IL34830A - N-formyl-alpha-nitro-alkane carboxylic acid amides and their production - Google Patents

Description

The invention concerns new N-formyl-a-nitro-alkane carbox- ylic acid amides and a process for the production thereof.

From the literature it is known to react activated aromatic compounds with a formylating agent based on an N-disubstituted formamide and a halogenating agent for the production of aldehydes (Vilsmeier-Haak reaction) .

According to the present invention, N-formyl-a-nitro-alkane carboxylic acid amides of the Formula I ° wherein R^ represents an alkyl radical having 2 to 12 carbon atoms , and R2 and R^ independently of each other each represent a lower alkyl radical, are produced by reacting an alkane carboxylic acid amide of the 5 Formula II wherein R^, and have the meaning given for Formula I, with the formamide of a secondary amine and a halogenating agent, nitrating the complex intermediate thus obtained at a temperature between -10 and +30°C, and then hydrolyzing it at a temperature below +30°C.

For the process according to the invention, the starting materials N-alkyl-carboxylic acid amide, formamide and halogenating agent are preferably employed in a molar ratio of 1:1:2. The formamide can, however, also be employed in a multiple of the molar amount, the excess serving as solvent and/or diluent. In general, an aprotic solvent or diluent is necessary in the reaction forming the complex compound. Besides formamide, aliphatic halogenated hydrocarbons such as dichloromethane , chloroform, chlortanated ethanes, aromatic hydrocarbons and halcgenated hydrocarbons, as well as ether and ether-type compounds, etc. may be employed as aprotic solvents and diluents. Aprotic solvents are those which do not give off protons under the given reaction conditions.

Suitable as carboxylic acid amides of Formula II are the N-lower alkyl amides of the following alkane carboxylic acids: ethane carboxylic acid (propionic acid) , propane carboxylic acids (butyric acid, isobutyric acid), butane carboxylic acid (valeric acid, isovaleric acid, butane-2-carboxylic acid), pentane carboxylic acids (caproic acid, isocaproic acid, etc.), hexane carboxylic acid (enanthic acid, etc.), heptane carboxylic acids (caprylic acid, etc.), octane carboxylic acids (pelargonic acid, etc.), nonane carboxylic acids (capric acid, etc.), decane carboxylic a cids , undecane carboxylic acids (e.g. lauric acid), dodecane carboxylic acids, tridecane carboxylic acids (myristic acid) .

The formaraides of secondary amines employed correspond to the Formula III R' .

N - CHO (III) Ru In this formula: R' represents an alkyl radical having 1 to 5 carbon atoms R" represents an alkyl radical having 1 to 5 carbon atoms a phenyl, benzyl or cycloalkyl radical, or R' and RM together with the adjacent nitrogen atom represent a heterocyclic ring which can contain further hetero atoms.

Preferably the following formamides of Formula III are employed: N ,N-dimethylformamide , ,N-diethylformamide , N-methyl-formanilide, N- formylmorpholine , in particular, however, N,N-di-methyIformamide .

Suitable as halogenating agents are, in particular, the halides of the following inorganic oxyacids: phosphorus oxy-chloride, phosphorus trichloride, phosphorus pentachlor.ide , phosphorus tribromide, phosphorus oxybromide, thionyl chloride, sulfuryl chloride, phosgene, oxalyl chloride or benzoyl bromide.

For the nitration, preferably nitrating acid, i.e. a mixture of concentrated or fuming nitric acid and concentrated sulfuric acid, is used. In order to attain as quantitative a nitration as possible, it is advantageous to use the nitrating acid in excess; preferably the double to fivefold molar amount of HNO^ is used, calculated on the amount of alkane carboxylic acid amide used. When a nitrating acid consisting of concentrated nitric acid, concentrated sulfuric acid and sulfur trioxide is used, the molar ratio of nitric acid to alkane carboxylic acid amide can be 1:1.

When performing the process according to the invention, it has proved expedient to start with the formamide, adding the halogenating agent at temperatures between 0° and 40°C, preferably between 0° and 10°C, while stirring thoroughly. When the formamide is used in equimolar amounts, calculated on the carboxylic acid amide, it is necessary to perform the reaction in the presence of an organic aprotic solvent or diluent. Then the alkane carboxylic acid amide is added. Both of the last-mentioned reaction components , the halogenating agent and the alkane carboxylic acid amide, can be employed in the reaction dissolved in one of the aprotic solvents mentioned above such as benzene, chloroform, etc. To increase the velocity of the . reaction, which in itself proceeds smoothly at temperatures in the range of 0 to 40°C, the reaction mixture can be heated to temperatures of not more than 120°C, preferably to 60 to 85' C. After completion of the reaction, it is expedient to remove the solvent at 0 to 40°C in vacuum and to add the complex intermediate product obtained directly to the nitrating acid. Also for this step in the nitration, it is essential that the temperature be kept below 30CC, preferably at 10°C. The nitrating mixture is finally hydrolyzed with ice water, the temperature not being more than 30°C, preferably not more than 15°C.

