DE2032628A1 - N-Formyl-apha-mtro-alkanecarboxamides and process for their preparation - Google Patents

Description

«T. ^ L · ^¥ - ^ ¹¹¹ "· * · ¹ ·» «· η. - Dr, B. Aeemann Dr, ft Ko.nifl« b »rg.r - WpI. Phy · .R. Holzhauer ς_ o _n o _Q * Dr. P. Zom.Uln fun.5a- JO 89 *

P ο t · η »ο * wa 11 · 8 MOncfian 2, Iräufcoujjtroö · 4 / III

N-formyl-a-nitro-alkanecarboxamides and process for their preparation

The invention relates to new N-formyl-a-nitro-alkanecarboxamides and a method for their production.

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

According to the present invention, N-formyl-anitro-alkanecarboxamides are used of formula I,

- CHO L

in the i '-

R- ^ is an alkyl radical with 2 to 12 carbon atoms, R2 and Ro each independently represent a lower alkyl radical, . '. prepared by adding an alkanecarboxamide of the formula II,

(II)

^ H

R £ "NHR ₃

in which R ,, R2 and R ^ have the meaning given under formula I, 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 then at

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Temperatures below +30 ⁰ C hydrolyzed.

For the process according to the invention, the starting materials N-AlIy 1-carboxylic acid, formamide and halogenating agent are preferably used in a molar ratio of 1: 1: 2. However, a multiple of the molar amount of formamide can also be used, an excess serving as a solvent and / or diluent. In general, the presence of an organic aprotic solvent or diluent is required in the course of the complex formation. In addition to formamide, aliphatic halogenated hydrocarbons, such as dichloromethane, chloroform, chlorinated ethanes, aromatic hydrocarbons and halogenated hydrocarbons, and ethers and ethereal compounds, etc., can be used as aprotic solvents or diluents. Aprotic solvents are those which do not release any protons under the chosen reaction conditions.

^: As carboxamides of the formula II, the N-lower alkylamides of the following alkanecarboxylic acids come into consideration: ethyl carbonic acid (propionic acid), propanecarboxylic acids (butyric acid, isobutyric acid), butanecarboxylic acids (valeric acid, isovaleric acid, butane-2-carboxylic acid), pentanecarboxylic acids (caproic acid) »Isocaproic acid etc.), hexanecarboxylic acids (oenanthic acids etc.)» Heptanecarboxylic acids (caprylic acid etc.), octanecarboxylic acids (pelargonic acid etc.), nonanecarboxylic acids (capric acid etc.), decanecarboxylic acids, uodecarboxylic acids (e.g. lauric acid), dodecanecarboxylic acids, tridecanecarboxylic acids ).

The formamides used correspond to a secondary amine of formula III:

- CHO (III)

In this formula:

R ^{1 is} an alkyl radical with 1 to 5 carbon atoms,

R "is an alkyl radical with 1 to 5 carbon atoms * a phenyl, Benzyl or cycloalkyl radical, or

R ¹ and R "together with the adjacent nitrogen atom form a heterocyclic ring which can contain further heteroatoms.

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■ ■: - -: ■■■: -: ■ - 3 - ■ ^: ■ / ■■■. '

Preferred formamides of the formula III are N, N-dimethylformantide, N, N-diethyformamide, N-methylformanilide, N-formylmorpholine, but in particular Ν, Ν-dimethylformainide used.

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

"Mixed acid" (nitrating acid) is preferred for the nitration, i.e. a mixture of concentrated or fuming nitric acid and concentrated sulfuric acid are used. In order to achieve the most quantitative nitration possible, it is advisable to to use the nitrating acid in excess; it is preferred to use twice to 5 times the molar amount of HNOo, based on the alkanecarboxamide used. When using a nitrating acid, that from concentrated nitric acid, concentrated sulfuric acid and sulfur trioxide, the molar ratio can be from nitric acid to alkanecarboxamide 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. If the formamide is used in equimolar amounts, based on the carboxamide, the presence of an organic aprotic solvent or diluent is necessary. The alkanecarboxamide is then added. The two last-mentioned reactants, halogenating agents and alkanecarboxylic acid amide, can be used in the reaction as a solution in one of the aforementioned aprotic solvents, such as benzene, chloroform, etc. To accelerate the reaction, which actually proceeds smoothly in the temperature range of 0-4O ⁰ C, the reaction mixture can be ^{heated to temperatures not higher than 120 0} C, preferably to 60-85 ° C. After completion of the reaction it is expedient to add the Lbsungsmittel at 0-40 ⁰ C in vacuo to remove the complex intermediate obtained directly the nitrating » 'At this step of the nitriding, the temperature ist.es essential below 30 ⁰ C, preferably at Keep 10 ^{0 C.} The nitration mixture

109830/2096 r

. 4 - ■

is finally hydrolyzed with ice water, the temperature should not be more than 30 ⁰ C, preferably not more than 15 ° C.

