DE2359963A1 - METHOD FOR MANUFACTURING MALONIC ACIDIAL KYLESTERS - Google Patents

Description

! Broisdorf, November 30, 1973 OZ: 73 t14 C 2289)

DXHAMIO} ΚΌΒΕΙ, AKLTIENGESELLSCHAi ¹ I I'roisdorf, Bea. Cologne

Process for the preparation of dialkyl malonates

The present invention includes a process for the preparation of dialkyl maloates by reacting alkyl haloacetates with carbon monoxide and alcohols in the presence of metal carbonyls and basic compounds.

It is known by dialkyl malonate Conversion of monochloroacetic acid with alkali cyanide to cyanoacetic acid, Saponification of the ÜTltrile and subsequent esterification to produce diester (Ulimann (1960), 12th vol. p. 192). The unsatisfactory aspect of this process is the reaction sequence over several stages. In addition, dialkyl malonate starting from chloroacetic acid ester with stoichiometric Amounts of the Ha salt of cobalt tetracarbonyl hydrogen below Leakage of NaCl and formation of an intermediate product and its subsequent carbonylation and decomposition can be obtained (R.P. Heck and D.S. Breslow, J. Am. Chem. Soc., 85, 2779-82 (1963) \ However, this method gives poor yield.

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It has now been found that Malonsäuredialkyleser in a simple manner by carbonylation of Halogenessigsäurealkyl- esters at pressures between 0.5 and 150 at in the presence of catalytic Amounts of metal carbonyls and alcohols, in the presence of basic agents, can be prepared.

The invention therefore relates to a method for production of malonic acid dialkyl esters by converting haloacetic acid alkyl esters with carbon monoxide and alcohol, which is characterized in that the reaction of the haloacetic acid ester carried out with carbon monoxide and alcohol in the presence of basic agents and catalytic amounts of metal carbonyls will.

The reaction takes place according to the equation

HalCH ₂ -C00R + C0 + R ^f 0H-> ROOC-CH ₂ -COOR ¹ + HHaI

In the reaction equation, R and R 'mean primary, secondary or tertiary alkyl groups with 1 to 8 carbon atoms, where R and R ' can be different or the same of the radicals or groups mentioned, and Hal denotes chlorine, bromine or iodine. The educated Hydrogen halide is bound by the basic agent.

According to the present invention, malonic esters are produced in a very simplified and economical manner in a one-step process Procedure accessible. Furthermore, the mixed esters of malonic acid, which are difficult to obtain in any other way, are so light

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representable. For example, when chloroacetic acid methyls & Gr are reacted with CO in the presence of cobalt carbonyls and K ₂ CO ₇ in ethanol, methyl ethyl malonate is obtained in good yield.

As a rule, the reaction is carried out with thorough mixing of the reactants and auxiliaries in solution or suspension thereof. _;

The reaction can be carried out in various ways. All the basic means necessary for the implementation can be dissolved or suspended together with the metal carbonyl and the haloacetic ester added. Haloacetate and basic agents can, however, also be metered into the solution of the metal carbonyl. After all, he can ■ Haloacetic ester present together with the solution of the metal carbonyls and the basic agent dissolved or suspended in be added to the alcohol in question.

The amount of the basic agent should be at least 1 mol of a mono-acidic basic agent or 0.5 mol of a two-acidic one basic agent per mole of haloacetic ester. The i basic agent can also be used in excess. as basic agent such compounds can be used, in the presence of which under the given reaction conditions the There is no further reaction of the malonic ester formed with haloacetic esters.

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_ a -

Suitable "basic gowns" are basic salts of the Alkali or alkaline earth metals such as carbonates, bicarbonates, acetates, sec. u. tert. Phosphates, oxides of the alkaline earth metals such as MgO and CaO, and tert. Amines such as triethylamine.

Suitable alcohols are those primary, secondary or tertiary with 1 to 8 carbon atoms, polygons if necessary, for example with alkyl groups of 1 to 3 carbon atoms, such as Methanol, ethanol, propanol, isopropanol, tert. Butanol,

n-butanol, 2-ethylhexanol. [

The reaction of said reactants is in the temperature range of 10 C to 200 C, preferably between 20 C and 15O ⁰ C, performed. The reaction time is between 1 and 6 hours, depending on the selected temperature and the selected pressure and the mixing.

