JPS60123431A - Production of phenoxyacetone compound - Google Patents

Abstract

PURPOSE:To produce the titled substance useful as an intermediate of agricultural chemicals and pharmaceuticals, in high yield, by contacting a 3-phenoxypropylene compound with an alkyl nitrite in the presence of water, alcohol and Pd catalyst. CONSTITUTION:The titled substance can be produced by reacting 1mol of 3-phenoxypropylene with 2.1-5mol of an alkyl nitrite in the presence of 10-100mol of water, 0.5-10l of an alcohol (preferably an alcohol having 1-10C alkyl group or benzyl group) and a Pd catalyst at 10-90 deg.C for 10min-5hr. The Pd catalyst is Pd salt (e.g. palladium chloride), Pd complex [e.g. dimer of dichloroethylene palladium (II)], etc., and its amount is 0.003-0.1mol per 1mol of the 3-phenoxypropylene compound. The use of a copper compound (e.g. CuCl) in combination with the Pd catalyst improves the selectivity and increases the yield of the objective compound per unit catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing phenoxyacetones.

Phenodiacetones are intermediate raw materials for agricultural chemicals such as insecticides and herbicides, and intermediate raw materials for pharmaceuticals such as coronary artery dilators, antihypertensive agents, and central nervous system sedatives.

It is a useful f-hybrid compound.

Conventionally, phenoxyacetones have been produced by heating phenols and monohalogenated acetone under alkaline conditions. However, this method uses monohalogenated acetone.

For example, monochloroacetone and monobromoacetone are lachrymatory and toxic compounds, so they should be handled accordingly.

It is necessary to take great care in storage and transportation, and this method is not necessarily satisfactory from an industrial standpoint.

The present inventor conducted extensive research in order to establish an industrially advantageous manufacturing method for phenoxyacetones.

As a result, 3-phenoxypropylene and water.

The present invention has been achieved based on the discovery that phenoxyacetones can be produced in high yield by contacting with an alkyl nitrite ester in the presence of an alcohol and a palladium catalyst.

Next, nine aspects of the present invention will be described in detail.

One of the raw materials of the present invention is 3-7 enoxypropylene, and the benzene ring of this 3-phenoxypropylene may have a substituent. Examples of substituents include hydroxyl group, halogen atom, nitro group, optionally N-substituted amine group, lower alkyl group with 6 or less carbon atoms, lower alkoxy group with 6 or less carbon atoms, carboxyl group, lower Alkylcarbonyl group, lower alkylcarbonyl group.

N-optionally substituted amide 7 carbonyl group.

Examples include a cyan group and a cyclobexol group which may have a substituent. These substituents can be attached to the benzene ring in a total number of up to three. Therefore 1
The 3-phenoxy7propylene used in the present invention has the 9th order (
+) can be expressed by the formula.

(x, y, and z are hydrogen atoms and hydroxyl groups, respectively.

A halogen atom, a nitro group, an optionally N-substituted amine group, a lower alkyl group, a lower alkoxy group, a carboxyl group, a lower alkylcarbonyl group.

=bQ, They may be the same or may differ by 1L. Also, X, Y.

Any two of Z may cooperate with a part of the benzene ring to form a 5- to 7-membered heterocycle containing 1 to 21 oxygen atoms. ) The above 3-phenoxypropylenes represented by the formula
CH,,Cl! It can be easily obtained by reaction with (e.g.).

Another raw material of the present invention is an alkyl nitrite ester, which can be represented by formula (II).

RONO (II) (Here, R is an aliphatic, aromatic or alicyclic alkyl group, preferably an alkyl group having 1 to 10 carbon atoms or a benzyl group.) In addition, the above formula (II) In particular, R is methyl or ethyl.

Preferred are aliphatic groups such as propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl, or aralkyl groups such as benzyl, among which aliphatic alkyl groups having 1 to 4 carbon atoms, i.e., methyl,
Ethyl, n-propyl.

Isopropyl, n-butyl, 1sO-butyl, 5ec-
Butyl and the like are preferred.

As can be seen from the reaction formula below, it is necessary to use at least 2 moles of nitrous alkyl ester per mole of 3-phenoxypropylene, and in the actual reaction, 3-7-phenoxypropylene Add 1 mole to 1 mole and 2 to 1
0 mol, preferably 2.1 to 5 mol is used.

In the present invention, the amount of water introduced into the reaction system is usually 1 to 30% per mole of 3-phenoxypropylene as a raw material.
It is within the range of 0 mol (preferably 10 to 100 mol). If the amount of water is less than the lower limit of the above range, the yield of the target phenoxyacetones will decrease. Even if the amount of water r is greater than the upper limit of the above range, it will not interfere with the progress of the reaction.

Many; 11. On the other hand, washing eggs in water does not have any particular effect.

2) A problem arises in that the process of recovering the alcohol after completion of the process becomes troublesome.

Although it is not clearly known how nitrite alkyl esters and water are involved in the reaction used in "Fukkari J or Daiichi", it is likely that 3-phenoxypropylenes and nitrite alkyl esters are involved in the reaction. It is presumed that 1-phenyl-2,2-dialkoxypropanes are produced, which are hydrolyzed by water to become phenoxyacetones.

