WO1995019341A2 - Process for making 5-nitrobarbituric acid and salts thereof - Google Patents
Process for making 5-nitrobarbituric acid and salts thereof Download PDFInfo
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- WO1995019341A2 WO1995019341A2 PCT/US1995/000031 US9500031W WO9519341A2 WO 1995019341 A2 WO1995019341 A2 WO 1995019341A2 US 9500031 W US9500031 W US 9500031W WO 9519341 A2 WO9519341 A2 WO 9519341A2
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- WIPO (PCT)
- Prior art keywords
- acid
- process according
- nitrobarbituric
- salts
- group
- Prior art date
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- ABICJYZKIYUWEE-UHFFFAOYSA-N 5-nitro-1,3-diazinane-2,4,6-trione Chemical compound [O-][N+](=O)C1C(=O)NC(=O)NC1=O ABICJYZKIYUWEE-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 150000003839 salts Chemical class 0.000 title claims abstract description 48
- 238000000034 method Methods 0.000 title claims description 36
- 239000004202 carbamide Substances 0.000 claims abstract description 23
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 22
- 150000001768 cations Chemical class 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 238000011065 in-situ storage Methods 0.000 claims abstract description 17
- 150000007530 organic bases Chemical class 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 6
- 239000007859 condensation product Substances 0.000 claims abstract description 5
- 230000003472 neutralizing effect Effects 0.000 claims abstract description 5
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 22
- -1 nitrogen containing organic base Chemical class 0.000 claims description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 13
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims description 13
- 229910017604 nitric acid Inorganic materials 0.000 claims description 13
- 230000000802 nitrating effect Effects 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 238000002955 isolation Methods 0.000 claims description 8
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims description 7
- KJBJCAJCBCPBGV-UHFFFAOYSA-N 2-nitropropanedioic acid Chemical compound OC(=O)C(C(O)=O)[N+]([O-])=O KJBJCAJCBCPBGV-UHFFFAOYSA-N 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 6
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 6
- 229910001960 metal nitrate Inorganic materials 0.000 claims description 6
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 5
- 229940106681 chloroacetic acid Drugs 0.000 claims description 5
- DAKKWKYIQGMKOS-UHFFFAOYSA-N diethyl 2-nitropropanedioate Chemical compound CCOC(=O)C([N+]([O-])=O)C(=O)OCC DAKKWKYIQGMKOS-UHFFFAOYSA-N 0.000 claims description 5
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims description 5
- 239000013067 intermediate product Substances 0.000 claims description 5
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Inorganic materials [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-O hydrazinium(1+) Chemical compound [NH3+]N OAKJQQAXSVQMHS-UHFFFAOYSA-O 0.000 claims description 4
- YIXJRHPUWRPCBB-UHFFFAOYSA-N magnesium nitrate Inorganic materials [Mg+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O YIXJRHPUWRPCBB-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Inorganic materials [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 claims description 4
- DHEQXMRUPNDRPG-UHFFFAOYSA-N strontium nitrate Inorganic materials [Sr+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O DHEQXMRUPNDRPG-UHFFFAOYSA-N 0.000 claims description 4
- KNRUQUSSDKZTSQ-UHFFFAOYSA-O 1h-tetrazol-1-ium-1-amine Chemical compound NN1C=[NH+]N=N1 KNRUQUSSDKZTSQ-UHFFFAOYSA-O 0.000 claims description 3
- MPSUGQWRVNRJEE-UHFFFAOYSA-O 1h-triazol-1-ium-1-amine Chemical compound NN1C=C[NH+]=N1 MPSUGQWRVNRJEE-UHFFFAOYSA-O 0.000 claims description 3
- SEDZOXVYXQIFLY-UHFFFAOYSA-O 2H-tetrazol-1-ium-1-ylhydrazine Chemical compound N(N)[N+]=1NN=NC=1 SEDZOXVYXQIFLY-UHFFFAOYSA-O 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- HAMNKKUPIHEESI-UHFFFAOYSA-O carbamohydrazonoylazanium Chemical compound NC(N)=N[NH3+] HAMNKKUPIHEESI-UHFFFAOYSA-O 0.000 claims description 3
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Inorganic materials [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 claims description 3
- FQQQSNAVVZSYMB-UHFFFAOYSA-O diamino(diaminomethylidene)azanium Chemical compound N[NH+](N)C(N)=N FQQQSNAVVZSYMB-UHFFFAOYSA-O 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- MIVBAHRSNUNMPP-UHFFFAOYSA-N manganese(II) nitrate Inorganic materials [Mn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O MIVBAHRSNUNMPP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 claims description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 2
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 238000006386 neutralization reaction Methods 0.000 claims 1
- 238000009833 condensation Methods 0.000 description 15
- 230000005494 condensation Effects 0.000 description 15
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000006482 condensation reaction Methods 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 5
- 238000006396 nitration reaction Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- PJFLCUVEMVGOAP-UHFFFAOYSA-N 2-cyano-2-nitroacetic acid Chemical compound OC(=O)C(C#N)[N+]([O-])=O PJFLCUVEMVGOAP-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 239000001103 potassium chloride Substances 0.000 description 3
