DE1213395B - Process for the preparation of N- (gamma-oxoalkyl) -carbamic acid esters - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

Number:
File number:
Registration date:
Display day:

C07c

C07d
German class: 12 ο -17/01

1,213,395
F36098IVb / 12o
February 23, 1962
March 31, 1966

The preparation of carbamic acid esters containing oxo groups is already known.

It has been found that N- (γ-oxoalkyl) carbamic acid esters obtained when α-substituted N-alkyl-carbamic acid esters of the general formula

X —CH-N —COOR '

(D

in which R 'represents an alkyl, cycloalkyl, aralkyl or aryl radical or a heterocyclic radical, R stands for a hydrogen atom or the radical R ', X stands for halogen atom, the - OR, - OCOR radical, a urethane group of the general formula

N-COOR 'R

(Π)

a dialkylamino group of the general formula

R "
R "'

N -

(III)

a dialkylammonium or trialkylammonium group of the general formula

R "n

R "'

R "

Process for the preparation of N- (γ-oxoalkyl) -carbamic acid esters

Applicant:

Paint factories Bayer Aktiengesellschaft,
Leverkusen

Named as inventor:

Dr. Gerhard Müller,

Dr. Rudolf Merten, Leverkusen;

Dr. Helmut Kritzler, Cologne-Flittard

Nitroaryl, chloraryl or acetylaryl radical is converted to compounds of the general formula

R ₂

Ri-CO- C -CH- N-COOR '(VI)
R ₄ RR

in which R, Ri, R2 and R 'are those given above Have meaning and R4 for the radicals mentioned for R3 or for

- CH - N - COOR '

(IV)

is, wherein R and R 'have the meaning given above and R "is a hydrogen atom or denotes an alkyl radical, with oxo compounds of the general formula

Ri - CO - CH R ₃

(V)

in which Ri, R2 and R3 represent a hydrogen atom, an alkyl, cycloalkyl, aralkyl, aralkenyl or aryl radical or a heterocyclic radical or two of the radicals each represent members of a closed ring, R _x furthermore represents an alkoxycarbonylalkyl, ketoalkyl -, chloroalkyl, aralkyl,

stands.

For example, acetophenone and N - chloromethyl - N - methyl - carbamic acid ester are converted into the link

CO - CH ₂ - CH ₂ - N - COOR '

CH ₃
obtain.

Aliphatic and cycloaliphatic aldehydes are used as oxo compounds for the purposes of the invention and ketones in question which have at least one CH bond in the α-position, such as, for example Acetaldehyde, substituted acetaldehyde, such as phenylacetaldehyde, propionaldehyde, butyraldehyde and isobutyraldehyde, Isovaleraldehyde, hexahydrobenzaldehyde, acetone, 1,1-diphenylacetone, methyl ethyl ketone, methyl isopropyl ketone, Cyclopentanone, cyclohexanone,

609 540/423

substituted cyclopentanones and hexanones. Mixed aliphatic-aromatic ketones are also suitable, e.g. B, acetophenone, substituted _{acetophenones, etc.,} such as 3- or 4-nitroacetophenone, 3- or 4-halo-acetophenone and ω-halo-acetophenone, propiophenone, benzalacetone, deoxybenzoin.

Compounds can also be used as starting substances which, in addition to the oxo group contain other functional groupings, insofar as these do not influence each other, such as for example levulinic acid ester, acetonylacetone and diacetyl-berizole.

