AU599950B2 - Method of preparing 1-functionally-substituted-alkylidene-1, 1-diphosphonic acids and mixtures thereof - Google Patents
Method of preparing 1-functionally-substituted-alkylidene-1, 1-diphosphonic acids and mixtures thereof Download PDFInfo
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- AU599950B2 AU599950B2 AU67607/87A AU6760787A AU599950B2 AU 599950 B2 AU599950 B2 AU 599950B2 AU 67607/87 A AU67607/87 A AU 67607/87A AU 6760787 A AU6760787 A AU 6760787A AU 599950 B2 AU599950 B2 AU 599950B2
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- 239000002253 acid Substances 0.000 title claims description 53
- 150000007513 acids Chemical class 0.000 title claims description 42
- 238000000034 method Methods 0.000 title claims description 30
- 239000000203 mixture Substances 0.000 title description 59
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 18
- 150000001735 carboxylic acids Chemical class 0.000 claims description 17
- 239000011541 reaction mixture Substances 0.000 claims description 16
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 claims description 13
- 150000003840 hydrochlorides Chemical class 0.000 claims description 10
- -1 aliphatic amines Chemical class 0.000 claims description 5
- 125000001477 organic nitrogen group Chemical group 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 235000014113 dietary fatty acids Nutrition 0.000 description 16
- 239000000194 fatty acid Substances 0.000 description 16
- 229930195729 fatty acid Natural products 0.000 description 16
- 150000004665 fatty acids Chemical class 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 15
- 229910052698 phosphorus Inorganic materials 0.000 description 13
- 239000011574 phosphorus Substances 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 238000009835 boiling Methods 0.000 description 10
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000000413 hydrolysate Substances 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 235000021314 Palmitic acid Nutrition 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000005703 Trimethylamine hydrochloride Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- SZYJELPVAFJOGJ-UHFFFAOYSA-N trimethylamine hydrochloride Chemical compound Cl.CN(C)C SZYJELPVAFJOGJ-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- RHVWSRKGJFLDFG-UHFFFAOYSA-N [aminooxy(hydroxy)phosphoryl]methylphosphonic acid Chemical compound NOP(O)(=O)CP(O)(O)=O RHVWSRKGJFLDFG-UHFFFAOYSA-N 0.000 description 2
- BFDMEODWJJUORJ-UHFFFAOYSA-N [dimethylamino(phosphono)methyl]phosphonic acid Chemical compound CN(C)C(P(O)(O)=O)P(O)(O)=O BFDMEODWJJUORJ-UHFFFAOYSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003518 caustics Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000005188 flotation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 150000002484 inorganic compounds Chemical class 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 238000012355 ph-metric titration Methods 0.000 description 2
- 238000006068 polycondensation reaction Methods 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001174 sulfone group Chemical group 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- XOLBLPGZBRYERU-UHFFFAOYSA-N tin dioxide Chemical compound O=[Sn]=O XOLBLPGZBRYERU-UHFFFAOYSA-N 0.000 description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- OMSBSIXAZZRIRW-UHFFFAOYSA-N 2-methylpyridine;hydrochloride Chemical compound Cl.CC1=CC=CC=N1 OMSBSIXAZZRIRW-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- NQLSAZAZMCKLJN-UHFFFAOYSA-N [dimethylamino(phosphono)methyl]phosphonic acid;hydrate Chemical compound O.CN(C)C(P(O)(O)=O)P(O)(O)=O NQLSAZAZMCKLJN-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000003113 alkalizing effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- ICXXXLGATNSZAV-UHFFFAOYSA-N butylazanium;chloride Chemical compound [Cl-].CCCC[NH3+] ICXXXLGATNSZAV-UHFFFAOYSA-N 0.000 description 1
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 210000003298 dental enamel Anatomy 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000010436 fluorite Substances 0.000 description 1
- 150000004820 halides Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- TYCXRAVZVQSHSC-UHFFFAOYSA-N n-dodecylformamide Chemical compound CCCCCCCCCCCCNC=O TYCXRAVZVQSHSC-UHFFFAOYSA-N 0.000 description 1
- 150000002898 organic sulfur compounds Chemical class 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 239000002367 phosphate rock Substances 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- MAPFUJCWRWFQIY-UHFFFAOYSA-K tripotassium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxymethyl)amino]acetate;dihydrate Chemical class O.O.[K+].[K+].[K+].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O MAPFUJCWRWFQIY-UHFFFAOYSA-K 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/386—Polyphosphonic acids containing hydroxy substituents in the hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3839—Polyphosphonic acids
- C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
-
- H—ELECTRICITY
- H02—GENERATION; CONVERSION OR DISTRIBUTION OF ELECTRIC POWER
- H02G—INSTALLATION OF ELECTRIC CABLES OR LINES, OR OF COMBINED OPTICAL AND ELECTRIC CABLES OR LINES
- H02G3/00—Installations of electric cables or lines or protective tubing therefor in or on buildings, equivalent structures or vehicles
- H02G3/02—Details
- H02G3/04—Protective tubing or conduits, e.g. cable ladders or cable troughs
- H02G3/0462—Tubings, i.e. having a closed section
- H02G3/0468—Corrugated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Architecture (AREA)
- Civil Engineering (AREA)
- Structural Engineering (AREA)
- Insulating Bodies (AREA)
Description
*I
5 9950 COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952 Form COMPLETE SPECIFICATION FOR OFFICE USE Short Title: Int. Cl: Application Number: Lodged: Complete Specification-Lodged: Accepted: Lapsed: Published: Priority: This document contains the amendments made under Section 49 and is correct for printing.
Related Art: TO BE COMPLETED BY APPLICANT C C C c c v Name of Applicant: Address of Applicant: Actual Inventor: Address for Service: INSTITUT KHIMICHESKOI KINETIKI I GORENIA SIBIRSKOGO OTDELENIA AKADEMII NAUK SSSR Ulitsa Institutskaya 3, Novosibirsk,
U.S.S.R.