The conversion of the haloacetic ester takes place at a low CO pressure of, for example, 0.5 at. Appropriately one works at higher pressures in the range up to 150 at, to achieve a higher space / time yield. Preferably works at pressures between 5 and 80 at.

From the group of metal carbonyls, preferred carbonyls of cobalt and iron are used as catalysts. the Catalysts can be used in bulk or in suitable solvents.

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Suitable solvents for this are, inter alia, aliphatic or cyclic ethers such as diethyl ether, dipropyl ether, 1,2-di-,

methoxyethane, tetrahydrofuran, dioxane, alcohols with 1 to 8 C-atoms, ketones such as acetone or methyl ethyl ketone, esters such as Esters of acetic acid with lower alcohols, especially alcohols with 1 to 3 carbon atoms. j

The metal carbonyl is conveniently in the form of a solution that by carbonylating a metal compound, e.g. cobalt carbonate, in one of the above. Solvent among the usual Carbonylation conditions is formed.

The molar ratio of metal carbonyl to .Halogenessigsäure-! ester can be between 1: 2 to 1: 500, preferably from 1: 5 to ' 1: 100 lie.

The starting materials for the dialkyl malonate are monohaloacetic acid alkyl esters, such as chlorine, bromine or iodoacetic acid esters. The chloroacetic esters are used because of their good accessibility preferred.

The CO and optionally the basic agent are metered in over a period of 1 to 6 hours. Instead of of pure CO can also be a CO diluted with inert gas. e.g. Water gas can be used. . ·

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The malonic acid esters produced by the process according to the invention are known to be worthwhile chemical intermediates e.g. for the production of pharmaceuticals.

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example 1

30 g of Co ₂ (CO) ₈ and 80 g (2 mol) of MgO are heated together in 400 ml of ethanol in a 2 l-lift autoclave at a pressure of 3 at to 55 ° C. 245 g (2 mol) of ethyl chloroacetate are metered into 200 ml of ethanol over the course of 3 hours, with CO reacted off being replenished to a pressure of 5 atm every half hour. The mixture is left for 2 hours at 55 ⁰ C. After completion of Re ~ ■

action is mixed with water, with H «SO, acidified and with: Aether extracted. Distillation gives 23 g of chlorine

ethyl acetate and.181 g malonic acid diethyl ester i

( $ 62.5>yield).;

Example 2

Under the conditions given in Example 1, but using 400 ml of methanol and 160 g (1.15 mol) of K ₀ CO. * And at a pressure of 50 at CO, 216 g (2 Mol) methyl chloroacetate metered in 200 ml of CH, OH. After the reaction, the reaction mixture is filtered off with suction from the precipitated salt and distilled. In addition to 16.6 g of methyl chloroacetate, 238 g of dimethyl malonate (97.5% yield) are obtained.

Example 3

Analogous to Example 2, but using 60 g (1.1 mol) CaO as a basic agent, after the reaction about 32 g

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Methyl chloroacetate 154 g of dimethyl malonate (68.5 % yield) were obtained.

Example 4

Analogous to the example. 2, but using 108 g (1 mol) of methyl chloroacetate, 10 g of Co ₂ (CO) ₈ and 180 g (1.1 mol) of Na «HPO. as the "basic agent in methanol", 60.5 g of dimethyl malonate (yield 49 #) are isolated after the reaction in addition to 1 g of methyl Cl acetate.

Example 5

Analogous to Example 4, but with 82 g (0.5 mol) of Fa ₅ PO. as a basic agent, after the reaction, in addition to 1.5 g of methyl acetate, 98.5 g of dimethyl malonate (yield 76 %) are isolated.

Example 6

Analogous to Example 4, but with 112 g of triethylamine as basic agent, in addition to 8 g of methyl chloroacetate, 81.5 g of dimethyl malonate are added after the reaction (Yield 67 #) isolated.

Example 7

Analogously to Example 2, 340 g (1.65 mol) of chloroacetic acid

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2-ethylhexyl ester, 130 g (0.93 mol) of E ₂ CO ₅ , 700 ml of 2-ethylhexanol and 25 g of Co ₂ ( ^c °) ß are used. There are 347 g of Malon-. acid di-2-ethylhexyl ester (yield 66 $) isolated.