The α-substituted N-alkyl-carbamic acid esters used for the reaction with the oxo compounds correspond to the general formula

X —CH-Ν —COOR '

Carbamic acid esters can be obtained from carbamic acid esters and formaldehyde and then converted into alkoxymethyl carbamic acid esters with alcohols.
The preparation of compounds of the formula

wherein R and R 'have the above meaning, where for R' z. B. the following groups are listed: Methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, hexyl, octadecyl, allyl, vinyl, Benzyl, phenyl, chlorophenyl, nitrophenyl, tolyl, Pyridyl, naphthyl, cyclohexyl, ß-phenethyl group. The production of these compounds is known in part. This is how connections with X become the same Halogen already described in British patent specification 471 130. They are preserved through direct conversion of a urethane with formaldehyde-hydrochloric acid. A preferred method used ■ to produce this class of compounds consists in the cleavage of hexahydro-s-triazines or Schiff's bases with chloroformic acid esters or phosgene, according to the information provided by the German Patents 1153 756. Such compounds can then with alcohols or alcoholates in l-alkoxy-alkyl compounds or with carboxylic acid salts be converted into IrAcyloxy-alkyl compounds. Other known methods of manufacture of such compounds consist in the action of bromine and alkali metal alcoholates on alkoxyacetamides or in the reaction of alkoxyacetic acid azide with absolute alcohol. Oxymethyl-NHCOOR '

R-CH

NHCOOR '

is also known and is made, for example, from the corresponding aldehydes (R-CHO) and carbamic acid esters (NH2COOR ') in water or by distilling off the water, optionally on an azeotropic basis Ways, or by implementing malonic acid diazides

CON ₃

R-CH

CON ₃

with alcohols (ROH).

Also known in principle is the preparation of carbamic acid esters where X is (R ") 2N - or (R") ₃ N® · - "by reacting, for example, dialkylamine in a Mannich reaction with aldehyde and carbamic acid ester in aqueous, alcoholic or glacial acetic acid solution or without The quaternization to the ammonium salt can then be carried out in a customary manner, for example by the action of methyl joelide.

In numerous cases, the carbamic acid esters of the general formula

X— CH (R) - N (R) - COOR '

condensed with the oxo compounds immediately after their preparation without prior isolation will. In the table below are a number of starting compounds of the general formula

45 X - CH (R) - N (R) - COOR '

listed.

CH ₂ X — CH — N — COOR '
II
RR Made of Bp. ⁰ C Cl- CH ₂ H ₃ CO
- N — C — 0 —CH ₃ 1,3,5-trimethyl-hexahydro-s-triazine-
Methyl chloroformate Kp.12 = 70 to 72 Cl- CH ₂ H ₃ CO
- N — C — 0 —C2H5 1,3,5-trimethyl-hexahydro-s-triazine-
Ethyl chloroformate Kp.11 = 74 to 76 Cl- CH ₂ H ₅ CO
-NC-OC ₆ H ₅ 1,3,5-trimethyl-hexahydro-s-triazine-
Phenyl chloroformate Bp 12 = 154 H ₃ CO
-NCO-CH ₂ - C ₆ H ₅ 1,3,5-trimethyl-hexahydro-s-triazine-
Benzyl chloroformate Bp 0.85 = 121 to 122

continuation

X - CH- Ν— COOR '
II
RR 0
NHCOC ₂ H ₅ Made of Bp. ⁰ C iso-C 1,3,5-triisobutyl-hexahydro-s-tri-
azine — chloroformic acid methyl
ester Kp.i8 = 98 : 4H9
O
Il Cl - CH ₂ - N - C - O - CH ₃ 1,3,5-triallyl-hexahydro-
s-triazine-chloroformic acid
methyl ester Kp.i3 = 91 to 92 CH =
H ₂ CC Cl-CH ₂ -NC N-methyl-N-chloromethyl-carbatnin-
ethyl acid ester — sodium ethylate Kp.i3 = 77 to 78 CH ₂
) N-methyl-N-chloromethyl-carbamine-
acid chloride — sodium ethylate Kp.i3 = 77 to 78 KJ L-Xl ₃ N-methyl-N-chloromethyl-carbamine-
ethyl acid ester — potassium acetate Kp.i3 = 105 to 107 H ₃ CO
H ₅ C ₂ - 0 - CH ₂ -Ν - C - 0 - C ₂ H ₅ Carbamic acid ethyl ester
Formaldehyde-methanol Kp.is = 97 to 100 H ₁ O
H ₅ C ₂ - 0 - CH ₂ -Ν - C - 0 - C ₂ H ₅ Carbamic acid ethyl ester
Formaldehyde-ethanol Kp.is = 106 to 108 OH ₃ CO
Il I Il
CH ₃ -CO-CH ₂ -N-COC ₂ H ₅ Ν, Ν-Bischloromethyl-carbamic acid-
chloride - 3 moles of methylate Kp.ii = 83 to 85 O
Il
H ₃ C - O - CH ₂ - NH - C - O - C ₂ H ₅ Carbamic acid ethyl ester
Formaldehyde-diethylamine Kp.o, i5 = 75 to 80 O
H ₅ C ₂ - O - CH ₂ - NH - C - O - C ₂ H ₅ Carbamic acid ethyl ester
Formaldehyde-dimethylamine Bp 0.6 = 82 to 84 (CH ₃ OCH ₂ ) ₂ N - COOCH ₃ O
Il
(C ₂ Hs) ₂ -N-CH ₂ -NHCOC ₂ H ₅ (CH ₃ ) ₂ N - CH ₂ -

