independently selected from one of the following: phenyl, substituted phenyl, halogen, C1-C4 alkoxy.

Further, the fatty aldehyde is preferably one of the following: n-dodecaldehyde, cyclohexyl formaldehyde, 1-adamantane formaldehyde, 3-phenylpropionaldehyde, cinnamaldehyde, α-methyl cinnamaldehyde, new ocean jasmonal, N-Boc -4-Piperidinecarbaldehyde.

In the present invention, the organic solvent is N,N'-dimethylformamide, dimethyl sulfoxide, acetonitrile, preferably acetonitrile.

In the present invention, the metal salt is NaBF ₄ , NaCl, KPF ₆ is preferably KPF ₆ .

In the present invention, the molar ratio of the reaction substrate fatty aldehyde to metal salt, TEMPO, TBN is 100:5~25:5~25:5~25, preferably 100:10~20:10~20:10~20 .

In the present invention, the molar ratio of the reaction substrate fatty aldehyde to HMDS is 1:1.5-3.5, preferably 1:2-3.

In the present invention, the mass dosage of the solvent is recommended to be 45 to 100 times that of the reaction substrate.

In the present invention, the reaction temperature is 25-50°C, preferably 30-40°C.

In the present invention, the reaction time is 6-20 h, preferably 8-12 h.

Usually the method of post-treatment of the reaction solution is as follows: after the reaction is finished, add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, evaporate the solvent under reduced pressure, and then carry out column chromatography separation to obtain A mixture of ethyl acetate/petroleum ether with a volume ratio of 1:100 was used as the eluent, and the eluate containing the target compound was collected, and the solvent was evaporated to obtain the product fatty nitrile.

The present invention specifically recommends that the method for synthesizing fatty nitriles with fatty aldehydes as reaction substrates is carried out according to the following steps: in an acetonitrile solvent, add 2,2,6,6-tetramethylpiperidine-1-oxygen free radicals ( TEMPO), inorganic salts, tert-butyl nitrite (TBN) and hexamethyldisilazane (HMDS), under normal pressure oxygen conditions, slowly add the reaction substrate fatty aldehyde at 30~40°C, react 8~12 After h, sodium thiosulfate solution was added to the reaction solution and stirred, then extracted with ether, the organic layer was separated, the solvent was evaporated under reduced pressure, and then column chromatography was used to separate the mixture with ethyl acetate/petroleum ether volume ratio of 1:100. The mixed solution is the eluent, the eluate containing the target compound is collected, and the solvent is evaporated to obtain the product fatty nitrile; the molar ratio of the reaction substrate fatty aldehyde to metal salt, TEMPO, TBN is 100:10~20:10 ~20:10~20; the molar ratio of the reaction substrate fatty aldehyde to HMDS is 1:2~3.

The synthetic method of the present invention is easy and safe to operate, and its beneficial effects mainly lie in:

_A ) Compared with conventional oxidants that use stoichiometric amounts, such as _I2 and NaCl2, in the present invention, TEMPO is used as the catalyst, and clean oxygen is used as the terminal oxidant, which reduces environmental costs.

B) The side reaction of aldol condensation of α-unsaturated aldehydes is overcome, and the yield of such reaction substrates is greatly improved.

detailed description

The present invention will be further described below through specific examples, but the protection scope of the present invention is not limited thereto.

The structural formulas of the fatty aldehydes used in the following examples are shown in formulas (1-1) to (1-8):

The corresponding structural formulas of the prepared fatty nitriles are shown in formulas (2-1) to (2-8):

Embodiment 1: Preparation of n-dodecanonitrile (formula (2-1))

In a 100ml flask, add 50mL of acetonitrile, 10mmol of HMDS, 0.4mmol of TEMPO, 0.4mmol of KPF ₆ and 0.6mmol of TBN, replace the air in the bottle with oxygen, seal the mouth of the bottle with a rubber stopper, insert an oxygen bulb, and put the reaction Put the bottle into a preheated water bath and heat to 30°C, slowly add 4 mmol of dodecanal (formula (1-1)), and react for 8 hours. Add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, distill off the solvent under reduced pressure, and then perform column chromatography separation, using ethyl acetate/petroleum ether with a volume ratio of 1:200 as the eluent, collect the eluate containing the target compound, evaporate the solvent to obtain dodecanonitrile, and the separation yield is 75%.