Ivan Sergeevich Alferiev Nikolai Vasilievich Mikhalin Izrail Lvovich Kotlyarevsky and Aza Vasilievna Krasnukhina GRIFFITH HASSEL FRAZER 71 YORK STREET SYDNEY NSW 2000
AUSTRALIA
Complete Specification for the invention entitled: METHOD OF PREPARING 1-FUNCTIONALLY-SUBSTITUTED- ALKYLIDENE-1,1-DIPHOSPHONIC ACIDS AND MIXTURES THEREOF The following statement is a full description of this invention, including the best method of performing it known to me/us:- 2368A:rk T T x i i: 1 t -1A- The present invention relates to the chemistry of organophosphorus compounds with a C-P bond, particularly, to mthods of preparing 1-functionally-substituted-alkylidene-1,1-diphosphonic acids and their i-retu a' Said products find extensive application as complexforming agents for flotation dressing of non-suphide ores, e.g. such as cassiterite, anatite, phosphorite, fluorite, and others. Some of these' acids find application in the medicine.
There is a number of methods for preparing 1-functionally-substituted-alkylidene-1,1-diphosphonic acids, miAxtue-e9 and salts thereof by reacting carboxylic acids or their derivatives with compounds of trivalent phosphorus under dehydrating conditions (see FRG Patent No. 2943, 498).
Usually as inorganic compounds of trivalent phosphorus use is made of a mixture of phosphorous acid ard phosphorus trichloride; quite often phosphorous acid is obtained in the course of synthesis, a portion of phosphorus trichloride being hydrolyzed with a calculated amount of water.
A characteristic feature common to these methods is the necessity of using a carboxylic acid or its derivatives in a considerable excess. This is due to the C C.
CE~r r C Ct C C .I 9 a" :a j; ii r el. ~i~ii L 1 sm~ I r 2 fact that in the course of reaction under dehydrating conditions polycondensation products of polyphosphonic acids are formed, which are very viscous or solid compounds.To preclude thickening of the reaction mass because of formation of polycondensates, one has to use carboxylic acids or their derivatives in excessive amounts, this involving serious technological difficulties associated with the removal of said excessive amounts.
Attempts to use inert diluents for the same purpose prove to be either inefficient (for instance, in the case of hydrocarbons or chlorinated hydrocarbons which are poorly miscible with the polycondensation mass) or add Ji too much to the cost of the technological process, as in the case of sulphone, which is difficult to isolate from the reaction mixture and makes the isolation of the desired product more difficult. Moreover, under the reaction conditions sulphones become to a certain extent reduced to volatile organosulphur compounds (Ese D. Curry, D. et Nicholson, O.J. Quimbly, Topics in Phosphorus Chemistry, 1972, 7.75).
o One more method is known for preparing derivatives of 1-functionally-substituted-alkylidene-1,1-diphosphonic acids, namely, 1-hydroxyalkylidenediphosphonic acids.
The method resides in that a mixture of carboxylic acids Scomprising from 6 to 10 carbon atoms and used in twofold excess is mixed with compounds of phosphorus trichloride under dehydrating conditions. The resulting mixture is heated gradually for 4-5 hours to a temperature ;B I: r Ir -3on the order of 110-150°C.
Such long and gradual heating is dictated by an extreme temperature-sensitivity of the reaction. A more rapid heating leads to the reaction becoming uncontrollable, and this creates serious difficulties.
On completion of the heating the reaction mixture is kept at the above-stated temperature for a period of from 5 hours to 15 minutes.
As a result, polycondensates of 1-hydroxyalkylidene- Sdiphosphonic acids are formed. Then the resulting polycondensates are subjected to hydrolysis with excess water at a temperature of 80-110°C during 5-12 hours.
The hydrolysis gives 1-bydroxyalkylidene-1,1-diphpohonic acids, which are precipitated with the aid of sodium hydroxide in the form of disodium salts with a yield S of up to The method allows the desired reaction products to be isolated from excess carboxylic acids, but filtering and subsequent washing of the precipitated dioo sodium salts are quite difficult operations, requiring much time and considerable consumption of the solvent.
Furthermore, regeneration of excess carboxylic acids also involves technological difficulties (see UK Patent No. 1,469,894 of 1974).
1i i, >4 I- 1XII,~:_
II:
r h 1 t The invention provides such a method of preparing 1-functionally-substituted-alkylidene-1,1-diphosphonic acids and salts thereof,which would make it possible to simplify the process technology, to increase the process efficiency, and to obtain the desired products with a sufficiently high yield.
Thus a method of preparing 1-functionally-substitutedalkylidene-1,1-diphosphonic acids and salts thereof is provided, by reacting carboxylic acids or their derivatives with phosphorous acid under dehydrating conditions created by the addition of phosphorus trichloride in the presence of hydrochlorides of organic nitrogen bases to dilute the reaction mixtures.
**3 t 0 -4 t c S -4-
I
0329s/MS 1 l I t ta r uce C IC I rt 111 It IL 'I 11 I It DiI I I p.oano of hydroohI-or-ido of nitrogen basos.
As carboxylic acids one can use mono- and dicarboxylic aliphatic acids C -C20, as well as carboxylic acids with an amino acid or halide substituent in the hydrocarbon chain. As derivatives of carboxylic acids via the carboxylic group it is possible to use their chlorides, anhydrides, amides, and substituted amides. In some cases said derivatives of carboxylic acids via the carboxyl group are formed at the initial stage of the process, when the initial compounds are carboxylic acid and phosphorus trichloride.
As inorganic compounds of trivalent phosphorus is possible to use, for example, phosphorus trichloride, the latter being partically hydrolysed with water in a molar ratio of PC13:H20 equal to 1:1.55-2.21. It is possible to use phosphorous acid. Phosphorus acid may be introduced in combination with phosphorus trichloride. It may be not introduced at all, since this acid is formed during the reaction of phosphorus trichloride with water.
As stated above, the reaction of carboxylic acids or their derivatives via the carboxyl group is effected at a temperature of 20-1800C. The choice of the process temperature depends on the stability of the initial and final products of the reaction. Thus, in the case of unsubstituted carboxylic acids the reaction should preferably be carried out at higher temperatures, since the react.,n i time till be materially cut down and the process efficiency will be appreciably increased.
Bii ii:;
AU
7 NT 6 The use of hydrochlorides of nitrogen bases as diluents makes it possible to diminish the quantity of carboxylic acids or their derivatives and to utilize them in the reaction practically completely, bringing the yield of desired products, as calculated for the carboxylic acids, up to 100%. Furthermore, the use of said diluents makes the reaction less temperature-sensitive, the process thus becoming easily controllable.
