JPS5883671A - Preparation of tryptamine derivative - Google Patents

Abstract

PURPOSE:To obtain the titled useful compound having a physiological activity in high yield by one process, by reacting an inexpensive and easily obtainable 3-aminomethylindole as a raw material with carbon monoxide and hydrogen in the presence of a catalyst of a metal (compound) of VIII group. CONSTITUTION:A compound shown by the formulaI(R1-10 are H, halogen, hydroxyl group, alkoxy, cyano, acyl, aryl, or 1-20C alkyl; R7 and R8 or R9 and R10 may be linked through a saturated or unsaturated carbon chain) is reacted with carbon monoxide and hydrogen in the presence of a catalyst comprising at least one of a metal or a metal compound of elements of VIII group such as iron, ruthenium, cobalt, etc. in a solvent such as preferably dioxane, etc. at normal temperature -300 deg.C, preferably 30-200 deg.C, to give a compound shown by the formula II. 1H-Indole-3-methanamine, N,N-dimethyl-1H-indole-3-methanamine, etc. may be cited as the concrete examples of the compound shown by the formulaI.

Description

[Detailed description of the invention] The present invention relates to a novel method for producing tryptamine derivatives.

Further, in detail, in the presence of a catalyst containing at least one metal of group (I) or its compound, the general formula (1) (wherein R1 to RIO are hydrogen atoms), a rogen atom, a hydroxyl group, an alkoxy group , represents a cyano group, an acyl group, an aryl group, or an alkyl group having 1 to 20 carbon atoms, and R7 and R8 or Kagome and RIO may be connected by a saturated or unsaturated carbon chain). ,
- A novel method for producing a tryptamine derivative represented by the general formula (1) (wherein R1-Rlo has the same meaning as in the general formula (1,)) by reacting with carbon oxide and hydrogen. .

The tryptamine derivative represented by the general formula (II) is known as one of the important amines that itself has physiological activity. Methods for synthesizing these tryptamine derivatives include (1) a method of cyclizing phenylhydrazoyl having a nitrogen atom at an appropriate position; (A, s);

pjyAyu,, tr, (3z侃, Sσc,,,
q9.270 (1911), E, S 斤Ja-pi,
it<a<a, , (3hLB44 ,,63.120
(1930)), (2) A method of halogenating tryptophole and further substituting the halogen with an amino group (T
, HσAυn6atvl Ic, 5Lityruyc
laLbn, J wdwi LLdrLpi A7
L? l, Omm,.

520, 19 (1935), M. Jv-ILa,
J, Iyemu7L arul H,I gdcnB
uiJl, 5erO, Qmu7L, F4. , 1060
(1962)) is known.

However, method (1) requires complicated operations in order to obtain a carbonyl compound having an amine group or a group that can replace it, and cannot be said to be an industrially advantageous method.

Furthermore, method (2) has the disadvantage of using an expensive tryptohol rust conductor as a raw material.

Furthermore, as another method, a method of reducing α-ketoamide produced by adding an amine to a reaction product of indoles and oxalyl chloride (S, mzJ徂ATULW, O,
A uncle 4, J, AM OL enemy, Sαc...
766208 (1954)), but this also requires a large number of reaction steps and requires an expensive metal hydride for reduction, so it cannot be said to be an industrially advantageous enamel.

As a result of extensive research into a method for producing tryptamine derivatives that does not have these drawbacks, the present inventors have determined that 3-aminomethylindoles, which are inexpensive and easily obtained, are reacted with carbon monoxide and hydrogen in the presence of a catalyst. The present inventors have discovered that this can be easily converted into tryptamines in a single step in a high yield, and have completed the present invention.

The raw material compound used in the method of the present invention has the general formula (
1) As a specific compound, 1
H-indole-3-methanamine, N,N-dimethyl-
1H-indole-5-methanamine, N,N-diethyl-1H-indole-3-methanamine, N,N-dimethyl-11(-5-methylindole-6-methanamine, N,N-dimethyl-1H-4- Chlorindole =
Ro-methanamine, N-skatylpiperidine, N,N-dibutyl-1H-indole-3-methanamine, 1H-5
-Methoxyindole-3-methanamine, N,N-dimethyl-1H-5-methoxyindole-ro-methanamine, etc. are often used.

There are no particular restrictions on the amount of hydrogen and carbon monoxide used in the method of the present invention and the ratio of the two used. Generally, the ratio of hydrogen and carbon monoxide used in H2@co is in the range of 1:10 to 10:1, and the amount necessary for the reaction may be used.

Furthermore, these gases may be used after being diluted with an inert gas such as nitrogen, carbon dioxide, or methane.

The catalyst used in the method of the present invention is a catalyst containing at least one metal of group (I) or a compound thereof. Examples of metals include iron, ruthenium, ruthenium, nickel, rhodium, palladium, and platinum.