Embodiment 2: Preparation of n-dodecanonitrile (formula (2-1))

The reaction steps were the same as in Example 1, except that acetonitrile was changed to N,N'-dimethylformamide, and the reaction was performed for 20 hours. The isolated yield of dodecanonitrile was 46%.

Embodiment 3: Preparation of n-dodecanonitrile (formula (2-1))

The reaction steps were the same as in Example 1, except that acetonitrile was changed to dimethyl sulfoxide, and after 20 hours of reaction, the isolated yield of dodecanonitrile was 53%.

Embodiment 4: Preparation of n-dodecanonitrile (formula (2-1))

The reaction steps are the same as in Example ₁ , except that KPF6 is changed to NaBF4, reacted for 8h, and the isolated yield of dodecanonitrile is 73%.

Embodiment 5: Preparation of n-dodecanonitrile (formula (2-1))

The reaction steps were the same as in Example ₁ , except that KPF was changed to NaCl, and the reaction was 8h, and the isolated yield of dodecylnitrile was 63%.

Embodiment 6: Preparation of n-dodecanonitrile (formula (2-1))

The reaction steps are the same as in Example 1, except that the amounts of TEMPO, KPF ₆ and TBN are all changed to 0.8 mmol, and the reaction is 6 hours, and the separation yield of dodecanonitrile is 80%.

Embodiment 7: Preparation of n-dodecanonitrile (formula (2-1))

The reaction steps were the same as in Example 1, except that the amount of HMDS was changed to 14 mmol, and the reaction was carried out for 8 hours. The isolated yield of dodecanonitrile was 72%.

Embodiment 8: Preparation of cyclohexylcarbonitrile (formula (2-2))

In a 100ml flask, add 50mL of acetonitrile, 10mmol of HMDS, 0.4mmol of TEMPO, 0.4mmol of KPF ₆ and 0.6mmol of TBN, replace the air in the bottle with oxygen, seal the mouth of the bottle with a rubber stopper, insert an oxygen bulb, and put the reaction Put the bottle into a preheated water bath and heat to 30°C, slowly add 4 mmol of cyclohexyl formaldehyde (such as formula (1-2)), and react for 8 hours. Add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, distill off the solvent under reduced pressure, and then perform column chromatography separation, using ethyl acetate/petroleum ether with a volume ratio of 1:200 as the eluent, collect the eluate containing the target compound, evaporate the solvent to obtain cyclohexylcarbonitrile, and the separation yield is 76%.

Example 9: Preparation of 1-adamantanecarbonitrile (formula (2-3))

In a 100ml flask, add 50mL of acetonitrile, 10mmol of HMDS, 0.4mmol of TEMPO, 0.4mmol of KPF ₆ and 0.6mmol of TBN, replace the air in the bottle with oxygen, seal the mouth of the bottle with a rubber stopper, insert an oxygen bulb, and put the reaction Put the bottle into a preheated water bath and heat to 25°C, add 4mmol of 1-adamantanecarbaldehyde (such as formula (1-3)), and react for 12h. Add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, distill off the solvent under reduced pressure, and then conduct column chromatography separation, and use a mixture of ethyl acetate/petroleum ether with a volume ratio of 1:100 as eluent, collect the eluate containing the target compound, evaporate the solvent to obtain 1-adamantanecarbonitrile, and the separation yield is 85%.

Example 10: Preparation of 1-adamantanecarbonitrile (Formula (2-3))

The reaction steps are the same as in Example 9, except that the reaction temperature is 30° C., the reaction is 8 hours, and the isolated yield of 1-adamantanecarbonitrile is 97%.

Example 11: Preparation of 1-adamantanecarbonitrile (Formula (2-3))

The reaction steps are the same as in Example 9, except that the reaction temperature is 40° C., the reaction is 6 hours, and the isolated yield of 1-adamantanecarbonitrile is 89%.

Example 12: Preparation of 1-adamantanecarbonitrile (Formula (2-3))

The reaction steps were the same as in Example 9, except that the amount of HMDS was 6 mmol, the reaction temperature was 30° C., and the reaction was 8 hours. The isolated yield of 1-adamantanecarbonitrile was 70%.

Example 13: Preparation of 1-adamantanecarbonitrile (Formula (2-3))

The reaction steps are the same as in Example 9, except that the amount of TBN used is 0.4 mmol, the reaction temperature is 30° C., and the reaction time is 12 hours. The isolated yield of 1-adamantanecarbonitrile is 74%.