- 235000011164 potassium chloride Nutrition 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- UKFXDFUAPNAMPJ-UHFFFAOYSA-N ethylmalonic acid Chemical compound CCC(C(O)=O)C(O)=O UKFXDFUAPNAMPJ-UHFFFAOYSA-N 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 150000001457 metallic cations Chemical class 0.000 description 2
- JCZMXVGQBBATMY-UHFFFAOYSA-N nitro acetate Chemical compound CC(=O)O[N+]([O-])=O JCZMXVGQBBATMY-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- PZBPKYOVPCNPJY-UHFFFAOYSA-N 1-[2-(allyloxy)-2-(2,4-dichlorophenyl)ethyl]imidazole Chemical compound ClC1=CC(Cl)=CC=C1C(OCC=C)CN1C=NC=C1 PZBPKYOVPCNPJY-UHFFFAOYSA-N 0.000 description 1
- HRRVLSKRYVIEPR-UHFFFAOYSA-N 6-hydroxy-5-nitroso-1H-pyrimidine-2,4-dione Chemical compound OC1=NC(O)=C(N=O)C(O)=N1 HRRVLSKRYVIEPR-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- CWVZGJORVTZXFW-UHFFFAOYSA-N [benzyl(dimethyl)silyl]methyl carbamate Chemical compound NC(=O)OC[Si](C)(C)CC1=CC=CC=C1 CWVZGJORVTZXFW-UHFFFAOYSA-N 0.000 description 1
- 229920000180 alkyd Polymers 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- LEKPFOXEZRZPGW-UHFFFAOYSA-N copper;dicyanide Chemical compound [Cu+2].N#[C-].N#[C-] LEKPFOXEZRZPGW-UHFFFAOYSA-N 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- CZHKGPGJCQSKJL-UHFFFAOYSA-N dibutyl 2-nitropropanedioate Chemical compound CCCCOC(=O)C([N+]([O-])=O)C(=O)OCCCC CZHKGPGJCQSKJL-UHFFFAOYSA-N 0.000 description 1
- GLKRAUOJZYHDSB-UHFFFAOYSA-N dimethyl 2-nitropropanedioate Chemical compound COC(=O)C([N+]([O-])=O)C(=O)OC GLKRAUOJZYHDSB-UHFFFAOYSA-N 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- NTNWEEMGNVJAAB-UHFFFAOYSA-N dipropan-2-yl 2-nitropropanedioate Chemical compound CC(C)OC(=O)C([N+]([O-])=O)C(=O)OC(C)C NTNWEEMGNVJAAB-UHFFFAOYSA-N 0.000 description 1
- UBSFWEDLQMWFMD-UHFFFAOYSA-N dipropyl 2-nitropropanedioate Chemical compound CCCOC(=O)C([N+]([O-])=O)C(=O)OCCC UBSFWEDLQMWFMD-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- IXBPPZBJIFNGJJ-UHFFFAOYSA-N sodium;cyanoiminomethylideneazanide Chemical compound [Na+].N#C[N-]C#N IXBPPZBJIFNGJJ-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229910001631 strontium chloride Inorganic materials 0.000 description 1
- AHBGXTDRMVNFER-UHFFFAOYSA-L strontium dichloride Chemical compound [Cl-].[Cl-].[Sr+2] AHBGXTDRMVNFER-UHFFFAOYSA-L 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Inorganic materials [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/62—Barbituric acids
Definitions
- the present invention concerns improved processes for making 5-nitrobarbituric acid and salts thereof.
- a conventional process for making 5-nitrobarbituric acid, sometimes referred to as dilituric acid, is the direct nitra ⁇ tion of barbituric acid.
- the procedure is described in publications such as, for instance, Organic Synthesis, Coll. Vol. II, pp. 440-41 and Journal of the American Chemical Society, Vol. 62, pp. 590-593 (1940).
- barbituric acid is first prepared.
- One well-known synthesis of barbituric acid starts with the reaction of chloroacetic acid with sodium dicyanamide and esterification with absolute ethanol in the presence of sulfuric acid to form diethyl malonate which is isolated and purified by distilla- tion.
- the diethyl malonate is subsequently allowed to condense with urea under basic conditions and then acidified to afford barbituric acid.
- Other conventional processes for preparing barbituric acid include the action of phosphorus oxychloride on malonic acid and urea as described in Co pt. Rend.. Vol. 87, p. 752 (1878) , the reaction of ethyl malonate and a sodium derivative of urea obtained from urea and sodium in liquid ammonia as described in U.S. Patent No.
- Salts of 5-nitrobarbituric acid are obtained by isolating the 5-nitrobarbituric acid and then forming the salt in water.
- 5-nitrobarbituric acid and salts thereof It would be a further advance in the art to provide a process suitable for the large scale manufacture of 5-nitrobarbituric acid and salts thereof.
- the processes for producing 5-nitrobarbituric acid of the present invention include in situ preparation of a compound the formula (I)
- R, and R 2 are the same or different and are H, alkyl or substituted alkyd, aryl, or substituted aryl, and jln situ condensation with an effective amount of urea to obtain 5-nitrobarbituric acid.
- Salts are obtained by treating the reaction product, 5-nitrobarbituric acid, with an effective amount of a compound such as an organic base or another cation source (MX) .
- the processes according to the present invention are simpler and more cost-effective than conventional processes for making 5-nitrobarbituric acid and its salts. Isolation and purification of reaction intermediates in the synthesis of 5-nitrobarbituric acid and its salts are not required in practicing the present inventions. For instance, according to the present invention isolation of a compound represented by formula (I) , barbituric acid, and 5-nitrobarbituric acid is avoided.
- the present invention provides processes for producing 5-nitrobarbituric acid and its salts.
- R.. and R 2 are the same or different and are H, C ( to C 8 alkyl or substituted C. to C 8 alkyl, aryl, or substituted aryl, is condensed with an effective amount of urea to obtain 5-nitrobarbituric acid at a pH which is sufficient to allow the condensation reaction to proceed.