Therefore, the reaction on which the production method of the present invention is based is as follows.

It can be considered as follows.

0-0H2-CH=CH2 The reaction proceeds advantageously in the presence of an alcohol and a palladium catalyst. Alcohol used here (D
9L! : t, -c, methyl alcohol, ethyl alcohol, flobyl alcohol, phthyl alcohol, /<
octyl alcohol, hexyl alcohol, heptyl alcohol, octyl alcohol.

Alcohols having an alkyl group or a benzyl group having 1 to 10 carbon atoms, such as nonyl alcohol, te/ter alcohol, and benzyl alcohol, are preferable. Talented 1
Using an alcohol having the same alkyl group as the alkyl group of the nitrite alkyl ester used in the reaction has the advantage of making it easier to recover and reuse the alcohol from the reaction solution, so it is recommended to select such an alcohol. preferable. Such alcohol is usually used in an amount of 0.5 to 1 mole of 3-phenoxypropylene used.
01 is used.

In addition, since the above alcohol also acts as a reaction solvent,
Although there is no particular need to use other solvents.

Other solvents can be used if desired. Such a solvent is not particularly limited as long as it is substantially inert to the reaction utilized in the present invention. An example of a suitable solvent is ethyl acetate.

Lower fatty acid esters such as butyl acetate, ethers such as dioxano, dibutyl ether, and tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene, and xylene, alicyclic hydrocarbons such as cyclohexane, and aliphatic hydrocarbons such as n-hexane. can be mentioned.

The palladium catalyst used in the present invention includes:

Mention may be made of palladium salts or palladium complexes. As palladium salts, palladium chloride, palladium bromide, palladium iodide, palladium with a halogen ratio of 7i are particularly useful, and palladium acetate, p-palladium sulfate, palladium nitrate, and the like can also be used. Also.

Examples of palladium complexes include dichloroethylene palladium (II) doublet, dibromoethylene palladium (n
) dimer of dichloropropylene palladium (■)
dimer of dibromopropylene palladium (■),
Bis(acetonitrile)palladium(II) chloride, bis(acetonitrile)palladium(n) bromide, bis(benzonitrile)haladium A(n) chloride, bis(benzonitrile)palladium(II) bromide, bis(dimethylsulfoxide)palladium( It
) chloride, bis(N,N-dimethylformamide)
Palladium (■) chloride, bis(N.

N'-dimethylacetamido)palladium(II) chloride, tetrakis(acetonitrile)palladium(I)
I) Tetrafluoroborate, tetrakis(acetonitrile)palladium (■) barchlorate, bis(acetylacetonato)palladium ([), tetrachloropalladium (n) dazzling sodium salt, tetrabromopalladium (II) I'R lithium term, Bis(oxalate)
Examples include palladium(II) acid lithium salt, tetranitropalladium(II) IW sodium salt, and the like.

These palladium catalysts are generally 1 mol, 0.001 to 0.2 mol, per mol of 3-phenoxypropylene,
And, preferably 0.003 to 0.1 mol is used. If the amount of catalyst used is less than the lower limit of this range, the reaction will not proceed to the optical stage, and even if the amount of catalyst used is greater than the upper limit of iλ (iλ), the reaction rate will not increase. This is not preferable because it makes almost no contribution, and on the other hand, it becomes time-consuming to recover the catalyst, and the loss of the catalyst increases during catalyst recovery.

In the method of the present invention, it is also possible to coexist a copper compound with the palladium catalyst. In this case.

The selectivity of the target product is further improved, and the amount of target product produced per unit amount of palladium catalyst is increased, which makes it possible to reduce the use of expensive palladium catalysts. Examples of copper compounds include halogenated steel,
Sulfuric acid steel, copper nitrate, hydroxide, copper oxide, etc. may be mentioned. Among these, cuprous chloride, cupric chloride, and cuprous bromide.

Copper halides such as cupric bromide are preferred. It's 1.

In case of use of copper compounds other than copper halides.

It is preferable to coexist about 0.1 to 5 moles of hydrohalic acid per mole of the rectangular compound. The amount of these copper compounds used is usually 30 mol or less, preferably 1 to 10 mol, per mol of palladium catalyst used. If the amount used is less than the lower limit of this range, no promoter effect is expected.

Also, there is no particular effect even if you use more than the upper limit.

Rather, the separation and recovery of the catalyst becomes complicated, so it is preferable to use Zγ
stomach.

The reaction of the present invention can be carried out at a temperature of 0 to 150°C. At temperatures higher than 150°C, the isomerization reaction 1. Side reactions such as S tend to proceed, and at temperatures lower than 0°C, 5
On the other hand, the speed becomes small and it is not practical. Incidentally, a practically preferable reaction temperature is a temperature within the range of 10 to 90°C. Buta 1 reaction time is a reaction! Generally, the time can be selected from within the range of 10 minutes to 5 hours, although it varies depending on the reaction conditions such as suction.

There is no particular limit to the pressure in the reaction system of the tail and time.

