N-(1-cyano-2-iodo-1-phenylalkyl)amide derivatives and method for producing the same

Abstract

To provide a novel N-(1-cyano 2-iodine-1-phenylalkyl)amide derivative, and a method for producing the same.SOLUTION: Provided is a method for producing a N-(1-cyano-2-iodine-1-phenylalkyl)amide derivative shown by the following formula (1), comprising reacting an enamide substrate with cyanogen iodide using tris(pentafluorophenyl)borane as a catalyst (where R1 is an acetyl group or a benzoyl group; R2 is a hydrogen atom or an alkyl group (C=1-10); R3 is any of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group and a halogen atom; R4 is any of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group and a halogen atom; and R5 is any of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group and a halogen atom).SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to N-(1-cyano-2-iodo-1-phenylalkyl)amide derivatives and a method for producing the same. [Background technology]

[0002] The halofunctionalization reaction of carbon-carbon double bonds is an excellent reaction format that allows the introduction of halogen atoms, which are a stepping stone for synthetic development, and nucleophiles, which are functional groups, in one step. Although halofunctionalization reactions using various types of nucleophiles have been invented so far, halocyanation, which uses cyanide ions as a nucleophile, is still in its infancy.

[0003] As a conventional technique, the bromocyanation of enamines is described in the following Non-Patent Documents 1 and 2. The fluorocyanation of enamines is described in the following Non-Patent Document 3, the fluorocyanation of vinyl azides in the following Non-Patent Document 4, and the fluorocyanation of vinyl ethers in the following Non-Patent Document 5. In addition, an example of the iodocyanation of ketene acetals is described in the following Non-Patent Document 6. Furthermore, an example of the iodocyanation of silyl enolates is described in the following Non-Patent Document 7. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] H. Ahlbrecht, D. Liesching, "1-Cyanoenamine durch Cyanierung von Enaminen mit Bromcyan" Synthesis 1977, 495. [Non-Patent Document 2] N. De Kimpe, R. Verhk, L. De Buyck, N. Schamp, "Synthesis of α-Cyanoenamines by Cyanation of α-Bromoimmonium Bromides and Dehydrobromination of β-Bromo-α-(dialkylamino)nitriles" Chem. Ber. Rev. 1983 , 116 ,

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[0005] However, the halocyanation of enamide substrates under mild conditions, such as room temperature, has not yet been achieved, and development of such a method is desirable.

[0006] In view of the above problems, an object of the present invention is to provide a novel N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative and a method for producing the same. [Means for solving the problem]

[0007] The present inventors have conducted intensive research into the above-mentioned problems and have discovered that novel N-(1-cyano-2-iodo-1-phenylalkyl)amide derivatives can be obtained by reacting an enamide substrate with cyanogen iodide in dichloromethane in the presence of trispentafluorophenylborane as a catalyst, thereby completing the present invention.

[0008] That is, a method for producing an N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative comprises reacting an enamide substrate with cyanogen iodide in the presence of trispentafluorophenylborane as a catalyst.

[0009] According to the above-mentioned production method, it is possible to obtain an N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative represented by the following formula (1). [ka]

[0010] In the above formula (1), R 1 is an acetyl group or a benzoyl group. 2 is a hydrogen atom or an alkyl group (C=1-10). 3 is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom. 4 is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom. 5 is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom.

[0011] Here, without being limited thereto, R 3 , R 4 , R 5 Examples of the aryl group in R include a phenyl group, a 1-naphthyl group, and a 2-naphthyl group. 3 , R 4 , R 5 Examples of halogen atoms in the formula include F, Cl, Br, I, and At.

[0012] In addition, in the above formula (1), R 1 ~R 5 is the structure provided by the enamide substrate. Effect of the Invention

[0013] As described above, the present invention can provide a novel N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative and a method for producing the same. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, an embodiment of the present invention will be described. However, the present invention can be embodied in many different forms and is not limited to the embodiment described below.

[0015] The N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative according to this embodiment can be produced by reacting an enamide substrate with cyanogen iodide in the presence of trispentafluorophenylborane as a catalyst.

[0016] Specifically, in the presence of trispentafluorophenylborane (B(CF)) as the catalyst according to this embodiment, zeolite (molecular sieves 3A (MS3A) manufactured by Aldrich) is added, and an enamide substrate is reacted with cyanogen iodide (ICN) in a non-polar solvent, as shown in the reaction represented by the following formula (2), to synthesize an N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative.

[0017] [ka]

[0018] According to the production method of this embodiment, the N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative represented by the following formula (1) can be obtained in high yield.

[0019] The reaction of the enamide substrate with cyanogen iodide using trispentafluorophenylborane as the catalyst according to this embodiment is preferably carried out in a non-polar solvent, particularly in dichloromethane.

[0020] In addition, the reaction of the enamide substrate with cyanogen iodide using trispentafluorophenylborane as the catalyst according to this embodiment is preferably carried out at room temperature.

[0021] In addition, in the reaction of an enamide substrate with cyanogen iodide using trispentafluorophenylborane as a catalyst according to an embodiment, the amount of cyanogen iodide used is preferably in the range of 1.1 moles or more and 1.9 moles or less, and more preferably in the range of 1.4 moles or more and 1.6 moles or less, relative to 1 mole of the enamide substrate.