The compounds prepared in this way are due to their generally low hydrolytic stability in as anhydrous form as possible.

The reaction between the α-substituted N-alkyl carbamic acid esters and the oxo compounds can be carried out directly, but it is advantageous to add catalysts, such as, for example are known for the Friedel-Crafts reaction in anhydrous form.

Examples include: anhydrous organic and inorganic acids such as sulfuric acid, Phosphoric acid, perchloric acid, hydrogen halides, fluorosulfonic acid, chlorosulfonic acid, trichloroacetic acid, Methanesulfonic acid, toluenesulfonic acid, technical sulfonic acid mixtures of aliphatic or aromatic nature, such as long-chain paraffin substituted by sulfonic acid groups with z. B. 10 to 18 carbon atoms, sulfonated polymers based on polyvinyl compounds, etc., which may be crosslinked Polystyrene or phenol-formaldehyde condensates; also anhydrous acting as Lewis acids Metal or non-metal halides, such as boron trifluoride and its adducts with ether or acetic acid, Boron trichloride, phosphorus halides, phosphorus oxyhalides, aluminum chloride, zinc chloride, Tin (IV) chloride, iron (III) chloride, antimony (V) chloride or chromium (II) chloride.

Because of the simple work-up, BF3 and its adducts z. B. on ether used.

In addition to the acidic catalysts described above, alkaline catalysts such as NaOH, KOH or K ₂ CO ₃ can also be used. The amount of catalyst that may be required depends on the nature of the reaction components and can vary within wide limits. To avoid undesirable side reactions, the smallest possible amounts of catalyst should be used, but in special cases amounts of up to 30%, based on the oxo compound, can also be used.
The proportions between the oxo compounds and the α-substituted N-alkyl-carbamic acid esters can, for example, be varied largely due to the fact that the carbamic acid ester used can be N-substituted several times.

In general, the starting components will be used in roughly calculated amounts, so far not one reactant as particularly valuable with an excess of the other component should be brought to the most complete implementation possible.

To carry out the reaction, the components are subjected to conditions that are as anhydrous as possible, optionally in the presence of the catalysts, combined, with when using of N-Cl-chloroalkyrj-carbammic acid ester in the absence basic groups, is developed in the molecule HCl. The reaction is generally after a few hours, e.g. B. free application of temperatures of 40 to 120 ° C, ended, in the In most cases, the use of solvents such as aliphatic, aromatic or chlorohydrocarbons, is beneficial. Working up is carried out in the usual way, for. B. by distillation or crystallization, after the acidic catalyst has optionally been removed beforehand is. The reaction products obtained by the process according to the invention represent intermediates, z. B. for the production of amines. They can also be used as stabilizers, plasticizers and can be used as biocidal components.

