DE2032628B - - Google Patents

Description

CH-C

R ₂

N-CHO
R ₃

in which R ₁ denotes the methyl group or an alkyl group with 2 to 12 carbon atoms, R ₂ denotes a hydrogen atom or a lower alkyl group and R ₃ denotes a lower alkyl group, characterized in that an alkanecarboxamide of the general formula II

R ₁

CH-C

R ₂

(H)

NHR ₃

in which R ₁ , R ₂ and R _{3 have} the meaning given above, reacts with a formamide of a secondary amine and a halogenating agent and nitrates the complex intermediate product obtained at temperatures between -10 and +30 ⁰ C and then at temperatures below +30 ⁰ C hydrolyzed.

2. The method according to claim 1, characterized in that that when carrying out the reaction with formamide and carboxamide in a molar ratio of 1: 1, an aprotic solvent clogs.

The reaction of activated aromatic compounds with a formylating reagent is known from the literature based on an N-disubstituted formamide and a halogenating agent for the preparation known from aldehydes (Vilsmeier-Haack reaction).

According to the process of the present invention, N-formyl-a-nitro-alkanecarboxamides are the general formula I.

R ₁ NO ₂ O

R ₁

(D

N-CHO

in which R _{1 is} the methyl group or an alkyl radical with up to 12 carbon atoms, R _{1 is} a hydrogen atom or a lower alkyl radical and R _{3 is} a lower R ₂

NHR ₃

ίο in which R ₁ , R ₂ and R _{3 have} the meaning given above, reacts with the formamide of a secondary amine and a halogenating agent and nitrates the complex intermediate product obtained at temperatures between -10 and +30 ⁰ C and an-

closing hydrolyzed at temperatures below +30 ⁰ C.

A preferred embodiment of the method of the invention is that when carrying out the reaction with formamide and carbon

acid amide in a molar ratio of 1: 1 is an aprotic solvent clogs.

The starting materials for the process according to the invention are N-alkylcarboxamide, formamide and halogenating agents are preferably used in a molar ratio of 1: 1: 2. One can but also use a multiple of the molar amount of formamide, with an excess as a solution and / or diluent is used. In general, the reaction step involves complex formation the presence of an organic aprotic solvent or diluent is required. Except The formamide can include aliphatic halogenated hydrocarbons such as dichloromethane, chloroform, chlorinated Ethanes, aromatic hydrocarbons and halogenated hydrocarbons, as well as ethers and ethereal ones Compounds can be used as aprotic solvents or diluents. Aprotic Solvents are those which do not release any protons under the selected reaction conditions.

The carboxamides of the general formula II are the N-lower-alkylamides of the following alkanecarboxylic acids into consideration: ethanecarboxylic acid (propionic acid), propanecarboxylic acids (butyric acid, isobutyric acid), Butanecarboic acids (valeric acid, isovaleric acid, Butane-2-carboxylic acid), pentane carboxylic acids (caproic acid, isocaproic acid), hexacarboxylic acids (Oenanthic acids), heptane carboxylic acids (caprylic acid), octane carboxylic acids (pelargonic acid). Nonarboxylic acids (Capric acid), decanoic acids, undecanoic acids (e.g. lauric acid), dodecanoic acids. Tridecanecarboxylic acids (myristic acid). The formamides used of a secondary Amines correspond to the general formula III:

55 R '

R "

N - CHO

(III)

60 R 'denotes an alkyl radical with I to 5 carbon atoms, R "denotes an alkyl radical with I to S carbon atoms, a phenyl, benzyl or cycloalkyl radical or R' and R" together with the be » adjacent nitrogen atom a heterocyclic ring which may contain further heteroatoms.

Preferred formamides of the general formula III are N, N · dimethylformamide, Ν, Ν-di »

ethyl formanilide, N - methylformanilide, N - formylmorpholine, but especially N.N-dimethylformamide, used.

Particularly suitable halogenating agents are the halides of the following inorganic oxygen acids are possible; Phosphorus oxychloride, phosphorus trichloride, Phosphorus pentachloride, phosphorus tribromide, phosphorus oxybromide, thionyl chloride, sulfuryl chloride, Phosgene, oxalyl chloride or benzoyl bromide,

"Mixed acid" (nitrating acid), ie a mixture of concentrated or fuming nitric acid and concentrated sulfuric acid, is preferably used for the nitration. In order to achieve the most quantitative possible nitration, it is advisable to use the nitrating acid in excess; it is preferred to use twice to 5 times the molar amount of HNO ₃ , based on the alkanecarboxamide used. When using a nitrating acid consisting of concentrated nitric acid, concentrated sulfuric acid and sulfur trioxide, the molar ratio of nitric acid to alkanecarboxamide can be 1: 1.

