DD301662A7 - METHOD FOR PRODUCING MONOFLUOROPHOSPHOR COMPOUNDS - Google Patents

Abstract

Monofluorophosphorus compounds of the general formula R exp 1 R exp 2 P (Y) F with Y = O, S are of particular interest because of the bioactivity observed in many representatives of this class of substance. The aim of the invention is to enable a new, more economical synthesis of the title compounds in high yields from readily available starting materials. The preparation of the compounds is possible directly in a process step by the reaction of compounds having a PH bond, R exp 1 R exp 2 P (Y) H, or in the case of Y = O also a trivalent phosphorus compound having at least one alkoxy group, R exp 1 R exp 2 P (OR exp 3), with polyhalogenated hydrocarbons and an organylammonium fluoride in the presence of a base.

Description

Field of application of the invention

The invention relates to a process for the preparation of monofluorophosphorus compounds of the general formula

"Y

where Y = O or S and R 'and R ² are independent or in any way interconnected organic radicals, such as. B. alkyl, aryl, alkoxy, Alklythio-, Aroxy-, arylthio or Diorganylamidogruppen and N-heterocycles can be.

Of a number of such compounds, their high biological activity is known.

Characteristic of the known technical solutions

For the preparation of monofluorophosphorus compounds of the abovementioned general formula, the following processes are known (Houben-Weyl "Methods of Organic Chemistry", 4th ed., Vol. XII / 2 and extension and following states E 1 and E 2):

1. Exchange reactions on four-coordinate phosphorus compounds, eg. Example of chloride, amide, thioorganyl, cyano and trichloromethyl groups to fluoride or chloride or fluoride to amide or alk (ar) oxy groups.

2. Cleavage of phosphorus compounds with P-O-P or P-S-P bridges by hydrogen fluoride.

3. Oxidation of trivalent alkoxy compounds of phosphorus with simultaneous dealkylation, z. B. with heptafluoro-2-nitrosopropane, 2,2-dichloroperfluorobutane, Chlordiethylaminosulfan, -Fluorosuli'onylketonen (AFErmelov et al., Zh. Org Khim. (1982), 18'16) or electrochemically in the presence of hexafluorosilicates (EV Nikitin ua SU 791 755 dated 30.12.1980, see EV Nikitin et al., Dokl. Akad. Nauk SSSR 252, 922 (19801).

Ί. Oxidation of trivalent phosphorus compounds with sulfur, sulfur dioxide (R.W. Light, R.T. Paine, Phosphorus Sulfur 8.255 11980!) Or chlorine (with subsequent conversion of the dichlorophosphoranes into phosphoryl or thiophosphoryric bonds).

5. Reaction of AlkoxyphosphordlDfluoriden with alkyl halides (Arbusov reaction).

6. Oxidation of four-coordinate phosphorus compounds with a P-H function to corresponding P-Cl compounds followed by chlorine-fluorine exchange. As oxidizing agents are described: chlorine, carbon tetrachloride,

Sulfuryl chloride and N-chlorosuccinimide. Only in one case (Houbon-Weyl, Vol. XII / 2, p. 266) did oxidation and chlorine-fluorine exchange take place in a displacement step (equation 1).

(RO) ₂ P (O) H + Cl ₂ + NaF (RO) ₂ P (O) F + NaCl + HCl (1)

R = ethyl

Boi 7O ⁰ C is orroicht after 16 hours a yield of 30%.

7. Direct Conversion of ^ P (O) H and i P (O) OH Groups to> P (O) F Using SO ₂ CIF (A.Lopusinski, J. Michalski, Angew.

Chem., 94, 302 (19821) and perchloryl fluoride, respectively (I.V. Vigalok et al., Zh., Obshch., Khim., 40, 936 (19701).

Dio disadvantages of the known ancestors consist mainly in the fact that the required starting compounds aufwundig, often over several, mostly chlorine-containing intermediates dargostellt have wordan, resulting in poor yields (based on the starting compound of the synthesis), a high rate of waste products and eino aufwondigo technology result.

Goal Her invention

The aim of the invention is to enable a new, economically more favorable synthesis, dio dio the representation of the title compounds in as little as one step from easily accessible starting materials in high yields.

Explanation of the essence of the invention

The object of the invention is to develop a process for the preparation of monofluorophosphorus compounds from readily available starting materials.