Though said hydrochlorides of aitrogen bases are solid, and sometimes even very high-melting compounds, they not only efficiently dilute reaction mixtures, but provide a pocsibility for carrying out reactions at high temperatures (so that the reaction rates can be increased sharply) and with no excess of carboxylic acids or their derivatives via the carboxyl group.
For preparing salts of 1-functionally-substituted alkylidene-1,1-diphosphonic acids and their mixtures,to a hydrolysate containing the target product a caustic I F alkali is added to the pH of the medium of 9-12, a solution being thus formed, containing salts of 1-functionalc, ly-substituted-alkylidene-1,1-diphosphonic acids and ni- SCt trogen bases, the latter being then removed from the reaction mixture.
As to their purpose, particularly for flotation dressing of non-sulphide ores, the acids proposed herein ~and their .ixtures are equivalent to their salts, but it is reasonable to convert the acids and rmixtures thereof into salts, since then the product is easier to transl l i l l r r l .4 7 -7port.
As a caustic alkali it is recommendable to use potassium hydroxide or sodium hydroxide.
As hydrochlorides of nitrogen bases it is recommendable to use hydrochlorides of aliphatic-amines or hydrochlorides of heterocyclic nitrogen bases.
The herein-proposed method of preparing 1-functionally-substituted-alkylidene-1,1-diphosphonic acids and their mixtures allows an essential simplification of the process technology without requiring the use of carboxylic acids in excess and their subsequent isolation from the reaction products; the method also makes it possible to easily control the process (to run it at a higher temperature) and to raise the process efficiency due to the specific action of the hydrochlorides of nitrogen bases.
The realization of the present method ensures a sufficiently high yield of the desired product, that reaches 90-100%.
C' 'It The possibility of converting the target acids into salts, which are equivalent to the acids in application C r allows one to transport them to the user in steel tanks.
S *I The present method of preparing 1-functionally-sub- S stituted-alkylidene-1,1-diphosphonic acids and their mixtures is simple tecLnologically and is effected in the Sfollowing manner.
A carboxylic acid or its derivatives via the carboxyl group, water, hydrochloride of a nitrogen base,and sometimes, instead of water, also a certain quantity 1 C t
C
1~
C
Cs
C
r S ii' S I
C,
44 '1 4 I 4 4 I 1.040 4 4 41
S
III 4 4 4 0 -8 of phosphorous acid, are charged into an enamel-coated steel or steel-titanium reactor; then phosphorus trichloride is gradually introduced into the reactor at a temperature of 20 to 1800C, end the mixture is kept from two minutes to several hours. As a result, a reaction mixture is formed, containing polycondensates of polyphosphonic acids. The reaction mixture thus obtained is transferred to another reactor, excess water is added thereto, and at a temperature of 100-1300C the polycondensates of polyphosphonic acids are hydrolyzed to desired products: 1-flunctionally-substituted-alkylidene-1 ,1-phosphonic acids or their mixtures.
Depending on their purpose, these acids or mixtures thereof are isolated by conventional methods, for instance, by changing the solvent.
If the desired products are employed for ore decreasing, the former are converted into salts. This is done by adding sodium hydroxide of potassium hydroxide to the hydrolysate to p1H 9-12. The nitrogen base is isolated from the resultir solution, and an aqueous solution of salts of the desired acids thus obtained is used as such.
The nitrogen base is isolated quantitatively. It is converted into hydrochloride and reused at the stage of preparing the desired product.
For a better understanding of the present invention, specific examples of its embodiment are given h~re*nb- 4w.by way of illustration.
1 1 1 -9- Pr P C C, .I r 4- P. t 20 Example 1 To a mixture of 37.2 g (0.250 mole) of synthetic fatty acids of C 7
-C
9 fraction, having an average molecular weight of 148.5, 20 ml (0.19 mole) of diethylamine and 15.1 g (0.840 mole) of water are added under stirring and at a temperature gradually increasing from 2000 C to 1250C 73.0 g (0.532 mole) of phosphorus trichloride. Then the resulting reaction mass is kept at a temperature of 125- -130 0 °C for 1 hour. Hydrogen chloride that evolves upon mixing the reagents in the course of condensation is absorbed with water. Iodometric determination of the ohosphorous acid content in an absorption bottle has shown 0.025 mole of PC1 3 to be entrained with the stream of HC1. Thus, the overall quantity thereof, with allowance for losses, is 0.507 mole. The RCOOH:H 2 0:PC1 3 ratio is 0.47:1.58:1.
To the reaction mixture 40 ml of water and 10 ml of concentrated hydrochloric acid are added, and the mixture thus obtained is hydrolyzed at low boiling (105-1080C) for 10 hours. The resulting hydrolysate is alkalized with an aqueous solution of sodium hydroxide (about 45 g of NaOH), and then diethylamine is distilled off till the temperature in the vapours becomes 990 C. As a result, pH of the mixture is 9. The content of the desired 1-hydroxyalkylidene-1,1-diphosphonic acids in the solution of sodium salts thus obtained is determined by the NMR (31P) method. The solution contains 0.21 mole of 1-hydroxyalkylidene-1,1-diphosphonic acids. The yield is 83%.
_li 10 If 1-hydroxyalkylidene-1,1--diphosphonic acids are prepared in accordance with the procedure described above by using 15 ml (0.11 mole) of triethylamine instead of diethylamine, the yield of the 1-hydroxylidene-1,1-diphosphonic acids is 78%; with the use of 14.5 g (0.15 mole) of trimethylamine hydrochloride the yield is while with the use of 20.8 g (0.19 mole) of n-butylamine hydrochloride the yield is 73%.
In case the content of PC13 is lowered to 52.2 g (0.380 mole) and the reaction is carried out in the presence of 15 ml of diethylamine, the yield drops down to
RCOOH:H
2 0:PC1 3 0.66:2.21:1.
Example 2 Under the same conditions as in Example 1 a mixture of synthetic fatty acids of C -C fraction, water, and ml (0.42 mole) of tri-n-butylamine are introduced into the reaction with PCI3.PCI 3 losses arc U.032 mole, 0.500 <mole of PCI 3 has entered into the reaction.
The RCOOH:H 2 0:0:PC1 3 ratio is 1.47:1.58:1.