- Rj and R 2 are, independently of one.
- an alkyl group such as, for instance, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, or an alkyl substituted with, for instance, methoxy, ethoxy, or halo (such as chloro or bromo) , or an aryl group such as, for instance, phenyl or benzyl.
- the pH is greater than about 7.
- the pH can be in the range of 10 to 14, except when Rj and R 2 are hydrogen at which time the reaction is typically run at a pH less than 7, generally 2 ⁇ pH ⁇ 5, although the precise pH is not critical as long as the condensation reaction proceeds.
- the reaction rate can, however, be controlled by selecting and maintaining a pH or range of pH.
- nitrated diethyl malonate can be obtained by allowing a haloacetic acid, such as chloroacetic acid, bromoacetic acid or a mixture thereof, to react with an effective amount of at least one cyanide source to obtain a salt of cyanoacetic acid at a pH of, for instance, about 10 to about 14, and reacting the cyanoacetic acid salt with an effective amount of nitric acid at a pH less than 7, preferably less than about 3, followed by addition of an effective amount of ethanol.
- a haloacetic acid such as chloroacetic acid, bromoacetic acid or a mixture thereof
- nitrated diethyl malonate a compound according to formula (I) , by the direct nitration of cyanoacetic acid is described in, for instance, Gazzeta Chimica Italiana. Vol. 42, p. 223, the complete disclosure of which is incorporated herein by reference.
- the nitrations can be conducted at a pH in the range of about 1 to about 5.
- Other compounds represented by formula (I) can be prepared by replacing ethanol with another alcohol such as, for instance, methanol, propanol, butanol, hexanol, and mixtures thereof.
- Exemplary cyanide sources include, among others, alkali metal cyanide, such as sodium cyanide and potassium cyanide, alkaline earth metal cyanide, such as calcium cyanide, and Cu(CN) 2 .
- other exemplary nitrating reagents include, among others, acetic acid or acetic anhydride with ammonium nitrate, acetic acid or acetic anhydride with one or more metal nitrates of which Mn(N0 3 ) 2 , Cu(N0 3 ) 2 , NaN0 3 , Ca(N0 3 ) 2 , Mg(N0 3 ) 2 , and Sr(N0 3 ) 2 are illustrative.
- these nitrating reagents are only used in slight excess because the substrate is facilely nitrated.
- the pH of the in situ reaction mixture is adjusted to a pH > 7, preferably higher, during, or just before, the condensation with urea.
- the cyanoacetic acid can be nitrated and the cyano group hydrolyzed to form nitromalonic acid (compound (I) , wherein Rj and R 2 are H) .
- Nitromalonic acid can be directly converted to dilituric acid by adding an effective amount of a dehydrating agent, such as anhydride, and urea to effect the condensation.
- a dehydrating agent such as anhydride
- exemplary anhydrides include, among others, acetic anhydride, propionic anhydride, butyric anhydride, and benzoic anhydride. Typical reaction conditions are similar to those described in Chem. Ber.. Vol. 54, p. 1035 (1921) regarding the condensation of malonic acid with urea to form barbituric acid.
- a compound of formula (I) is obtained by nitrating a compound of formula (II)
- nitrating reagents include, among others, nitric acid, acetic acid or acetic anhydride with ammonium nitrate, acetic acid or acetic anhydride with one or more metal nitrates of which Mn(N0) 2 , Cu(NO) 2 , NaN0 3 , Ca(N0 3 )2, Mg(N0 3 ) 2 , and Sr(N0 3 ) 2 are illustrative.
- the compound of formula (I) is condensed with an effective amount of urea under conditions described hereinabove.
- the acid is treated in situ with an effective amount of a compound such as an organic base or another appropriate cation source to form the desired salt.
- Salts of 5-nitrobarbituric acid are obtained without need to first isolate barbituric acid or 5-nitrobarbituric acid.
- salts of 5-nitrobarbituric acid are obtained by allowing the above-des- cribed condensation reaction with urea to proceed and treating the 5-nitrobarbituric acid in situ with an organic base and/or wish another cation source (MX) .
- MX cation source
- the latter treatment can be conducted either concurrently with the condensation or subse ⁇ quently to the completion of the condensation reaction. If the latter condensation has been carried out at low pH, the addition of the base would preferably occur after completion of the condensation.
- the base cane be added concurrently and can be used to control the pH as in the case of, for instance, potassium hydroxide, unless the base will interfere with the condensation as would be expected for many high nitrogen bases such as, for instance, ammonia, hydrazine, and guanidine.
- the compound used to form the salt can be an organic base, or other cation source.
- the appropriate organic base or other cation source useful for neutralizing the urea condensation product can be selected to provide the desired cation.
- Non- metallic cations can be selected, for instance, from among organic cations and, in principle, cations of non-carbon heterocycles such as borazines.
- the cation can be a non- metallic cation of a high nitrogen-content base.
- Exemplary non-metallic cations include, among others, ammonium, hydra- zinium, guanidinium, aminoguanidinium, diaminoguanidinium, triaminoguanidinium, biguanidinium, aminotriazolium, guanizini- um, aminotetrazolium, and hydrazino tetrazolium.
- the other cation source, MX can be selected from the group consisting of alkali metal salts, alkaline earth metal salts, and salts of transition metals.
- Exemplary other cation sources MX include potassium hydroxide, potassium chloride, Zn(N0 3 ) 2 , NaOH, SrCl 2 , and the like.
- organic base or other cation source is selected to obtain salts which are readily recovered without extensive work-up.