example 1

To a mixture of 60 parts by weight of acetophenone and 76 parts by weight of N-chloromethyl-N-methyl-carbaminsäureäthylester 5 parts by volume of BF3 etherate are added dropwise at 85 ⁰ C in 2 hours. HCl develops immediately. The mixture is kept at 85 ° C. for a further 6 hours, the cooled reaction mixture is diluted with 150 parts by volume of benzene, extracted with water and the benzene is removed in vacuo. 102 parts by weight of a dark-colored, liquid residue remain, which is purified by distillation in vacuo. 37 parts by weight of the light yellow colored co- (N-carbethoxy-N-methyl) -aminomethyl-acetophenone with a boiling point of 138 to 140 ° C., n% ° = 1.5258 are obtained. The elemental analysis and the IR spectrum confirm the assumed structure.

The analogous reaction of acetophenone with N - chloromethyl - N - methyl - carbamic acid ethyl ester without a catalyst leads to the same reaction product, but in a lower yield:

Eg game 2

In a manner analogous to Example 1, 67 parts by weight of propiophenone are condensed with 76 parts by weight of N-chloromethyl-N-methyl-carbamic acid ethyl ester in the presence of 5 parts by volume of BF3 etherate. After working up, 98 parts by weight of a crude product remains. Distillation gives 34 parts by weight of the pale yellow 1-phenyl-2-methyl-3-(N-carbethoxy-N-methyl) -amino-1-oxopropane of bp .0.1 = 130 to 131 ° C, ni ° = 1.5148. Elemental analysis and IR spectrum are correct for the assumed structure.

Example 3

A solution of 23 parts by weight of benzalacetone, 24 parts by weight of N-chloro-methyl-N-methyl-carbamic acid ethyl ester and 1 part by volume of BF3 etherate in 100 parts by volume of anhydrous benzene is heated at 80 ° C. for 8 hours. The reaction mixture is then extracted by shaking with water and the solvent is distilled off. The remaining liquid residue in an amount of 33 parts by weight is distilled in vacuo. The «- (Ν-carbethoxy - N - methyl) - aminomethylbenzalacetone with a boiling point of 0.13 = 94 to 101 ° C. is obtained in an amount of 14 parts by weight, n% = 1.5412. Elemental analysis and IR spectrum speak for the assumed structure.

Example 4

To a solution of 95 parts by weight of methylenebisurethane and 15 parts by volume of BF3 etherate in 150 parts by volume of anhydrous benzene are in

43 parts by weight of methyl isopropyl ketone were added dropwise at 80 ° C. under nitrogen for 2 hours. It is held at 80 ° C. for a further 8 hours and worked up in the manner described. From the liquid crude product obtained in an amount of 66 parts by weight, 7 parts by weight of unreacted methylene-bisurethane crystallize out and are filtered off with suction. By distilling the crude product, 35 parts by weight of 1-N-carbethoxyamino-2,2-dimethyl-butanone- (3), which after redistillation ^{boils at bp 0.1 = 87 to 88 0} C, ni ° = 1, 4525. The structure is confirmed by elemental analysis, IR and nuclear magnetic resonance spectrum.

Example 5

To a solution of 95 parts by weight of methylene bisurethane and 10 parts by volume of BF3 etherate in 100 parts by volume of anhydrous benzene are in

49 parts by weight of cyclohexanone was added dropwise for 3 hours at 8O ⁰ C. The mixture is left for a further 10 hours at 8O ⁰ C to react, operates in the usual way and obtained 61 parts by weight of a liquid reaction product. The distillation of this gives 20 parts by weight of 2-N-carbethoxyaminomethyl-cyclohexanone- (1), which boils in the redistillation at bp 0.2 = 117 ° C., nf = 1.4788. Elemental analysis and IR spectrum apply to the assumed structure.