The hydrolyzed mixture is alkalized with NaOH and the liberated tributylamine is extracted with carbon tetrachloride. 0.209 mole of 1-hydroxyalkyl-1,1-diphosphonic acids is found in the aqueous layer; the yield is 84%.
I- C~ 4. *C 4 Example 3 To a mixture consisting of 169.1 g (0.884 mole) of synthetic fatty acids of C10 -C13 fraction, having a 11 aa a a a aaa a aeat a La a a ~aa aa a a a (at a a ata( aa at a tat a ta a I I a La
I
4 an average molecular weight of 191.3, and 93.2 g of 35.4% hydrochloric acid comprising 60.2 g (3.340 mole) of water and 33 g (0.905 mole) of HCl 100 ml (0.965 mole) of diethylamine is added with stirring; and cooling with water.
Then 286.6 g (2.072 mole) of phosphoris trichioride are introduced into the mixture at a temperature of 20-125 0C and the mixture is kept for 1 more hour at a temperature of 125-130 0C. P01 losses are U.118 mole, 1.964 mole of PCi 3 as entered into the reaction. The ,-ZCJH:H 2 O:PCl 3 10 ratio is 0.42:1.60:1.
50 ml of concentrated hydrochloric acid and 130 ml of water are added to the mixture, Pnd then it is :iydrolyzed at a boil (about 10500C) during 10 h. A 25,, aqueous solution of potassium hydroxide (about 330 e, of X01I) is added to the hydrolyzed mixture, and diethylamine is distilled off till the temperature in the vapours becomes 9900C. A solution of ot-assium salts of 1-hydroxyalkylidene-1,1dichosphonic acids C0oC 13 is obtained. In this solution the 14'1'.R .(31p) spectrum analysis reveals t',he following 20 1,h1osphorus-containin- compounds (the values of chemical shlifts are cvlculated with respect to 85 1APO4): 19.6 p.p*m. tJ 11 11-z), 85%, R-C(OH< 2 3.6 p.p.m.
Jyr 563 Iliz) H 3
PO
3 3.4 2% 3 P0 4 nonidentified compounds, about If synthetic fatty acids of 010-0 16 ar Ie introduced into the reaction, under the sa-me conditions a solution of potassium salts of 1-hydroalkylidene-1,1-diphosphonic acids is obtained with the yield of 82% for the reacted PC1 3 and of 91% for the syn- .1.
.0 0 a. 4 ill i :L -mrru 12 thetic fatty acids.
Example 4 Synthetic fatty acids of C10-C16 fraction, having an average molecular weight of 224.6, are chlorinated with gaseous 012 at a temperature of 95-105 0 C till a 49;L gain in weight. The reaction mass thus obtained is kept at the temperature of 100 C in a vacuum of 1 mm Hg, the gaseous and low-boiling products are removed. An elementary analysis of the resulting chlorinated synthetic fatty acids has shown the content of 33.59% Cl, this corresponding to the introducing of 3.16 Cl atoms per molecule of the synthetic fatty acids and giving an average molecular weight of the chlorinated synthetic fatty acids of 333.4.
To a mixture of 161.8 g (0.485 mole) of the chlorinated synthetic fatty acids and 51.1 g of 35.4% hydrochloric acid comprising 33.0 g (1.832 mole) of water, 55 ml
C
(0.53 mole) of diethylamine is added with stirring rnd cooling; then 160.0 g (1.164 mole) of phosphorus trichloride is introduced at a temperature of 20-1150C, and the S m20 mixture is kept at a temperature of 110-1150C for 8 E C hours more. PC13 losses are U.123 mole, 1.041 mole of PC01 ias reacted. RCOOHi: 2 0:PC1 3 0.42:1.57:1. The mixture is hydrolyzed with aqueous HC1, and amine is isolated by alkalyzing the hydrolysate with a solution of KOI as in the preceding Example. A solution of potassium salts of a mixture of 1-hydroxychloralkylidene-1,1-diphosphonic acids is thus obtained, containing 0.485 mole of desired compounds, the yield being 79% for PC1 and 85% for the C. 3 vow, 7j
I:
R
1 I 13 chlorinated synthetic fatty acids.
Example 37.2 g (0.250 mole) of synthetic fatty acids of C7-
-C
9 fraction, 20 ml (0.14 mole) of triethylamine, 15.1 g (0.840 mole) of water are mixed under the copditions of Example 1, and 73.0 g (0.532 mole) of phosphorus trichloride is introduced into the mixture at a temperature of 20-150 0 C. Then the mixture is kept for 15 min at the temperature of 1500C. After that the mixture is hydrolyzed and amine is isolated from the hydrolyzate as in Example 1. RCOOH:H 2 0:PC1 0.47:1.58:1. The yield of 1-hydroxyalkylidene-1,1-diphosphonic acids is 77%.
S An increase in the temperature of the mixture while adding PC13 to 170-180°C and subsequent keeping at this temperature for 2 minutes make the yield of 1-hydroxyalkylidene-1,1-diphosphonic acids Carrying out the reaction with synthetic fatty acids in excess, at a temperature of 170-180 C has the yield of 1-hydroxyalkylidene-1,1-diphosphonic acids to 20 (3 min keeping) and to 32% (10 min keeping).
Example 6 To a mixture of 25.6 g (0.100 mole) of palmitic acid, 6.81 g (0.378 mole) of water and 10 ml (0.095 mole) of diethylamine 32.5 g (0.237 mole) of PC1 is added with stirring at a temperature of 20-1350C, the resulting mixture is kept for 40 min at a temperature of 130-135 C,and hydrolyzed with dilute aqueous hydrochloric acid. PC1 3 losses with exit gases is 0.010 mole, 0.227 mole of PC1 3 I li i.
r I 14 tf r c: r(I has reacted.
RCOOH:H
2 0:PC13 0.42:1.59:1.
A sample of the reaction mixture is dissolved in water, triethylamine is acded thereto (pH 11.5), and the resultant mixture is analyzed NMR (1P)-spectrometrically.
The following phosphorus-containing compounds are present in the mixture: 19.0 p.p.m. Jpy 13 Hz), 68%, (OH) 3CPO 2 2.4 p.p.m. JP 613 Hz), 7%, HPO: 0.4 p.p.m. H3PO 4 unidentified compounds, about 3%.