Usually normal pressure to 200 K9/crrt (gauge pressure)
A range of pressures can be selected.

The present invention can be implemented, for example, by the following method.

The raw material 3-phenoxypropylene is in the reactor! :,
Add water, flucol, palladium catalyst, and copper compound if necessary, add 1 alkyl ester τ of nitrous, and add 1
In the evening, the reaction is allowed to proceed under certain conditions.

However, there is no particular restriction on the order in which these raw materials, catalysts, etc. are added. After the completion of the reaction, 1 reaction liquid was distilled to reduce the amount of N generated.
o gas, unreacted raw materials, alcohol.

Separate and obtain the desired reaction products (phenoxyacetones). The unreacted raw materials and alcohol recovered here are recycled and recycled.The No gas also recovered is J1! of nitrous 1.5 alkyl ester! ! It can also be used for construction.

Next, nine examples of the present invention will be shown.

In addition, the reaction rate of the raw material and the yield of the target product in the 1% example are 1
The value is calculated according to the formula shown below.

Reaction rate of raw material [3-phenoxypropylenes] (candy) -
Diction of CyA material ↓゛6 weight (mol) ÷ amount of raw material charged (mol)) x 100 Yield (%) of 1:l fishing proboscis [phenoxyacetones] - [
Chemical formula 1 ζ Amount of target product (mol) ÷ Preparation page of raw material (mol)) xlo○ Oxita. The "r Pd turnover number on each side" is a value calculated using a 7th order equation as a measure of the activity of the palladium catalyst.

Example].

0.10 mol of 3-phenoxypropylene as a raw material.

367 t of water, 0.5 t of methanol, and 0.003 t of palladium chloride as a catalyst were charged into a molke reactor, and while stirring, methyl nitrite gas (diluted to 15 voJ% with N2 scum) was blown into the liquid at 20°C for 1. No reaction occurred for 51 yen.

It should be noted that after about 1 hour after the start of 1st L6, the generation of No gas almost completely disappeared.

Reaction: The finished dust 1 reaction solution was subjected to gas chromatography (VC) to quantify unreacted raw materials and the generated target product, phenoxyacetone, in the 1 reaction solution.

The results are shown in Table 1.

k-use 1 tari 2-20 raw materials (7) instead of 3-phenoxypropylene.

First, each of the following 3-phenoxypropylenes is 0,]
○ Did you implement anything other than using molar? 1” Reaction 4 using the same procedure as in 1.
went. The results are shown in Table 1.

Table 1 Peck on the batter Continued from Table 1 Continued from Table 1 Implementation cases 1121-28 0.10 mol each of 3-phenoxypropylene 2+4 shown in Table 2 was used, and the palladium catalyst shown in Table 2 was used. A practical operation was carried out in the same manner as in Example 1, except that 0.003 mol of each was used. The results are shown in Table 2.

Table 2 Continuation of Table 2 *: Implemented 4 hours 128 times, 0.003 mol in terms of Pd atoms.

In other words, 0.0015 mol is used as a two-emotional body.

Implementation i; l 29-36 Each of the 3-phenoxypropylenes shown in Table 3 was added at 0.1
0 mol, water 367, methanol 0.57. 0.0005 mol of palladium chloride, cuprous chloride (CuC4)
Or 0.002 of cupric chloride (CuCffi2)
Charge 5 mol of nitrite into a reactor and add methyl nitrite gas (
The reaction was carried out at 20° C. for 1.5 hours while blowing a solution (diluted to 15 vof% with N2 gas) into the liquid.

Note that approximately 1 hour after the start of the first reaction, the generation of NO gas almost ceased.

After the reaction was completed, the same analytical operations as in Example 1 were carried out. The results are shown in Table 3.

Table 3 Continuation of Table 3 Examples 37 to 45 3-Phenoxypropylene Ml) shown in Table 4 40.1
0 mol, water 36y, curved salt r? n-butyl 025
mol, n-butyl alcohol o, 5 t, and 3 mol of palladium catalysts o and oo shown in the fourth column were charged into 9 reactors, and the reaction was carried out at a reaction temperature of 60° C. for 1.5 hours with stirring. After the reaction was completed, the same 1:1 operation as in Example 1 was performed. The results are shown in Table 4.

Table 4 Continuation of Table 4 Examples 45 to 50 0.1 each of the 3-phenox7 propylene shown in No. 5
0 mol, water 36 g, n-butyl nitrite 025 mol, n-
Butyl alcohol 0.5t, catalyst palladium chloride 0.
0,005 mol of cupric chloride and 1 d of cupric chloride.
0025 mol was charged into a reactor, and the reaction was carried out under stirring (F-reaction temperature: 60°C for 15 hours).

After the reaction was completed, the same analytical operation as in Example 1 was performed.

The results are shown in Table 5.

Table 5 Continuation of page 1 ■Int, CI,' Identification symbol Internal organization t59- (issue G

Claims (1)

[Claims] 1. A method for producing phenoxyacetones, which comprises contacting 3-phenoxypropylenes with an alkyl nitrite ester in the presence of water, alcohol and a palladium catalyst.