NO761050L - - Google Patents
Info
- Publication number
- NO761050L NO761050L NO761050A NO761050A NO761050L NO 761050 L NO761050 L NO 761050L NO 761050 A NO761050 A NO 761050A NO 761050 A NO761050 A NO 761050A NO 761050 L NO761050 L NO 761050L
- Authority
- NO
- Norway
- Prior art keywords
- acid
- mol
- bis
- aryl
- ethylenediamine
- Prior art date
Links
- -1 cyano, hydroxycarbonyl Chemical group 0.000 claims description 72
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000004104 aryloxy group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 9
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- IWOKCMBOJXYDEE-UHFFFAOYSA-N sulfinylmethane Chemical compound C=S=O IWOKCMBOJXYDEE-UHFFFAOYSA-N 0.000 claims description 8
- 239000005864 Sulphur Substances 0.000 claims description 7
- 125000004442 acylamino group Chemical group 0.000 claims description 7
- 239000000969 carrier Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 7
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 7
- 150000003457 sulfones Chemical class 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000003435 aroyl group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 3
- 125000005333 aroyloxy group Chemical group 0.000 claims description 3
- 150000001540 azides Chemical class 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 3
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 239000011593 sulfur Substances 0.000 claims 2
- 239000003524 antilipemic agent Substances 0.000 claims 1
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 229960005222 phenazone Drugs 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 130
- 229910052757 nitrogen Inorganic materials 0.000 description 94
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- 238000004458 analytical method Methods 0.000 description 56
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 23
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 239000013543 active substance Substances 0.000 description 19
- 239000003208 petroleum Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- 238000001816 cooling Methods 0.000 description 17
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 15
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 15
- 230000007935 neutral effect Effects 0.000 description 15
- 229960002703 undecylenic acid Drugs 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 229960005141 piperazine Drugs 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- IPIVAXLHTVNRBS-UHFFFAOYSA-N decanoyl chloride Chemical compound CCCCCCCCCC(Cl)=O IPIVAXLHTVNRBS-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 150000002430 hydrocarbons Chemical group 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- MZFGYVZYLMNXGL-UHFFFAOYSA-N undec-10-enoyl chloride Chemical compound ClC(=O)CCCCCCCCC=C MZFGYVZYLMNXGL-UHFFFAOYSA-N 0.000 description 9
- 239000000825 pharmaceutical preparation Substances 0.000 description 8
- 235000011121 sodium hydroxide Nutrition 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 150000001735 carboxylic acids Chemical class 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- SMUKODJVMQOSAB-UHFFFAOYSA-N 2-ethylbutanoyl chloride Chemical compound CCC(CC)C(Cl)=O SMUKODJVMQOSAB-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 6
- 239000003925 fat Substances 0.000 description 6
- 235000019197 fats Nutrition 0.000 description 6
- 125000001624 naphthyl group Chemical group 0.000 description 6
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 6
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical compound [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 150000004985 diamines Chemical class 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 230000000055 hyoplipidemic effect Effects 0.000 description 5
- FBUKVWPVBMHYJY-UHFFFAOYSA-N noncarboxylic acid Natural products CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 5
- 239000004006 olive oil Substances 0.000 description 5
- 235000008390 olive oil Nutrition 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000012265 solid product Substances 0.000 description 5
- 241000416162 Astragalus gummifer Species 0.000 description 4
- NTQYXUJLILNTFH-UHFFFAOYSA-N Chloride-Nonanoic acid Natural products CCCCCCCCC(Cl)=O NTQYXUJLILNTFH-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 229920001615 Tragacanth Polymers 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 239000000196 tragacanth Substances 0.000 description 4
- 235000010487 tragacanth Nutrition 0.000 description 4
- 229940116362 tragacanth Drugs 0.000 description 4
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 3
- SVWCVXFHTHCJJB-UHFFFAOYSA-N 4-methylpentanoyl chloride Chemical compound CC(C)CCC(Cl)=O SVWCVXFHTHCJJB-UHFFFAOYSA-N 0.000 description 3
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- UYBWIEGTWASWSR-UHFFFAOYSA-N 1,3-diaminopropan-2-ol Chemical compound NCC(O)CN UYBWIEGTWASWSR-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- MGIRLRNQAIYENH-UHFFFAOYSA-N 1-n,2-dimethylpropane-1,2-diamine Chemical compound CNCC(C)(C)N MGIRLRNQAIYENH-UHFFFAOYSA-N 0.000 description 2
- MUXPPYATEKVUBJ-UHFFFAOYSA-N 2,2-diethylbutanoyl chloride Chemical compound CCC(CC)(CC)C(Cl)=O MUXPPYATEKVUBJ-UHFFFAOYSA-N 0.000 description 2
- GUXJIZSHMPDGAT-UHFFFAOYSA-N 2-[3-(1-cyanoethylamino)propylamino]propanenitrile Chemical compound N#CC(C)NCCCNC(C)C#N GUXJIZSHMPDGAT-UHFFFAOYSA-N 0.000 description 2
- PIXGBDYTPDEVNS-UHFFFAOYSA-N 2-ethylpentanoyl chloride Chemical compound CCCC(CC)C(Cl)=O PIXGBDYTPDEVNS-UHFFFAOYSA-N 0.000 description 2
- KUSYIGBGHPOWEL-UHFFFAOYSA-N 2-methyl nonaoic acid Chemical compound CCCCCCCC(C)C(O)=O KUSYIGBGHPOWEL-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000206672 Gelidium Species 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Ornithine Chemical compound NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000005239 aroylamino group Chemical group 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 201000005577 familial hyperlipidemia Diseases 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
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- RPFLHSUTRACMOS-UHFFFAOYSA-N n,n'-dibutyl-n'-[2-(butylamino)ethyl]ethane-1,2-diamine Chemical compound CCCCNCCN(CCCC)CCNCCCC RPFLHSUTRACMOS-UHFFFAOYSA-N 0.000 description 1
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- MRULVAADQTWBTF-UHFFFAOYSA-N n-methyl-2-[2-[2-(methylamino)ethoxy]ethoxy]ethanamine Chemical compound CNCCOCCOCCNC MRULVAADQTWBTF-UHFFFAOYSA-N 0.000 description 1
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- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229960003506 piperazine hexahydrate Drugs 0.000 description 1
- AVRVZRUEXIEGMP-UHFFFAOYSA-N piperazine;hexahydrate Chemical compound O.O.O.O.O.O.C1CNCCN1 AVRVZRUEXIEGMP-UHFFFAOYSA-N 0.000 description 1
- RHPBLLCTOLJFPH-UHFFFAOYSA-N piperidin-2-ylmethanamine Chemical compound NCC1CCCCN1 RHPBLLCTOLJFPH-UHFFFAOYSA-N 0.000 description 1
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- PZZICILSCNDOKK-UHFFFAOYSA-N propane-1,2,3-triamine Chemical compound NCC(N)CN PZZICILSCNDOKK-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- IJDNQMDRQITEOD-UHFFFAOYSA-N sec-butylidene Natural products CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 239000005049 silicon tetrachloride Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- PFXVKGGZWQQTSE-UHFFFAOYSA-N sulfuryl dicyanide Chemical compound N#CS(=O)(=O)C#N PFXVKGGZWQQTSE-UHFFFAOYSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- FAGUFWYHJQFNRV-UHFFFAOYSA-N tetraethylenepentamine Chemical compound NCCNCCNCCNCCN FAGUFWYHJQFNRV-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- LDHQCZJRKDOVOX-UHFFFAOYSA-N trans-crotonic acid Natural products CC=CC(O)=O LDHQCZJRKDOVOX-UHFFFAOYSA-N 0.000 description 1
- IGBBVTAVILYDIO-MDZDMXLPSA-N trans-undec-2-enoic acid Chemical compound CCCCCCCC\C=C\C(O)=O IGBBVTAVILYDIO-MDZDMXLPSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
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- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/35—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/36—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
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Description
Karboksylsyreamider, fremgangsmåte til deres fremstilling, samt deres anvendelse som legemiddel. , ' . Carboxylic acid amides, process for their preparation, as well as their use as medicine. , ' .
Oppfinnelsen vedrører nye karboksylsyreamider,. en fremgangsmåte til deres fremstilling, samt deres anvendelse som legemiddel, spesielt som hypolipidemika. The invention relates to new carboxylic acid amides. a method for their preparation, as well as their use as medicine, especially as hypolipidemics.
Forbindelser med en sammenlignbar struktur og en lignende virkningsprq£il har hittil ikke vært kjent. Compounds with a comparable structure and a similar mechanism of action have so far not been known.
Det er funnet at de nye karboksylsyreamider med den generelle formel It has been found that the new carboxylic acid amides of the general formula
hvor where
R<1>, R2 og; R^ er like eller forskjellige og betyr R<1>, R2 and; R^ are the same or different and mean
en rettlinjet,forgrenet, syklisk mettet og umettet hydrokarbonrest, idet eventuelt karbonkjedén er avbrutt ved to-bindige heteroelementer eller grupperinger som oksygen, svovel, sulfin, sulfon, karMo-nyl, fenylen, eventuelt er substituert med substituenter som halogen, alkoksy, acyloksy, aryl, aryloksy, arylmercapto, aroyl, alkylmercapto, alkylsulfin og alkylsulfon, acylamino, aroylamino, cyano, alkoksykårbonyl, aroksykarboriyl eller aminokarbonyl, idet aminokarbonylrestén ig(j§n eventuelt er substituert med alkyl eller aryl, a straight, branched, cyclically saturated and unsaturated hydrocarbon residue, where the carbon chain is optionally interrupted by two-bonded heteroelements or groupings such as oxygen, sulphur, sulfine, sulfone, carMonyl, phenylene, optionally substituted with substituents such as halogen, alkoxy, acyloxy, aryl, aryloxy, arylmercapto, aroyl, alkylmercapto, alkylsulfine and alkylsulfone, acylamino, aroylamino, cyano, alkoxycarbonyl, aroxycarboryl or aminocarbonyl, the aminocarbonyl residue being optionally substituted with alkyl or aryl,
R^ og R^ er like eller forskjellige og betyr hydrogen eventuelt substituert aryl eller en rettlinjet, forgrenet, syklisk mettet og umettet hydrokarbonrest, idet karbonkjedén eventuelt er atorutt med heteroatomer eller grupperinger som oksygen, svovel, sulfo\n, Sulfin, karbonyl, fenylen og eventuelt er substituert med substituenter som hydroksy, alkoksy, halogen, acyloksy, acylamino, aryl, aryloksy, aroyl, alkylthio, alkylsulfon og alkylsulfin, cyano,-alkoksykårbonyl, aroksykarbonyl eller aminokarbonyl, idet aminokarbonylresten igjen eventuelt er substituert med alkyl. R^ and R^ are the same or different and mean hydrogen optionally substituted aryl or a straight, branched, cyclically saturated and unsaturated hydrocarbon residue, the carbon chain optionally being atomized with heteroatoms or groupings such as oxygen, sulphur, sulphon, sulphin, carbonyl, phenylene and is optionally substituted with substituents such as hydroxy, alkoxy, halogen, acyloxy, acylamino, aryl, aryloxy, aroyl, alkylthio, alkylsulfone and alkylsulfine, cyano, -alkyloxycarbonyl, aroxycarbonyl or aminocarbonyl, the aminocarbonyl residue being again optionally substituted with alkyl.
eller arylrester eller hvorior aryl residues or wherein
R^ og R-* for det tilfelle at n = 0 ellers betyr en alkylen-kjede som med de to nitrogenatomer danner en Iheterocyklisk ring eller hvori R^ and R-* in the event that n = 0 otherwise means an alkylene chain which with the two nitrogen atoms forms a heterocyclic ring or in which
R^ eller R^ betyr en alkylenrest som med den naboplaserté X R^ or R^ means an alkylene residue as with the neighboring placerté X
danner en nitrogenhbldig ring, X betyr en rettlinjet, forgrenet, cyklisk mettet forms a nitrogen-containing ring, X means a linear, branched, cyclically saturated
og umettet hydrokarbonkjede, idet kjeden eventuelt er avbrutt med heteroatomer eller grupperinger som oksygen, svovel, sulfin, sulfon, arylaza, alkylaza, and unsaturated hydrocarbon chain, the chain possibly being interrupted by heteroatoms or groupings such as oxygen, sulphur, sulfine, sulfone, arylase, alkylase,
karbonyl eller fenylen og eventuelt er.substituert med substituenter som alkoksy, halogen, aroksy, hydroksy, cyano, hydroksykarbonyl, alkoksykårbonyl, carbonyl or phenylene and is optionally substituted with substituents such as alkoxy, halogen, aroxy, hydroxy, cyano, hydroxycarbonyl, alkoxycarbonyl,
acylamino, aroksykarbonyl, alkylthio, alkylsulfin, alkylsulfon, arylthio, aryl eller aminokarbonyl, idet aminokarbonylresten igjen eventuelt er substituert med alkyl eller aryl og acylamino, aroxycarbonyl, alkylthio, alkylsulfine, alkylsulfone, arylthio, aryl or aminocarbonyl, the aminocarbonyl residue being optionally substituted with alkyl or aryl and
n betyr ét helt tall fra 0 til 4, idetn means an integer from 0 to 4, where
alle under R1, R2, R^,r4, R^ og X definerte arylrester inneholder 6 eller 10 C-atomer og eventuelt er substituert, all aryl residues defined under R1, R2, R^, r4, R^ and X contain 6 or 10 C atoms and are optionally substituted,
har sterke hypolipidemiske egenskaper.has strong hypolipidemic properties.
Videre ble det funnet at man får karboksylsyreamidene med den generelle formel I, idet aminer med den generelle formel II Furthermore, it was found that the carboxylic acid amides of the general formula I are obtained, whereas amines of the general formula II
hvori in which
r<4>,r<5>og X har ovennevnte betydning,r<4>,r<5>and X have the above meaning,
omsetter eventuelt i nærvær av syrebinder eller vanntil^trekkende midler og inerte oppløsningsmidler med karboksylsyre- eller karboksylsyrederivater med den generelle formel III optionally reacts in the presence of acid binders or water-attracting agents and inert solvents with carboxylic acid or carboxylic acid derivatives of the general formula III
hvori in which
B betyr substituentene R , R og RJ som har ovennevnte betydning og B means the substituents R, R and RJ which have the above meaning and
A betyr hydroksy eller en syregruppe aktiverende A means hydroxy or an acid group activating
reste som halogen, azid, cyan, alkoksy, alkylthio, acyloksy, cyanmetyloksy, aryloksy, arylthio, aroyloksy, succinimido-N-oksy, ftalimido-N-oksy, idet arylgruppene eventuelt kan være substituert en eller flere ganger. residue such as halogen, azide, cyano, alkoxy, alkylthio, acyloxy, cyanomethyloxy, aryloxy, arylthio, aroyloxy, succinimido-N-oxy, phthalimido-N-oxy, the aryl groups possibly being substituted one or more times.
Karboksylsyrederivatenes omsetning med di- og poly.aminene kan også utføres trinnvis. The reaction of the carboxylic acid derivatives with the di- and polyamines can also be carried out in stages.
Ved forbindelser med den generelle formel III som som substituenter har en hydroksy- eller aminogruppe, kan det.også foregå en etterfølgende acylering av disse funksjonelle grupper. In the case of compounds with the general formula III which have a hydroxy or amino group as substituents, a subsequent acylation of these functional groups can also take place.
I stedet for de frie aminer kan det ved omsetning ifølge oppfinnelsen også anvende slike forbindelser, hvorav aminene avspaltes. Instead of the free amines, such compounds can also be used in the reaction according to the invention, from which the amines are split off.
Overraskende viser karboksylsyreamidene ifølge oppfinnelsen en sterkt hypolipidemisk virkning. Fra stoff-klassen ifølge oppfinnelsen er det hittil ikke kjent noen forbindelser med sammenlignbar virkning. Forbindelsene ifølge oppfinnelsen er å anse som nye ytterligere hypolipidemika. De kan også anvendes som tilsetningsstoffer ved næringsmidler og medfører således en berikelse av farmasien. Surprisingly, the carboxylic acid amides according to the invention show a strong hypolipidemic effect. From the substance class according to the invention, no compounds with comparable effects are known to date. The compounds according to the invention are to be considered new additional hypolipidemics. They can also be used as food additives and thus lead to an enrichment of the pharmacy.
Anvender man 11-metoksy-undekansyreklorid og 1,2-diaminopropan som utgangsstoffer, kan reaksjonsforløpet gjen-gis ved følgende formelskjerna: If 11-methoxy-undecanoic acid chloride and 1,2-diaminopropane are used as starting materials, the course of the reaction can be reproduced by the following formula core:
De ifølge oppfinnelsen anvendbare aminer med den generelle formel II er enten kjent eller kan fremstilles etter kjente metoder /"S.Patai (utgiver), The Chemistry of The amines with the general formula II that can be used according to the invention are either known or can be prepared by known methods /" S.Patai (publisher), The Chemistry of
the Amino Group, Interscience Publishers, London, New York, Sydney I968i S.R Sandler, W. Caro, Functional Group Preparations, vol. I, side 318, Academic Press, New York og London 1968; the Amino Group, Interscience Publishers, London, New York, Sydney I968i S.R Sandler, W. Caro, Functional Group Preparations, vol. I, page 318, Academic Press, New York and London 1968;
Wi Schneider, J. Hoyer, W. Ehr enst ein, R. Haller., W. Hausel,Wi Schneider, J. Hoyer, W. Ehr enst ein, R. Haller., W. Hausel,
W. Schneider, K. Lehmann, J.J.Roth, H. Sehonenberger,W. Schneider, K. Lehmann, J. J. Roth, H. Sehonenberger,
B. Camerino, G.F. Cainelli, M. Feries i F. Korte Methodicum Chimicum, bind 6, side 449»Georg Thieme Verlag Stuttgart,1974; B. Camerino, G.F. Cainelli, M. Feries in F. Korte Methodicum Chimicum, volume 6, page 449» Georg Thieme Verlag Stuttgart, 1974;
Houben-Weyl, Methoden der organischen Chemie, bind ll/l,Houben-Weyl, Methoden der organischen Chemie, volumes ll/l,
Georg Thieme Verlag, Stuttgart 195^7.Georg Thieme Verlag, Stuttgart 195^7.