Thus, the yield of the desired l-hydroxyhexadecylidene-l,l-diphospaonic acid is 88% for PC13 and about 100% for palmitic acid.
The reaction mixture is diluted with 200 ml of methanol and a solution of 49 g (0.6 mole) of sodium acetate in 110 ml of water is added thereto at boiling.The precipitated disodium salt on completion of crystallization is filtered off, washed with a mixture consisting of 5 volumes of methanol and 1 volume of water, then 20 with boiling methanol. After drying in a vacuum at the temperature of 100 0 C 38.2 g of disodium salt of 1-hydroxyhexadecylidene-ll-diphosphonic acid are obtained, this corresponding to the yield of 75% for the reacted PC3 and 86% for palmitic acid.
For preparing an analytic sample, the product is dissolved in hot water, auding a two-fold molar quantity of NaOH, the mixture is filtered and precipitated, acidulating it with a small excess of acetic acid. The t c r c t t Ct(! 8 tt &ro a~ i', P i:i: 9 i i r 15 precipitate is washed with water and methanol, then dried in a vacuum at the temperature of 100 0
C.
Elementary analysis data: Found, C 45.40; H 7.66,C 1 6
H
4 0P 2 Na 2 Calculated, C 43.05; H 7.68.
For preparing i-hydroxyhexadecylidene-l,l-diphosphonic acid 5.0 g of its purified disodium salt are suspended in 30 ml of ether, 20 ml of 307 aqueous H 2 S0 4 is added thereto, and the mixture is stirred till the solid phase disappears. The ethereal layer is separated, riltered to remove droplets of the aqueous layer, and the other is evaporated. The residue crystallizes after short-term standing. 4.3 g of crystalline 1-hydroxyhexadecylidene- 1,1-diphosphonic acid are obtained (about 100% for the disodium salt). For preparing an analytic sample, the product is recrystallized twice from acetone.
M 107-108°C(sinters).
Elementary analysis data: Found, C 47.15; H 9.05. C 16
H
6 0 7
P
2 20 Calculated, C 47.75; H 9.02.
Example 7 Under the conditions of Example 1 33.0 g (0.250 mole) of enanthic acid, 15.1 g (0.840 mole) of water, ml (0.14 mole) of triethylamine and 73.0 g (0.532 mole) of phosphorus trichloride are entered into the reaction. PC13 losses are 0.027 mole, 0.505 mole of PCl3 has reacted. The RCOOH:H 2 0:PCl 5 ratio is 0.47:1.58:1.
The reaction mixture is bydrolyzed with 50 ml of
I~,
I
16 water for 11 hours at boiling (100-105C), neutralized with a solution of 40 g NaOH in 80 ml of water, triethylamine is distilled off. The solution of disodium salts thus obtained contains 0.202 mole of 1-hydroxyheptylidene- -1,1-diphosphonic acid, the yield being 80% for the reacted PC1. The solution is acidulated at a temperature of 80-100 0 C with 150 ml of acetic acid, 100 ml of ethanol is added thereto, and the mixture is allowed to stand
S
r till crystallization of the disodium salt ceases. Then the precipitate is tiltered off, washed with acetic acid, ethanol, and boiling toluene. After drying in a vacuum at the temperature of 100°C 58.8 g of disodium salt of 1-hydroxyheptylidene-l,1-diphosphonic acid are obtained, this corresponding to the 73% yield for PC1.
For a final purification the salt is converted to £ree l-bydroxyheptylideae-l,1-dirosphonic acid. To this end, the salt is suspended in isopropanol, saturated with gaseous hydrogen chloride, the NaCl precipitate is filtered off, the Ziltrate is evaporatea in vacuum. To remove, c 20 isopropanol, HC1 and traces of water, the syrup-like residue is dissolved in ethylacetate, an equal volume of I benzene is added thereto, and the solvents are distilled off in vacuum. This operation is repeated till the product has crystallized, the crystals are dried in vacuum S* over H 2 S,0, then they are recrystallized from an ace- :i tate-chloroform mixture. M.p. 144-1460C (siaters).
Elementary analysis data: Found, C 50.37; H 6.74.C 17
H
18 2 i 1 17 et C t c crr Ctt 1 t i Ci r c r
SF-
C c.
r' r C C C Ct.
1.S j t tti e: r Calculated, C 30.44; H 6.57.
Example 8 Under the conditions of Example 7 22.0 g (0.250 mole) of n-butjric acid are introduced into the reaction.
PC1 3 losses are 0.017 mole, 0.515 mole of PCI 3 has reacted. RCOOH:H 2 0:PC1l 0.47:1.58:1. After hydrolysis, alkalizing and removal of amine, 0.210 mole of 1-hydroxybutylidene-l,l-diphosphonic acid is identified in the resulting solution, the yield being 81% for the reacted PC1 3 The solution is acidulated with acetic acid to pH evaporated in a vacuum till a viscous crystalline suspension is obtained, diluted with an equal volume of ethanol, and crystals of a sodium salt are filtered off.
The crystals are washed with ethanol and dried in a vacuum. 52.3 g of disodium salt of l-hydroxybutylidene-1,1diphosphonic acid monohydrate are obtained, the yield being 68% for PC1 3 An analytic sample is repricipitated with ethanol from water.
Elementary analysis data: Found, C 16.27; H 4.09. C 4
H
10 0 P 2 Na 2
H
2 0.
Calculated, C 16.32; H 4.06.
1-Hydroxybutylidene-ll-diphosphonic acid is obtained by passing an aqueous solution of sodium salts through a column with a cation-exchange resin. After evaporating an aqueous eluate free acid is obtained in the form of a non-crystallizing syrup.
Example 9 To a mixture comprising 19.7 g (71 mmole) of synrtsit
-I:
18 c I thetio fatty acids of C17-C20 fraction, having an average molecular weight of 274.3, and 7.48 g of 35.0% hydrochloric acid containing 4.86 g (270 mmole) of water and 2.62 g (72 mmole) of HC1 11.1 ml (80 mmole) of triethylamine are added dropwise, and then at a temperature of -120 0 C 23.9 g (74 mmole) of phosphorus trichloride are introduced, the mixture is kept at a temperature of 115- -120°C for 2 hours, then excess water (18 ml) is added thereto, and the mixture is hydrolyzed at a temperature of 100-105 0 C (low boiling). After that it is neutralized with 0OH and triethylamine is distilled off in a manner similar to that described in Examples 3 and 4.