_: Example 8:

: Analogous to Example 2, but using 700 ml of ethanol

-

; are used instead of methanol after work-up |

: I.

'80g methyl chloroacetate,
: 106 g of methyl ethyl ester and

'-. 105 g malonic acid diethyler isolated.

Example 9!

Analogous to Example 2, but using 216 g of methyl chloroacetate, 20 g of Co ₂ (CO) ₈ and 60 g of CaO as
basic agent in methanol, will be next after the reaction
33 g of methyl chloroacetate (15 ^) 131 g of dimethyl malonate (yield 59.5 #) were obtained.

Example 10

Analogous to example 2, but using 5 g of Co ₀ (CO) ₀

C. O

and at 100 C as the reaction temperature, after the reaction, in addition to 38 g of methyl chloroacetate, 180 g of methyl methyl ester (83> 5% yield) isolated.

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Example 11

Analogously to Example 2, but using 83.5 g of ethyl bromoacetate, 8 g of Co ₂ (CO) ₈ and 80 g of E ₂ CO., As a basic agent in ethanol, 57 g of diethyl malonate (yield 71 #) are obtained.

Example 12

Analogously to Example 2, but using 250 g of ethyl chloroacetate, 10 g of Co ₂ (CO) ₈ and 106 g of Na ₂ CO as the basic agent, 141 g of ethyl chloroacetate (56 μg) and 90 g of diethyl malonate (yield 65%) are obtained after the reaction fi) received.

Example 13

108 g (1 mol) of methyl chloroacetate are carbonylated under the conditions given in Example 2. Instead of pure CO, a 1: 1 mixture of C0: H _? used by 70 at. The distillation gives 11.8 g of methyl chloroacetate and 108.2 g of dimethyl malonate (yield 91 #).

Example 14

250 ml of ethanol, 76 g (0.55 mol) of K _£ CO ₅ , 7.5 g of basic cobalt carbonate, 1 g of Fa ₂ S ₂ O ₄ , 0.5 g of Co (OH) ₂ and 0.5 g

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Co ₂ (CO) ₈ are reacted for one hour in a 21-stroke antoclave at 130 C and 100 at cold pressure. Then 250 ml; Ethanol "is metered in over the course of 4 hours. After working up, 82 g of diethyl malonate are obtained (yield 51.2 $>) , in addition to ethyl hydroxyacetate. J

Example 15!

The 2-1 Hubautoklaven 76 g (0.55 mol) of K ₂ CO ₃ 300 mL "j of methanol and 5 ml Pe (CO) j- presented. At 60 ⁰ C and at 48 at 108 g (1 mole) Methyl chloroacetate and 200 ml of methanol are added over the course of 5 hours. The reaction mixture is mixed with H ^ O, _{acidified with H 2} SO. And extracted with ether. 44.2 g of methyl chloroacetate and 12 g of dimethyl malonate are obtained (yield 15.5%). ) obtain.

Example 16

150 ml of a 10% solution of Co ₂ (CO) ₈ in methyl acetate are placed in a round bottom flask together with 150 ml of methanol. Then, with stirring, CO is passed through at an excess pressure of 600 mm Hg for 30 minutes and heated ^{to 55 ° C.} 108 g (1 mol) of methyl chloroacetate are added dropwise over the course of 3 hours and 40 g of MgO (1 mol) are added in portions while CO is constantly being passed through.

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2353963

N AOHOEREIOHT

Then stir. 2 hours until no CO uptake more is done. The reaction mixture is then mixed with water, acidified with sulfuric acid and extracted with ether. If the ether is removed, 46 g of dimethyl malonate are isolated (Yield 36 #) and 4.5 g of methyl chloroacetate.

Example 17

Under the conditions given in Example 9, but using 10 g of Co ₂ (CO) ₈ , dissolved in 150 ml of methanol, 70 g of Ep CO, (0.5 mol) are used as the basic agent and 108 g (1 Mol) methyl chloroacetate reacted with CO. The reaction mixture is separated from the precipitated salt and first the methanol and finally the product are distilled off. There are recovered 44 »g Chloressigsäuremethylester 5 and 46 g of dimethyl malonate (59,2 yield).