- the sodium salt of 5-nitrobarbituric acid can be formed, but the sodium salt is harder to recover owing to its solubility in water.
- Organic bases and other cation sources for making salts from 5-nitrobarbituric acid are described in Journal of the American Chemical Society. Vol. 62, p. 590 (1940), the complete disclo- sure of which is incorporated herein by reference.
- the 5-nitrobarbituric acid salts can be recovered using techniques known to those skilled in the art. For instance, with those salts having low solubility constants (Ksp) the salt precipitates and can be recovered by filtration or centrifuga- tion. The salts can be further purified, if desired, by re- crystallization.
- the reaction conditions selected by a person skilled in the art will be apparent given the disclosure herein. For instance, the displacement of the chloride in chloroacetic acid is typically conducted at reflux in ethanol or DMF. The nitrations are typically carried out at lower temperatures in nitric acid, or in acetic acid/acetic anhydride with nitric acid (acetyl nitrate) .
- the esterifications and condensations are generally carried out at reflux in an appropriate solvent, such as ethanol for the esterification, ethanol for the base catalyzed condensations, acetic acid for the acid catalyzed - anhydride mediated condensations.
- Base forming reactions if not conducted in situ, will be conducted at room temperature, although the reactions could, if desired, be conducted at higher or lower temperatures.
- Condensation reactions should be conducted with exclusion of moisture by, for instance, a drying tube on the reflux condenser or under dry nitrogen.
- Urea should be essentially anhydrous.
- Nitric acid can be the conventional 98%, although lower concentrations such as 70% can be used as well.
- the process conditions can be adjusted, if desired, to enhance recovery the salt of 5-nitrobarbituric acid.
- the temperature can, of course, be controlled, i.e. raised or lowered or the like, to induce or regulate the rate of precipitation of the desired salt.
- Dilituric acid is useful as a reagent for isolating various organic and inorganic bases, for the isolation of magnesium and for the separation of potassium from binary mixtures containing sodium and potassium.
- Dilituric salts have a variety of uses.
- the potassium salt of dilitu ⁇ ric acid is useful in gas generant compositions as described in U.S. Patent No. 5,015,309, the complete disclosure of which is incorporated herein by reference. The invention is described further in the following non-limiting examples.
- Example 1 Nitration of diethyl malonate in nitric acid (70%) is conducted, followed by base treatment (potassium ethoxide, ethanol) to obtain the desired pH. Urea is added. The condensation mixture is heated to reflux to yield the potassium diliturate salt. The salt is recovered by filtration.
- Nitration of malonic acid with acetyl nitrate in acetic acid/acetic anhydride was conducted to obtain nitromalonic acid.
- Various salts are separately prepared from the dilituric acid in situ using as cation sources potassium chloride, ammonia, and guanidinium chloride.
- the potassium diliturate salt, ammonium diliturate, guanidinium diliturate salts are each recovered and isolated by filtration.
- Example 3 Various salts of dilituric acid were prepared in situ. Nitrocyanoacetic acid is prepared according to Gazzeta Chimica Italiana. Vol. 42, p. 223 (chloroacetic acid plus NaCN, then nitric acid) . To the nitrocyanoacetic acid is added a minimal amount of water to hydrolyze the acid. Heating to reflux yields the nitromalonic acid in situ. Various salts are separately prepared from the dilituric acid in situ using as cation sources potassium chloride, ammonia, and guanidinium chloride. The potassium diliturate salt, ammonium diliturate, guanidinium diliturate salts are each recovered and isolated by filtration.
- Example 4 Nitrocyanoacetic acid is prepared as in Example 3 and is esterified by the addition of ethanol and heated to reflux to afford the diethyl nitromalonate in situ. To the diethyl nitromalonate is added potassium ethoxide and ethanol to obtain the desired pH. Urea is added. The condensation mixture is heated to reflux to yield the potassium diliturate salt. The salt is recovered by filtration.
Abstract
A process for preparing salts of 5-nitrobarbituric acid involves allowing an in situ generated a compound represented by formula (I) wherein R1 and R2 are the same or different and are H, C1 to C8 alkyl or substituted C1 to C8 alkyl, aryl or substituted, aryl, to condense with urea to obtain a condensation product; and neutralizing the condensation product with at least one organic base and another cation source (MX) at a pH » 7 and recovering the resulting salt of 5-nitrobarbituric acid.
Description
PROCESS FOR MAKING 5-NITROBARBITϋRIC ACID AND SALTS THEREOF
Field of the Invention The present invention concerns improved processes for making 5-nitrobarbituric acid and salts thereof.
Background of the Invention A conventional process for making 5-nitrobarbituric acid, sometimes referred to as dilituric acid, is the direct nitra¬ tion of barbituric acid. The procedure is described in publications such as, for instance, Organic Synthesis, Coll. Vol. II, pp. 440-41 and Journal of the American Chemical Society, Vol. 62, pp. 590-593 (1940). In the conventional process barbituric acid is first prepared. One well-known synthesis of barbituric acid starts with the reaction of chloroacetic acid with sodium dicyanamide and esterification with absolute ethanol in the presence of sulfuric acid to form diethyl malonate which is isolated and purified by distilla- tion. The diethyl malonate is subsequently allowed to condense with urea under basic conditions and then acidified to afford barbituric acid. Other conventional processes for preparing barbituric acid include the action of phosphorus oxychloride on malonic acid and urea as described in Co pt. Rend.. Vol. 87, p. 752 (1878) , the reaction of ethyl malonate and a sodium derivative of urea obtained from urea and sodium in liquid ammonia as described in U.S. Patent No. 2,090,594, and a reaction sequence involving dissolving finely cut sodium in absolute alcohol, adding ethyl malonate, adding dry urea in hot absolute ethanol and refluxing before recovering the product as described in Organic Synthesis. Coll. Vol. II, pp. 60-61. Other methods for preparing barbituric acid are mentioned in Organic Synthesis. Coll. Vol. II, pp. 60-61. The barbituric acid is isolated and then nitrated with fuming or concentrated nitric acid to obtain 5-nitrobarbituric acid.