An NMR 3 1 P)-spectrometric analysis of the reaction mixture has shown the yield of hydroxyalkylidenediphosphonic acids C 1 7
-C
2 0 to be 86% (19.5 JPH 12 Hz)j of phosphorous acid, 8% (3.4 d., JPH 565 Hz); of phosphoric acid, 6% (3.3 p.p.m.).PC1 3 losses are 4.8 mmole, 169 mmole of PC13 have reacted.
The RCOOH:H 2 0:PCl 3 ratio is 0.43:1.6:1. The yield of l-hydroxyalkylidene-l,l-diphosphonic acids for the synthetic fatty acids C 1 7
-C
2 0 is practically quantitative.
Example To a mixture comprising 16.3 g (125 mmole) of enanthic acid, 10.0 g (73 mmole) of anhydrous triethylamine hydrochloride and 7.5 g (416 mmole) of water 36.8g (268 mmole) of PC1 3 are added with stirring at a temperature of 20-180 0 C. PCl3 having been added and the temperature having reached 180 C, the reaction mixture is t
"'I
1 .i tt -f'~ff fl*!.A
I
11 1* 19 cooled rapidly to a temperature of 100-110 0 °C by immersing the flask into a water bath, then 20 ml of water are added into the flask, and its contents are hydrolyzed and treated as in Example 7. PC13 losses are 15 mmole, 253 mmole of PC1 3 have reacted. The C 6
H
1 3
COOH:H
2 0:PC13 ratio is 0.47:1.55:1.0 for the introduced PC1. and 0.49:1.64: for the reacted PC1. The yield of 1-hydroxyheptylidene-l,l-diphosphonic acid is 96.5 mmole 28.5g of its disodium salt are isolated.
Example 11 To a mixture comprising 37.2 g (0.250 mole) of synthetic fatty acids of C 7
-C
9 fraction and 37.0 g of an aqueous 59.2% solution of pyridine nydrochloride, consisting of 15.1 g (0.858 mole) of water and 21.9 g (0.190 *mole) of pyridine hydrochloride, 73.2 g (0.533 mole) of phosphorus triculoride are added, as in example 1. PC1 3 losses are 0.031 mole, 0.502 mole of PC1 nas reacted.
The RCOOH:H 2 0:PC1 3 ratio is 0.47:1.57:1.0 for the introduced PC1 3 and 0.50:1.67:1.0 for the reacted PC1 3 The mixture is hydrolyzed with aqueous hydrochloric acid as in Example 1, the yield of 1-hydroxyalkylidenediphosphonic acids is 0.198 mole Example 12 To a mixture comprising 35 g of anhydrous dimethylamine hydrochloride, 15.2 g (0.185 mole) of anhydrous phosphorous acid and 11.7 g (0.26 mole) of formamide 32.7 g (0.238 mole) of phosphorus trichloride is added dripwise, with stirring and the temperature rising gra- C C c .1 20
I'
L
I
dually from 20 to 8000°C. The mixture immediately becomes liquid and homogeneous. After adding PC1 3 the temperature of the mixture is kept at 80-85°C for 10 h, then the resulting viscous mass is hydrolyzed with 60 ml of 7% hydrochloric acid for 12 hours at boiling. The NMR (31p) spectrometric analysis of the hydrolyzed mixture gives a 79% yield of aminomethylenediphosphonic acid for the reacted trivalent phosphorus, whose quantity with allowance for the losses of PC01 3 with the evolved hydrogen chloride (0.083 mole), is 0.34 mole. After diluting the mixture with methanol 25.0 g of crystalline aminomethylenediphosphonic acid are obtained (77.6% for the reacted trivalent phosphorus).
The same results are obtained if calculated quantities of water and phosphorus trichioride are used instead of phosphorous acid.
Example 13 To a mixture comprising 6.58 g of trimethylamine hydrochloride, 3.88 g (47.3 mmole) of phosphorous acid o 20 and 9.13 g (42.8 mmole) of dodecylformamide 6.73 g (49.0 mmole) of phosphorus trichloride is added at a temperature of 20-90 0 C, then the mixture is heated at a temperature of 90-95 0 C for 10 h and hydrolyzed with 30 ml of hydrochloric acid for 5 hours at boiling. To the hydrolyzed mixture 100 ml of isopropanol is added, and upon cooling a precipitate is filtered off, which is then washed with isopropanoi and acetone. The yield of N-dodecylarinomethylenediphosphonic acid is 12.77 g or, h. :1 c 21 with allowance for the PCI 3 losses (10.7 mmole), 6ad for the reacted trivalent phosphorus.
The same results are obtained if a mixture of water and phosphorus trichloride is used instead of phosphorous acid.
Example 14 To a mixture comprising 22.2 g (0.2>v mole) of J3- -alanine, 28.9 g of trimethylamine ydrochloride and 14.6 g (0.810 mole) of water 77.0 g (0.561 mole) of phosphorus trichloride is added with stirring and at a temperature of 20 to 9000. The resulting mixture is stirred at the temperature of 9000°C for 1 hour more and then it is hydrolyzed with excess hydrochloric acid. The NMR 3 1 P)-spectrometry gives the yield of 3-amino-l-hbydroxy- ,propylidene-l,l-diphosphonic acid to be 727 for the reacted PC1 3 (the quantity of which, with allowance for the PC13 losses with exit gases, is 0.488 mole). Crystals precipitate from the reaction mixture when the latter is allowed to stand. These crystals are filtered off, washed with water and dried. 37.5 g of 3-amino-l-hydroxypropylidene-l,l-diphosphonic acid are obtained, the yield being 65% (for the reacted PC13). An analytic sample is recrystallized from water. At a temperature above 20000 the product decomposes without melting.
Elementary analysis data: Found, C 15.56; H 4.88. C 3
H
1 1 N0 7 2 Calculated, C 15.33; H 4.72.