Som eksempler for de ifølge oppfinnelsen anvend-As examples for those according to the invention used
bare aminer med den generelle formel II skal'det nevnes: only amines with the general formula II should be mentioned:
1,2-diaminoetan1,2-diaminoethane
N-metyi-1,2-diaminoetanN-methyl-1,2-diaminoethane
N-etyl-1,2-diaminoetan N,N<f->diisopropyl~l,2-diaminoetan N-ethyl-1,2-diaminoethane N,N<f->diisopropyl~1,2-diaminoethane
N-metyl-N'-etyl-l,2-diaminoetanN-methyl-N'-ethyl-1,2-diaminoethane
N-propyl-1,2-diaminoetanN-propyl-1,2-diaminoethane
N,N<*->bis ^-brometyl/"-1,2-diaminoetan N,N<*->bis ^-bromomethyl/"-1,2-diaminoethane
N,N'-dipentyl-1,2-diarafaoetan N,N'-dipentyl-1,2-diaraphaoethane
N-oktyl-1,2-diaminoetanN-octyl-1,2-diaminoethane
N,N<*->dihexadecyl-1,2-diaminoetan N,N<*->dihexadecyl-1,2-diaminoethane
N-allyl-1,2-diaminoetan N-allyl-1,2-diaminoethane
N,N*-dimetallyl-1,2-diaminoétanN,N*-dimethallyl-1,2-diaminoethane
bis-j/2-aminoetyi.T-amin 2,2t<->bis-/metylamino/-dietylamin bis-j/2-aminoethyl.T-amine 2,2t<->bis-/methylamino/-diethylamine
l-butyl-dietylentriaminl-butyl-diethylenetriamine
1,5-diamin.o-3»6-diazaoktan 1,5-diamino.o-3»6-diazaoctane
1,ll-diamino-3 >6,9-triazå-undecan1,11-diamino-3>6,9-triaz-undecane
metyl-bis-Z^-aminoetyl^-aminmethyl-bis-Z^-aminoethyl^-amine
1,4,7-tribtTtyl-dietylentriamin1,4,7-tributyldiethylenetriamine
N,N<*->di-(n-metyl)-propylendiamin N,N'-di-(n-butyl)-propylendiamin 3-amino-l-metylamino-propan 1,3-bis-metylaraino-propan 1,3-bis-heptylamino-propan 3- araino-l-dodecylaminopropan 1 ,g-diamino-3,7-d:i-azanonan 1.2- diamino-butan N,N<*->di-(n-methyl)-propylenediamine N,N'-di-(n-butyl)-propylenediamine 3-amino-1-methylamino-propane 1,3-bis-methylaraino-propane 1, 3-bis-heptylamino-propane 3-araino-1-dodecylaminopropane 1,g-diamino-3,7-d:i-azanonan 1,2-diamino-butane
2-amino-l-dodecylatntno-butan 1.3- bis-etylamino-butan 4- amtno-l-(3-brompropylamino)-butan 4-ainino-l-isopentylaminobutan 2.3- diaminobutan 2-amino-l-dodecylamino-butane 1.3- bis-ethylamino-butane 4- amino-l-(3-bromopropylamino)-butane 4-amino-l-isopentylaminobutane 2.3- diaminobutane
1,2-diamino-2-metylpropan 2-amino-l-metylamino-2-metyl-propan 2-amino-l-butylamino-2-metylpropan 4-amino-l-isopropylamino-pentan 1.4- diamino-pentan 1,2-diamino-2-methylpropane 2-amino-l-methylamino-2-methyl-propane 2-amino-l-butylamino-2-methylpropane 4-amino-l-isopropylamino-pentane 1.4-diamino-pentane
1.2- diamino-pentan 1.2-diamino-pentane
2,4-diamino-pentan 2,4-diamino-pentane
1.3- diamino-2-metyl-butan 1.3- diamino-2-2-dimetyl-propan 1,6-diaminohexan 1.3-diamino-2-methyl-butane 1.3-diamino-2-2-dimethyl-propane 1,6-diaminohexane
1,6-bis-propylamino-hexan 1.4- diamino2,3-dimetyl-buten-(2) 1,4-diamino-butin-(2) 1,4-bis-metylamino-butin-(2) 1,4-bis-butylamino-butin-(2) 1,2,3-triaminopropan bis-^-aniinoetylT-eter 2.3- diamino-l-metoksy-propan bis-/2-aminoetyX/-sulfoksyd bis-Z2-aminoetyl/-sulfon bis-/2-aminoetyL/-disulfid Z=cystamin/ 2,6-diaza-spiro-/3,3/heptan 1.4- diaza-spiro-/4»5/decan 2-klor-l,3-diamino-propan 1,3-diamino-2-hydroksypropan N,N'-dietyl-1,3-butadien-l,4-diarain 1,8-diamino-2,5-oktadien 1,8-diaraino-3,6-oktadien 1,6-bis-propylamino-hexane 1,4-diamino2,3-dimethyl-butene-(2) 1,4-diamino-butyne-(2) 1,4-bis-methylamino-butyne-(2) 1,4- bis-butylamino-butyn-(2) 1,2,3-triaminopropane bis-^-aniinoethyl T-ether 2.3- diamino-1-methoxy-propane bis-/2-aminoethylX/-sulfoxide bis-Z2-aminoethyl/-sulfone bis -/2-aminoethyl/-disulfide Z=cystamine/ 2,6-diaza-spiro-/3,3/heptane 1.4- diaza-spiro-/4»5/decane 2-chloro-1,3-diamino-propane 1 ,3-diamino-2-hydroxypropane N,N'-diethyl-1,3-butadiene-1,4-diarene 1,8-diamino-2,5-octadiene 1,8-diaraino-3,6-octadiene
2,3-diamino-bicyklo/2,2,2/bktan N,N'-difenyl-etylendiamin 2,3-diamino-bicyclo/2,2,2/bctane N,N'-diphenyl-ethylenediamine
N ,N '-dibenzyl-etylendiamin N,N'-dibenzyl-ethylenediamine
etylenglykol-bis-/2-metylaminoetyl/-eter 2,2'-bis-metylamino-dietyleter 1,6-diamino-cyklohexen-(L) ethylene glycol bis- (2-methylaminoethyl) ether 2,2'-bis-methylamino-diethyl ether 1,6-diamino-cyclohexene-(L)
2,3-diamino-norbornan2,3-diamino-norbornane
1.3- diarainopropanon 1,3- diarainopropanone
2,6-diamino-2,6-dimetyl-heptanon-(4) 3»4-diamino-adipinsyre 2,6-diamino-2,6-dimethylheptanone-(4)3»4-diamino-adipic acid
3.4- diamino-adipinsyredietylester 3»4-diamino-adipinsyre-di-n-.butylest er 3,4-diamino-adipinsyrediamid. 2,9-diamino-sebacinsyre 3,4-diamino-adipic acid diethyl ester 3,4-diamino-adipic acid di-n-butyl ester is 3,4-diamino-adipic acid diamide. 2,9-diamino-sebacic acid
1,2-diamino-cyklobutan 1,2-diamino-cyclobutane
1- , 2-diamino-cyklopentan 1-, 2-diamino-cyclopentane
1.2- diamino-cyklohexan 1.2-diamino-cyclohexane
1.3- diamino-cyklohexan 1.3-diamino-cyclohexane
2- amino-l-aminometyl-cyklopentan 1.4- diaminocyklooktan 3»5-diamino-l,1-dimetylcyklohexan 1,6-diaraino-cyklodecan 2-amino-1-aminomethyl-cyclopentane 1.4-diaminocyclooctane 3'5-diamino-1,1-dimethylcyclohexane 1,6-diaraino-cyclodecane
2,3-diamino-propionsyre 2,3-diamino-propionic acid
2,3-diamino-propionsyrenitril 2,3-diamino-propionsyreamid 2,3-diamino-propionic acid nitrile 2,3-diamino-propionic acid amide
2,3-diamino-propionsyre-metylester 2-amino-l-metylamino-propionsyreetylester 1,2-bis-/metylamino/-propionsyre 1.2- bis-Zmetylarainoy-pro*ionsyre-etylester 2.3- diamino-buttersyre 2,3-diamino-propionic acid methyl ester 2-amino-l-methylamino-propionic acid ethyl ester 1,2-bis-/methylamino/-propionic acid 1.2- bis-Zmethylarainoy-pro*ionic acid ethyl ester 2.3- diamino-butyric acid
2.4- diaraino-buttersyre2,5-diamino-valeriansyre (Ornithin) 2.5- diamino-valeriansyre-metylester 2.6- diaraino-hexansyre (Lysin) 2,6-diamino-hexansyre-etylester 6-amino-2-metylamino-hexansyre 2-amino-6-metylamino-hexansyre 2,6-diamino-hfcxansyre-f enylester piperazin 2.4- diaraino-butyric acid 2,5-diamino-valeric acid (Ornithine) 2.5- diamino-valeric acid methyl ester 2.6- diaraino-hexanoic acid (Lysine) 2,6-diamino-hexanoic acid ethyl ester 6-amino-2-methylamino-hexanoic acid 2-amino -6-methylamino-hexanoic acid 2,6-diamino-hexanoic acid phenyl ester piperazine
1,3-diamino-2-r2,4,4-tetrametyl-cyklobutan 1,3-diamino-2-r2,4,4-tetramethyl-cyclobutane
1,5-diaza-cyklooktan1,5-diaza-cyclooctane
2,5-dimetyl-piperazin2,5-dimethyl-piperazine
lTamino-2-anilino-propan 1-amino-2-anilino-propane
l-amino-2-anilino-butan1-amino-2-anilino-butane
N,N-bis-/aminoetyl/-anilinN,N-bis-/aminoethyl/-aniline
N-fenyletylendiaminN-phenylethylenediamine
4-aminobenzylamin4-aminobenzylamine
1-fenyl-etylendiamin 1-phenyl-ethylenediamine
N ,N' -bis-/^.-klorf enyl/-propan-1,3-diamin N-benzyl-N'-fenyl-etylendiamin N,N'-bis-N'-chlorophenyl-propane-1,3-diamine N-benzyl-N'-phenyl-ethylenediamine
N,N'-difenacyl-etylendiamin N,N'-diphenacyl-ethylenediamine
N,N'-bis(2-metylmercaptoetyl)-etylendiamin N,N<f->bis-)2-metylsulfinyl-etyl)-etylendiamin N,N♦-bis-(2-metylsulfonyl-etyl)-etylendiamin N,N'-bis(a-metylbenzyl)-etylendiamin N,N'-dibenzyl-etylendiamin 1,1,10,10-tetrametyl-trietylentetramin 1,10-dimetyl-l,10-difenyl-trietylentetramin 2,2,10,10-tetrametyl-3,9-diokso-5,8-diaza-undecan N ,N'-bis-(2-.p-tolyletyl)-etylendiamin N-hydroksyetyl-etylendiarain N-kloretyl-etylendiamin N7N'-bis-(2-hydroksyetyl)-etylendiamin N-yN' -bis (2-kloretyl) -etylendiamin N,N'-bis-(3-etoksypropyl)-etylendiamin N, N'-bis-(3-metoksyetyl)-etylendiamin N,N'-bis-(2-fenoksyetyl)-etylendiamin N,N<*->bis-(2-n-butylmercaptoetyl)-etylendiamin N,N'-bis-(2-n-butylsulfinyletyl)-etylendiamin N, N'-bis-(2-n-butylsulfonyletyl)-etylendiamin N,N'-bis-{2-etoksykarbonylmetylsulfonyl-etyl)-etylendiamin N,W-bis-(2-cyanoetyl)-etylendiamin N,N'-bis-(2-fenylmercaptoetyl)-etylendiamin N,N'-bis(2-methylmercaptoethyl)-ethylenediamine N,N<f->bis-)2-methylsulfinyl-ethyl)-ethylenediamine N,N♦-bis-(2-methylsulfonyl-ethyl)-ethylenediamine N,N '-bis(α-methylbenzyl)-ethylenediamine N,N'-dibenzyl-ethylenediamine 1,1,10,10-tetramethyl-triethylenetetramine 1,10-dimethyl-1,10-diphenyl-triethylenetetramine 2,2,10,10- tetramethyl-3,9-dioxo-5,8-diaza-undecane N ,N'-bis-(2-.p-tolylethyl)-ethylenediamine N-hydroxyethyl-ethylenediamine N-chloroethyl-ethylenediamine N7N'-bis-(2- hydroxyethyl)-ethylenediamine N-yN'-bis(2-chloroethyl)-ethylenediamine N,N'-bis-(3-ethoxypropyl)-ethylenediamine N,N'-bis-(3-methoxyethyl)-ethylenediamine N,N'- bis-(2-phenoxyethyl)-ethylenediamine N,N<*->bis-(2-n-butylmercaptoethyl)-ethylenediamine N,N'-bis-(2-n-butylsulfinylethyl)-ethylenediamine N,N'-bis- (2-n-butylsulfonylethyl)-ethylenediamine N,N'-bis-{2-ethoxycarbonylmethylsulfonyl-ethyl)-ethylenediamine N,W-bis-(2-cyanoethyl)-ethylenediamine N,N'-bis-(2-phenylmercaptoethyl) -ethylenediamine
I formel II betyrIn formula II means
R^ og R^ som kan være like eller forskjellige fortrinnsvis hydrogen, fenyl eller naftyl, eventuelt substituert med 1-3 substituenter eller en rettlinjet, forgrenet R^ and R^ which may be the same or different are preferably hydrogen, phenyl or naphthyl, optionally substituted with 1-3 substituents or a straight, branched
/ ' I/ ' I
cyklisk mettet og umettet hydrokarbonrest med '■ii .. - • cyclic saturated and unsaturated hydrocarbon residue with '■ii .. - •
1-3,2 C-atomer, idet hydrokarbonkjeden eventuelt er avbrutt med heteroatomer eller grupperinger som oksygen, svovel, c.ulfon, sulfin, karbonyl, 1-3.2 C atoms, the hydrocarbon chain possibly being interrupted by heteroatoms or groupings such as oxygen, sulphur, carbon, sulfine, carbonyl,
. fenylen og eventuelt er substituert med substi-, tuenter som hydroksy, alkoksy med 1-12 C-atomer, halogen som fluor, klor, brom, jod, acyloksy . phenylene and optionally substituted with substituents such as hydroxy, alkoxy with 1-12 C atoms, halogen such as fluorine, chlorine, bromine, iodine, acyloxy
ellér acylamino med hver 1-15 C-atomer, aryl, aryloksy, aroyl, alkylthio, alkylsulfon, og alkylsulfin med 1-12 C-atomer, cyano, alkoksykårbonyl med 1-12 C-atomer, aroksykarbbnyl, aminokarbonyl, idet aminokarbonylresten igjen eventuelt er substituert med alkyl med 1-6 C-atomer, fenyl eller naftyl, or acylamino each with 1-15 C atoms, aryl, aryloxy, aroyl, alkylthio, alkylsulfone, and alkylsulfine with 1-12 C atoms, cyano, alkoxycarbonyl with 1-12 C atoms, aroxycarbonyl, aminocarbonyl, the aminocarbonyl residue remaining optionally is substituted by alkyl with 1-6 C atoms, phenyl or naphthyl,
eller for det tilfelle at n - 0 som betyr en alky-lenkjede med 1-4 C-atomer, som med de to nitrogen-atomér danner en ring, eller en av substituentene R^" og R^ betyr en alky-len-rest med 1-5 C-atomer som med den naboplaserte X danner en nitrogenholdig ring, or for the case that n - 0 which means an alkylene chain with 1-4 C atoms, which with the two nitrogen atoms forms a ring, or one of the substituents R^" and R^ means an alkylene residue with 1-5 C atoms which with the neighboring X form a nitrogen-containing ring,
X betyr fortrinnsvis en rettlinjet, forgrenet, cyklisk mettet.bg umettet hydrokarbonkjede med 2-20, spesielt med 2-15 C-atomer, idet denne kjede eventuelt kan være avbrutt med heteroatomer eller X preferably means a straight, branched, cyclically saturated.bg unsaturated hydrocarbon chain with 2-20, especially with 2-15 C atoms, this chain possibly being interrupted by heteroatoms or
grupperinger som oksygen, svovel, sulfin, sulfon, groupings such as oxygen, sulphur, sulfine, sulfone,
arylaza, alkylaza med 1-6 C-atomer, karbonyl, arylase, alkylase with 1-6 C atoms, carbonyl,
fenyl og eventuelt substituert med substituenter som halogen, spesielt fluor, klor bg brom, alkoksy phenyl and optionally substituted with substituents such as halogen, especially fluorine, chlorine bg bromine, alkoxy
med 1-6 C-atomer, aroksy, hydroksy, cyano, hydroksykarbonyl, alkoksykårbonyl med 1-15 C-atomer, acylamino med 1-15 C-atomer, aroksykarbonyl, eventuelt med en eller to alkylgrupper med 1-6 C-atomer eller med aryl substituert aminokarbonyl, alkylthio, alkylsulfin eller alkylsulfon med hver 1-6 C-atomer i alkylgruppen, arylthio, aryl,. with 1-6 C atoms, aroxy, hydroxy, cyano, hydroxycarbonyl, alkoxycarbonyl with 1-15 C atoms, acylamino with 1-15 C atoms, aroxycarbonyl, optionally with one or two alkyl groups with 1-6 C atoms or with aryl substituted aminocarbonyl, alkylthio, alkylsulfine or alkylsulfone with each 1-6 C atoms in the alkyl group, arylthio, aryl,.