Another known process for preparing 5-nitrobarbituric acid is the oxidation of violuric acid as described in Ber.. Vol. 16, p. 1134 (1883) .
Salts of 5-nitrobarbituric acid are obtained by isolating the 5-nitrobarbituric acid and then forming the salt in water.
Although seemingly facile, the conventional processes for making 5-nitrobarbituric acid and its salts are cumbersome and unsuited for large scale production of 5-nitrobarbituric acid and salts thereof. In some conventional processes, five separate direct synthetic operations are carried out, with isolation of intermediate products and, in at least one instance, purification of an isolated intermediate product being required. For instance, the isolation and purification of 5-nitrobarbituric acid can be time consuming and difficult. It would, therefore, be a significant advance in the art to provide a simpler and more cost-effective process for making
5-nitrobarbituric acid and salts thereof. It would be a further advance in the art to provide a process suitable for the large scale manufacture of 5-nitrobarbituric acid and salts thereof.
Such processes are disclosed and claimed herein.
Summary and Objects of the Invention The processes for producing 5-nitrobarbituric acid of the present invention include in situ preparation of a compound the formula (I)
wherein R, and R2 are the same or different and are H, alkyl or substituted alkyd, aryl, or substituted aryl, and jln situ condensation with an effective amount of urea to obtain 5-nitrobarbituric acid. Salts are obtained by treating the reaction product, 5-nitrobarbituric acid, with an effective
amount of a compound such as an organic base or another cation source (MX) .
The processes according to the present invention are simpler and more cost-effective than conventional processes for making 5-nitrobarbituric acid and its salts. Isolation and purification of reaction intermediates in the synthesis of 5-nitrobarbituric acid and its salts are not required in practicing the present inventions. For instance, according to the present invention isolation of a compound represented by formula (I) , barbituric acid, and 5-nitrobarbituric acid is avoided.
Detailed Description of the Invention The present invention provides processes for producing 5-nitrobarbituric acid and its salts.
In one embodiment, a compound having the formula (I)
wherein R.. and R2 are the same or different and are H, C( to C8 alkyl or substituted C. to C8 alkyl, aryl, or substituted aryl, is condensed with an effective amount of urea to obtain 5-nitrobarbituric acid at a pH which is sufficient to allow the condensation reaction to proceed. Rj and R2 are, independently of one. another, H, an alkyl group such as, for instance, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, or an alkyl substituted with, for instance, methoxy, ethoxy, or halo (such as chloro or bromo) , or an aryl group such as, for instance, phenyl or benzyl.
In general, in the aforementioned condensation with urea, the pH is greater than about 7. The pH can be in the range of 10 to 14, except when Rj and R2 are hydrogen at which time the reaction is typically run at a pH less than 7, generally 2 < pH < 5, although the precise pH is not critical as long as the condensation reaction proceeds. The reaction rate can,
however, be controlled by selecting and maintaining a pH or range of pH.
The compound of formula (I) is prepared in situ. For instance, nitrated diethyl malonate can be obtained by allowing a haloacetic acid, such as chloroacetic acid, bromoacetic acid or a mixture thereof, to react with an effective amount of at least one cyanide source to obtain a salt of cyanoacetic acid at a pH of, for instance, about 10 to about 14, and reacting the cyanoacetic acid salt with an effective amount of nitric acid at a pH less than 7, preferably less than about 3, followed by addition of an effective amount of ethanol. Preparing nitrated diethyl malonate, a compound according to formula (I) , by the direct nitration of cyanoacetic acid is described in, for instance, Gazzeta Chimica Italiana. Vol. 42, p. 223, the complete disclosure of which is incorporated herein by reference. The nitrations can be conducted at a pH in the range of about 1 to about 5. Other compounds represented by formula (I) can be prepared by replacing ethanol with another alcohol such as, for instance, methanol, propanol, butanol, hexanol, and mixtures thereof. Exemplary cyanide sources include, among others, alkali metal cyanide, such as sodium cyanide and potassium cyanide, alkaline earth metal cyanide, such as calcium cyanide, and Cu(CN)2. Besides nitric acid, other exemplary nitrating reagents include, among others, acetic acid or acetic anhydride with ammonium nitrate, acetic acid or acetic anhydride with one or more metal nitrates of which Mn(N03)2, Cu(N03)2, NaN03, Ca(N03)2, Mg(N03)2, and Sr(N03)2 are illustrative. By preference, these nitrating reagents are only used in slight excess because the substrate is facilely nitrated.
As will be apparent, the pH of the in situ reaction mixture is adjusted to a pH > 7, preferably higher, during, or just before, the condensation with urea.
In another embodiment, the cyanoacetic acid can be nitrated and the cyano group hydrolyzed to form nitromalonic acid (compound (I) , wherein Rj and R2 are H) . Nitromalonic acid can be directly converted to dilituric acid by adding an
effective amount of a dehydrating agent, such as anhydride, and urea to effect the condensation. Exemplary anhydrides include, among others, acetic anhydride, propionic anhydride, butyric anhydride, and benzoic anhydride. Typical reaction conditions are similar to those described in Chem. Ber.. Vol. 54, p. 1035 (1921) regarding the condensation of malonic acid with urea to form barbituric acid.