*'1 r I II e 22 Example To a mixture comprising 56.5 g (0.250 mole) of adipic acid and 115.6 g of an aqueous solution of trimethylamine hydrochloride, consisting of 85.4 g of Me3N-C1 and 30.2 g (1.676 mole) of water, 165.0 g (1.201 mole) of phosphorus trichloride is added at a temperature of -125 0 C. The mixture is kept for 30 min at a temperature of 125-130 0 C, then it is hydrolyzed with excess water. The r o NMR P)-spectrometric analysis of the hydrolysate gives the yield of the desired tetraphosphonic acid to be 68% for the reacted PC13 (whose quantity with allowance for the losses is 1.024 mole). l,6-Dihydroxyhexane-l,l,6,6- -tetrayltetraphosphonic acid is isolated in the form of a trisodium salt dihydrate and recrystallized from water.
pH-metric titration data: Found: Equiv.
1 554.0; Equiv.
2 180.5.
Calculated: Equiv., 540.1; Equiv., 180.0.
Example 16 STo a mixture comprising 66.2 g of anbydrous pyri- 20 dine hydrochloride, 36.9 g (0.450 mole) o anhydrous phosphorous acid and 35.9 g (0.491 mole) of dimethylformamide 61.7 g (0.449 mole) of phosphorus trichloride is Sadded dropwise with stirring and at a temperature of 20-85°C. The resulting homogeneous mass is stirred for h at a temperature of 85-90°C and then hydrolyzed 31 P)-pecsco-1 t with excess water at boiling. The NMR (31P)-spectroscopic analysis of the hydrolysate shows the yield of dimethylaminomethylenediphosphonic acid to be 92% for the '4 23 reacted trivalent phosphorus (whose quantity with allowance for the PC13 losses is 0.802 mole). The major quantity of the dimethylaminomethylenediphosphonic acid crystallizes from the reaction mixture when the latter is left to stand. An analytic sample is recrystallized from water, and after drying it in a vacuum at room temperature dimethyl aminomethylenediphosphonic acid monohydrate is obtained.
I pH-metric titration data: Found: Equiv.
l 239.4; Equiv.
2 119.2 Calculated: Equiv. 237./1 Equiv.
2 118.6 1 SThe same results are obtained when equivalent quantities of water and phosphorus trichloride are used instead of phosphorous acid and an equivalent quantity of picoline hydrochloride is used instead of pyridine hy- S* drochloride.
Example 17 To a mixture of 30.0 g (0.500 mole) of acetic acid f r c and 43.2 g of an aqueous solution-of diethylamine hydrochloride consisting of 31.7 g of an anhydrous substance, and 11.5 g (0.658 mole) of water 73.5 g (0.535 mole) of phosphorus trichloride is added at a temperature of S!e -125°C, the resulting mixture is kept for 5 min at a tem- Sperature of 125-130 C, and then hydrolyzed with excess of dilute hydrochloric acid. The NMR (3 1 P)-spectrometric I analysis of the hydrolysate shows the yield of 1-hydroxyethylidene-l,l-diphosphonic acid to be 75% for the rer^ acted phosphorus trichioride (whose quantity with allow- 1 ance for the PU 3 losses is 0.510 mole).
The solution is acidul.ated with NaUH, diethylamine is distilled off, and trisodium salt of 1-hydroxyethylidene-l,1-diphosphonic acid is isolated from the residue.
After drying in a vacuum at the temperature of 100 0 C zhe salt has the cowposition of a monochydrate. 50.5 g of pure salt-are obtained.
Elementary analysis data: Found, C 8.51; H 2.49. C 2
H,
7 0 8
P
2 Na 3.
Calculated, C 8.28; H 2.43.
C C C ;4 V C V 4t C C I CCI I C I C I C I I '-1
"I
Claims (5)
1. A method of preparing 1-functionally-substituted alkylidene-l,l-diphosphonic acids and salts thereof by reacting carboxylic acids or their derivatives with phosphorous acid under dehydrating conditions created by the addition of phosphorus trichloride in the presence of hydrochlorides of organic nitrogen bases to dilute the reaction mixtures.
2. A method according to claim 1, wherein the hydrochlorides of organic nitrogen bases are hydrochlorides of aliphatic amines, and of nitrogen-containing heterocyclic compounds.
3. A method of preparing 1-functionally-substituted alkylidene-l,l-diphosphonic acids and salts thereof substantially as herein described with reference to any one of Examples 1 to 17.
4. 1-functionally-substituted alkylidene-l,1-diphosphonic acids and salts thereof when prepared by any one of claims 1 to 3.
5. A method of preparing 1-functionally-substituted alkylidene-l,1-diphosphonic acids and salts thereof as defined in claim 1 and substantially as herein described. DATED this 14th day of May 1990 INSTITUT KHIMICHESKOI KiNETIKI I GORENIA SIBIRSKOGO OTDELENIA AKADEMII NAUK SSSR By their Patent Attorneys GRIFFITH HACK CO. .1 I L tt It t 25 C t t 2 .r e 11C To 9s/MS
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19873700772 DE3700772A1 (en) | 1987-01-13 | 1987-01-13 | Process for the preparation of 1-functionally substituted alkylidene-1,1-diphosphonic acids and their mixtures |
DE8804948U DE8804948U1 (en) | 1987-01-13 | 1988-04-14 | Sheath insulation for high voltage conductors |
Publications (2)
Publication Number | Publication Date |
---|---|
AU6760787A AU6760787A (en) | 1988-07-21 |
AU599950B2 true AU599950B2 (en) | 1990-08-02 |
Family
ID=39339877
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU67607/87A Ceased AU599950B2 (en) | 1987-01-13 | 1987-01-15 | Method of preparing 1-functionally-substituted-alkylidene-1, 1-diphosphonic acids and mixtures thereof |
Country Status (3)
Country | Link |