Example 18

Under the conditions given in Example 9, but using 50 ml of a 20 # solution of Co ₂ (CO) ₈ in tetrahydrofuran, 60 g (0.6 mol) of CaCO, as the basic agent and 350 ml of methanol as the solvent, 108 g (1 mol) of methyl chloroacetate reacted with carbon monoxide. 67 g of methyl chloroacetate and 5 g of dimethyl malonate are isolated.

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I - 13 -

I example 19

^: Analogous to Example 9, but using 10 g of Co ₂ (CO) ₈ i and 84 g (I.Mol) of HaHCO ,, are after work-up

! 89.9 $> chloroacetic acid methylsers and; 8 fo malonic acid dimethyler

i received.

i Example 20

\ In analogy to Example 9, but using, of 10 g of Co ₂ ι (C0) _Q and 164 g (2 mol) of Ka-acetate, g is obtained after working up a fraction _t of 88.5, which, according to gas chromatogram

I 62.3 # chloroacetic acid methyl esters and

I 18.8 <$> malonic acid dimethyl ester

'contains.

Example 21

122.5 g (1 mol) of ethyl chloroacetate are obtained using 10 g of Co ₂ (CO) ₈ , 76 g (0.55 mol) of K ₂ CO ₅ and 400 ml of tert-butanol in the 2 1-Hubanto class at 7O ⁰ C and 60 at Co carbonylated for 6 hours. The reaction mixture is with H _? 0 added, with H ₂ SO. acidified and extracted with ether. Distillation yields 6.8 g of ethyl chloroacetic acid and 11.4 g

Malonsäurediäthyleser (yield 7.5 $) _s 114 g Malonsätirreätb.j ^r l-tert-butyl ester (yield 64 $) and traces Malonssäuredi tert-butyl ester.

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Claims (1)

2353963 Claims; Process for the production of Malonsäuredialky! Esters by reacting Halogenessigsäurealkylesern with carbon monoxide and. Alcohol, characterized in that ""_; the reaction of the haloacetic acid esters with carbon monoxide and alcohol in the presence of hasischer means and kata-; lytic amounts of metal carbonyls is carried out. j 2. The method according to claim 1, characterized in that ι as a metal carbonyl of cobalt and / or iron carbonyl 'is used. .; 3. The method according to claim 2, characterized in that the metal carbonyl used is cobalt octacarbonyl. ! 4. The method according to any one of claims -1 to 3, characterized in that ! indicates that the metal carbonyl is a cobalt carbonyl ^; is used, which is obtained by carbonylation of a cobalt i salt in a solvent from the group of alcohols, ; Ethers, ketones or esters. 5. The method according to any one of claims 1 to 4, characterized in that that metal carbonyl and haloacetic acid ester in a molar ratio of 1: 2 "to 1: 500," preferably from 1: 5 to 1: 100 can be used. 509 82 3/097 7 6. The method according to any one of claims 1 to 5 _f, characterized in that colche compounds are used as the basic coat, in the presence of which under the given reaction conditions the further drying of the malonic esters formed with haloacetic esters does not occur. 7. The method according to any one of claims 1 to 6, characterized in that that as a basic coat, basic salts of the alkali or alkaline earth metals such as carbonates. Bicarbonates, acetates, sec, and tert. Phosphates, oxides of alkaline earth metals such as MgO or CaO and tert. Amines used will. 8. The method according to any one of claims 1 to 7, characterized in that a primary, secondary or tertiary alcohol of C ₁ to C ₈ , which may optionally be substituted, is used as the alcohol. 9. The method according to any one of claims 1 to 8, characterized in that the reaction in the temperature range from 10 to 200 ⁰ C, preferably from 20 to 150 ° 0 is carried out. 10. The method according to any one of claims 1 to 9, characterized in, that the reaction is carried out at a carbon monoxide pressure of 0.5-150 atm. 5 0 9 8 2 3/0977 ^BAD original 2359983- 11. decay according to any one of claims 1 to 10, characterized in that that the reaction with an era by inert gas diluted carbon oxide is carried out. Dr. Ia / I »oe 509823/0977 ORiGaNAL INSPECTED