In yet another embodiment, a compound of formula (I) is obtained by nitrating a compound of formula (II)
wherein R! and R2 are as described above, with an effective amount of a nitrating reagent. For example, diethyl malonate can be nitrated to obtain a compound represented by formula (I) . Suitable nitrating reagents include, among others, nitric acid, acetic acid or acetic anhydride with ammonium nitrate, acetic acid or acetic anhydride with one or more metal nitrates of which Mn(N0)2 , Cu(NO)2, NaN03, Ca(N03)2, Mg(N03)2, and Sr(N03)2 are illustrative. The compound of formula (I) is condensed with an effective amount of urea under conditions described hereinabove. The acid is treated in situ with an effective amount of a compound such as an organic base or another appropriate cation source to form the desired salt.
Other compounds represented by formula (I) , such as, for instance, dimethyl nitromalonate, dipropyl nitromalonate, diisopropyl nitromalonate, dibutyl nitromalonate, and dibenzyl nitro magnate, as well as their counterpart compounds of formula (II) can be prepared as above-described.
Salts of 5-nitrobarbituric acid are obtained without need to first isolate barbituric acid or 5-nitrobarbituric acid. According to an embodiment of the present invention, salts of 5-nitrobarbituric acid are obtained by allowing the above-des- cribed condensation reaction with urea to proceed and treating the 5-nitrobarbituric acid in situ with an organic base and/or wish another cation source (MX) . The latter treatment can be
conducted either concurrently with the condensation or subse¬ quently to the completion of the condensation reaction. If the latter condensation has been carried out at low pH, the addition of the base would preferably occur after completion of the condensation. If the condensation is conducted at a high pH, the base cane be added concurrently and can be used to control the pH as in the case of, for instance, potassium hydroxide, unless the base will interfere with the condensation as would be expected for many high nitrogen bases such as, for instance, ammonia, hydrazine, and guanidine.
The compound used to form the salt can be an organic base, or other cation source. The appropriate organic base or other cation source useful for neutralizing the urea condensation product can be selected to provide the desired cation. Non- metallic cations can be selected, for instance, from among organic cations and, in principle, cations of non-carbon heterocycles such as borazines. Thus, the cation can be a non- metallic cation of a high nitrogen-content base. Exemplary non-metallic cations include, among others, ammonium, hydra- zinium, guanidinium, aminoguanidinium, diaminoguanidinium, triaminoguanidinium, biguanidinium, aminotriazolium, guanizini- um, aminotetrazolium, and hydrazino tetrazolium. The other cation source, MX, can be selected from the group consisting of alkali metal salts, alkaline earth metal salts, and salts of transition metals. Exemplary other cation sources MX include potassium hydroxide, potassium chloride, Zn(N03)2, NaOH, SrCl2, and the like. By preference the organic base or other cation source (MX) is selected to obtain salts which are readily recovered without extensive work-up. For instance, the sodium salt of 5-nitrobarbituric acid can be formed, but the sodium salt is harder to recover owing to its solubility in water. Organic bases and other cation sources for making salts from 5-nitrobarbituric acid are described in Journal of the American Chemical Society. Vol. 62, p. 590 (1940), the complete disclo- sure of which is incorporated herein by reference.
The 5-nitrobarbituric acid salts can be recovered using techniques known to those skilled in the art. For instance,
with those salts having low solubility constants (Ksp) the salt precipitates and can be recovered by filtration or centrifuga- tion. The salts can be further purified, if desired, by re- crystallization. In general, the reaction conditions selected by a person skilled in the art will be apparent given the disclosure herein. For instance, the displacement of the chloride in chloroacetic acid is typically conducted at reflux in ethanol or DMF. The nitrations are typically carried out at lower temperatures in nitric acid, or in acetic acid/acetic anhydride with nitric acid (acetyl nitrate) . The esterifications and condensations are generally carried out at reflux in an appropriate solvent, such as ethanol for the esterification, ethanol for the base catalyzed condensations, acetic acid for the acid catalyzed - anhydride mediated condensations. Base forming reactions, if not conducted in situ, will be conducted at room temperature, although the reactions could, if desired, be conducted at higher or lower temperatures. Condensation reactions should be conducted with exclusion of moisture by, for instance, a drying tube on the reflux condenser or under dry nitrogen. Urea should be essentially anhydrous. Nitric acid can be the conventional 98%, although lower concentrations such as 70% can be used as well.
The process conditions can be adjusted, if desired, to enhance recovery the salt of 5-nitrobarbituric acid. For instance, the temperature can, of course, be controlled, i.e. raised or lowered or the like, to induce or regulate the rate of precipitation of the desired salt.
Dilituric acid is useful as a reagent for isolating various organic and inorganic bases, for the isolation of magnesium and for the separation of potassium from binary mixtures containing sodium and potassium. Dilituric salts have a variety of uses. For example, the potassium salt of dilitu¬ ric acid is useful in gas generant compositions as described in U.S. Patent No. 5,015,309, the complete disclosure of which is incorporated herein by reference.
The invention is described further in the following non-limiting examples.
Example 1 Nitration of diethyl malonate in nitric acid (70%) is conducted, followed by base treatment (potassium ethoxide, ethanol) to obtain the desired pH. Urea is added. The condensation mixture is heated to reflux to yield the potassium diliturate salt. The salt is recovered by filtration.
Example 2
Various salts of dilituric acid are prepared.