Example 14: Preparation of 3-phenylpropionitrile (Formula (2-4))

In a 100ml flask, add 50mL of acetonitrile, 10mmol of HMDS, 0.4mmol of TEMPO, 0.4mmol of KPF ₆ and 0.6mmol of TBN, replace the air in the bottle with oxygen, seal the mouth of the bottle with a rubber stopper, insert an oxygen bulb, and put the reaction Put the bottle into a preheated water bath and heat to 30°C, slowly add 4mmol of 1-adamantanecarbaldehyde (such as formula (1-4)), and react for 8h. Add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, distill off the solvent under reduced pressure, and then conduct column chromatography separation, and use a mixture of ethyl acetate/petroleum ether with a volume ratio of 1:100 as eluent, collect the eluate containing the target compound, evaporate the solvent to obtain 3-phenylpropionitrile, and the separation yield is 62%.

Example 15: Preparation of 3-phenylpropionitrile (Formula (2-4))

The reaction steps were the same as in Example 13, except that the amounts of TEMPO, KPF ₆ and TBN were all changed to 1 mmol, and after 6 hours of reaction, the isolated yield of 3-phenylpropionitrile was 66%.

Example 16: Preparation of Cinnamonitrile (Formula (2-5))

In a 100ml flask, add 30mL of acetonitrile, 10mmol of HMDS, 0.4mmol of TEMPO, 0.4mmol of KPF ₆ and 0.6mmol of TBN, replace the air in the bottle with oxygen, seal the mouth of the bottle with a rubber stopper, insert an oxygen bulb, and put the reaction Put the bottle into a preheated water bath and heat to 30°C, slowly add 4mmol of 1-cinnamaldehyde (such as formula (1-5)), and react for 7h. Add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, distill off the solvent under reduced pressure, and then conduct column chromatography separation, and use a mixture of ethyl acetate/petroleum ether with a volume ratio of 1:100 as eluent, collect the eluate containing the target compound, evaporate the solvent to obtain cinnamonitrile, and the separation yield is 60%.

Example 17: Preparation of Cinnamonitrile (Formula (2-5))

The reaction steps were the same as in Example 13, except that the amount of acetonitrile was changed to 50 mL, and the reaction was carried out for 8 hours. The isolated yield of cinnamonitrile was 68%.

Example 18: Preparation of α-methylcinnamonitrile (Formula (2-6))

In a 100ml flask, add 30mL of acetonitrile, 10mmol of HMDS, 0.4mmol of TEMPO, 0.4mmol of KPF ₆ and 0.6mmol of TBN, replace the air in the bottle with oxygen, seal the mouth of the bottle with a rubber stopper, insert an oxygen bulb, and put the reaction Put the bottle into a preheated water bath and heat to 30°C, slowly add 4 mmol of α-methylcinnamaldehyde (such as formula (1-6)), and react for 8 hours. Add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, distill off the solvent under reduced pressure, and then conduct column chromatography separation, and use a mixture of ethyl acetate/petroleum ether with a volume ratio of 1:100 as eluent, collect the eluate containing the target compound, evaporate the solvent to obtain α-methylcinnamonitrile, and the separation yield is 61%.

Example 19: Preparation of α-methylcinnamonitrile (Formula (2-6))

The reaction steps are the same as in Example 18, except that the reaction temperature is 50° C. and the amount of acetonitrile is changed to 50 mL, and the isolated yield of α-methylcinnamonitrile is 65%.

Example 20: Preparation of Xinyang Jasmonitrile (Formula (2-7))

In a 100ml flask, add 30mL of acetonitrile, 10mmol of HMDS, 0.4mmol of TEMPO, 0.4mmol of KPF ₆ and 0.6mmol of TBN, replace the air in the bottle with oxygen, seal the mouth of the bottle with a rubber stopper, insert an oxygen bulb, and put the reaction Put the bottle into a preheated water bath and heat to 30°C, slowly add 4 mmol of jasmonal (such as formula (1-7)), and react for 8 hours. Add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, distill off the solvent under reduced pressure, and then conduct column chromatography separation, and use a mixture of ethyl acetate/petroleum ether with a volume ratio of 1:100 as Eluent, collect the eluate containing the target compound, evaporate the solvent to obtain Xinyangjasmonitrile, and the separation yield is 72%.