idet de ovennévnte arylgrupper spesielt betyr fenyl eller naftyl, som på sin side kan være substituert med halogen som fluor, klor eller brom, alkyl, alkoksy, acyl eller alkylmercapto med hver the above-mentioned aryl groups in particular meaning phenyl or naphthyl, which in turn may be substituted with halogen such as fluorine, chlorine or bromine, alkyl, alkoxy, acyl or alkyl mercapto with each
1-4 C-atomer, cyano eller aminp, og1-4 C atoms, cyano or aminep, and
n betyr et helt tall fra 0 til 4»n means an integer from 0 to 4"
Ifølge oppfinnelsen anvendbare karboksylsyrer, resp. karboksylayrederivater er enten kjent eller kan fremstilles etter kjente fremgangsmåter (S.R. Sandler, W. Caro, Organic Functional Group Preparations, side 196, Academic Press, New York og Londong 1968; S. Patai, utgiver, The Chemistry of Carboxylic Acids and Esters. Interscience Publishers, London, New York, Sydney, Toronto 1969; According to the invention, usable carboxylic acids, resp. Carboxylic acid derivatives are either known or can be prepared by known methods (S.R. Sandler, W. Caro, Organic Functional Group Preparations, page 196, Academic Press, New York and Londong 1968; S. Patai, publisher, The Chemistry of Carboxylic Acids and Esters. Interscience Publishers, London, New York, Sydney, Toronto 1969;
H. Henecka i Houben-Weyl, Methoden der Organischen Chemie, bind 8, side 359, Georg Thieme Verlag, Stuttgart 1952; H. Henecka in Houben-Weyl, Methoden der Organischen Chemie, volume 8, page 359, Georg Thieme Verlag, Stuttgart 1952;
M.S. Ansell i S. Patai (utgiver), The Chemistry of Acyl Halides, side 35»Interscience Publishers, London, New York, Sydney, Toronto 1972»* F. Korte, Methodicum Chimicum, bind 8 .side 527* Georg Thieme Verlag, Stuttgart). Som eksempel for de ifølge oppfinnelsen anvendbare karboksylsyrer resp. karboksylsyrederivater, med den generelle formel III, skal nevnes: M.S. Ansell in S. Patai (publisher), The Chemistry of Acyl Halides, page 35»Interscience Publishers, London, New York, Sydney, Toronto 1972»* F. Korte, Methodicum Chimicum, volume 8 .page 527* Georg Thieme Verlag, Stuttgart ). As an example for the carboxylic acids that can be used according to the invention or carboxylic acid derivatives, with the general formula III, should be mentioned:
acetanhydridacetic anhydride
trifluoreddiksyretrifluoroacetic acid
klo.racetylkloridchlor.racetyl chloride
propionsyreanhydrid 3- klorpropionylklorid propionic anhydride 3-chloropropionyl chloride
smørsyreanhydridbutyric anhydride
4- klorsmørsyreklorid4- chlorobutyric acid chloride
pentansyré 2- metyl-butansyre pentanoic acid 2-methyl-butanoic acid
3- metyl-butansyreklorid pivalinsyreklorid 3- methyl butanoic acid chloride pivalic acid chloride
pivaloylazid pivaloyl azide
hexansyrefenylester (Capronsyrefenylester)Hexanoic acid phenyl ester (Caproic acid phenyl ester)
hexansyreazidhexanoic acid azide
2-klorhexansyremetylester2-chlorohexanoic acid methyl ester
6-klorhexansyreetylester 6-bromhexansyreetylester 6-chlorohexanoic acid ethyl ester 6-bromohexanoic acid ethyl ester
2-metylpentansyré-(1) 4- metylpentansyreklorid (Isocapronsyreklorid) 2-Methylpentanoic acid-(1) 4-Methylpentanoic acid chloride (Isocaproic acid chloride)
3- metyl-pentansyré-(1) 3.3- dimetylbutansyre-(1)-klorid dietyleddiksyreklorid (2-etyl-butansyreklorid) heptansyreanhydrid 2-raetylhexansyre-(1) 3- methylpentanoic acid-(1) 3.3-dimethylbutanoic acid-(1)-chloride diethylacetic acid chloride (2-ethyl-butanoic acid chloride) heptanoic anhydride 2-raethylhexanoic acid-(1)
4- metylhexansyre-(1) 4- methylhexanoic acid-(1)
2,2-dimetylpentansyre-(1) 4 > 4-d imetylpentansyre-(1) 3.4- dimetylpentansyreklorid oktansyrefenylester (Caprylsyrefenylester) oktansyreklorid 2,2-dimethylpentanoic acid-(1) 4 > 4-dimethylpentanoic acid-(1) 3.4- dimethylpentanoic acid chloride octanoic acid phenyl ester (Caprylic acid phenyl ester) octanoic acid chloride
2-raetyl-heptansyremetylester 2- etyl-hexansyreklorid (Dipropyleddisyreklorid) 4-metyl-heptansyre 2-raethyl-heptanoic acid methyl ester 2-ethyl-hexanoic acid chloride (Dipropylacetic acid chloride) 4-methyl-heptanoic acid
3- etyl-hexansyre 3- ethylhexanoic acid
2,2-dietyl-butansyreklorid (Trietyleddiksyreklorid) 2-isopropyl-3-metyl-butansyre (Diisopropyleddiksyre) 2,2,3,3-tetrametyleddisyreklorid nonansyre (Pelargonsyre) 2,2-diethyl-butanoic acid chloride (Triethylacetic acid chloride) 2-isopropyl-3-methyl-butanoic acid (Diisopropylacetic acid) 2,2,3,3-tetramethylacetic acid chloride Nonanoic acid (Pelargonic acid)
2- metyl-oktansyreetylester 4.5- dimetyl-heptansyre-(1) 3- metyl-2-propyl-pentansyre-klorid Dekansyreklorid (Caprinsyreklorid) 2-metyl-nonansyre. 2- methyl-octanoic acid ethyl ester 4.5-dimethyl-heptanoic acid-(1) 3- methyl-2-propyl-pentanoic acid chloride Decanoic acid chloride (Capric acid chloride) 2-methyl-nonanoic acid.
3"metyl~nonansyre 3"methyl~nonanoic acid
4- nietyl-nonansyre 4- niethyl nonanoic acid
2- butyl-pentansyreklorid 2-Butyl pentanoic acid chloride
2,7-diraetyl-oktansyre-(1) 3- etyl-6-metyl-heptansyreklorid Undekansyre 2,7-diethyloctanoic acid-(1) 3-ethyl-6-methylheptanoic acid chloride Undecanoic acid
Undekansyreklorid Undecanoic acid chloride
8-cyklopropyl-nonankarboksylsyre ll-klorundekansyreklorid-(1) 10- bromundekansyre-(1) 8-cyclopropyl-nonanecarboxylic acid ll-chloroundecanoic acid chloride-(1) 10- bromundecanoic acid-(1)
11- bromundekansyre-(1) 11-bromoundecanoic acid-(1)
10,11-dibromundekansyre-(1) 11-jodundekansyre-(1) 10,11-dibromoundecanoic acid-(1) 11-iodoundecanoic acid-(1)
3- metyl-dekansyreklorid 3- methyl-decanoic acid chloride
4- metyl-dekansyreklorid 4- methyl-decanoic acid chloride
3»8-dimetyl-nonansyre-(1) 2-butyl-3-JBetyl-hexansyre-(l) 5-propy1-oktansyre-(1) 3»8-dimethyl-nonanoic acid-(1) 2-butyl-3-JBethylhexanoic acid-(1) 5-propyl-octanoic acid-(1)
2,2-dipropyl-butansyreklorid-(1) (tripropyleddiksyreklorid) dodekansyre (laurinsyre) dodekansyre-klorid 2,2-dipropylbutanoic acid chloride-(1) (tripropylacetic acid chloride) dodecanoic acid (lauric acid) dodecanoic acid chloride
2-metyl-undekansyre-(1) 9-cyklopropyl~monansyre-metylester 2-methyl-undecanoic acid-(1) 9-cyclopropyl~monanoic acid methyl ester
tridekansyreklorid 2-metyl-dodekansyre tridecanoic acid chloride 2-methyl-dodecanoic acid
5-metyl-dodekansyre 5-methyl-dodecanoic acid
2-pentyl-heptansyreklorid-(1) tetradskansyre (myristinsyre) tetradekansyreklorid 2-pentyl-heptanoic acid chloride-(1) tetradecanoic acid (myristic acid) tetradecanoic acid chloride
tetradekansyre-S-metylester tetradekansyre-S-etylester tetradecanoic acid S-methyl ester tetradecanoic acid S-ethyl ester
2- etyldodekansyre-(1)2- ethyldodecanoic acid-(1)
krotonsyrecrotonic acid
metacrylsyremethacrylic acid
hexen-2-syreklorid hexene-2-acid chloride
4-metyl-penten-(4)-syre-(l) 4-metyl-pentansyreklorid 4-Methyl-pentene-(4)-acid-(1) 4-methyl-pentanoic acid chloride
hepten-(2) - syreklorid-(1) heptene-(2) - acid chloride-(1)
okten-(2)-syre-(1)-klorid nonen-(8)-syre-(1)-klorid octene-(2)-acid-(1)-chloride nonene-(8)-acid-(1)-chloride
decen-(2)-syre-(1)-klorid decene-(2)-acid-(1)-chloride
3- metyll-nonen-(2)-syre 2-allyl-heptansyre-(1) undecen-(10)-syre-(1) 3- methyl-nonene-(2)-acid 2-allyl-heptanoic acid-(1) undecene-(10)-acid-(1)
undecen-(10)-syrekloridundecene-(10)-acid chloride
undecen-{2)-syreundecene-{2)-acid
2-allyl-oktansyre-(1)2-allyl-octanoic acid-(1)
undecin-(10)-syre-{1) undecine-(10)-acid-{1)
undeein-(9)-syre-(1)Undeine-(9)-acid-(1)
undecin-(5)-syre-(l) 2,4-hexadier<i>syre-(l)-klorid (sorbinsyreklorid) 4»8-undekadiensyre-(1) undecine-(5)-acid-(1) 2,4-hexadier<i>acid-(1)-chloride (sorbic acid chloride) 4»8-undecadieno-(1)
2,4»6-oktatriensyre-(1) 2,4»6-octatrienoic acid-(1)
cyklohexankarboksylsyrecyclohexane carboxylic acid
, i 3-cyklohexyl-propionsyre-metylester 3-cyklohexen-l-karboksylsyre kanelsyreklorid , in 3-cyclohexyl-propionic acid methyl ester 3-cyclohexene-1-carboxylic acid cinnamic acid chloride
trans-kanelsyré-isopentylester 2- metylkanelsyreklorid 3- metylkanelsyre-metylester fenylacetylenkarboksylsyremetylester fenoksy-thioeddiksyre-S-fenylester fenoksyeddiksyre-p-nitrofenylester metoksyeddiksyreraetylester 11-metoksy-undekansyre 6-butoksy-hexansyre trans-cinnamic acid isopentyl ester 2- methylcinnamic acid chloride 3- methylcinnamic acid methyl ester phenylacetylenecarboxylic acid methyl ester phenoxy-thioacetic acid-S-phenylester phenoxyacetic acid-p-nitrophenylester methoxyacetic acid raethyl ester 11-methoxy-undecanoic acid 6-butoxy-hexanoic acid
6-fenoksy-hexansyre 6-phenoxy-hexanoic acid
6-(p-tert.-butylfenylmercapto)-hexansyre 2-fenoksy-undekansyre fenylmercaptoeddiksyreklorid fenylmercaptoeddiksyre-etylester 6-(n-butylraercapto)-hexansyre 6-{n-butylsulfin)-hexansyre 6-(n-butylsulfon)-hexansyre n-oktylmercaptoeddiksyre-etylester n-oktylsulfineddiksyre-etylester n-oktylsulfoneddiksyre-etylester 11-cyano-undekansyre 9-cyano-nonansyre 6-(p-tert-butylphenylmercapto)-hexanoic acid 2-phenoxy-undecanoic acid phenylmercaptoacetic acid chloride phenylmercaptoacetic acid ethyl ester 6-(n-butylraercapto)-hexanoic acid 6-{n-butylsulfin)-hexanoic acid 6-(n-butylsulfone)-hexanoic acid n- octyl mercaptoacetic acid ethyl ester n-octylsulfinacetic acid ethyl ester n-octylsulfoneacetic acid ethyl ester 11-cyano-undecanoic acid 9-cyano-nonanoic acid
8-cyano-oktansyre8-cyano-octanoic acid
diketenthe dike
N-butyl-N-metylglycin N-metyl-N-fenylglycin 11-fenraercapto-undekansyre 11-acetoksy-undekansyre 6-(p-tolyl)-hexansyre 4- tolyl-eddiksyreklorid glutarsyre-monometylester glutarsyre-raono-(N-etyl)-amid glutarsyremono-anilid adipinsyre-monoetylester adipinsyre-etylester-klorid 1 N-butyl-N-methylglycine N-methyl-N-phenylglycine 11-fenraercapto-undecanoic acid 11-acetoxy-undecanoic acid 6-(p-tolyl)-hexanoic acid 4- tolyl-acetic acid chloride glutaric acid monomethyl ester glutaric acid raono-(N-ethyl) -amide glutaric acid mono-anilide adipic acid monoethyl ester adipic acid ethyl ester chloride 1
adipinsyre-monoamid t pimelinsyre-metylesterklorid adipic acid monoamide t pimelic acid methyl ester chloride
pimelinsyre-monoamidpimelic acid monoamide
pimelinsyre-etylesterkloridpimelic acid ethyl ester chloride
kbrksyre-monometylesterkloridcarbonic acid monomethyl ester chloride
I formel III betyr B fortrinnsvis de tre substituenter R 1 , R 2 og R^ J In formula III, B preferably means the three substituents R 1 , R 2 and R 2 J
som kan være like eller forskjellige og som på sin side betyr rettlinjet, forgrenet, cyklisk . mettet og umettet hydrokarbonrest med 1-14 C-atomer, idet eventuelt hydrokarbonkjeden kan være avbrutt med to-bindige heteroelementer eller grupperinger som oksygen, svovel, sulfin, sulfon, karbonyl, fenylen og eventuelt er substituert med substituenter som halogen, spesielt fluor, klor eller brom, alkoksy med 1-12 C-atomer, acyloksy med 1-12 C-atomer aryl, aryloksy, arylmercapto, aroyl, alkylmercapto, alkylsulfin og alkylsulfon med hver 1-6 C-atomer,-acylamino med 1-15 C-atomer,. aroylamino, cyano-alkoksykarbonyl med 1-6 C-atomer, aroksykarbonyl eller aminokarbonyl, som kan være substituert med alkyl med 1-6 C-atomer, fenyl eller naftyl, which can be the same or different and which in turn means rectilinear, branched, cyclical. saturated and unsaturated hydrocarbon residue with 1-14 C atoms, where the hydrocarbon chain may be interrupted by divalent heteroelements or groupings such as oxygen, sulphur, sulfine, sulfone, carbonyl, phenylene and optionally substituted with substituents such as halogen, especially fluorine, chlorine or bromine, alkoxy with 1-12 C atoms, acyloxy with 1-12 C atoms aryl, aryloxy, arylmercapto, aroyl, alkylmercapto, alkylsulfine and alkylsulfone each with 1-6 C atoms, -acylamino with 1-15 C- atoms,. aroylamino, cyano-alkoxycarbonyl with 1-6 C atoms, aroxycarbonyl or aminocarbonyl, which may be substituted by alkyl with 1-6 C atoms, phenyl or naphthyl,
idet de ovennevnte arylgrupper spesielt betyr fenyl eller,naftyl, som på sin side kan være , in that the above-mentioned aryl groups in particular mean phenyl or, naphthyl, which in turn can be ,
substituert med halogen som.fluor, klor eller brom, alkyl, alkoksy, acyl eller alkylmercapto med hver 1-4 C-atomer, cyano eller amino, og substituted with halogen such as fluorine, chlorine or bromine, alkyl, alkoxy, acyl or alkyl mercapto each having 1-4 C atoms, cyano or amino, and
A betyr fortrinnsvis hydroksy eller en syregruppe aktiverende'rest som halogen, spesielt klor eller brom, azid, cyan, alkoksy, alkylthio, acyloksy med A preferably means hydroxy or an acid group activating' residue such as halogen, especially chlorine or bromine, azide, cyan, alkoxy, alkylthio, acyloxy with
hver 1-4 C-atomer, cyanmetyloksy, aryloksy, arylthib, aroyloksy, succinimido-N-oksy, ftalimido-N-oksy, idet arylgruppen spesielt betyr fenyl eller naftyl og eventuelt kan være en til tre ganger substituert med substituenter fra gruppen halogen, cyano, sulfon, nitro, amino, alkyl, alkyl-oksy, alkylmercapto eller acyl med hver 1-4 C-atomer each 1-4 C atoms, cyanomethyloxy, aryloxy, arylthib, aroyloxy, succinimido-N-oxy, phthalimido-N-oxy, the aryl group in particular means phenyl or naphthyl and can optionally be substituted one to three times with substituents from the group halogen, cyano, sulfone, nitro, amino, alkyl, alkyl-oxy, alkylmercapto or acyl with 1-4 C atoms each
Som oppløsnings-, resp. fortynnihgsmidler kommerAs resolution, resp. diluents are coming
det på tale alle oppløsningsmidler resp. oppløsningsmiddel-blandinger som er inerte ved reaksjonene som skal gjennomføres. Hertil hører fortrinnsvis etere som dietyleter, dioksan, di-isopropyleter, tetrahydrofuran, ketoner som dimetylketon, metyletylketon, hydrokarboner som petroleter, ligroin, benzen, toluen, xylen, halogenerte hydrokarboner (som kloroform, metylenklorid), toluen, esteré som eddiksyreetylester, propion-syremetylester, aprotiske oppløsningsmidler som dimetyl-sulfoksyd, dimetylformamid, dimetylacetamid, hexametylfosfor-syretriamid, tetrametylurinstoff, aminer som pyridin, kinolin og for bestemte omsetninger også alkoholer som metanol, etanol, isopro.panol, n-butanol elUér. også vann. that means all solvents or solvent mixtures which are inert to the reactions to be carried out. These preferably include ethers such as diethyl ether, dioxane, di-isopropyl ether, tetrahydrofuran, ketones such as dimethyl ketone, methyl ethyl ketone, hydrocarbons such as petroleum ether, naphtha, benzene, toluene, xylene, halogenated hydrocarbons (such as chloroform, methylene chloride), toluene, esters such as acetic acid ethyl ester, propion- acid methyl ester, aprotic solvents such as dimethylsulfoxide, dimethylformamide, dimethylacetamide, hexamethylphosphoric acid triamide, tetramethylurea, amines such as pyridine, quinoline and for certain reactions also alcohols such as methanol, ethanol, isopropanol, n-butanol etc. also water.