Nitration of malonic acid with acetyl nitrate in acetic acid/acetic anhydride was conducted to obtain nitromalonic acid. To the nitromalonic acid is added urea -to obtain a condensation reaction mixture which is refluxed to form dilituric acid in situ. Various salts are separately prepared from the dilituric acid in situ using as cation sources potassium chloride, ammonia, and guanidinium chloride. The potassium diliturate salt, ammonium diliturate, guanidinium diliturate salts are each recovered and isolated by filtration.
Example 3 Various salts of dilituric acid were prepared in situ. Nitrocyanoacetic acid is prepared according to Gazzeta Chimica Italiana. Vol. 42, p. 223 (chloroacetic acid plus NaCN, then nitric acid) . To the nitrocyanoacetic acid is added a minimal amount of water to hydrolyze the acid. Heating to reflux yields the nitromalonic acid in situ. Various salts are separately prepared from the dilituric acid in situ using as cation sources potassium chloride, ammonia, and guanidinium chloride. The potassium diliturate salt, ammonium diliturate, guanidinium diliturate salts are each recovered and isolated by filtration.
Example 4 Nitrocyanoacetic acid is prepared as in Example 3 and is esterified by the addition of ethanol and heated to reflux to afford the diethyl nitromalonate in situ. To the diethyl nitromalonate is added potassium ethoxide and ethanol to obtain the desired pH. Urea is added. The condensation mixture is heated to reflux to yield the potassium diliturate salt. The salt is recovered by filtration.
Other or mixed esters of nitromalonate can be obtained by adapting the procedures of this Example.
The present invention may be embodied in other specific forms without departing from its essential characteristics. The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the invention is, therefore, indicated by the appended claims rather than by the foregoing description. What is claimed is:
Claims
1. A process for preparing salts of 5-nitrobarbituric acid comprising allowing an in situ generated diethyl nitro malonate to condense with urea to obtain 5-nitrobarbituric acid and neutralizing said acid with a nitrogen containing organic base, ammonium, hydrazinium, a metal salt, or mixtures thereof, and recovering the resulting salt of 5-nitrobarbituric acid without distillation or isolation of intermediate products during the preparation of the 5-nitrobarbituric acid salts.
2. A process according to claim 1, wherein the cation in said another cation source (MX) is selected from the group consisting of alkali metal salts, alkaline earth metal salts, and salts of transition metals.
3. A process according to claim 1, wherein the cation of said another cation source (MX) is selected from the group consisting of ammonium and hydrazinium.
4. A process according to claim 1, wherein the cation of said organic base is selected from the group consisting of guanidinium, aminoguanidinium, diaminoguanidinium, triamino- guanidiniu , biguanidinium, aminotriazolium, guaniziniu , aminotetrazolium, and hydrazino tetrazolium.
5. A process according to claim 1, wherein the nitrated diethyl magnate is obtained by nitrating diethyl magnate with a nitrating reagent.
6. A process according to claim 5, wherein said nitrating reagent is selected from the group consisting of nitric acid, nitric acid and acetic anhydride, and a mixture of acetic acid and acetic anhydride with ammonium nitrate or at least one metal nitrate.
7. A process according to claim 6, wherein said nitrating reagent is acetic acid or acetic anhydride and a metal nitrate selected from the group consisting of Mn(N03)2, Cu(N03)2, NaN03, Ca(N03)2, Mg(N03)2, and Sr(N03)2.
8. A process according to claim 1, wherein the nitrated diethyl malonate is generated in situ by allowing at least one haloacetic acid to react with a cyanide anion source to obtain cyanoacetic acid, and allowing the cyanoacetic acid to react with ethanol in the presence of a nitrating reagent.
9. A process according to claim 8, wherein said haloacetic acid is bromoacetic acid, chloroacetic acid, or a mixture thereof.
10. A process according to claim 8, wherein said cyanide anion source is selected from the group consisting of alkali metal cyanides and alkaline earth metal cyanides.
11. A process according to claim 10, wherein said cyanide anion source is selected from the group consisting of sodium cyanide, potassium cyanide and cupric cyanide.
12. A process according to claim 8, wherein the reaction of cyanoacetic acid with ethanol is conducted at a pH < about
2.
13. A process according to claim 8, wherein said nitrating reagent is selected from the group consisting of nitric acid, nitric acid and acetic anhydride, and a mixture of acetic acid and acetic anhydride with ammonium nitrate or at least one metal nitrate.
14. A process according to claim 8, wherein said nitrating reagent is a mixture of acetic acid and acetic anhydride and at least one metal nitrate selected from the group consisting of Mn(N03)2, Cu(N03)2, NaN03, Ca(N03)2, Mg(N03)2, and Sr(N03)2.
15. A process for preparing salts of 5-nitrobarbituric acid comprising allowing an in situ generated a compound represented by formula (I) :
wherein Rj and R2 are the same or different and are, H, C, to C8 alkyl or substituted C. to C8 alkyl, aryl or substituted aryl, to condense with urea to obtain a condensation product; and neutralizing the condensation product with at least one member selected from the group consisting of an organic base and another cation source (MX) , and recovering the resulting salt of 5-nitrobarbituric acid without distillation or isolation of intermediate products during the preparation of the 5- nitrobarbituric acid salts.
16. A process for preparing a salt of 5-nitrobarbituric acid comprising adding a dehydrating reagent to nitromalonic acid and urea, and neutralizing the reaction product thereof to obtain a salt of 5-nitrobarbituric acid without distillation or isolation of intermediate products during the preparation of the 5-nitrobarbituric acid salts.
