Regiospecific synthesis of phosphonous acids

Details Regiospecific synthesis of phosphonous acids Regiospecific synthesis of phosphonous acids

2002-08-05

2004-04-06

Vollano, Jean F. (Department: 1625)

Organic compounds -- part of the class 532-570 series

Organic compounds

Phosphorus acids or salts thereof

Reexamination Certificate

active

06717007

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to an improved process for preparing organic phosphonous acids. More specifically the invention relates to regiospecific synthesis of organic phosphonous acids of formula (I), conforming to anti-Markonikoff addition,
where R
1
is straight or branched alkyl of 1 to 10 carbon atoms; alkyl substituted with halogen, trifluoromethyl, hydroxy, alkoxy, carboxy and amino groups; cycloalkyl of 3 to 7 carbon atoms; phenyl substituted with halogen, trifluoromethyl, hydroxy, amino, alkyl and alkyl substituted by halogen, trifluoromethyl, hydroxy, alkoxy, carboxy and amino groups; carboxylic acid or carboxylic acid ester; cyano; aldehyde; and a substituted five or six membered heterocyclic ring system, wherein the heteroatom is nitrogen,oxygen or sulfur and the substituent is an alkyl or carboxylic acid group; all of which may additionally contain functional groups sensitive to acidic conditions.
BACKGROUND ART
Phosphonous acids are commercially valuable as effective detergents and wetting agents, lubricants and lubricant additives, plasticizers for plastics and resins, corrosion inhibitors, chemicals including insecticides and pesticides, cobalt extractants and as key intermediates for preparation of commercially important angiotensin converting enzyme (ACE) inhibitors such as Ceranopril as disclosed in U.S. Pat. No. 4,452,790 and Fosinopril as disclosed in U.S. Pat. No. 4,337,201.
THE KNOWN ART OF SYNTHESIS OF PHOSPHONOUS ACIDS
A. Synthesis of organic phosphonous acids involve formation of a carbon-phosphorous linkage and in most of the early methods this was obtained by reactions of phosphorous-halogen compounds, such as:
a. reaction of alkyl halides with phosphine or by use of Grignard reagents.
b. reaction of phosphorous trichloride with an alcohol, followed by necessary isomerisation as described in J. Gen. Chem., (USSR), 4, 898-900 (1934).
c. reaction of phosphorous trichloride or phosphorous pentachloride with an olefin to form a phosphorous containing alkyl halide which on reaction with phosphorous pentoxide affords unsaturated phosphonates as disclosed in U.S. Pat. No. 2,425,766 and in J. Am. Chem. Soc., 67, 1864 (1945).
However, these methods have not found any commercial application due to use of hazardous chemicals, use of Grignard reagents, complex reactions involved, and poor yields.
B. Later preparative methods utilised the hydrophosphorylation of olefins for forming the carbon-phosphorous bond. This involved reaction of olefins with hypophosphorous acid or its salts or esters thereof in the presence of free radical initiators (usually organic peroxides) to give the corresponding phosphonous acid, its salts or dialkyl phosphonates. The reaction may be summarised as follows:
R may be alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, carboxylic acid or carboxylic acid ester, cyano, aldehyde etc.; A may be hydrogen, hydroxy or alkoxy, and B may be hydroxy, alkoxy or OM
+
, wherein M is sodium, potassium or calcium.
Such methods have been described in J. Am. Chem. Soc., 77,3411 (1955); Org. Reactions, 13, 150 (1963); J. Chem. Soc. Jpn., Ind. Chem. Sect., 68, 2080, A 112-113 (1965); J. Gen. Chem. (USSR), 37, 1293 (1967); Metody Issled. Org. Soedin., 19, 42, (1968); Usp. Khim., 47, 1565 (1978); U.S. Pat. No. 2,724,718; British Patent No. 660,918; U.S. Pat. No. 2,726,256; and U.S. Pat. No. 2,957,931.
In the methods described above the phosphonous acids were generally prepared employing high pressure reaction conditions (using autoclaves) and higher temperatures (120° C.-300° C.), which entails severe limitations on the operability of a commercial process. Moreover, longer duration of reaction (2-50 hours), moderate yields (15-70%), formation of polymeric materials, especially the dimeric compound (20-50%), as major by-products are further limitations imposed upon commercial applicability. In addition, isolation of the pure product is usually tedious. In most of the methods high vacuum distillation is employed, which further render the processes hardly practical.