Som. syrebindere ved omsetning av syrehalogénider kan det anvendes alle vanlige syrebindingsmidler. Hertil hører fortrinnsvis organiske baser som trietylamin, pyridin, kinolin, As. acid binders when converting acid halides, all common acid binders can be used. These preferably include organic bases such as triethylamine, pyridine, quinoline,
uorganiske baser som alkalikarbonater,. alkalihydroksyder (jfr. F. Moller i Houben-Weyl, Methoden der organischen Chemie, bind H/2, side 10, Georg Thieme Verlag, Stuttgart 1958). inorganic bases such as alkali carbonates,. alkali hydroxides (cf. F. Moller in Houben-Weyl, Methoden der organischen Chemie, volume H/2, page 10, Georg Thieme Verlag, Stuttgart 1958).
Dehydratiseringen ved omsetning av aminene med .kafboksylsyrene kan foregå ved azetropavdestillering av'vann eller ved tilsetning:av et dehydratiseringsmiddel. Som dehydratiseringsmiddel kommer det på tale alle vanlige reagenser (jfr. F. Moller i Houben-Weyl, Methoden der organischen Chemie, 4« opplag»bind VIII, side654»Georg Thieme Verlag,'Stuttgart 1958,8.R. Sandler, W. Caro, Organic-Functional Group Preparation, vol. I, side 27O, Dehydration by reaction of the amines with the carboxylic acids can take place by azetropic distillation of water or by the addition of a dehydrating agent. As a dehydrating agent, all common reagents can be used (cf. F. Moller in Houben-Weyl, Methoden der organischen Chemie, 4th edition, volume VIII, page 654, Georg Thieme Verlag, Stuttgart 1958, 8. R. Sandler, W. Caro, Organic-Functional Group Preparation, vol. I, page 270,
Academic Press, New York, Lond<p>nj; 1968, U. Kraatz i F.Korte Methodicum Chimicum, bind 6, side 682, Georg Thieme Verlag, Stuttgart I974). Hertil hører fortrinnsvis karbodiimider som cyklohexylkarbodiimid, fosforforbindelser som fosfor(V)-oksyd, fosfor(III)-klorid, focforoksyklorid, triarylfosfit, triarylfosfin, hexaklorcyklotrifosfatriazer og andre dehydra-tiseringsmidler som dimetylaminoacetylen, silisiumtetraklorid. Academic Press, New York, Lond<p>nj; 1968, U. Kraatz in F.Korte Methodicum Chimicum, volume 6, page 682, Georg Thieme Verlag, Stuttgart I974). These preferably include carbodiimides such as cyclohexylcarbodiimide, phosphorus compounds such as phosphorus (V) oxide, phosphorus (III) chloride, phosphorus oxychloride, triaryl phosphite, triarylphosphine, hexachlorocyclotriphosphate triazines and other dehydrating agents such as dimethylaminoacetylene, silicon tetrachloride.
Reaksjonstemperaturene kan varieres i. et stort område og avhenger av den anvendte reaksjon. Vanligvis arbeider man ved temperaturer mellom -20°C og 250°C, fortrinnsvis ved -10 til 150°C. The reaction temperatures can be varied over a wide range and depend on the reaction used. Generally, one works at temperatures between -20°C and 250°C, preferably at -10 to 150°C.
Aminene med den generelle formel II kan også an- ..' vendes som salter, f.eks. som hydroklorider eller hydrogen-sulfater. Her tilsetter man for frigjøring av aminene minst The amines of the general formula II can also be used as salts, e.g. such as hydrochlorides or hydrogen sulphates. Here, the minimum is added to release the amines
den ekvivalente mengde av en organisk eller uorganisk base. the equivalent amount of an organic or inorganic base.
Omsetningene kan utføres ved normalt trykk, menThe turnovers can be carried out at normal pressure, but
også fortrinnsvis omsetningen av frie karboksylsyrer og karboksylsyreestere ved forhøyet trykk i autoklaver. also preferably the reaction of free carboxylic acids and carboxylic acid esters at elevated pressure in an autoclave.
Ved gjennomføring av fremgangsmåten ifølge oppfinnelsen anvender man vanligvis på en aminogruppe "et mol karboksylsyre resp. karboksylsyrederivat. Karboksylsyrene When carrying out the method according to the invention, one mole of carboxylic acid or carboxylic acid derivative is usually applied to an amino group. The carboxylic acids
resp. karboksylsyrederivatene kan også anvendes i et over-skudd. respectively the carboxylic acid derivatives can also be used in excess.
Som mye virksomme stoffer skal det ved siden avLike many active substances, it must be added
de eksemplene oppførte forbindelser nevnes: bis-(2-undecenoylamino-étyl)-sulfon the compounds listed as examples are: bis-(2-undecenoylamino-ethyl)-sulfone
bis-(2-undecenoylamino-etyl)-sulfoksyd bis-(2-undecenoylamino-ethyl)-sulfoxide
bis-(2-undecenoylamino-etyl)-sulfid bis-(2-undecenoylamino-ethyl)-sulfide
bis-/2-(10-undecénoyl)-aminoetyi<y->sulfid bis-(10-undecenoyl)-aminoethyl<y>sulfide
N,N'-bis-^2-(10-undecenoyl)-aminoetylT^anilin N,N'-bis-[2-(10-undecenoyl)-aminoethyl]-aniline
W,N'-bis-^-(2-undecenoyl)-aminoetyL/-anilin N^^bis-^/tdietylacetyD-amfhoetylZ-anilin N, N'-bis-(diet yla cetyl)-1,2-diamiho^-2-met oksy- propan N,N'-bis-^-(2-undecenoyl)-aminoethyl/-aniline N^^bis-^/tdiethylacetyD-amphoethylZ-aniline N,N'-bis-(dietyl cetyl)-1,2-diamiho^ -2-metoxypropane
N,W'-bis (dietylacétyl)-1,3-diamino-2-f^enoksy-propan N,N<?->bis-(dietylacetyl)-1,3-diamino-2-cyano-propan H, W',N"-tris-(10-undécenoyl)-1,2,3-triamino-propan N,NT ,K"-tris-(decanoyl)-l,2,3-triamino-propan. M,N<T>,N"-tris-(2-etyl-hexanoyl)-1,2,3-triamino-propan N,W<*->bis-(dietylacetyl)-1,3~diamino-2-(n-butylmercapto)-propan N,W'-bis(diethylacetyl)-1,3-diamino-2-phenoxy-propane N,N<?->bis-(diethylacetyl)-1,3-diamino-2-cyano-propane H, W ',N"-tris-(10-undecenoyl)-1,2,3-triamino-propane N,NT ,K"-tris-(decanoyl)-1,2,3-triamino-propane. M,N<T>,N"-tris-(2-ethylhexanoyl)-1,2,3-triamino-propane N,W<*->bis-(diethylacetyl)-1,3~diamino-2- (n-butyl mercapto)-propane
■N, N'-bis-(dietylacetyl)-1,3-diamino-2-(n-butylsulfonyl)-propan I, 2-bis-(10-undecenoylamino)propionsyre* N,N'-bis-(10-undecenoyl)-1-amino-l,l-dimetyl-2-metylamino-etan W,N?-bis-(dodekanoyl)-1-amino-l,l-dimetyl-2-metylamino-etan N,N<T->bis-(10-undecenoyl)-1-amino-l,l-dimetyl-2-(n-pentylamino)-etan N,N'<*->bis-(dodekanoyl)-1-amino-l,l-dimetyl-2-(n-pentylamino)-etan NjN^dibenzyl-N^^bis-dO-undecenoyD-etylendiamin N,N'-bis-(10-undecenoyl)-l-amino~2-aminometyl-cyklopentan ■N, N'-bis-(diethylacetyl)-1,3-diamino-2-(n-butylsulfonyl)-propane I, 2-bis-(10-undecenoylamino)propionic acid* N,N'-bis-(10- undecenoyl)-1-amino-1,1-dimethyl-2-methylamino-ethane W,N?-bis-(dodecanoyl)-1-amino-1,1-dimethyl-2-methylamino-ethane N,N<T- >bis-(10-undecenoyl)-1-amino-1,1-dimethyl-2-(n-pentylamino)-ethane N,N'<*->bis-(dodecanoyl)-1-amino-1,1- dimethyl-2-(n-pentylamino)-ethane NjN^dibenzyl-N^^bis-dO-undecenoyD-ethylenediamine N,N'-bis-(10-undecenoyl)-l-amino~2-aminomethyl-cyclopentane
N,N'-di-(p-fenoksyetyl)-N,N'-bis-(decanoyl)-etylendiamin N, N'-di-(p-butylmercaptoetyl)-N,N'-bis-(decanoyl)-etylendiamin N ,N'-di-(p-hydroksyetyl) -N ,N'-bis-(heptanoyl)-etylendiamin N,N'-di-(p-butylsulfinyletyl)-N,N'-bis-(decanoyl)-etylendiamin N,N *-di-(p-butylsulfonyletyl)-N,N'-bis-(decanoyl)-etylendiamin N-(p-hydroksy-etyl)-N,N'-bis-(nonanoyl)-etylendiamin N-(p-nonanoyloksy-etyl)-N,N-bis-(nonanoyl)-etylendiamin N-(p-cyanoetyl)-N,N'-bis-(nonanoyl)-etylendiamin N,N *-bis-(10-undecenoyl) -N ,N'-bis-(1-etoksykarbonyletyl)-etylendiamin N,N'-bis-(6-etoksykarbonylhexanoyl)-N,N'-bis-(1-etoksykarbonyletyl)-etylendiamin N, N' -bis- (undecanoyl) -N, N' -bis- (1-aminokarbonyletyl ).-etylendiamin N,N'-bis-(undecanoyl)-N,N•-bis-(1-anilinokarbonyletyl)-etylendiamin N,N'-bis-(undecanoyl)-N,N'-bis-(1-dietylaminokarbonyletyl)-etylendiamin N,N'-dicyklohexyl-N,N'-bis-(9-undecenoyl)-etylendiamin N,N'-di-(p-phenoxyethyl)-N,N'-bis-(decanoyl)-ethylenediamine N,N'-di-(p-butylmercaptoethyl)-N,N'-bis-(decanoyl)-ethylenediamine N,N'-di-(p-hydroxyethyl)-N,N'-bis-(heptanoyl)-ethylenediamine N,N'-di-(p-butylsulfinylethyl)-N,N'-bis-(decanoyl)-ethylenediamine N,N *-di-(p-butylsulfonylethyl)-N,N'-bis-(decanoyl)-ethylenediamine N-(p-hydroxy-ethyl)-N,N'-bis-(nonanoyl)-ethylenediamine N-( p-nonanoyloxy-ethyl)-N,N-bis-(nonanoyl)-ethylenediamine N-(p-cyanoethyl)-N,N'-bis-(nonanoyl)-ethylenediamine N,N*-bis-(10-undecenoyl) -N ,N'-bis-(1-ethoxycarbonylethyl)-ethylenediamine N,N'-bis-(6-ethoxycarbonylhexanoyl)-N,N'-bis-(1-ethoxycarbonylethyl)-ethylenediamine N,N'-bis-( undecanoyl)-N,N'-bis-(1-aminocarbonylethyl).-ethylenediamine N,N'-bis-(undecanoyl)-N,N•-bis-(1-anilinocarbonylethyl)-ethylenediamine N,N'-bis- (undecanoyl)-N,N'-bis-(1-diethylaminocarbonylethyl)-ethylenediamine N,N'-dicyclohexyl-N,N'-bis-(9-undecenoyl)-ethylenediamine
(cis og trans)(cis and trans)
N,N'-dicyklohexyl-N,N<T->bis-(2-undecenoyl)-etylendiamin N, N * -dicyklohexyl-N, N * -bis- (8- cyklopropyl-oktanoyl) -etylendiamin N,N'-dietyl-N,N'-bis-(11-acetylaminoundecanoyl)-etylendiamin N,N'-dietyl-N,N *-bis-(11-jod-undecanoyl)-etylendiamin N ,N'-diisovaleryl-N ,N'-bis-(N-butyryl-4-.aminobutyryl)- N,N'-dicyclohexyl-N,N<T->bis-(2-undecenoyl)-ethylenediamine N,N*-dicyclohexyl-N,N*-bis-(8-cyclopropyl-octanoyl)-ethylenediamine N,N' -diethyl-N,N'-bis-(11-acetylaminoundecanoyl)-ethylenediamine N,N'-diethyl-N,N *-bis-(11-iodo-undecanoyl)-ethylenediamine N ,N'-diisovaleryl-N ,N '-bis-(N-butyryl-4-.aminobutyryl)-
etylendiamin N,N'-diisovaleryl-N,N'-bis-/TN-benzoyl)-4-aminobutyryl/- ethylenediamine N,N'-diisovaleryl-N,N'-bis-(TN-benzoyl)-4-aminobutyryl/-
etylendiamin N,N<1->bis-(2-undecenoyl)-2,5-dimetyl-piperazin ethylenediamine N,N<1->bis-(2-undecenoyl)-2,5-dimethyl-piperazine
N,N,-bis-(9-undecenoyl)-2,5-diraetyl-piperazin (cis og trans) N,N'-bis-(N-valeryl-2-aminopropionyl)-2,5-dimetyl-piperazin N,N f-bis-(4-fenyloksy-valeryl)-piperazin N,N,-bis-(9-undecenoyl)-2,5-diraethyl-piperazine (cis and trans) N,N'-bis-(N-valeryl-2-aminopropionyl)-2,5-dimethyl-piperazine N ,N f -bis-(4-phenyloxy-valeryl)-piperazine
N,N*-bis-(N-hexanoyl-N-fenyl-aminoacetyl)-piperazin N,N*-bis-(N-hexanoyl-N-phenyl-aminoacetyl)-piperazine
N,N'-bis-(N-hexanoyl-N-metyl-aminoacetyl)-piperazin N,N'-bis-(N-hexanoyl-N-methyl-aminoacetyl)-piperazine
N^N *-bis-(n-oktyloksy-acetyl)-piperazin N^N *-bis-(n-octyloxy-acetyl)-piperazine
N,N'-bis-(2-undecenoyl)-propylendiarain N,N'-bis-(2-undecenoyl)-propylene diaraine
N,N'-bis-(9-undecenoyl)-propylendiamin (cis og trans) N,N *-bis-(n-oktyloksy-acetyl)-propylendiamin N,N'-bis-(9-undecenoyl)-propylenediamine (cis and trans) N,N*-bis-(n-octyloxy-acetyl)-propylenediamine
N,N'-bis-(decanoyl)-L-lysin-anilid N,N'-bis-(decanoyl)-L-lysine anilide
N,N<*->bis-(decanoyl)-L-lysin-(di-n-propyl)-amid N,N<*->bis-(decanoyl)-L-lysine-(di-n-propyl)-amide
Til foreliggende oppfinnelse hører farmasøytiske tilberedninger som ved siden av ikke^-toksiske, inerte farma-søytiske egnede bærestoffer inneholder en eller flere forbindelser med formel I og/eller deres salter eller som består av en eller flere forbindelser av formel I og/eller deres salter, samt fremgangsmåte til fremstilling av disse tilberedninger. The present invention relates to pharmaceutical preparations which, in addition to non-toxic, inert pharmaceutical suitable carriers, contain one or more compounds of formula I and/or their salts or which consist of one or more compounds of formula I and/or their salts , as well as methods for producing these preparations.
Til foreliggende oppfinnelse hører også farmasøy-tiske, tilberedninger i doseringsenheter. Dette betyr at til-beredningene "foreligger i form av enkelte deler f.eks. The present invention also includes pharmaceutical preparations in dosage units. This means that the preparations "are available in the form of individual parts, e.g.
tabletter, dragéer, kapsler, piller, suppositorier og ampuller, hvis virksomme stoffinnhold utgjør en brøkdel eller flere ganger en enkeltdose. Doseringsenhetene kan f.eks. inneholde 1, 2, 3 eller 4 enkeltdoser, eller l/2,. l/3 eller 1/4 av en enkeltdose. En enkeltdose inneholder fortrinnsvis den mengde virksomt stoff som administreres ved en applikasjon og som vanligvis tilsvarer l/l, l/2, l/3 eller 1/4 av en dagsdose. tablets, dragées, capsules, pills, suppositories and ampoules, whose active ingredient content is a fraction or several times a single dose. The dosage units can e.g. contain 1, 2, 3 or 4 single doses, or l/2,. l/3 or 1/4 of a single dose. A single dose preferably contains the amount of active substance that is administered in one application and which usually corresponds to 1/1, 1/2, 1/3 or 1/4 of a daily dose.
Med ikke-toksiske, inerte farmasøytiske egnede bærestoffer er det å forstå faste, halvfaste eller flytende for-tynningsmidler, fyllstoffer eller formuleringshjelpemidler av enhver type. By non-toxic, inert pharmaceutical suitable carriers is meant solid, semi-solid or liquid diluents, fillers or formulation aids of any type.