17. A process according to claim 16, wherein said dehydrating reagent is an organic anhydride.
18. A process according to claim 7, wherein said consisting of acetic anhydride, propionic anhydride, butyric anhydride, and benzoic anhydride.
19. A process according to claim 16, wherein said neutralization is carried out with a reagent having a cation selected from the group consisting of ammonium and hydrazinium, guanidinium, aminoguanidinium, diaminoguanidinium, triaminoguanidinium, biguanidinium, aminotriazolium, guanizinium, aminotetrazolium, and hydrazino tetrazolium.
20. A process for preparing 5-nitrobarbituric acid comprising generating in situ diethyl nitromalonate and condensing the diethyl nitromalonate with urea and recovering the resulting 5-nitrobarbituric acid.
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| US08/178,215 US5472534A (en) | 1994-01-06 | 1994-01-06 | Gas generant composition containing non-metallic salts of 5-nitrobarbituric acid |
| US08/179,737 US5428165A (en) | 1994-01-06 | 1994-01-10 | Process for making 5-introbarbituric acid and salts thereof |
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| CN101525290B (en) * | 2009-04-28 | 2012-06-13 | 安徽金邦医药化工有限公司 | Preparation method of diethyl malonate |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3719604A (en) * | 1970-02-03 | 1973-03-06 | Dynamit Nobel Ag | Pressurizing-gas-producing charges containing an aminoguanidine tetrazole and an oxygen-liberating or gas-evolving additive |
| US4142029A (en) * | 1976-07-16 | 1979-02-27 | Ciba-Geigy Corporation | Bis-tetrazoles as chemical blowing agents for foaming thermoplastic resins |
| US4608102A (en) * | 1984-11-14 | 1986-08-26 | Omark Industries, Inc. | Primer composition |
| US4948439A (en) * | 1988-12-02 | 1990-08-14 | Automotive Systems Laboratory, Inc. | Composition and process for inflating a safety crash bag |
| US5015309A (en) * | 1989-05-04 | 1991-05-14 | Morton International, Inc. | Gas generant compositions containing salts of 5-nitrobarbituric acid, salts of nitroorotic acid, or 5-nitrouracil |
| US5035757A (en) * | 1990-10-25 | 1991-07-30 | Automotive Systems Laboratory, Inc. | Azide-free gas generant composition with easily filterable combustion products |
| US5084118A (en) * | 1990-10-23 | 1992-01-28 | Automotive Systems Laboratory, Inc. | Ignition composition for inflator gas generators |
| US5139588A (en) * | 1990-10-23 | 1992-08-18 | Automotive Systems Laboratory, Inc. | Composition for controlling oxides of nitrogen |
| US5197758A (en) * | 1991-10-09 | 1993-03-30 | Morton International, Inc. | Non-azide gas generant formulation, method, and apparatus |
-
1995
- 1995-01-04 WO PCT/US1995/000031 patent/WO1995019341A2/en active Application Filing
- 1995-01-04 AU AU15569/95A patent/AU1556995A/en not_active Abandoned
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3719604A (en) * | 1970-02-03 | 1973-03-06 | Dynamit Nobel Ag | Pressurizing-gas-producing charges containing an aminoguanidine tetrazole and an oxygen-liberating or gas-evolving additive |
| US4142029A (en) * | 1976-07-16 | 1979-02-27 | Ciba-Geigy Corporation | Bis-tetrazoles as chemical blowing agents for foaming thermoplastic resins |
| US4608102A (en) * | 1984-11-14 | 1986-08-26 | Omark Industries, Inc. | Primer composition |
| US4948439A (en) * | 1988-12-02 | 1990-08-14 | Automotive Systems Laboratory, Inc. | Composition and process for inflating a safety crash bag |
| US5015309A (en) * | 1989-05-04 | 1991-05-14 | Morton International, Inc. | Gas generant compositions containing salts of 5-nitrobarbituric acid, salts of nitroorotic acid, or 5-nitrouracil |
| US5084118A (en) * | 1990-10-23 | 1992-01-28 | Automotive Systems Laboratory, Inc. | Ignition composition for inflator gas generators |
| US5139588A (en) * | 1990-10-23 | 1992-08-18 | Automotive Systems Laboratory, Inc. | Composition for controlling oxides of nitrogen |
| US5035757A (en) * | 1990-10-25 | 1991-07-30 | Automotive Systems Laboratory, Inc. | Azide-free gas generant composition with easily filterable combustion products |
| US5197758A (en) * | 1991-10-09 | 1993-03-30 | Morton International, Inc. | Non-azide gas generant formulation, method, and apparatus |
Non-Patent Citations (4)
| Title |
|---|
| HARTMAN ET AL.: 'Nitrobarbituric Acid' ORGANIC SYNTHESIS vol. II, 1943, pages 440 - 441 * |
| NUTUI ET AL.: 'New syntheses of dilituric acid' REV. ROUMAINE, CHIM. vol. 16, 1971, pages 919 - 923 * |
| REDEMANN ET AL.: 'The diliturates (5-nitrobarbiturates) of some physiologically important bases' JOURNAL OF AMERICAN CHEMICAL SOCIETY vol. 62, 1940, pages 590 - 593 * |
| VAN ALPHEN J.: 'The nitration of 4-methoxy and 4-ethoxy benzophenone' RECVIEL TRAV. CHEM. vol. 8, 1930, PAY-BAS, pages 381 - 382 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101525290B (en) * | 2009-04-28 | 2012-06-13 | 安徽金邦医药化工有限公司 | Preparation method of diethyl malonate |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1995019341A3 (en) | 1995-08-31 |
| AU1556995A (en) | 1995-08-01 |
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