When carrying out the process according to the invention, it has proven to be expedient to initially charge the formamide and to add the halogenating agent at temperatures between 0 and 40 ° C., preferably between 0 and 10 ^° C., with thorough stirring the carboxamide is used, the presence of an organic aprotic solvent or diluent is necessary. The alkanecarboxamide is then added. The last two reaction components, halogenating agent and alkanecarboxamide, can be used in the reaction as a solution in one of the aforementioned aprotic solvents, such as benzene or chloroform To accelerate the reaction, which actually proceeds smoothly in the temperature range from 0 to 40 "C., the reaction mixture can be heated to temperatures not higher than 120" C., preferably to 60 to 85 "C. After the reaction has ended, it is advisable to remove the solvent at 0 to 40 ° C. in vacuo and to add the complex intermediate product obtained directly to the nitrating acid. For this nitration step, too, it is essential to keep the temperature below 30.degree. C., preferably at 10.degree. The nitration mixture is finally hydrolyzed with ice water, the temperature not exceeding 30.degree. C., preferably not exceeding 15.degree.

The new N-formyl-rj-nitro-alkanecarboxamides are obtained according to the invention in very good yields. They are important intermediate products from which α-amino acids are produced by reduction of the nitro group and subsequent hydrolysis will.

The following examples illustrate the process of the invention. The temperatures are given in degrees Celsius and the boiling points are uncorrected.

Example I.

11.9 ml of dimethylformamide are dissolved in 250 ml of chloroform submitted and at 0 to 5 ° with 26.3 ml of phosphor

phosphorus oxychloride was added dropwise. The mixture is then stirred for 1 hour at 5 °, then with a solution of 13.6 g of isobutyric acid methylamide ("5." + 1.4405, bp 56 to 6070.005 torr) in 120 ml Added chloroform, 1 hour at room temperature

ίο stirred and then heated to reflux temperature for 10 hours. The reaction mixture is then cooled and concentrated in vacuo. A nitration mixture, obtained from 22 ml of concentrated nitric acid and 120 ml of concentrated sulfuric acid, is added dropwise to the residue with stirring at 0 ° to 10 °. The mixture is then poured onto ice and extracted several times with chloroform. After the chloroform has been dried and distilled off, the residue is fractionated in vacuo. The α-nitro-isobutleric acid-N-formyl-N-methylamide has the boiling point 75 to 85 / 0.001 Torr; Refractive index n $ = 1.4780; Yield: 65% of theory.

Example 2

26.3 ml of phosphorus oxychloride are added dropwise to 12 ml of dimethylformamide and 100 ml of chloroform at 20 ° and the mixture is stirred at the same temperature for 30 minutes. A solution of 15.2 g of isovaleric acid-N-methylamide (boiling point 74 to 76 "/ 0.01 Torr, refractive index ni ° = 1.4444) is then added dropwise to the mixture at 20" and the mixture is stirred at 20 'for 1 hour and then boiled for 10 hours at reflux temperature. The mixture is then concentrated in vacuo. The residue will be at 0 to 10 '

with a nitration mixture obtained from 22 ml of conc. Nitric acid and 120 ml conc. Sulfuric acid, drop by drop added, then poured onto ice and extracted with chloroform. After drying and distilling off of the solvent, the residue is fractionated in vacuo. The a-nitroisovaleric acid-N-formyl-N-methylamide has a boiling point of 80 to 90'70.0Ol Torr;

Refractive index / 1? = 1.4764; Yield: 54.5% of theory.

In the way described in the previous examples using the appropriate Carboxamides of the general formula II, dimethylformamide and phosphorus oxychloride, which are in the connections listed in the following table:

connection

(i-Nitro-lauric acid-N-formyl-N-methylamide.
Yield: 9% of theory

(i-nitro-lauric acid-N-formyl-Nn-butylamide,
Yield; 32% of theory

Physical data

Kp. 145 to 150 /
0.05 torr

M.p. 52 to 54 °

Claims (1)

Patent claims: I. Process only production of N-Formyi-H-nitroalkanecarboxamides of the general formula I. Alkyirest mean, prepared by adding an alkanecarboxamide of the general formula II