The new N-formyl-a-nitro-alkane carboxylic acid amides are obtained according to the invention in very good yields.. They are important intermediates from which, by reduction of the nitro group and subsequent hydrolosis a-amino acids are produced.

The following examples illustrate the invention. ' The temperatures are given in degrees centigrade and the boiling points are uncorrected.

Exam le 1 11.9 ml of di eth lformamide in 250 ml of chloroform are treated dropwise at 0 to 5° with 26.3 ml of phosphorus oxychloride. The mixture' is then stirred, for one hour at 5° , then treated with a solution of 13.6 g of isobutyric acid-methyl amide : 1.4405, b.p. 56- 0° /0.005 Torr) in 120 ml of chloroform, stirred for one hour at room temperature and then refluxed for 10 hours. The reaction mixture is then cooled and concentrated in vacuum. A nitrating mixture obtained from 22 ml of concentrated nitric acid and 120 ml of concentrated sulfuric acid is then added dropwise to the residue at 0 to 10°with stirring. The mixture is then poured onto ice and extracted several times with chloroform. After drying and removal of the chloroform by distillation, the residue is fractionated in vacuum. The cc-nitro-isobutyric acid-N- formy1-N-methyl-amide has a boiling on point of 75-85°/0.001 Torr. Refraction index nD = 1.4780.

Example 2 12 ml of dimethylformamide and 100 ml of chloroform are treated dropwise at 20° with 26.3 ml of phosphorus oxychloride and stirred for 30 minutes at the same temperature. The mixture is then treated dropwise at 20° with a solution of 15.2 g of isovaleric acid-N-methylamide (b.p. 74-76V0.01 Torr, refraction index ηβ = 1.4444), stirred for one hour at 20° and subsequently refluxed for 10 hours.. The mixture is then concentrated in vacuum. The. residue is treated dropwise at 0 to 10a with a nitrating mixture obtained from 22 ml of concentrated nitric acid and 120 ml of concentrated sulfuric acid, then poured onto ice and extracted with chloroform. After cooling and removal of the solvent by distillation, the residue is fractionated in vacuum. The a-nitro-isovaleric acid-N-formyl-N-methylamide has a boiling point of 80-90°/0.001 Torr, refraction index r^20 = 1.4764.

In the manner described in the preceding examples , using the appropriate carboxylic acid amides of Formula II, dimethyl- formamide and phosphorus oxychloride, there are obtained the compounds listed in the following table: Compound physical data a-nitro-lauric acid-N-formyl- b.p. 145- 150° 10.05 Torr N-methylamide a-nitro-lauric acid-N-formyl- N-n-butylamide

Claims (8)

What we claim is:

1. N-Formyl-a-nitro-alkane carboxylic acid amides of the Formula I R, 0 0 (I) I N - CHO - wherein represents an alkyl radical having 2 to 12 carbon atoms , and R and R¾ independently of each other each represent a lower alkyl radical.

2. Process for the production of N- formyl-a-nitro-alkane carboxylic acid amides of the Formula I R wherein , R2 and R^ have the meanings given for Formula I in Claim 1, characterized by reacting an alkane carboxylic acid of the Formula II (II) with the formamide of a secondary amine and a halogenating agent, nitrating the complex intermediate product obtained and subsequently hydrolyzing it.

3. Process according to Claim 2, characterized by employ ing dimethylformamide as formamide of a secondary amine, and halides of inorganic oxyacids as halogenating agent.

4. A. Process according to Claims 2 and 3, characterized by employing phosphorus trichloride, phosphorus tribromide, phosphorus oxyehloride, phosphorus pentachloride , phosgene or thionyl chloride as halogenating agent,

5. Process according to Claim 2, characterized by performing the nitration with a . mixture consisting of nitric acid and sulfuric acid.

6. Process according to Claims 2 and 5, characterized by nitrating the intermediate product at temperatures between -10 and +30° C.

7. Process according to Claims 2 and 5, characterized by performing the hydrolysis at temperatures below +30° C.

8. Process according to Claim 2, characterized by performing the reaction in the presence of organic aprotic solvents and/or diluents.