---|---|
AU (1) | AU599950B2 (en) |
BE (1) | BE1000075A4 (en) |
DE (2) | DE3700772A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6878846B2 (en) * | 2001-06-28 | 2005-04-12 | Rhodia Consumer Specialties Ltd. | Solvent systems |
EP2050785A1 (en) | 1997-10-31 | 2009-04-22 | Metabolix, Inc. | Use of organic phosphonic or phosphinic acids, or of oxides, hydroxides or carboxylic acid salts of metals as thermal stabilizers for plasticized polyhydroxyalcanoates |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL91362A0 (en) * | 1989-08-20 | 1990-03-19 | Yissum Res Dev Co | Bisphosphonates,process for preparing them and pharmaceutical compositions containing them |
US6410520B2 (en) | 2000-02-01 | 2002-06-25 | The Procter & Gamble Company | Selective crystallization of 3-pyridyl-1-hydroxyethylidene-1, 1-bisphosphonic acid sodium as the hemipentahydrate or monohydrate |
US6562974B2 (en) | 2000-02-01 | 2003-05-13 | The Procter & Gamble Company | Process for making geminal bisphosphonates |
WO2003008425A1 (en) * | 2001-07-16 | 2003-01-30 | Universite Paris 13 | Novel bisphosphonate derivatives, their preparation methods and uses |
ITMI20020908A1 (en) * | 2002-04-29 | 2003-10-29 | Chemi Spa | ALENDRONATE SODIUM PREPARATION PROCESS |
US7038083B2 (en) | 2002-05-17 | 2006-05-02 | Teva Pharmaceutical Industries, Ltd. | Process for making bisphosphonic acids using diluents other than halogenated hydrocarbons |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4060546A (en) * | 1961-07-03 | 1977-11-29 | Henkel Kommanditgesellschaft Auf Aktien | Process for the manufacture of acylation products of phosphorous acid |
FR1491248A (en) * | 1965-03-30 | 1967-08-11 | Procter & Gamble | Process for the preparation of organic phosphorus compounds, in particular ethane-1-hydroxy-1, 1-diphosphonic acid |
FR1521962A (en) * | 1966-05-05 | 1968-04-19 | Monsanto Co | Process for the preparation of 1-hydroxy, organo-1, 1-diphosphonic acids and new products thus obtained |
FR1521961A (en) * | 1966-05-05 | 1968-04-19 | Monsanto Co | Process for the preparation of 1-hydroxy, lower alkylidene-1, 1-diphosphonic acids and new products thus obtained |
US3496223A (en) * | 1966-12-19 | 1970-02-17 | Monsanto Co | Process for preparing phosphonic acids |
US3666675A (en) * | 1970-01-21 | 1972-05-30 | Univ Temple | Method for producing luminescence using complex luminescent materials |
BE769136A (en) * | 1970-06-29 | 1971-12-28 | Monsanto Co | PROCESSES FOR THE CONTINUOUS PREPARATION OF 1-HYDROXY, ORGANO-1,1-DIPHOSPHONIC ACIDS AND NEW PRODUCTS THUS OBTAINED |
BE769137A (en) * | 1970-06-29 | 1971-12-28 | Monsanto Co | PROCESS FOR THE PREPARATION OF 1-HYDROXY, ORGANO-1,1- DIPHOSPHONIC ACIDS AND NEW PRODUCTS THEREFORE |
DE2115737C3 (en) * | 1971-03-31 | 1979-11-08 | Henkel Kgaa, 4000 Duesseldorf | Process for the preparation of 1-aminoalkane-1,1-diphosphonic acids |
GB1398844A (en) * | 1971-07-22 | 1975-06-25 | Albright & Wilson | Manufacture of 1-hydroxyethane 1,1-diphosphonic acid |
DD106654A1 (en) * | 1972-10-13 | 1974-06-20 | ||
US3959360A (en) * | 1975-07-31 | 1976-05-25 | Monsanto Company | Process for preparing 1-hydroxy, ethylidene-1,1-diphosphonic acid |
DE2745083C2 (en) * | 1977-10-07 | 1985-05-02 | Henkel KGaA, 4000 Düsseldorf | Hydroxydiphosphonic acids and processes for their preparation |
DE2943498C2 (en) * | 1979-10-27 | 1983-01-27 | Henkel KGaA, 4000 Düsseldorf | Process for the preparation of 3-amino-1-hydroxypropane-1,1-diphosphonic acid |
US4332736A (en) * | 1980-09-22 | 1982-06-01 | Air Products And Chemicals, Inc. | Production of 1-hydroxyalkylidene-1, 1-diphosphonic acid esters |
DD213929A1 (en) * | 1983-02-15 | 1984-09-26 | Piesteritz Stickstoff | PROCESS FOR PREPARING ETHANHYDROXYDIPHOSPHONIC ACID IN THE MIXTURE WITH PHOSPHORIC ACID |
DD222598A1 (en) * | 1983-11-09 | 1985-05-22 | Adw Ddr | PROCESS FOR THE PREPARATION OF 1-AMINO-ALKAN-1,1-BISPHOSPHONESAEURES |
DD224321A1 (en) * | 1984-05-29 | 1985-07-03 | Piesteritz Agrochemie | PROCESS FOR PRODUCING SUBSTITUTED AMINOALKANDIPHOSPHONIC ACID |
IT1196315B (en) * | 1984-10-29 | 1988-11-16 | Gentili Ist Spa | PROCEDURE FOR THE PREPARATION OF DIPHOSPHONIC ACIDS |
DD249482A1 (en) * | 1986-05-30 | 1987-09-09 | Akad Wissenschaften Ddr | PROCESS FOR PREPARING FORMAMIDINOMETHANE-BISPHOSPHONIC ACID AND AMINOMETHANE-BISPHOSPHONIC ACID |
-
1987
- 1987-01-13 DE DE19873700772 patent/DE3700772A1/en not_active Withdrawn
- 1987-01-15 AU AU67607/87A patent/AU599950B2/en not_active Ceased
- 1987-01-16 BE BE8700024A patent/BE1000075A4/en not_active IP Right Cessation
-
1988
- 1988-04-14 DE DE8804948U patent/DE8804948U1/en not_active Expired
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2050785A1 (en) | 1997-10-31 | 2009-04-22 | Metabolix, Inc. | Use of organic phosphonic or phosphinic acids, or of oxides, hydroxides or carboxylic acid salts of metals as thermal stabilizers for plasticized polyhydroxyalcanoates |
US6878846B2 (en) * | 2001-06-28 | 2005-04-12 | Rhodia Consumer Specialties Ltd. | Solvent systems |
Also Published As
Publication number | Publication date |
---|---|
BE1000075A4 (en) | 1988-02-02 |
DE8804948U1 (en) | 1988-06-09 |
DE3700772A1 (en) | 1988-07-21 |
AU6760787A (en) | 1988-07-21 |
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