Som foretrukne farmasøytiske tilberedninger skal * det nevnes tabletter, dragéer, kapsler, piller, granulater, suppositorier, oppløsninger, suspensjoner og emulsjoner, pasta, salver, geleer, kremer, lotions, pudder og sprays. Tablets, dragées, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays should be mentioned as preferred pharmaceutical preparations.
Tabletter, dragéer, kapsler, piller og granulater kan inneholde det eller de virksomme stoffer ved siden av de vanlige bærestoffer, som a) fyll- og drøyemiddel, f.eks. stivelse, melkesukker, rørsukker, glukose, mannit og kiselsyre, Tablets, dragées, capsules, pills and granules may contain the active substance(s) in addition to the usual carriers, such as a) fillers and thickeners, e.g. starch, milk sugar, cane sugar, glucose, mannitol and silicic acid,
b) bindemiddel, f.eks. karboksymetylcellulose, alginat, gelatin, polyvinylpyrrolidon, c) fuktemiddel, f.eks. glyserol, d) sprengmiddel, f.eks. agar-agar, kalsiumkarbonat og natrium-bikarbonat, e) oppløsnihgsforsinkere, f.eks. parafin og f) resorbsjonsakselerator, f.eks. kvarternære ammoniumforbin-delser, g) fuktemiddel, f.eks. cetylalkohol, glyserolmono-steårat, h) adsorbsjonsmiddel, f .eks. , kaolin og bentonit og b) binder, e.g. carboxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone, c) wetting agent, e.g. glycerol, d) explosive, e.g. agar-agar, calcium carbonate and sodium bicarbonate, e) dissolution retarders, e.g. paraffin and f) resorption accelerator, e.g. quaternary ammonium compounds, g) wetting agent, e.g. cetyl alcohol, glycerol monostearate, h) adsorbent, e.g. , kaolin and bentonite and
i) glidemiddel f.eks. talkum-, kalsium- og magnesiumstearat og. faste polyetylenglykoler eller blandinger av de under punktene a)-i) oppførte stoffer. i) lubricant e.g. talc, calcium and magnesium stearate and. solid polyethylene glycols or mixtures of the substances listed under points a)-i).
Tabletter, dragéer, kapsler, piller og granulater kan være utstyrt med de vanlige eventuelt opakiseringsmiddel-holdige overtrekk og hylser og også være sammensatt således at det eller de virksomme stoffer.bare eller fortrinnsvis avgis i en bestemt del av fordøyelseskahalen, eventuelt forsinket, idet det som innleiringsmasse f.eks. kan anvendes polymer-stoffer og voks. Tablets, dragées, capsules, pills and granules can be equipped with the usual coverings and sleeves, possibly containing opacifiers, and also be composed so that the active substance(s) are only or preferably released in a specific part of the digestive tract, possibly delayed, as the as an embedding mass, e.g. polymer substances and wax can be used.
Det eller de virksomme stoffer, kan eventuelt foreligge med.en eller flere av de ovennevnte bærestoffer også The active substance(s) may possibly be present with one or more of the above-mentioned carrier substances as well
i mikroinnkapslet form.in microencapsulated form.
Suppositorier kan ved siden av det eller de virksomme stoffer inneholde de vanlige vannoppløselige eller vann-uoppløselige bærestoffer, f.eks. polyetylenglykol, fett, f.eks. kakaofett og høyere estere (f .eks. C-^- alkohol med fett-syre) eller blandinger av disse stoffer. Suppositories can contain the usual water-soluble or water-insoluble carriers in addition to the active substance(s), e.g. polyethylene glycol, fat, e.g. cocoa butter and higher esters (e.g. C-^- alcohol with fatty acid) or mixtures of these substances.
Salver, Pastaer, kremer og geleer kan ved sidenav det eller de virksomme stoffer inneholde de vanlige bærestoffer, f.eks. dyrisk fett og plantefett, voks, parafin, stivelse, tragant, cellulosederivater, polyetylenglykol, silikoner, behtoniter,.kiselsyre, talkum og sinkoksyd eller blandinger av disse stoffer. Ointments, pastes, creams and gels can contain the usual carrier substances, e.g. animal fat and vegetable fat, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicones, behtonites, silicic acid, talc and zinc oxide or mixtures of these substances.
Pudder og sprays kan ved siden av det eller de virksomme stoffer inneholde de vanlige bærestoffer, f.eks. melkesukker, talkum, kiselsyre, aluminiumhydroksyd, kalsium-silikat og polyamidpulvér eller blandinger av disse stoffér. Sprays kan i tillegg inneholde de vanlige drivmidler f.eks. klorfluorhydrokarboner. Powders and sprays can contain the usual carrier substances in addition to the active substance(s), e.g. milk sugar, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also contain the usual propellants, e.g. chlorofluorocarbons.
Oppløsninger og emulsjoner kan ved siden av det eller de virksomme stoffer inneholde de vanlige bærestoffer, som oppløsningsmidler, oppløsningsformidlere og emuigatorer, f.eks. vann,, etylalkohol, isopropylalkohol, etylkarbonat, etylacetat, benzylalkohol,; benzylbenzoat, propylenglykol, 1,3-butylenglykol, dimetylformamid, oljer, spesielt bomulls-frøolje, jordnøttolje, mais,kimolje, olivenolje, ricinusolje og sesamoljé, glyserol, glyserolformal, tetrahydrofurfuryl-alkohol, polyetylenglykol og fettsyreestere av sorbitan eller blandinger av disse stoffer. Solutions and emulsions can contain, in addition to the active substance(s), the usual carriers, such as solvents, dissolution mediators and emulsifiers, e.g. water,, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol,; benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, especially cottonseed oil, peanut oil, corn, germ oil, olive oil, castor oil and sesame oil, glycerol, glycerol formal, tetrahydrofurfuryl alcohol, polyethylene glycol and fatty acid esters of sorbitan or mixtures of these substances.
Til parenteral applikasjon kan oppløsningene og emulsjonene også foreligge i steril og blodisotonisk form. For parenteral application, the solutions and emulsions can also be available in sterile and blood isotonic form.
' 't, ' 't,
Suspensjonene kan ved siden av det eller de virksomme stoffer inneholde de vanlige bærestoffer som flytende . fortynningsmidier, f.eks. vann, etylalkohol, propylenglykol,/suspenderingsmidler, f.eks. etoksylerte isostearylalkohpler, polyoksyetylensorbit- og sorbitanestere, mikrokrystallinsk cellulose, aluminiummetanhydroksyd, bentonit, agar-agar og tragant eller blandinger av disse stoffer. In addition to the active substance(s), the suspensions may contain the usual liquid carriers. dilution media, e.g. water, ethyl alcohol, propylene glycol,/suspending agents, e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methane hydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.
De nevnte formuléringsformer kan også inneholde farvemidler, konserveringsstoffer samt lukt- og smaksforbed-rende tilsetninger, f#ks. peppermynteolje og eukalyptusolje og søtningsmidler f*eks. sakkarin. The aforementioned formulations may also contain coloring agents, preservatives as well as odor and taste-improving additives, e.g. peppermint oil and eucalyptus oil and sweeteners e.g. saccharin.
De terapeutisk virksomme forbindelser bør være til-stede i de ovenfor anførte farmasøytiske tilberedninger, fortrinnsvis i en konsentrasjon fra ca. 0,1 til 99»5.fortrinnsvis fra ca. 0,5 til 95 vékt-$ av den samlede blanding. The therapeutically active compounds should be present in the pharmaceutical preparations listed above, preferably in a concentration from approx. 0.1 to 99.5, preferably from approx. 0.5 to 95 wt% of the total mixture.
De ovenfor anførte farmasøytiske tilberedninger kan foruten forbindelse med formel I og/éller deres salter også inneholde andre farmasøytiske virksomme stoffer. The pharmaceutical preparations listed above may, in addition to the compound of formula I and/or their salts, also contain other pharmaceutical active substances.
Fremstillingen av de ovenfor anførte farmasøy-tiske tilberedninger foregår på vanlig måte etter kjente metoder, f.eks. ved blanding av det eller de virksomme stoffer med bærestoffet eller bærestoffene. The preparation of the above-mentioned pharmaceutical preparations takes place in the usual way according to known methods, e.g. by mixing the active substance(s) with the carrier substance(s).
Til foreliggende oppfinnelse hører også anvendelsen av forbindelsen med formel I og/eller deres salter, samt anvendelse av farmasøytiske tilberedninger som inneholder en eller flere, forbindelser med formel I og/eller deres salter i human- og veterinærmedisin for å hindre» bedre og/eller helbrede de ovennewnte sykdommer. The present invention also includes the use of the compound of formula I and/or their salts, as well as the use of pharmaceutical preparations containing one or more compounds of formula I and/or their salts in human and veterinary medicine to prevent" better and/or cure the above diseases.
De virksomme stoffer eller de farmasøytiske tilberedninger kan appliseres oralt, parenteralt, intraperito-. neralt og/eller rectalt, fortrinnsvis oralt. The active substances or the pharmaceutical preparations can be applied orally, parenterally, intraperito-. nerally and/or rectally, preferably orally.
Generelt har det såvel i human- som i veterinærmedisin vist seg fordelaktig å administrere det eller de virksomme stoffer i mengder på f ra ca. 0,5 til ca.. 500» fortrinnsvis 5 til 100 mg/kg legemsvekt pr. 24 timer, fordelt på 1 til 6 administreringer, nemlig før eller/og under eller/og etter In general, both in human and veterinary medicine it has proven advantageous to administer the active substance(s) in amounts of from approx. 0.5 to approx. 500", preferably 5 to 100 mg/kg body weight per 24 hours, divided into 1 to 6 administrations, namely before or/and during or/and after
måltidene. En enkeltdose inneholder det eller de virksomme the meals. A single dose contains the active ingredient(s).
stoffer, fortrinnsvis i mengder fra ca. 0,1 til 100 mg/kg substances, preferably in amounts from approx. 0.1 to 100 mg/kg
legemsvektv Det kan imidlertid være nødvendig å avvike fra de nevnte doseringer, nemlig avhengighet av type og legemsvekt av objektet som skal behandles, type og tyngde av sykdom, type og tilberedning og applikasjon av legemidlet, såvel som tidsrom resp. intervallet, innen hvilket administreringen foregår. Det kan i noen tilfeller være tilstrekkelig å komme ut med mindre enn den ovennevnte mengde virksomt stoff, mens i andre tilfeller må ovennevnte mengde av virksom stoff overskrides.;Fastleggelse av hver gang nødvendig optimal dosering og applikasjonstype av det virksomme stoff kan lett foregå av enhver fagmann på grunn av hans fagkunnskaper. body weight It may, however, be necessary to deviate from the aforementioned dosages, namely depending on the type and body weight of the object to be treated, the type and severity of the disease, the type and preparation and application of the medicine, as well as the time period resp. the interval within which the administration takes place. In some cases it may be sufficient to come out with less than the above-mentioned amount of active substance, while in other cases the above-mentioned amount of active substance must be exceeded. Determining the optimal dosage and application type of the active substance required each time can easily be done by anyone professional because of his professional knowledge.
De virksomme stoffer ifølge oppfinnelsen fører til en mindre alimentær hyperlipemi etter fettholdig næring og samtidig hemming av kolesterolabsorbsjon ved dyr og The active substances according to the invention lead to less alimentary hyperlipemia after fatty food and at the same time inhibition of cholesterol absorption in animals and
mennesker, såledés at de kan anvendes til behandling av fettstoffskifte-forstyrrelser (f.eks. hyperlipoproteinemi, adipositas). humans, so that they can be used to treat fat metabolism disorders (e.g. hyperlipoproteinaemia, adiposity).
Den hypolipidemiske virkning, se Tabell 1, ved hjelp av eksempler på forbindelser som er omtalt i eksemplene. The hypolipidemic effect, see Table 1, with the help of examples of compounds discussed in the examples.
Virkningspåvisningen ble tilveiebragt ved følgende forsøksanordning på rotter: For frembringelse av en alimentær hyperlipemi etter applikasjon av fett får en gruppe fra 5 til 10 rotter 2,5 ml/kg olivenolje p.o. Hver &ang 5 til 10 andre rotter får i tillegg 90 minutter før og samtidig med fettapplikasjon det virksomme stoff i' den i tabellen oppførte dosering som suspensjon i tragantslim med sluksonde. En ytterligere kontrollgruppe fra 5 til 10 rotter får bare tragantslim. 2 timer etter applikasjon av olivenolje bestemmes konsentrasjonen av sérumtriglyserid i alle tre grupper av rgtter etter én modifikasjon av metoden til Eggstein og Kreutz /M. Eggstein og F.H. Kreutz, Klin. Wschr. 44, 262 (I966V med en biokjemisk test-kombinasjon av Fa. Boehringer, Mannheim. To timer etter fettapplikasjon viser de bare med olivenolje behandlede rotter i forhold til rottene uten fettapplikasjon en tydelig økning av serumtriglyserider. Ved denne økning som ble satt lik 100$ ble serumtriglyseridøkningBn hos dyrene be-- handlet med de virksomme stoffer og olivenolje sammenlignet og tilsvarende uttrykt prosentuelt. The proof of effect was provided by the following test arrangement on rats: To produce an alimentary hyperlipemia after the application of fat, a group of 5 to 10 rats receives 2.5 ml/kg of olive oil p.o. Every 5 to 10 other rats additionally receive 90 minutes before and at the same time as the fat application the active substance in the dosage listed in the table as a suspension in tragacanth mucus with a drain tube. A further control group of 5 to 10 rats receives tragacanth mucilage only. 2 hours after the application of olive oil, the concentration of serum triglyceride is determined in all three groups of rats according to one modification of the method of Eggstein and Kreutz /M. Eggstein and F.H. Kreutz, Klin. Wschr. 44, 262 (I966V with a biochemical test combination by Fa. Boehringer, Mannheim. Two hours after fat application, the rats treated only with olive oil compared to the rats without fat application show a clear increase in serum triglycerides. At this increase, which was set equal to 100$ the serum triglyceride increase Bn in the animals treated with the active substances and olive oil was compared and correspondingly expressed as a percentage.
Av Tabell 1 fremgår det at forbindelsen ifølge From Table 1 it appears that the compound according to
. oppfinnelsen tydelig nedsetter økningen av serumtriglyserid-konsentrasjonen. . the invention clearly reduces the increase in the serum triglyceride concentration.
De nevnte forbindelser utmerker seg ved en meget liten toksisitet: LD^q ligger ved engangs oralapplikasjon hos mus over 2000 mg/kg. The mentioned compounds are distinguished by a very low toxicity: LD^q lies in a single oral application in mice above 2000 mg/kg.
Eksempel 1 Example 1
N, N'- bis-( 10- undekenoyl)- trimetylendiamlnN,N'-bis-(10-undekenoyl)-trimethylenediamn
H2C = CH-(CH2)g-Cb-WH-{C<H>2<j>5-NH-C0r(CH2)3-CH = CH2 H2C = CH-(CH2)g-Cb-WH-{C<H>2<j>5-NH-C0r(CH2)3-CH = CH2
Oppløsningen av 3>7g (0,05 mol) 1,3-diaminopropan, 11,1 g (0,11 mol) trietylamin og 200 ml abs. tetrahydrofuran ble avkjølt .til 5°C. Under omrøring og isavkjøling tildryppet man 22,3 S (0,11 mol) undecylensyreklorid i JO ml abs. THF, lar det komme til romtemperatur og omrører enda 2 timer ved 60°C. Reaksjonsblandingen ble helt i vann, det faste produkt suget fra og omkrystallisert ved etanol/acetonitril. The solution of 3>7g (0.05 mol) of 1,3-diaminopropane, 11.1 g (0.11 mol) of triethylamine and 200 ml of abs. tetrahydrofuran was cooled to 5°C. While stirring and cooling with ice, 22.3 S (0.11 mol) undecylenic acid chloride was added dropwise in JO ml abs. THF, allow to come to room temperature and stir for another 2 hours at 60°C. The reaction mixture was poured into water, the solid product was sucked off and recrystallized from ethanol/acetonitrile.
Utbytte: 17,2 g (84$), smp. : 112-11§°CYield: 17.2 g ($84), m.p. : 112-11§°C
Analyse: C25 H^g N202 (406,5) Analysis: C25 H^g N2 O2 (406.5)
Eksempel 2 Example 2
N, W *- bis-( 10- undecenoyl)- tetrametylendiamin.N,W*-bis-(10-undecenoyl)-tetramethylenediamine.
H2C = CH-(CH2)g-CO-NH-(C<H>2)^-NH-C0-(CH2)8-CHCH2H2C = CH-(CH2)g-CO-NH-(C<H>2)^-NH-C0-(CH2)8-CHCH2
ble fremstilt av 4>4 g (0,05 mol) 1,4-diaminobutan, 11,1. g (0,13L mol) trietylamin og 22,3 g (0,11 mol) undecylensyreklorid i abs. tetrahydrofuran etter den i Eksempel 1 angitte was prepared from 4>4 g (0.05 mol) of 1,4-diaminobutane, 11.1. g (0.13L mol) triethylamine and 22.3 g (0.11 mol) undecylenic acid chloride in abs. tetrahydrofuran according to that specified in Example 1
forskrift.regulation.
Utbytte: 17,2 g (82$), smp.: 139-140°C (acetonitril) Yield: 17.2 g (82$), mp: 139-140°C (acetonitrile)
Analyse: C^ H^g N202 (420,5)Analysis: C^ H^g N 2 O 2 (420.5)
Eksempel 3 Example 3
M, N'- bis-( dodecanoyl)- propylendiaminM,N'-bis-(dodecanoyl)-propylenediamine
Til oppløsningen av 3>7S- (0,05 mol) propylendiamin, 11,2 g (piil mol) trietylamin og.100 ml abs. tetrahydrofuran dryppet man under isavkjøling 24>1 g (0,11 mol) dodecanoylklorid. Det ble etteromrørt natten over og deretter oppvarmet enda 2 timer til 60°C. Etter avkjøling blandet man med vann, frasuget utfelt produkt og omkrystalliserte to ganger ved eddikester. To the solution of 3>7S- (0.05 mol) propylenediamine, 11.2 g (piil mol) triethylamine and 100 ml of abs. tetrahydrofuran, 24>1 g (0.11 mol) of dodecanoyl chloride were added dropwise under ice-cooling. It was stirred overnight and then heated for a further 2 hours to 60°C. After cooling, it was mixed with water, the precipitated product was filtered off with suction and recrystallized twice with acetic acid.