Example 6

To a solution of 95 parts by weight and 15 parts by volume Methylenbisurethan BFe etherate in 200 parts by volume of anhydrous toluene 67 parts by weight propiophenone are added dropwise in 2 hours at 100 ⁰ C under nitrogen. ^{The mixture is kept at 100 °} C. for a further 10 hours, as already described, for working up the reaction mixture is shaken out with water and the solvent is removed in vacuo. After standing for a while, 3 parts by weight of unreacted methylene-bisurethane with a melting point of 132 ° C. separate from the liquid residue obtained in an amount of 117 parts by weight, and these are filtered off with suction. Distillation of the crude product gives 60 parts by weight of 1-N-carbethoxyamino-2-methyl-3-phenyl-3-oxopropane, which passes over during redistillation at boiling point 0.07 = 146 ° C., n ^z S = 1.5220 . Elemental analysis and IR spectrum confirm the assumed structure.

Example 7

53 parts by weight of benzaldehyde and 89 parts by weight of carbamic acid ethyl ester. dissolved in 250 parts by volume Benzene, are condensed in the presence of 1 part by volume of BF3 etherate to form benzyl bisurethane, the water of reaction in an azeotropic way

Will get removed. To the reaction solution for a further 10 parts by volume of BF3 etherate are added and dropped in 3 hours at 80 ⁰ C under nitrogen, 60 parts by weight of acetophenone. The mixture is left for another 10 hours at 80 ⁰ C to react, works in the manner übliehen and a viscous, honey-yellow residue obtained in an amount of 121 parts by weight, which consists of lN-Carbäthoxyamino-l ^ -diphenyl-3-oxopropan. The IR spectrum speaks for the specified structure.

Example 8

To a solution of 55 parts by weight of N, N'-dimethyl-methylene-bisurethane and 10 parts by volume of BF3 etherate in 100 parts by volume of anhydrous toluene, 30 parts by weight of acetophenone are added dropwise over 4 hours at 100.degree. It is held at 100 ^° C. for a further 10 hours, the reaction solution is washed with water until it reacts neutral and the solvent is removed in vacuo. The liquid crude product remaining in an amount of 45 parts by weight is distilled in vacuo and yields 14 parts by weight of w- (N-carbethoxy-N-methyl) aminomethyl-acetophenone, which after redistillation at boiling point o8 = 140 to 145 ⁰ C boils, nf = 1.5275. The IR spectrum shows that the reaction product obtained is identical to that shown in Example 1.

Example 9

30th

To a solution of 15 parts by volume of BF3 etherate in lOOVoIumteilen anhydrous toluene are added dropwise 67 parts by weight propiophenone and 74 parts by weight of N-ethoxymethyl-carbaminsäureäthylester simultaneously over 4 hours at 90 ⁰ C. The reaction mixture is allowed to react for a further 8 hours at 100.degree. C., worked up in the manner described and 109 parts by weight of a liquid crude product are obtained which, after vacuum distillation, yields 63 parts by weight of 1-N-carbethoxyamino-2-methyl-3-phenyl-3-oxopropane. After redistillation, this boils at b.p.o.is = 142 to 150 ⁰ C, κ !? = 1.5185. The IR spectrum is identical to the reaction product from Example 6.

Example 10

45

To a solution of 36 parts by weight of isobutyraldehyde, and 76 parts by weight of N-chloromethyl-N-methyl-carbaminsäureäthylester in 100 parts by volume of anhydrous benzene 5 parts by volume BFe etherate are added dropwise in 2 hours at 8O ⁰ C under nitrogen. Is maintained for a further 8 hours at 8O ⁰ C, shaken with water, and receives a 57 parts by weight of a concentrated dark-colored, liquid residue, which is purified by distillation in vacuo. The /? - (N-carbethoxy-N-methyl) -amino-a, a-dimethylpropionaldehyde formed boils at a boiling point of 0.15 = 73 to 74 ° C. and is obtained in an amount of 39 parts by weight; nff = 1.4449. The structure is verified by elemental analysis and IR spectrum.