[0022] Using trispentafluorophenylborane as the catalyst according to the above embodiment, an N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative was actually produced. Specific explanation will be given below. EXAMPLES

[0023] This Example 1 shown in the following formula (3) was carried out by reacting 0.0161 g of N-(1-phenylvinyl)acetamide as an enamide substrate and 0.0168 g of cyanogen iodide in 1 ml of dichloromethane in the presence of trispentafluorophenylborane as a catalyst and zeolite (Molecular Sieves 3A manufactured by Aldrich) at room temperature for 1 hour. As a result, 0.0295 g of N-(1-cyano-2-iodo-1-phenylethyl)amide was obtained. The yield of N-(1-cyano-2-iodo-1-phenylethyl)amide was 94%.

[0024] [ka]

[0025] The results of measuring the proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and infrared absorption spectrum of the N-(1-cyano-2-iodo-1-phenylethyl)amide obtained in Example 1 are shown below.

[0026] 1 HNMR(400MHz,CDCl3)δ7.52-7.56(m,2H),7.41-7.48(m,3H),6.16(s,1H),3.88(d,J=10.9Hz,1H),3.71(d,J=10.9Hz,1H),2.11(s,3H).

[0027] 13 C NMR(125MHz,Acetone-d6)δ164.0,146.1,133.8,124.8,123.9,114.3,109.9,108.3,65.7,43.3,27.3.

[0028] IR(neat):3331,3251,3054,3034,2943,2831,2216,2044,1651,1539,1493,1449,1410,1372,1302,1211,1182,1026,764,695cm -1 . EXAMPLES

[0029] This Example 2 shown in the following formula (4) was carried out by reacting 0.0175 g of (Z)-N-(1-phenylprop-1-en-1-yl)acetamide as an enamide substrate and 0.0229 g of cyanogen iodide in 1 ml of dichloromethane in the presence of trispentafluorophenylborane as a catalyst and zeolite (Molecular Sieves 3A manufactured by Aldrich) at room temperature for 15 hours. As a result, 0.0305 g of N-(1-cyano-2-iodo-1-phenylpropyl)amide was obtained. The yield of N-(1-cyano-2-iodo-1-phenylpropyl)amide was 93% (dr=4:1).

[0030] [ka]

[0031] The results of measuring the proton nuclear magnetic resonance and carbon-13 nuclear magnetic resonance of the main and minor diastereomers of N-(1-cyano-2-iodo-1-phenylpropyl)amide obtained in Example 1, as well as the infrared absorption spectrum at a diastereomeric ratio of 4:1, are shown below.

[0032] Major diastereomer 1H NMR(500MHz,CDCl3)δ7.54-7.57(m,2H),7.40-7.43(m,3H),6.48(s,1H),4.88(q,J=7.0Hz,1H),2.14(s,3H),1.81(d,J=7.2Hz,3H).

[0033] Minor diastereomer 1 H NMR(400MHz,CDCl3)δ7.51-7.53(m,2H),7.38-7.43(m,3H),6.32(s,1H),4.37(q,J=6.9Hz,1H),2.08(s,3H),1.85(d,J=6.8Hz,3H).

[0034] Major diastereomer 13 C NMR(125MHz, CDCl3)δ169.5,133.8,129.5,128.6,126.2,116.7,62.3,30.7,23.4,23.2.

[0035] Minor diastereomer 13 C NMR(125MHz, CDCl3)δ168.8,134.9,129.3,129.1,125.5,116.1,64.1,30.9,23.7,23.2.

[0036] dr=4:1 IR(neat):3284,3203,3051,2930,2241,1963,1658,1532,1492,1448,1369,1288,1208,1182,1140,1057,1036,1001,937,903,753,697cm -1 .

[0037] As described above, it was confirmed that, according to this example, N-(1-cyano-2-iodo-1-phenylalkyl)amide derivatives could be obtained in high yields. [Industrial Applicability]

[0038] The present invention can provide previously unreported N-(1-cyano-2-iodo-1-phenylalkyl)amide derivatives in high yields. These derivatives are useful for the development and production of pharmaceuticals and agricultural chemicals, and have industrial applicability. For example, they can be used as lead compounds in the development of pharmaceuticals and agricultural chemicals, and as molecular probes in biochemical research.

Claims

【Request 1】 A method for producing an N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative represented by the following formula (1) by reacting an enamide substrate with cyanogen iodide using trispentafluorophenylborane as a catalyst. １ is an acetyl group or a benzoyl group. ２ is a hydrogen atom or an alkyl group (C=1 to 10). ３ is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom. ４ is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom. ５ is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom. 【Chemistry 1】 【Request 2】 An N-(1-cyano-2-iodo-1-phenylalkyl)amide derivative represented by the following formula (1). (where R １ is an acetyl group or a benzoyl group. ２ is a hydrogen atom or an alkyl group (C=1 to 10). ３ is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom. ４ is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom. ５ is any one of a hydrogen atom, an alkyl group (C=1-10), an alkoxy group (C=1-10), an aryl group, and a halogen atom. 【Chemistry 1】

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