It has been found that compounds of the general formula

wherein Y = O or S and R 'and R ² are independent or in any way interconnected organic radicals, such as alkyl, aryl ·. Alkoxy, Alkvlthio-, Aroxy-, arylthio and Diorganylamidogruppen and N-heterocycles may be, by the reaction of corresponding compounds having a PH bond, R'R ² P (Y) H, or in the case of Y = O also a trivalent phosphorus compound having at least one alkoxy group, R ¹ R ² P (OR ³ ), with polyhalohydrocarbons, eg carbon tetrachloride, and a fluoride or hydrogen fluoride, preferably an organylammonium salt, in the presence of a base in an inert solvent, e.g. As acetonitrile, or without solvent addition in good yields

 The general reaction equations are:

R ¹ R ² P (Y) H + C ₁ H _n X ₁ , + F "- ' ¹ R ¹ R ² P (Y) F + C _n H _n ., X _k _, + X" (2)

R ¹ R ² P (OR ³ ) + C _m H "X" + HF ¹ R ¹ R ² P (O) F + C ₁ H _n ., X _k _, + R ³ X (3)

X = halogen, R ³ = alkyl.

The process according to the invention has the following decisive advantages:

1. Easily accessible and partly cheap starting materials can be used.

2. The formation of the title compounds from the starting materials takes place in a single process step.

3. The resulting by-products (e.g., chloroform using carbon tetrachloride as polyhalohydrocarbon and organyl ammonium chlorides) can be readily made available for reuse.

4. The organylammonium fluorides used as fluorinating agents are readily available from corresponding amines and hydrogen fluoride. The preferably used Organylammoniumfluoride are easy to handle and do not attack the candidate temperature range glass, so that you can work in glass equipment.

5. High yields are achieved.

6. There are no harmful to the environment and corrosive hydrogen halides.

embodiments

The presentation of the title compounds is based on the following general rules:

1. From P-H-functional compounds

To a solution of 0.05 mol CCI ₄ , 0,0Ö27mol NEt ₃ · 2,8HF as a fluorinating agent (Et = ethyl) and 0.015 mol of triethylamine in 0.2 mc acetonitrile with stirring at room temperature within a minute 0.05 mol R ¹ R ² P (Y) H, dissolved in a little acetonitrile. The reaction is slightly exothermic. The forming triethylammonium chloride, NEt ₁ HCl, usually crystallizes out and can then be separated largely by filtration. The filtrate contains, in addition to acetonitrile and excess CCI ₄ and NEt3, the monofluorophosphorus compound formed, R ¹ R ² P (Y) F, and chloroform. It can be worked up by distillation.

The following conversions to the target compounds were determined by NMR spectroscopy:

R ¹ R ² Y

OEt OEt 0 95

PH OEt 0 70

NEt ₂ NEt ₂ 0 50

OEt OEt S 80

2. From trivalent azoxy compounds of phosphorus.

To a solution of 0.05 mol of a trivalent phosphorus Vorvorbindung with at least one alkoxy group, R ¹ R ² P (OR ³ ) and 0.07 mol of CCI ₄ in 0.3 mol of acetonitrile at 70 ° C within two hours 0.09 mol NEt ₃ x 2.8 HFaI fluorination agent added dropwise. The Monofluorophosphorverbindung is obtained in yields up to 45% and can be separated by distillation from the reaction mixture. By-products are mainly triethylammonium fluorophosphates and esters of phosphoric acids. Example: R ¹ , R ² , R ³ = Et; Ί4% (EtO) ₂ P (O) F.

Claims (5)

1. Verfahron for the preparation of Monofluorophosphorverbindungen the general formula R. R ¹ Y wherein Y = O or S and R 'and R ^{2 may} be independent or in any way interconnected organic radicals, such as alkyl, aryl, alkoxy, alkylthio, Aroxy-, arylthio and Diorganylamidogruppen and N-heterocycles , characterized in that a compound having a PH bond, R ¹ R ² P (Y) H, or in the case of Y = O also a trivalent phosphorus compound having at least one alkoxy group, R ¹ R ² P (OR ³ ), wherein R ³ = alkyl, is reacted with a polyhalohydrocarbon and an ionic fluoride or hydrogen fluoride in the presence of a base. 2. The method according to item 1, characterized in that is used as polyhalohydrocarbon predominantly carbon tetrachloride. 3. The method according to item 1, characterized in that triethylammonium hydrogen fluorides are used as the preferred ionic fluoride or hydrogen fluoride, triethylamine is added to the complete or partial neutralization of Hydrogenfluoridprotonen. 4. The method according to item 1, characterized in that acetonitrile is used when using a solvent. 5. The method according to item 1, characterized in that is used as the base predominantly a trialkylamine.