Utbytte: 14,1 g (64,456), smp. : II9-I2O<0>Yield: 14.1 g (64.456), m.p. : II9-I2O<0>
Analyse: C2y ^54. N202(438,7)Analysis: C2y ^54. N202(438.7)
Eksempel 4 Example 4
N, PP - bis-( 8- metoksykarbonyl- oktanoyl)- propylendiamin h3co-co-(ch2)^-co-nh-?h<2>ch2-nh-co-(ch2)7-co-och3N, PP - bis-(8- methoxycarbonyl- octanoyl)- propylenediamine h3co-co-(ch2)^-co-nh-?h<2>ch2-nh-co-(ch2)7-co-och3
fremstilles analogt Eksempel 3 under anvendelse.av 3»7g (0,05 mol) propylendiamin, 11,2 g (0,11 mol)trietylamin i abs. tetrahydrofuran. med 24,2 g (0,11 mol) 8-klorformyloktansyre-metylester. is prepared analogously to Example 3 using 3.7 g (0.05 mol) propylenediamine, 11.2 g (0.11 mol) triethylamine in abs. tetrahydrofuran. with 24.2 g (0.11 mol) of 8-chloroformyloctanoic acid methyl ester.
Utbytte: 9,6 g (43>4#). smp. IO4-IO60Yield: 9.6 g (43>4#). m.p. IO4-IO60
Analyse:<H>^2 Ng Og (442,6) Analysis:<H>^2 Ng And (442.6)
Eksempel 5- 14 (Tabell 2) Example 5- 14 (Table 2)
TII en omrørt oppløsning av 0,1 mol av i følgende tabell angitte karboksylsyré i 150 ml abs. dimetylformamid ble det satt 10,1 g (0,1 mol) trietylamin, avkjølt til -10°C, TII a stirred solution of 0.1 mol of the carboxylic acid specified in the following table in 150 ml abs. dimethylformamide, 10.1 g (0.1 mol) triethylamine was added, cooled to -10°C,
og ved denne temperatur tildryppet under omrøring 10,8 g (0,1 mol) klormaursyreetylester. Man omrørte denne i 3° min. and at this temperature, 10.8 g (0.1 mol) ethyl chloroformic acid is added dropwise with stirring. This was stirred for 3 min.
ved -10°C og tildryppet deretter 3>7 g (0,05 mol) propylendiamin at -10°C and then added dropwise 3>7 g (0.05 mol) of propylenediamine
i 50 tøl abs. dimetylformamid. Watten over lot man temperaturen komme til romtemperatur og omrørte enda i 2 timer ved 60°C in 50 tol abs. dimethylformamide. The mixture was allowed to reach room temperature and stirred for a further 2 hours at 60°C
og avkjølte. Reaksjonsblandingen ble helt i 500 ml vann, det faste produkt ble frasuget og omkrystallisert. and cooled. The reaction mixture was poured into 500 ml of water, the solid product was sucked off and recrystallized.
Eksempel 15 Example 15
N,Nt;-bis-( 9-kaeboksykarbonyl) -nonanoyl) -propylendiamin N,Nt;-bis-(9-caecarboxycarbonyl)-nonanoyl)-propylenediamine
Til den omrørte oppløsning av 3>7g (0,05 mol) propylendiamin., . 10,1 g, (0,1 mol) trietylamin og 200 ml eddikester ble det under isavkjøling dryppet 24»9S (0,1 mol) 9-klorf>ormyi-nonansyreetylester. Etter omrøring natten over oppvarmet man det i 2 timer ved 50°C, helte i isvann og adskilte den orgar To the stirred solution of 3>7g (0.05 mol) propylenediamine., . 10.1 g (0.1 mol) of triethylamine and 200 ml of acetic acid were added dropwise under ice-cooling to 24.9S (0.1 mol) 9-chloroformylnonanoic acid ethyl ester. After stirring overnight, it was heated for 2 hours at 50°C, poured into ice water and separated from the
niske fase. Etter vasking med vann og tørking (NagSO^) ble oppløsningsmidlet fjernet og residuet ble omkrystallisert fra acetonitril. low phase. After washing with water and drying (NagSO 4 ), the solvent was removed and the residue was recrystallized from acetonitrile.
Utbytte: 19,0 g (82 %), smp. 118-120°Yield: 19.0 g (82%), m.p. 118-120°
Analyse: 0^ H^<N>2Og . (498,7) Analysis: 0^ H^<N>2Og . (498.7)
Eksempel 16 1, Irdimetyl- N, N*- bis-(10-undecénoyl)-etylendiamin Example 16 1, Irdimethyl-N,N*-bis-(10-undecenoyl)-ethylenediamine
l8,4 g (0,1 mol) undecylensyre ble oppløst i ca* 200 ml abs. tetrahydrofuran. Étter tilsetning av 10,1 g (0,1 mol) trietylamin avkjølte man til -10°C og tildryppet 10,8 g (0,1 mol) klormaursyreétylester. Etter én times ett<e>romrøring ble det tildryppet 8,0 g (0,05 mol) 1,l-dimetylétylendiamin i 30 ml abs. tetrahydrofuran ved -10°C. Man lot det natten over komme til romtemperatiur og helte det ut i 500 ml vann. Reaks jbnsblandingen.ble opparbeidet ved ekstrahering med kloroform, vasking av kloroformoppløsningen med vann og fjerning av bppløsningsmidlet» Etter kromatografering over aluminiumoksyd (nøytral) og eluering med petroleter ble det omkrystallisert fra petroleter (kokepunkt 60-lQ0°G). 18.4 g (0.1 mol) of undecylenic acid was dissolved in approx. 200 ml of abs. tetrahydrofuran. After addition of 10.1 g (0.1 mol) of triethylamine, it was cooled to -10°C and 10.8 g (0.1 mol) of chloroformic acid ethyl ester was added dropwise. After one hour of one<e>room stirring, 8.0 g (0.05 mol) of 1,1-dimethylethylenediamine was added dropwise in 30 ml of abs. tetrahydrofuran at -10°C. It was allowed to come to room temperature overnight and poured into 500 ml of water. The reaction mixture was worked up by extraction with chloroform, washing the chloroform solution with water and removing the solvent. After chromatography over aluminum oxide (neutral) and elution with petroleum ether, it was recrystallized from petroleum ether (boiling point 60-100°G).
. Utbytte: 9,5 g (45.3$)» smp. 44-45°C.. Yield: 9.5 g ($45.3)» m.p. 44-45°C.
Analyse: CggH^gNgOg (420,5)Analysis: CggH^gNgOg (420.5)
Eksempel 17 Example 17
H, N'-bis-(10-undecenoyl)-propylendiamin H, N'-bis-(10-undecenoyl)-propylenediamine
H2C=CH-(GH2)g-CO-NH-CH(CH^)-QHg-NH-CO^(CH2)g-CH=CH2H2C=CH-(GH2)g-CO-NH-CH(CH^)-QHg-NH-CO^(CH2)g-CH=CH2
ble fremstilt analogt Eksempel 12 av 18,4 g (0,1 mol) undecylensyre, 10,1 g (0,1 mol) trietylamin, 10,8 g (0,1 mol) klormaursyreétylester og 3»7g (0»05 fflol) 1,2-diaminopropan. Utbytte: 17,0 g (84$) smp. 105-106°C (acetonitril) was prepared analogously to Example 12 from 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) chloroformate ethyl ester and 3.7 g (0.05 fl ) 1,2-diaminopropane. Yield: 17.0 g ($84) m.p. 105-106°C (acetonitrile)
Analyse: C25H^6<N>2°2(4-06,5)Analysis: C25H^6<N>2°2(4-06.5)
Eksempel 18 2»5- dimetvl- K, N 1 - bis-( undecanoyl)- 2, 5- diaminohexan. Example 18 2,5-dimethyl-K,N1-bis-(undecanoyl)-2,5-diaminohexane.
Til 7,2 g (0,05 mol) 2,5-dimetyl-2,5-diaminohexan og 10,1 g (0,1 mol) trietylamin i 150 ml abs. tetrahydrofuran ble det - ' To 7.2 g (0.05 mol) of 2,5-dimethyl-2,5-diaminohexane and 10.1 g (0.1 mol) of triethylamine in 150 ml of abs. tetrahydrofuran it became - '
under isavkjøling tildryppet 18,6 g (0,1 mol) undecansyreklorid, Man lot det komme til romtemperatur, oppvarmet det enda én time ved 40°C, avkjølte og helte i 500 ml isvann. Den hvite utfelling ble suget,fra, vasket méd vann og omkrystallisert fra eddikester. under ice-cooling, 18.6 g (0.1 mol) of undecanoic acid chloride were added dropwise. It was allowed to come to room temperature, heated for another hour at 40°C, cooled and poured into 500 ml of ice water. The white precipitate was sucked off, washed with water and recrystallized from acetic acid.
Utbytte: 20 g;(42$), smp. 113-115°CYield: 20 g;(42$), m.p. 113-115°C
Analyse: C^øHggNgOg (480,8)Analysis: C^øHggNgOg (480.8)
Eksempel 19 . Example 19.
N, NT, N"- tris-( 10- undecenoyl)- dietylentriamin N,NT,N"-tris-(10-undecenoyl)-diethylenetriamine
ble fremstilt analogt Eksempel l8 av l8,4 g (0,1 mol) undecylensyre, 10,2 g (0,1 mol) trietylamin, 10,8 g (0,1 mol) was prepared analogously to Example 18 from 18.4 g (0.1 mol) undecylenic acid, 10.2 g (0.1 mol) triethylamine, 10.8 g (0.1 mol)
klormaursyreétylester og 3»3g (°,33 m°D dietylentriamin i tetrahydrofuran. chloroformic acid ethyl ester and 3»3g (°.33 m°D diethylenetriamine in tetrahydrofuran.
Utbytte: 11,0 g (55,7$), smp. : 70-73°C (acetonitril) Yield: 11.0 g ($55.7), m.p. : 70-73°C (acetonitrile)
Analyse: Coy<H>^N^<Oo>(<60>1,9)Analysis: Coy<H>^N^<Oo>(<60>1.9)
Eksempel 20. Example 20.
N, N* . N",^'*- tetra-( 10- undecenoyl)- trietylentetramin N, N*. N",^'*- tetra-(10- undecenoyl)- triethylenetetramine
Til 4,3 g (0,03mol) trietylendiamin og 13,1.g (0,13 mol) trietylamin i 200 ml abs. tetrahydrofuran dyppet man under om-røring og isavkjøling 26,2 g (0,13 mol) undecylensyreklorid. Etter henstand natten over helte man det i vann,yfrasuget og omkrystalliserte fra alkohol og fra acetonitril. To 4.3 g (0.03 mol) triethylenediamine and 13.1 g (0.13 mol) triethylamine in 200 ml abs. 26.2 g (0.13 mol) of undecylenic acid chloride were dipped into tetrahydrofuran while stirring and cooling with ice. After standing overnight, it was poured into water, suction filtered and recrystallized from alcohol and from acetonitrile.
Utbytte: 11,0 g (45»3%) , smp. 136-137°CYield: 11.0 g (45»3%), m.p. 136-137°C
Analyse: C^qH^qN^O^/(8<1>1,2}Analysis: C^qH^qN^O^/(8<1>1,2}
Eksempel 21. Example 21.
N^ N', , N", N" T , K" w- pentadecanovl- tétraetylenpentamin N^ N', , N", N" T , K" w- pentadecanovel- tetraethylenepentamine
3,8 g (0,2 mol) tetraetylenpentamin og 10,1 g (0,1 mol) trietylamin ble oppløst i 200 ml abs. tetrahydrofuran. Under isavkjøling og omrøring ble det tildryppet 19>0g (0,1 mol) kaprinsyréklorid. Etter omrøring natten over og helling i vann ble det ekstrahert med eter, eteroppløsningen ble vasket med vann og tørket (Na2S0^). Etter avdamping til tørrhet ble det omkrystallisert fra acetonitril og fra metanol. Utbytte: 10,5 g (54.7$) smp. 113-115°C. 3.8 g (0.2 mol) of tetraethylenepentamine and 10.1 g (0.1 mol) of triethylamine were dissolved in 200 ml of abs. tetrahydrofuran. During ice-cooling and stirring, 190 g (0.1 mol) of capric acid chloride were added dropwise. After stirring overnight and pouring into water, it was extracted with ether, the ether solution was washed with water and dried (Na 2 SO 4 ). After evaporation to dryness, it was recrystallized from acetonitrile and from methanol. Yield: 10.5 g (54.7$) m.p. 113-115°C.
Analyse: C58<H>113<N>5°5 (96l»7)Analysis: C58<H>113<N>5°5 (96l»7)
Eksempel 22. Example 22.
N , N' ,N" , N"' ?Nntt , N" n T- hexadecanoyl- pentaetylenhexamin N , N' ,N" , N"' ?Nntt , N" n T-hexadecanoyl- pentaethylenehexamine
Til 200 ml abs. tetrahydrofuran ble det satt 10,1 g (0,1 mol) trietylamin og 3»7g (0,016 mol) pentaetylenhexamin og det ble ' tildryppet under omrøring og isavkjøling 19,0 g (0,1 mol) decansyreklorid. Etter henstand natten over helte man i 500 ml vann, ekstraherte med eter, vasket eteroppløsningen med vann og tørket (NagSO^). Etter fjerning av eteren ble det omkrystallisert For 200 ml abs. tetrahydrofuran, 10.1 g (0.1 mol) of triethylamine and 3.7 g (0.016 mol) of pentaethylenehexamine were added and 19.0 g (0.1 mol) of decanoic acid chloride were added dropwise with stirring and ice-cooling. After standing overnight, it was poured into 500 ml of water, extracted with ether, the ether solution washed with water and dried (NagSO 4 ). After removal of the ether, it was recrystallized
fra éddikester. Utbytte: 8,5 g (45,8^), smp. 137-138°C from vinegar. Yield: 8.5 g (45.8^), m.p. 137-138°C
: Analyse: C^øH^gNgOg (1157,9): Analysis: C^øH^gNgOg (1157.9)
Eksempel 23 N , N*, N"- tris-( 10- undecenoyl)-/ bis-( 3- aminopropyl)- aminZ, Example 23 N,N*,N"-tris-(10-undecenoyl)-/bis-(3-aminopropyl)-amineZ,
Syntesen foregikk analogt Eksempel 18 under anvendelse av 20,2 g (0,1 mol) undecylensyreklorid og 3,6 g (0,03 ffi°D 3>3'-diamin0~dipropylamin, 10,1 g (0,1 mol) trietylamin i 150 ml abs. tetrahydrofuran. The synthesis took place analogously to Example 18 using 20.2 g (0.1 mol) undecylenic acid chloride and 3.6 g (0.03 ffi°D 3>3'-diamine0~dipropylamine, 10.1 g (0.1 mol) triethylamine in 150 ml abs tetrahydrofuran.
Utbytte: 16,0 g (84,7$), smp. 64-65° (2 x omkrystallisert fra lig.ro in) Yield: 16.0 g ($84.7), m.p. 64-65° (2 x recrystallized from lig.ro in)
Analyse: C^ft^N^'• (6<2>9,9) Analysis: C^ft^N^'• (6<2>9,9)
Eksempel 24 1, 2- bis-( 10- undecenoylaminometyl)- cyklobutan Example 24 1,2-bis-(10-undecenoylaminomethyl)-cyclobutane
ble fremstilt analogt Eksempel 16 idet det ble gått ut fra 18,4 g (0,1 mol) undecylensyre, 10,1 g (0,1 mol) trietylamin, 10,8 g (0,1 mol) klormaursyreétylester og 5,7 g (0,05 m°l) 1,2-bis-(aminometyl)-cyklobutan i abs. tetrahydrofuran. was prepared analogously to Example 16, starting from 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) chloroformic acid ethyl ester and 5.7 g (0.05 m°l) 1,2-bis-(aminomethyl)-cyclobutane in abs. tetrahydrofuran.
Utbytte : 14.4 g (65$), sm<p.>. 74-77° (acetonitril)Yield : 14.4 g ($65), sm<p.>. 74-77° (acetonitrile)
Analyse: CggH^NgOg (446,7)Analysis: CggH^NgOg (446.7)
EKsempel 25 M^ N1- bis-( 10- undecenoylj- cyklohexan- l^^- dlamin ( cis/ trans blanding) EXAMPLE 25 M^ N1-bis-(10-undecenoylj-cyclohexane-1^^-dlamine (cis/trans mixture)
kunne fremstilles analogt Eksempel 16 under anvendelse av 18,4 g (0,1 mol) undecylensyre, 10,1 g (0,1 mol) trietylamin, 10,8 g (0,1 mol) klormaursyreétylester og 4.7 g (0,55 mol) 1,2-diamino-cyklohexan (cis/trans-blanding) i abs. tetrahydrofuran. could be prepared analogously to Example 16 using 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) chloroformate ethyl ester and 4.7 g (0.55 mol) 1,2-diamino-cyclohexane (cis/trans mixture) in abs. tetrahydrofuran.