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

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

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Example L <5

11.9 ml of Dimetiiylformaraid are placed in 250 ml of chloroform and at 0 to 5 ° with 26.3 ml of phosphorus oxychloride added dropwise. The mixture is then stirred for one hour at 5 °, then

finally with a solution of 13.6 g of isobutyric acid methylamide

90
(rii + 1.4405, bp 56-60 ° / O, 005 Torr) in 120 ml of chloroform, stirred for one hour at room temperature and then for 10 hours
Heated to reflux temperature. Then, the P _v eaktionsgemisch 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 a-nitro-isobutyric acid-N-formyl-N-methyl-amide has the b.p .: 75-85 ° / O, OOl Torr.

20th

Refractive index n "- 1.4780.

Example 2

12 ml of dimethylformamide and 100 ml of chloroform are used in 26.3 ml of phosphorus oxychloride were added dropwise and the mixture was stirred at the same temperature for 30 minutes. The mixture is then at

20 ° dropwise with a solution of 15.2 g of isovaleric acid-N-

20th

methylamide (bp: 74-76 ° / O, Ol Torr, refractive index n _ß = 1.4444) added, stirred for 1 hour at 20 ° and then 10 hours at
Boiled at reflux temperature. The mixture is then concentrated in vacuo. The residue is at 0-10 ° with a nitration mixture,
obtained from 22 ml of conc. Nitric acid and 120 ml conc. Sulfuric acid, added dropwise, then poured onto ice and extracted with chloroform. After drying and distilling off the solvent, the residue is fractionated in vacuo. The a-nitro

Isovaleric acid-N-formyl-N-methylamide has a boiling point of 80-90 ° / 0.001

20th
Torr, refractive index n ~ = 1.4764.

On the beschr in the preceding examples, ie surrounded way of the corresponding carboxamides were prepared using the
Formula II, dimethylformamide and phosphorus xychloride obtained the compounds listed in the table below;

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2032628 link physical data a-nitro-lauric acid-N-forinyl-N-
methylamide
α-nitro.-lauric acid-N-forfnyl-N-
n-butylamide Bp: 145-150 ° / 0.05 torr

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Claims (8)

Claims
N-formyl-ot-nitro-alkanecarboxamides of the formula I, C-C N- CKO in the R-, an alkyl radical with 2 to 12 carbon atoms, R2 and R- each independently represent a lower alkyl radical. 2. Process for the preparation of N-formyl-'a-nitro-alkanecarboxamides of formula I, C-C (I) K ₂ N-CHO in which R- ,, R ^ ^{nn <} ^ ^ 3 ^^ ^e have the meanings given under formula I of claim 1, characterized in that an alkanecarboxamide of the formula II, CH - ^R 2 ^ with a formamide of a secondary amine and a halogenating agent and the complex intermediate product obtained is nitrated and then hydrolyzed. 3. The method according to claim 2, characterized in that the formamide is a secondary amine and dimethylformamide as halogenating agents, halides of inorganic oxo acids used.. 109830/2096 4. The method according to claims 2 and 3, characterized in that that the halogenating agent used is phosphorus trichloride, phosphorus tribromide, phosphorus oxychloride, phosphorus pentachloride, phosgene or thionyl chloride is used. 5. The method according to claim 2, characterized in that the nitration with one of nitric acid and sulfuric acid existing mixed acid carries out. 6. A process according to claims 2 and 5, characterized in that nitration of the intermediate product at temperatures between -10 and +30 ⁰ C. k 7. A process according to claims 2 and 5 _S characterized in that one carries out the hydrolysis at temperatures below 4-3O ° C. 8. The method according to claim 2, characterized in that the reaction is carried out in the presence of organic aprotic LUsungs- and / or diluents. Nu / aw / 5/22/70