The general reaction conditions described above were utilised for preparation of various phosphonous acids, which find other applications as well. Thus, U.S. Pat. No. 2,648,695, describes preparation of a phostone, obtained by heating a phosphonous acid. The phosphonous acids were in turn prepared by hydrophosphorylation of a hydroxy substituted olefin in the presence of an organic peroxide at 130° C.
Phostones are valuable intermediates for synthesis of polyfunctional phosphinic acids.
Yields are not reported in the patent and the hydrophosphorylation is carried out at higher temperature.
U.S. Pat. No. 4,108,889 discloses preparation of long-chain non-terminally substituted alkane phosphonic acids, useful as detergents which involves isomerisation of an &agr;-olefin to an internally unsaturated olefin using a macroreticular strong acid cation exchange resin, followed by reaction of the non-terminal alkene thus produced with a dialkyl phosphite in the presence of a free radical intiator at 135°-140° for 5-6 hours to form the diester, which is hydrolysed to the phosphinic acid. i-C
n
H
2n
and i-C
n
H
2n+1
stand for internally unsaturated olefin and non-terminally substituted alkane respectively and n ranges from 12 to 22 and X is Cl or Br.
Moisture of the resin used, temperature of isomerisation are critical parameters which determine the yield and amounts of dimeric compounds limiting the general applicability of the method. In addition, the hydrophosphorylation is carried out at higher temperature.
U.S. Pat. No. 4,185,031 describes preparation of numerous fluorinated phosphinic acids, useful as grease thickeners for liquid lubricants by reaction of fluorinated olefins and an acid containing one or more phosphorous hydrogen bonds in the presence of organic peroxides at 70° C. to 80° C. for 8 hours to 4 days. No yields are reported.
(CF
3
)
n
—CH═CH
2
+H
2
P(O)OH→[(CF
3
)
n
—CH
2
—CH
2
]
2
—P(O)OH  (1)
(CF
3
)
n
—CH═CH
2
+HRP(O)OH→[(CF
3
)
n
—CH
2
—CH
2
]—RP(O)OH  (2)
U.S. Pat. No. 4,321,213 and U.S. Pat. No. 4,374,780 disclose preparation of certain 2,4,4, trimethyl pentyl phosphinic acids, useful as cobalt extractants obtained by free radical reaction of mono-2,4,4′-trimethyl pentyl phosphine to an olefin in an autoclave, to form the carbon-phosphorous linkage, followed by oxidation with hydrogen peroxide to the phosphinic acids.
The reaction conducted at high pressure (550 psig) generally gives a complex mixture of products, from which the desired phosphinic acid is separated by distillation techniques.
These methods also suffer from similar limitations mentioned earlier.
C. Simplification of or improvements in the process were reported, which are as follows:
Nifantev et al. [Zhu. Obs. Khim., 50 (8), 1744-1752(1980)] demonstrated that hydrophosphorylation of olefins could be carried out at atmospheric pressure and at lower temperatures (75-85° C.) using sodium or potassium hypophosphite in the presence of an organic peroxide in aqueous dioxane. They used small excess of a mineral or organic acid and claimed faster reaction rates.
The reactions took 4-7 hours for completion. Moreover, the method would not be suitable for preparing phosphonous acids containing acid-sensitive groups.
Kleinar et al (U.S. Pat. No. 3,812,222) reported that alkane phosphonic acid diesters could be obtained in high yield (90-95%) if the reaction is conducted using &agr;-olefins which are sulfur free or nearly sulfur free.
However, higher temperatures (130° C.-250° C.) required for the reaction is a major limitation.
Wolf et al (U.S. Pat. No. 4,90,014) prepared mono- and bis-alkyl phosphinates by simultaneous addition of alcoholic solution of an olefinic compound and all of the radical source (organic peroxide) to a hot alcoholic solution (78-80° C.) of hyphophosphite at atmospheric pressure.
However, duration of the reaction is longer (5-55 hrs.) eventhough moderate to high yields (56-9

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