Utbytte: 10,3 g (46,3$), smp. I39-I4O<0>(acetonitril)Yield: 10.3 g ($46.3), m.p. I39-I4O<0>(acetonitrile)
Analyse: C28<H>5<0W>2°2(446,6)Analysis: C28<H>5<0W>2°2(446.6)
Eksempel 26 M, N'- bis-( lQ- undecenoylaminometyl)- cyklohexan ble fremstilt ifølge Eksempel 16 under anvendelse av l8,4 g (0,1 mol) undecylensyre, 10,1 g (0,1 mol) trietylamin, 10,8 g (0,1 mol) klormaursyreétylester i 150 ml abs. tetrahydrofuran med 7 g (0,05 mol) 4«4,_bis-(aminometyl)-cyklohexan. Utbytte: 8,6 g (36.,2$), smp. 174-1755° (omkrystallisert fra acetonitril/alkohol 2:1 og fra metanol) Analyse: ^3<0>^54^2^2(474»7) Example 26 M,N'-bis-(1Q-undecenoylaminomethyl)-cyclohexane was prepared according to Example 16 using 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10, 8 g (0.1 mol) chloroformate ethyl ester in 150 ml abs. tetrahydrofuran with 7 g (0.05 mol) of 4,4,-bis-(aminomethyl)-cyclohexane. Yield: 8.6 g ($36.2), m.p. 174-1755° (recrystallized from acetonitrile/alcohol 2:1 and from methanol) Analysis: ^3<0>^54^2^2(474»7)
Eksempel 27- 43 (Tabell 3) Example 27- 43 (Table 3)
Syntesene av disså forbindelser foregikk analogt forskriftene i Eksempel 1:, idet det ble gått ut fra 0,05. m°i diamin og 11, 1 g (0,11 mol) trietylamin i 150 ml abs. tetrahydrofuran ved omsetning med 22,3 g (0,11 mol) undecylensyreklorid. The syntheses of these compounds took place analogously to the regulations in Example 1:, starting from 0.05. m°i diamine and 11.1 g (0.11 mol) triethylamine in 150 ml abs. tetrahydrofuran by reaction with 22.3 g (0.11 mol) undecylenic acid chloride.
Eksempel 4- 6 . N. N'* - bis-( decanoyl )- D. L- ornit in Example 4-6. N. N'* - bis-( decanoyl )- D. L- ornithine in
Til blandingen av 200 ml eter , 100 ml benzen, 200 ml vann hadde man 20 g (0,5 mol) etznatron og 16,9 g (0,1 mol) D,L-ornitin-moirohydroklorid. Under god omrøring og avkjøling To the mixture of 200 ml of ether, 100 ml of benzene, 200 ml of water, 20 g (0.5 mol) of caustic soda and 16.9 g (0.1 mol) of D,L-ornithine moiro hydrochloride were added. Stir well and cool
tildryppet man 3^,0 g (0,2 mol) kaprinsyreklorid, idet temperaturen ble holdt rundt 0°C. Under omrøring lot man det komme til romtemperatur, surgjorde med saltsyre og adskilte den organiske fase. Etter vasking med vann, inndampning til 3^.0 g (0.2 mol) of capric acid chloride were added dropwise, the temperature being kept around 0°C. With stirring, it was allowed to come to room temperature, acidified with hydrochloric acid and the organic phase separated. After washing with water, evaporation to
tørrhet og omkrystallisering fra benzen ble det dannet 3& g (86,5$), smp. 125-127°C. dryness and recrystallization from benzene gave 3& g (86.5$), m.p. 125-127°C.
Analyse:..<C>25<H>4<8N>2°4Analysis:..<C>25<H>4<8N>2°4
Eksempel. 47 , N, MT- bis-( decanoyl)- L- lysinamid Example. 47 , N, MT-bis-(decanoyl)-L-lysinamide
10,9 g (°»°5 moD L-lysinamid x,2 HC1 ble avkjølt i 150 ml abs. dimetylformamid til ca. 0°C. Man tilsatte 20,2 g (0,2 mol) trietylamin og tildryppet deretter 19,0 g (0,1 mol) decansyreklorid. Man lot det natten over komme til romtemperatur, 10.9 g (°»°5 moD L-lysinamide x.2 HCl was cooled in 150 ml abs. dimethylformamide to approx. 0°C. 20.2 g (0.2 mol) triethylamine was added and then 19, 0 g (0.1 mol) of decanoic acid chloride.It was allowed to come to room temperature overnight,
helte i 5QQ ml\ann, frasuget det faste produkt og omkrystalli-serté. smp. 176°C. poured into 5QQ ml\ann, filtered off the solid product and recrystallised. m.p. 176°C.
Utbytte: 12,9 g (56,5$)Yield: 12.9 g ($56.5)
Analyse: C26H51N3°3 <457»7) Analysis: C26H51N3°3 <457»7)
■'■"'■' ■'■"'■'
Eksempel 48 3 Example 48 3
N,N'-bis- ( decanoyl)-D, L- ornitin- cyklohexylamid N,N'-bis-(decanoyl)-D,L-ornithine cyclohexylamide
ble fremstilt analogt Eksempel 4i under anvendelse av 14,2 g (0,05 moi) D,L~ornitincyklohexylamid, x 2 HC1. Smp. 157-158°C. was prepared analogously to Example 4i using 14.2 g (0.05 moi) D,L~ornithine cyclohexylamide, x 2 HCl. Temp. 157-158°C.
Utbytte: 15,2 g (58$)Yield: 15.2 g ($58)
Analyse: CyH^ jO^ (521,7). Analysis: C 1 H 2 H 2 O 2 (521.7).
Eksempel 49 N , N' T - bis-( decanoyl) - L- lysinetylester 12,4 g (0,05 mol) L-lysinetylester x 2 HG1 ble oppløst i 120 ml dimetylformamid. Etter tilsetning av 20,2 g (0,2 mol) trietylamin avkjølte man med isvann til ca. 5°C og tildryppet ved denne temperatur 19 g (0,1 mol) kaprinsyreklorid. Natten over lot man det komme til romtemperatur, oppvarmet kort til £0°C (0,5 timer), avkjølte og helte i vann. To ganger omkrystallisering fra eddiksyreetylester ga 65,5 g ( SQ%), smp. 89-90°• Analyse: C28<H>54<W>2°4 (482,7) Eksempel 50 M, N'- bis-( decanoyl)- 1 f3 - diamino- 2- hydroksypropan Example 49 N,N'T-bis-(decanoyl)-L-lysine ethyl ester 12.4 g (0.05 mol) L-lysine ethyl ester x 2 HG1 was dissolved in 120 ml of dimethylformamide. After adding 20.2 g (0.2 mol) of triethylamine, it was cooled with ice water to approx. 5°C and added dropwise at this temperature 19 g (0.1 mol) of capric acid chloride. It was allowed to come to room temperature overnight, heated briefly to 0°C (0.5 hours), cooled and poured into water. Twice recrystallization from acetic acid ethyl ester gave 65.5 g ( SQ%), m.p. 89-90°• Analysis: C28<H>54<W>2°4 (482.7) Example 50 M, N'-bis-(decanoyl)-1f3-diamino-2-hydroxypropane
Til en isavkjølt oppløsning av 22,5 g (0,25 mol) 1,3-diamino-2-hydroksypropan og 51 g (0,5 mol) trietylamin i 500 ml abs., tetrahydrofuran dryppet man 95 g (0,5 mol) kaprinsyreklorid. Under omrøring lot man det komme til romtemperatur, helte i 700 ml vann og frasuget det utfelte faste produkt. Etter-våSking med vann og omkrystallisering fra etanol ga 75»7g (76$), smp. 130-i31°C. To an ice-cooled solution of 22.5 g (0.25 mol) 1,3-diamino-2-hydroxypropane and 51 g (0.5 mol) triethylamine in 500 ml abs. ) capric acid chloride. While stirring, it was allowed to come to room temperature, poured into 700 ml of water and the precipitated solid product was sucked off. After washing with water and recrystallization from ethanol gave 75.7g (76$), m.p. 130-i31°C.
Analyse: C23<H>4<6N>2°3 (<3>98,6)Analysis: C23<H>4<6N>2°3 (<3>98.6)
Eksempel 51 Example 51
H , N *- bis-( decanoyl)- L- ornitin- metylester ... H , N *- bis-(decanoyl)- L- ornithine- methyl ester ...
Til 200 ml abs. dimetylformamid ble det satt 10,9 g (0,05 mol) L-ornitin-metylester-dihydroklorid og 20,2 g (0,2 mol) trietylamin. Man avkjølte til 0° og tildryppet 19'g (0,1 mol) kaprinsyreklorid. Man lot det komme til romtemperatur og oppvarmet enda i 4 timer ved 50°C, helte i' vann og frasuget. De hvite krystaller ble omkrystallisert fra ligroin. For 200 ml abs. dimethylformamide, 10.9 g (0.05 mol) of L-ornithine methyl ester dihydrochloride and 20.2 g (0.2 mol) of triethylamine were added. It was cooled to 0° and 19 g (0.1 mol) of capric acid chloride were added dropwise. It was allowed to come to room temperature and heated for a further 4 hours at 50°C, poured into water and suctioned off. The white crystals were recrystallized from ligroin.
Utbytte: 12,5 g (55,255), smp. 79-82°C..Yield: 12.5 g (55.255), m.p. 79-82°C..
Analyse:<C>26<H>50<N>2°2(454»5> Analysis:<C>26<H>50<N>2°2(454»5>
Eksempel ^ 2. Example ^ 2.
N, ST bis-( 10- undecenoyl)- L- lysinetylester N, ST bis-(10-undecenoyl)-L-lysine ethyl ester
l8,4 g (0,1 mol) 10-undecensyre ble oppløst i 200 ml dimetylformamid (abs.).Bttor tilsetning av 20,2 g (0,2 mol) trietylamin, avkjølte man til -10° og tildryppet ved denne temperatur under omrøring 10,8 g (0,1 mol) klormaursyreétylester. Man omrørte enda i 30 minutter ved -10° og tildryppet deretter 12,4 g (0,05 mol) L-lysinetylester-dihydroklorid, oppløst i 80 ml abs. DMF. Man lot det komme til værelsestemperatur natten over, omrørte enda i 4 timer ved 60° og helte i vann. Det.utfelte produkt ble suget fra og omkrystallisert fra acetonitril og fra petroleter/eddikester (2:1). 18.4 g (0.1 mol) of 10-undecenoic acid was dissolved in 200 ml of dimethylformamide (abs.). After the addition of 20.2 g (0.2 mol) of triethylamine, it was cooled to -10° and added dropwise at this temperature with stirring 10.8 g (0.1 mol) chloroformate ethyl ester. It was stirred for a further 30 minutes at -10° and then 12.4 g (0.05 mol) of L-lysine ethyl ester dihydrochloride, dissolved in 80 ml of abs. DMF. It was allowed to come to room temperature overnight, stirred for a further 4 hours at 60° and poured into water. The precipitated product was suctioned off and recrystallized from acetonitrile and from petroleum ether/acetic ester (2:1).
Utbytte: 12,5 g (50$), smp- 69-7I0Yield: 12.5 g ($50), mp 69-710
Analyse: . C^øH^NgO^ (<50>6,6)Analysis: . C^øH^NgO^ (<50>6.6)
Eksempel 53 N, N'- bis- Xdecanoyl)- L- lysin Example 53 N,N'-bis-Xdecanoyl)-L-lysine
ble fremstilt analogt Eksempel 46 under anvendelse av 18,27 g (0,1 mol) L-lysin-monohydroklorid. was prepared analogously to Example 46 using 18.27 g (0.1 mol) of L-lysine monohydrochloride.
Utbytte:36,2 g ((80#), smp. 104-105°C. Yield: 36.2 g ((80#), mp 104-105°C.
Analyse: C26%0N2°4 (454'7}Analysis: C26%0N2°4 (454'7}
Eksempel 54- 59 (Tabell 4) Example 54-59 (Table 4)
De i Tabell 4 oppførte forbindelser ble fremstilt analogt forskriften gitt,i Eksempel 18, idet det ble gått ut fra 0,05 mol diamin og 10,1 g (0,1 mol) trietylamin i I50 ml abs. tetrahydrofuran og 13,05 g (0,1 mol.) dietyleddiksyreklorid. The compounds listed in Table 4 were prepared analogously to the instructions given in Example 18, starting from 0.05 mol diamine and 10.1 g (0.1 mol) triethylamine in 150 ml abs. tetrahydrofuran and 13.05 g (0.1 mol.) diethylacetic acid chloride.
Eksempel 56 ble fremstilt under anvendelse av 0,02 mol diamin og tilsvarende mengder trietylamin og dietyleddiksyreklorid. Example 56 was prepared using 0.02 moles of diamine and corresponding amounts of triethylamine and diethylacetic acid chloride.
Eksempel 60 Example 60
N. N'- bis-( dietylacetyl)- 1. 3- diamino- propan- 2- on N. N'- bis-(diethylacetyl)- 1. 3- diamino- propan- 2- one
3,22 g (0,02 mol) l,3-diamino-propan-2-on-dihydroklorid ble oppløst i 100 ml vann. Etter tilsetning av 100 ml metylenklorid avkjølte man til ca. 0°C og tildryppet samtidig 1 N vandig NaOH og 5,2 g (0,04 mol) dietyleddiksyreklorid i 50 ml kloroform, således at den vandige oppløsning omtrent ble nøy-tral. Etter at reaksjonsblandingen under omrøring var kommet til værelsestemperatur, ble kloroformfasen adskilt, vasket med vann og inndampet til tørrhet for rotasjonsfordamper. Residuet ble bmkrystallisert fra eddikester og ligroin. 3.22 g (0.02 mol) of 1,3-diamino-propan-2-one dihydrochloride was dissolved in 100 ml of water. After adding 100 ml of methylene chloride, it was cooled to approx. 0°C and simultaneously added dropwise 1 N aqueous NaOH and 5.2 g (0.04 mol) diethylacetic acid chloride in 50 ml chloroform, so that the aqueous solution became approximately neutral. After the stirred reaction mixture had reached room temperature, the chloroform phase was separated, washed with water and evaporated to dryness on a rotary evaporator. The residue was recrystallized from acetic acid and naphtha.
Utbytte: 3,<1>5 g (55,5^), smp. I68-I7O0Yield: 3.<1>5 g (55.5^), m.p. I68-I7O0
Analyse: C15H28N2°3 ^284,4) Analysis: C15H28N2°3 ^284.4)
Eksempel 6l Example 6l
N , N*- bis-( dietylacetyl)- l, 3- diamino- 3- klorpropan N,N*-bis-(diethylacetyl)-1,3-diamino-3-chloropropane
(H5C2)2CH-CO-NH-<CH>2<->CHC1-CH2-NH-CO-CH(C2H5)2(H5C2)2CH-CO-NH-<CH>2<->CHC1-CH2-NH-CO-CH(C2H5)2
ble fremstilt analogt Eksempel 60, idet det ble gått utfra 3,53 g l,3-diamino-2-klorpropan-dihydroklorid (0,02 mol). Utbytte: 4.12 g (51$), smp. II7-II90 Analyse: C15H29<C>1N2°2* 3^4,9) was prepared analogously to Example 60, starting from 3.53 g of 1,3-diamino-2-chloropropane dihydrochloride (0.02 mol). Yield: 4.12 g (51$), m.p. II7-II90 Analysis: C15H29<C>1N2°2* 3^4.9)
Eksempel 62 Example 62
cis- og trans- N, N'- bis-( 2- etyl- hexanoyl)-1, 3- diamino- 2, 2, 4»4~ cis- and trans-N,N'-bis-(2-ethylhexanoyl)-1,3-diamino-2,2,4»4~
7*1 g (0,05 mol) l,3-diamino-2,2,4,4-tetrametyl-cyklobutan (cis/trans-blanding) ble omsatt analogt Eksempel 14 i I50 ml abs. tetrahydrofuran i nærvær av 10,1 g (0,1 mol) trietylamin med 16,3 g (o,l mol) 2-etylhexansyréklorid. Omkrystallisering fra eddikester.(etter den vanlige opparbeidelse) ga to produkter: A: Utbytte 4 6» smp. 213-216° (trans-produkt) 7*1 g (0.05 mol) 1,3-diamino-2,2,4,4-tetramethyl-cyclobutane (cis/trans mixture) was reacted analogously to Example 14 in 150 ml abs. tetrahydrofuran in the presence of 10.1 g (0.1 mol) of triethylamine with 16.3 g (0.1 mol) of 2-ethylhexane acid chloride. Recrystallization from acetic ester (after the usual work-up) gave two products: A: Yield 4 6" m.p. 213-216° (trans product)
B: Utbytte5,3 g,smp. 130° (cis-produkt)B: Yield 5.3 g, m.p. 130° (cis product)
Analyse: C24<H>4<6N>2°2<<>394,7)Analysis: C24<H>4<6N>2°2<<>394.7)
Eksempel 63 M^ M' - ( n- butyryl) - 1, 2- diamino- 2- hydroksypropan Example 63 M^ M' - (n-butyryl)-1,2-diamino-2-hydroxypropane
Til 9 g (0,1 mol) l,2-diaminopropanol-(2) i 100 ml eter ble det dryppet 31»^ g (0,2 mol) smørsyre-anhydrid. Etter 24 timers henstand fjernet man oppløsningsmidlet i vakuum, tilsatte 200 ml ligroin, frasugde det faste proéukt og omkrystalliserte fra acetonitril. To 9 g (0.1 mol) of 1,2-diaminopropanol-(2) in 100 ml of ether, 31 g (0.2 mol) of butyric anhydride was added dropwise. After standing for 24 hours, the solvent was removed in vacuo, 200 ml of ligroin were added, the solid product was filtered off with suction and recrystallized from acetonitrile.