These metals are used as catalysts in the form of metal powders, organic raw salts, inorganic acid salts, or compounds such as complexes, or by supporting them on carriers such as activated carbon, alumina, silica, and titanium. Particularly preferred examples of the catalyst include rhodium carbonyl and rhodium salts that easily produce rhodium carbonyl in the reaction system. In addition, in the reaction of the present invention, cocatalysts such as those used in hydroformylation reactions, such as phosphorus, nitrogen, and sulfur. If various ligands including oxygen, halogen, etc. are present, the reaction will proceed under milder conditions.

In the method of the present invention, it is sufficient that the amount of the catalyst metal or metal compound used is in the range of 0.0001 to 0.1 mol based on the raw material.

Although the reaction proceeds without a solvent, an organic solvent inert to the reaction may be used as the solvent. Examples of such organic solvents include aromatic hydrocarbons such as benzene, toluene, dichlorobenzene, diphenyl ether, and xylene, n-hexane,
Aliphatic hydrocarbons such as cyclohexane, pentane, and octane, ethers such as dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether, and others such as hexamethylene phosphoramide, dimethyl sulfoxide, and dimethyl formamide can be used. . Particularly preferred are dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and the like.

The reaction temperature ranges from room temperature to 300°C, preferably from 30 to 200°C in terms of reaction rate and selectivity. The reaction pressure is in the range of 3 to 500 atm, preferably 10 to 200 atm.

The target product obtained by the reaction can be easily isolated and purified by removing the solvent and crystallizing it with hexane or the like. Furthermore, if the target product is a liquid, it can be isolated and purified by distillation or a silica gel packed bed.

The present invention will be explained below with reference to Examples.

Example 1 N, N-dimethyl-1H-indole-3- was placed in a stainless steel electromagnetic stirring autoclave with an internal volume of 10 oml.
Methanamine 4g (23mmvl'), RJ6 (C0
)16 to 0.04 (1(0,038myrt61-
), 50ml of 1,4-dioxane was added, and hydrogen and carbon monoxide were mixed in a molar ratio of 1=1 to 200 to 9/
Press in until it reaches crl. After heating and stirring this at 140°C for 1 hour, heat and pressure inside the autoclave were released.

A portion of the reaction solution was taken and the product was isolated by silica gel column chromatography. The isolated product has a melting point of 46~
47°G, infrared absorption spectrum, nuclear magnetic resonance spectrum and mass spectrum were measured to determine that N,N-dimethyl-
It was confirmed that it was tryptamine.

Furthermore, when this reaction solution was quantified by internal charge method and gas chromatography, it was found that N,N-dimethyl-tryptamine was the raw material N,N-dimethyl-1H-indole-
It was obtained in a yield of 62% based on 6-methanamine.

Example 2 In the same autoclave as in Example 1, N,N-dimethyl-
1H-5-methoxyindole-6-methanamine 4.0
9 (20mrr-el), 004g (0,058m7yLel) of RJ6(00) 16, and 50ml of 1,2-dimethoxyethane were added, and a mixed gas of hydrogen and carbon monoxide at a molar ratio of 1:1 was pressurized to 2001477.

This was heated and stirred at 150° C. for 11 hours, and then subjected to heat radiation and pressure release. The reaction solution was treated in the same manner as in Example 1, and the target product was isolated, identified, and quantified. As a result, the target product was N, N-
Dimethyl-5-methoxytryptamine was obtained in a yield of 58 cm based on the starting material.

Example 3 N,N-dimethyl-1H-indole-3- as a raw material
4' instead of methanamine! (20rrL=ner
l) The reaction, isolation, identification, and quantification of N,N-diethyl-1H-indole-ro-methanamine were carried out in the same manner as in Example 1, except that triethylene glycol dimethyl ether was used instead of dioxane as the solvent. went.

As a result, N,N-diethyltryptamine was obtained in a yield of 56% based on the raw material.

Example 4 N,N-dimethyl-1H-indole-3- as a raw material
K, 4g (15mmα)) of N, N instead of methanamine
- Gyrei - Using butyl-1H-indole = 3-methanamine as a catalyst, [14 g (0, 15 mmvi
) 6-Rhodium chloride was used, and the reaction, separation, identification, and quantification were carried out in the same manner as in Example 1. As a result, N,N-zilooptiltryptamine was obtained in a yield of 49% based on the starting material.

Patent applicant: Mitsui Toatsu Chemical Co., Ltd.

Claims (1)

[Scope of Claims] 1) General formula (wherein R, ~RIO represent a hydrogen atom, a halogen atom, a hydroxyl group, an alkoxy group, a cyano group, an acyl group, an aryl group, or an alkyl group having 1 to 20 carbon atoms) , R7 and 8
8 or R9 and Rlo may be connected by a saturated or unsaturated carbon chain) and -1
1 is characterized by reacting carbon dioxide and hydrogen in the presence of a catalyst containing at least one metal of group Ⅰ element or its compound (wherein tLz -Rio is represented by the general formula (
A method for producing a tryptamine derivative represented by (having the same meaning as in 1).