Example 21: Preparation of Xinyang Jasmonitrile (Formula (2-7))

The reaction steps are the same as in Example 20, except that the amounts of TEMPO, KPF ₆ and TBN are all changed to 0.2 mmol, the reaction time is 12 h, and the separation yield of Xinyang jasmonitrile is 55%.

Example 22: Preparation of N-Boc-4-piperidinecarbonitrile (Formula (2-8))

In a 100ml flask, add 30mL of acetonitrile, 10mmol of HMDS, 0.4mmol of TEMPO, 0.4mmol of KPF ₆ and 0.6mmol of TBN, replace the air in the bottle with oxygen, seal the mouth of the bottle with a rubber stopper, insert an oxygen bulb, and put the reaction Put the bottle into a preheated water bath and heat to 30°C, slowly add 4mmol of N-Boc-4-piperidinecarbaldehyde (such as formula (1-8)), and react for 8h. Add sodium thiosulfate solution to the reaction solution and stir, then extract with ether, separate the organic layer, distill off the solvent under reduced pressure, and then conduct column chromatography separation, and use a mixture of ethyl acetate/petroleum ether with a volume ratio of 1:100 as Eluent, collect the eluate containing the target compound, evaporate the solvent to obtain N-Boc-4-piperidinecarbonitrile, and the separation yield is 70%.

Example 23: Preparation of N-Boc-4-piperidinecarbonitrile (Formula (2-8))

The reaction steps are the same as in Example 20, except that the amount of acetonitrile used is 80 mL, and the isolated yield of N-Boc-4-piperidinecarbonitrile is 73%.

Claims (6)

1. the catalysis oxidation synthetic method of Arneel SD, it is characterised in that：Using fatty aldehyde as reaction substrate, with 2,2,6,6- tetramethyls Piperidines -1- oxygen radicals（TEMPO）, alkali metal salt, nitrite tert-butyl（TBN）For catalyst, with HMDS （HMDS）For nitrogen source, oxygen is oxidant, reaction substrate in organic solvent, under normal pressure, under conditions of 25~50 DEG C of temperature Reaction, reaction obtains described Arneel SD through post processing after terminating；Described fatty aldehyde is saturation chain fatty aldehyde, unsaturated chain Shape fatty aldehyde, alicyclic ring aldehyde, the saturated heterocyclic aldehyde of substitution or the aldehyde with other functional groups；Described substituted saturated heterocyclic aldehyde Refer to be substituted by one or more substituents on the heterocycle containing the heteroatomic saturated heterocyclic aldehyde such as N, O, described substituent is each It is independently selected from one of following：C1-C4 alkyl, halogen, C1-C4 alkoxy, tertbutyloxycarbonyl；Described carries other functions The aldehyde of group refers to the saturation chain fatty aldehyde of substitution, the unsaturated chain fatty aldehyde of substitution, described substituted saturation chain fat Fat aldehyde, the unsaturated chain fatty aldehyde of substitution refer to the alkyl of saturation chain fatty aldehyde or unsaturated chain fatty aldehyde by one or Multiple substituent substitutions, described substituent is each independently selected from one of following：Phenyl, substituted-phenyl, halogen, C1-C4 alkane Epoxide.

2. the method as described in claim 1, it is characterised in that：The fatty aldehyde is preferably one of following：Positive lauric aldehyde, cyclohexyl Formaldehyde, 1- adamantane formaldehyde, 3-phenylpropion aldehyde, cinnamic acid, α-methylcinnamaldehyde, helional, N-Boc-4- piperidinealdehydes.

3. the method as described in claim 1, it is characterised in that：The alkali metal salt is NaBF₄、NaCl、KPF₆。

4. the method as described in claim 1, it is characterised in that：The reaction substrate fatty aldehyde and metal salt, 2,2,6,6- tetra- Methyl piperidine -1- oxygen radicals, the mol ratio of nitrite tert-butyl are 100：5~25：5~25：5~25.

5. the method as described in claim 1, it is characterised in that：The reaction substrate fatty aldehyde and HMDS HMDS Mole ratio 1：1.5~3.5.

6. the method as described in claim 1, it is characterised in that：The method of reaction solution post processing is：After reaction terminates, instead Answer and hypo solution stirring is added in liquid, then extracted with ether, isolate organic layer, remove solvent under reduced pressure, then carry out Column chromatography for separation, with ethyl acetate/petroleum ether volume ratio 1：100 mixed liquor is eluant, eluent, collects washing containing target compound De- liquid, is evaporated off solvent and produces product fatty nitrile.