Example 11

To a solution of 43 parts by weight of methyl isopropyl ketone and 76 parts by weight of N-chloromethyl-N-methyl-carbaminsäureäthylester anhydrous benzene in 5 parts by volume lOOVoIumteilen BFs etherate are added dropwise in 2 hours at 8O ⁰ C under nitrogen. It is allowed to further 8 hours at 8O ⁰ C react operates as described, and the liquid residue which remains in an amount of 55 parts by weight distilled. 40 parts by weight of 1- (N-carbethoxy-N-methyl) -amino-2,2-dimethyI-butanone- (3) with a boiling point of 78 ° C .; n!? = 1.4485. The IR spectrum confirms the assumed structure.

Example 12

To a solution of 12 parts by volume of BF3 etherate in lOOVoIumteilen anhydrous toluene 60 parts by weight of acetophenone and 74 parts by weight of N-Äthoxymethylcarbaminsäureäthylester are added dropwise at 90 ⁰ C in 4 hours simultaneously. The mixture is left for another 10 hours at 90 ⁰ C to react and worked up in conventional manner to give 102 parts by weight of a viscous residue which passes over in the distillation at Kp.o, i = 155 to 182 ° C in an amount of 46 parts by weight. From the pale yellow distillate, 20 parts by weight of the eo, co-bis (N-carbethoxy) aminomethyl acetophenone with a melting point of 71 to 73 ° C. crystallize in colorless needles. The liquid remainder of the distillate consists of w- (N-carbethoxy) aminomethyl acetophenone. The structures of the compounds are confirmed by the elemental analysis and the IR spectrum.

Example 13

To a solution of 95 parts by weight and 15 parts by volume Methylenbisurethan BF3 etherate in 200 parts by volume of anhydrous toluene 60 parts by weight of acetophenone are added dropwise in 4 hours at 100 ⁰ C under nitrogen. Is maintained for a further 8 hours at 100 ⁰ C, operates as described to give, after distillation of the crude reaction product 30 parts by weight of a fraction boiling at Kp.0,5 = 150-188 ⁰ C distillate, from which 16 parts by weight of the cy, co-bis- (N-carbethoxy) aminomethylacetophenone with a melting point of 71 to 73 ° C crystallize out. The remainder of the distillate consists of - (N-Carbethoxy) -aminomethyl-acetophenone. The IR spectra of the compounds agree with those from Example 12.

Claims (2)

Patent claims: 1. Process for the preparation of N- (y-oxoalkyl) -substituted Carbamic acid esters, denoted by the fact that one was α-substituted N-alkyl-carbamic acid esters of the general formula X —CH-N —COOR ' in which R 'represents an alkyl, cycloalkyl, aralkyl or aryl radical or a heterocyclic radical Radical, R stands for a hydrogen atom or the radical R ', X stands for halogen atom, the - OR-, - OCOR radical, a urethane group of the general formula -N-COOR ' a dialkylamino group of the general formula R " N - R "' (III) 609 540/423 a dialkylammonium or trialkylammonium group the general formula R " R '\ (IV) stands in which R and R 'have the meaning given above and R "is a hydrogen atom ίο or denotes an alkyl radical with oxo compounds of the general formula Ri CO CH
R ₃ (V) in which Ri, Rg and R3 represent a hydrogen atom, an alkyl, cycloalkyl, aralkyl, aralkenyl or aryl radical or a heterocyclic radical Remainder stand or two of the remainders each represent members of a closed ring, Ri continues for an alkoxycarbonylalkyl, ketoalkyl, Chloralkyl, aralkyl, nitroaryl, chloraryl or acetylaryl radical is converted into compounds the general formula R ₂
Ri - CO - C - CH - N-COOR ' R ₄ R (VI) in which R, Ri, Ra and R 'are those given above Have meaning and R4 for the radicals mentioned for R3 or for -CH
R. N-COOR 'R stands. 2. The method according to claim 1, characterized in that the condensation reaction in Is carried out in the presence of acidic or alkaline catalysts. Publications considered: Franch Simont & Friedmann, R 26, p. 226.