Utbytte: 15>5g (60$), smp. 128-129° Analyse: C13H26N2°3 (258,3) Yield: 15>5g ($60), m.p. 128-129° Analysis: C13H26N2°3 (258.3)
Eksempel 64- 68 (Tabell 5) Example 64-68 (Table 5)
Til 6,5 g (0,05 mol) N-(n-butyryl)-etylendiaminå To 6.5 g (0.05 mol) of N-(n-butyryl)-ethylenediamino
(fremstilt ifølge K.W. Rosemund, A.P. 19 2605, Chem.Ztbl.i933 II, 3616) i 100 ml abs. CHCl^ble det satt 5,1 g (0,05.mol) trietylamin . Under isavkjøling ble det tildryppet 0,05 mol av det i (prepared according to K.W. Rosemund, A.P. 19 2605, Chem.Ztbl.i933 II, 3616) in 100 ml abs. 5.1 g (0.05 mol) of triethylamine were added. During ice-cooling, 0.05 mol of it was added dropwise
Tabell 5 angitte syreklorid i 50 ml.abs. CHCl^Y Etter omrøring natten over ble det vasket med vann, kloroformen ble avdestil-lert og residuet kromatografert over nøytralt aluminiumoksyd. Eluert méd petroleter (kokepunkt 60-100°C)> Table 5 indicates acid chloride in 50 ml.abs. CHCl^Y After stirring overnight, it was washed with water, the chloroform was distilled off and the residue chromatographed over neutral alumina. Eluted with petroleum ether (boiling point 60-100°C)>
Eksempel 6Q- 85 .. (Tabell 6) Example 6Q- 85 .. (Table 6)
Til 18,4 g (P,l mol) undecylensyre.i 150 ml abs. tetrahydrofuran ble det satt 10,1 g (0,1 mol) trietylamin. Deretter avkjølte man til -10°C og tildryppet 10,8 g (0,1 mol) klormaursyreétylester. Man lot det etterreagere i en time ved^10°C og tildryppet deretter 0,05 mol av det i Tabell 6 nevnte N-mono-substituerte diamin i 50 mi tetrahydrofuran (abs.). Natten over lot man det komme til varelsetemperatur og helte deretter i ^ 00 ml vann. Produkter som adskiller seg som faste stoffer, ble sugd fra og omkrystallisert. Oljer ble ekstrahert med kloroform. Kloroformoppløsningen ble vasket med vann, opp-løsningsmidlet lie.fjernet på rotasjonsfordamper. Deretter kromatograferte man over nøytralte aluminiumoksyd. Det ble eluert med petroleter (kokepunkt 60-100°). To 18.4 g (P,l mol) undecylenic acid.in 150 ml abs. tetrahydrofuran, 10.1 g (0.1 mol) of triethylamine were added. It was then cooled to -10°C and 10.8 g (0.1 mol) of chloroformic acid ethyl ester was added dropwise. It was left to react for one hour at 10°C and then 0.05 mol of the N-mono-substituted diamine mentioned in Table 6 in 50 ml of tetrahydrofuran (abs.) was added dropwise. It was allowed to come to room temperature overnight and then poured into ^ 00 ml of water. Products that separate as solids were suctioned off and recrystallized. Oils were extracted with chloroform. The chloroform solution was washed with water, the solvent removed on a rotary evaporator. The mixture was then chromatographed over neutralized aluminum oxide. It was eluted with petroleum ether (boiling point 60-100°).
Eksempel 86 NjN,~ bis-( 10- uirdecenoyl)- 2~ amino- l- metylamino- 2~ metyl- propan Example 86 NjN,~ bis-(10-irdecenoyl)-2~ amino-1-methylamino-2~ methyl-propane
ble fremstilt analogt Eksempel l8 av 2-amino-l-metylainino-2-metylpropan og.undecylensyreklorid (olje) was prepared analogously to Example 18 from 2-amino-1-methylamino-2-methylpropane and undecylenic acid chloride (oil)
Utbytte: 37$; n<2?>1.4795Dividend: 37$; n<2?>1.4795
D D
Analyse: iC27H50N2°2 (434.2) Analysis: iC27H50N2°2 (434.2)
Eksempel 87 Example 87
N, N'- bis- ( 10- undecenoyl )- 2- amino- l- pentylamino- 2- metyl- propan N,N'-bis-(10-undecenoyl)-2-amino-l-pentylamino-2-methyl- propane
ble fremstilt "analogt Eksempel 18 av 2-amino-l-(n-pentylamino)-2-metylpropan og undecylensyreklorid (olje)i was prepared "analogous to Example 18 from 2-amino-1-(n-pentylamino)-2-methylpropane and undecylenic acid chloride (oil) in
Utbytte: 42$; n211.478<0>Dividend: 42$; n211.478<0>
D D
Eksempel 88- 121 (Tabell 7) Example 88-121 (Table 7)
Syntesene av de i Tabell 7 oppførte forbindelser foregikk analogt Eksempel 18 ved omsetning av de oppførte syre-klorider (fremgangsmåtevariant A) eller analogt Eksempel 16 The syntheses of the compounds listed in Table 7 took place analogously to Example 18 by reaction of the listed acid chlorides (method variant A) or analogously to Example 16
ved omsetning av de oppførte karboksylsyrer (fremgangsmåtevariant B) med 4.4 g (0.05 mol) N.W-dimetyletylendiamin. by reacting the listed carboxylic acids (method variant B) with 4.4 g (0.05 mol) N.W-dimethylethylenediamine.
Eksempel 122 ■. N, Nt- diben2vl- NtHf - bis-( 10- undecenoyl)- etylendiamin Example 122 ■. N, Nt-diben2vl- NtHf - bis-(10- undecenoyl)- ethylenediamine
kunne fremstilles, analogt Eksempel 18 av N,N<f->dibenzyl-•etylendiamin og undecylensyreklorid. Utbytte: 68$,; smp. 55-56° (petroleter) could be prepared, analogously to Example 18, from N,N<f->dibenzyl-•ethylenediamine and undecylenic acid chloride. Dividend: 68$,; m.p. 55-56° (petroleum ether)
Analyse: Analysis:
Eksempel 123 N- metyl- N^ N- bis- Zi- dO- undecenoyl- N^ metylaminoj- etan/ Example 123 N- methyl- N^ N- bis- Zi- dO- undecenoyl- N^ methylamino- ethane/
ble fremstilt analogt Eksempel 16 under anvendelse av 7»36(0,05 mol)N,N',N"-trimetyl-dietylentriamin i abs. tetrahydrofuran* Den dannede olje ble kromatografert over aluminiumoksyd (nøytral), idet det ble eluert med petroleter. was prepared analogously to Example 16 using 7"36(0.05 mol)N,N',N"-trimethyl-diethylenetriamine in abs. tetrahydrofuran* The oil formed was chromatographed over alumina (neutral), eluting with petroleum ether .
Utbytte: 13,0 g (54,7$)..n21 1-479<8>Yield: 13.0 g ($54.7)..n21 1-479<8>
D D
Analyse: C^qH^N n (477,7) Analysis: C^qH^N n (477.7)
Eksempel 124- 128 (Tabell 8 ) Example 124-128 (Table 8)
Syntesen av Eksemplene 124-128 foregikk analogt Eksempel 16, idet det ble omsatt 0,1 mol karboksylsyre, 10,1 g (0,1 mol)trietylamin,10,8 g (0,1 mol) klormaursyreétylester og 5,8 g (0,05 mol) N,Nf-dietyletylendiamin i abs. tetrahydrofuran. Etter opparbeidelse dannede olje ble kromatografert over aluminiumoksyd og eluert med petroleter. The synthesis of Examples 124-128 proceeded analogously to Example 16, in that 0.1 mol of carboxylic acid, 10.1 g (0.1 mol) of triethylamine, 10.8 g (0.1 mol) of chloroformic acid ethyl ester and 5.8 g ( 0.05 mol) N,Nf-diethylethylenediamine in abs. tetrahydrofuran. After working up, the oil formed was chromatographed over aluminum oxide and eluted with petroleum ether.
Eksempel 129 N, N *- bis-( dodecanoyl) - N , N'- di-( n- butyl)- etylendiamin <:>ble fremstilt av 20 g.(0,l mol) dedekansyre, 10,1 g (0,1 mol) trietylamin, 10,8 g (o,l mol) klormaursyreétylester og 8,6 g (0,05©pl) N,N'-di-n-butyletylendiamin i abs. tetrahydrofuran, som omtalt i Eksempel l6. .Kromatografi over nøytralt aluminiumoksyd ga 13 g (50$) av en olje n21 1.4676. Example 129 N,N*-bis-(dodecanoyl)-N,N'-di-(n-butyl)-ethylenediamine<:>was prepared from 20 g.(0.1 mol) of dedecanoic acid, 10.1 g (0 .1 mol) triethylamine, 10.8 g (0.1 mol) chloroformate ethyl ester and 8.6 g (0.05 µl) N,N'-di-n-butylethylenediamine in abs. tetrahydrofuran, as discussed in Example 16. .Chromatography over neutral alumina gave 13 g (50$) of an oil n21 1.4676.
D D
Analyse: C34*%8<N2>°2*536,8)Analysis: C34*%8<N2>°2*536.8)
Eksempel 130 N, MT- bis-( dodecanoyl)- 2- amino- l- metylamino- 2- metyl- propan Example 130 N, MT-bis-(dodecanoyl)-2-amino-1-methylamino-2-methyl-propane
ble fremstilt analogt Eksempel 18 av dodekansyreklorid og 2-amino-l-metylamino-2-metyl-propan i tetrahydrofuran. Den dannede olje kunne renses ved kromatografering over basisk aluminiumoksyd (eluering med benzen). was prepared analogously to Example 18 from dodecanoic acid chloride and 2-amino-1-methylamino-2-methyl-propane in tetrahydrofuran. The oil formed could be purified by chromatography over basic alumina (elution with benzene).
Utbytte: 8,0 g (34,5$), n<27>1.4718 Yield: 8.0 g ($34.5), n<27>1.4718
D D
Analyse:Analysis:
Eksempel 111 M, NT- bis-( 10- undecenoyl)- N. Nf- di-( n- butvl)- etylendiamin Example 111 M, NT-bis-(10-undecenoyl)-N.Nf-di-(n-butvl)-ethylenediamine
ble fremstilt som Eksempel under anvendelse av l8,4 g (6,1 mol) undecylensyre. was prepared as an example using 18.4 g (6.1 mol) of undecylenic acid.
Utbytte: 17,2 g oljeaktig produkt (68$), n^° 1.4738Yield: 17.2 g of oily product ($68), n^° 1.4738
Analyse: C32H6oW2°2^04,7) Analysis: C32H6oW2°2^04.7)
Eksempel 132- 136 (Tabell 9) Example 132-136 (Table 9)
Til oppløsningen av 8,-6 g (0,05 mol) N,N'-di-(tert.-butyl)-etylendiamin£,10,1 g (0,1 mol) trietylamin og 200 ml abs. tetrahydrofuran dryppet man under isavkjølingbg omrøring 0,1 mol syreklorid. Man lot det komme til værelsetemperatur, oppvarmet i enda 4 timer ved 50° c og helte i vann. De utfelte. krystaller ble frasuget og:omkrystallisert. To the solution of 8.6 g (0.05 mol) of N,N'-di-(tert-butyl)-ethylenediamine£, 10.1 g (0.1 mol) of triethylamine and 200 ml of abs. tetrahydrofuran, 0.1 mol of acid chloride was added dropwise under ice-cooling with stirring. It was allowed to come to room temperature, heated for a further 4 hours at 50°C and poured into water. They precipitated. crystals were aspirated and recrystallized.
- Eksempel 137 N, N*- bis-( 10- undecenoyl)- N, N'- di-( n- dodecyl)- etylendiamin Syntesen foregitt analogt Eksempel 16 av 19>8 g (0,05 mol) R, N^dodecyl-etylendiamin, 10,1 g (0,1 mol) trietylamin, 10,8 g (0,1 mol) klormaursyreétylester og l8,4 g (0,1 mol) undecylensyre i abs.-tetrahydrofuran. Utbytte: 15 g (41,3$), smp. 43-44° (av acetonitril og fra metanol) ■ " - Example 137 N,N*-bis-(10-undecenoyl)-N,N'-di-(n-dodecyl)-ethylenediamine The synthesis was carried out analogously to Example 16 of 19>8 g (0.05 mol) R, N^ dodecylethylenediamine, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) ethyl chloroformate and 18.4 g (0.1 mol) undecylenic acid in abs. tetrahydrofuran. Yield: 15 g ($41.3), m.p. 43-44° (from acetonitrile and from methanol) ■ "
Eksempel 138- 144 (Tabell 10) Example 138-144 (Table 10)
Syntesen av denne, forbindelse, foregikk analogt Eksempel 16, idet 0,1 mol karboksylsyre, 10,1 g (0,1 mol) trietylamin, 10,8 g (0,1 mol) klormaursyreétylester i abs. tetrahydrofuran ble omsatt med 10,0 g (0,05 mol) N,N*-diiso-valeryl^étylendiamin. Den etter opparbeidelsen dannede olje ble kromatografert over nøytralt aluminiumoksyd. Det ble eluert med petroleter (kokepunkt 60-loo£:) The synthesis of this compound proceeded analogously to Example 16, in that 0.1 mol of carboxylic acid, 10.1 g (0.1 mol) of triethylamine, 10.8 g (0.1 mol) of chloroformic acid ethyl ester in abs. tetrahydrofuran was reacted with 10.0 g (0.05 mol) of N,N*-diiso-valeryl-ethylenediamine. The oil formed after the work-up was chromatographed over neutral aluminum oxide. It was eluted with petroleum ether (boiling point 60-loo£:)
Eksempel 145- 152 (Tabell 11) Example 145-152 (Table 11)
Eksemplene 145-152 ble fremstilt under anvendelse av 12,2 g (0,05 mol) N,N<T->dicyklohexyl-etylendiamin ved omsetning med det tilsvarende syreklorid analogt Eksempel 18, (fremgangsmåtevariant A) eller ved omsetning med karboksylsyre Examples 145-152 were prepared using 12.2 g (0.05 mol) N,N<T->dicyclohexyl-ethylenediamine by reaction with the corresponding acid chloride analogous to Example 18, (method variant A) or by reaction with carboxylic acid
analogt Eksempel 11 (fremgangsmåtevariant B). Dannede oljer ble analogously to Example 11 (method variant B). Formed oils were
renset ved kromatografi over nøytral aluminiumoksyd og eluering med petroleter (kokepunkt 60-100°C). purified by chromatography over neutral alumina and elution with petroleum ether (boiling point 60-100°C).
:' Eksempel 155- 159 (Tabell 12) :' Example 155-159 (Table 12)
Syntesen av de i Tabell 12 oppstilte forbindelser foregikk ifølge Eksempel 16 av 18,4 g (0,1 mol) 2-undecensyre, 10,1 g (0,1 mol) trietylamin og 10,8 g (0,1 mol) klormaursyreétylester over dét blandede anhydrid. The synthesis of the compounds listed in Table 12 took place according to Example 16 from 18.4 g (0.1 mol) 2-undecenoic acid, 10.1 g (0.1 mol) triethylamine and 10.8 g (0.1 mol) chloroformate ethyl ester over the mixed anhydride.
Eksempel l60 Example l60
N, N- T - bis-( 10- undecenoyl )- N, N^ rdiallyl- etylendiamin N, N- T - bis-(10- undecenoyl )- N, N^ rdiallyl- ethylenediamine
Til trietylammoniumsaltet, tilberedt av 18,4 g (0,1 mol) undecylensyre og 10,1 g (0,1 mol) trietylamin i ca. 200 ml abs. tetrahydrofuran, dryppet man ved -10°C 10,8 g (0,1 mol) klormaursyreétylester. Man etteromrørte enda i én time og tilsatte deretter dråpevis 7 g (0,05 mol) N,N'-diallyl-étylendiamin, oppløst i 60 ml abs. THF. Natten over lot man det komme til værelsetemperatur, helte reaksjonsproduktet i vann og ekstraherte 3 ganger med hver gang 150 ml kloroform. Kloroformopp-løsningene ble vasket med vann og inndampet til tørrhet. Den gjenblivende olje ble kromatografert over nøytralt aluminiumoksyd. Man fikk.således 9,5 g (40,3$) av en olje n^1 I.4839. Analyse: C^0H52N202 (472,7) ; Eksempel l6l W, N t- bis-( 10- undeeenpyl)- 2, 3- diaminopropiorisyre Til den omrørte. blanding av 7 g (0,05 mol) 2,3-diaminopropionsyre -. HC1, 20 g (0,5 mol) NaOH, 100 ml isvann, 150 ml benzen og fjO ml eter ble det ved 0° dryppet 20,2 g (0,1 mol) undecylensyreklorid. Under omrøring lot man det komme til værelsetemperatur, surgjorde med halvkonsentrert saltsyre og adskilte den organiske fase. Etter vasking med vann og inndamping til tørrhet ble acetonitril omkrystallisert. To the triethylammonium salt, prepared from 18.4 g (0.1 mol) undecylenic acid and 10.1 g (0.1 mol) triethylamine in approx. 200 ml abs. tetrahydrofuran, 10.8 g (0.1 mol) chloroformate ethyl ester was added dropwise at -10°C. Stirring was continued for one hour and then 7 g (0.05 mol) of N,N'-diallyl-ethylenediamine, dissolved in 60 ml of abs, were added dropwise. THF. It was allowed to come to room temperature overnight, the reaction product was poured into water and extracted 3 times with 150 ml of chloroform each time. The chloroform solutions were washed with water and evaporated to dryness. The remaining oil was chromatographed over neutral alumina. 9.5 g (40.3$) of an oil n^1 I.4839 was thus obtained. Analysis: C 2 0 H 5 2 N 2 O 2 (472.7); Example 161 W,N t-bis-(10-undeenepyl)-2,3-diaminopropioric acid To the stirred. mixture of 7 g (0.05 mol) 2,3-diaminopropionic acid -. HC1, 20 g (0.5 mol) NaOH, 100 ml ice water, 150 ml benzene and fjO ml ether, 20.2 g (0.1 mol) of undecylenic acid chloride were added dropwise at 0°. While stirring, it was allowed to come to room temperature, acidified with semi-concentrated hydrochloric acid and separated the organic phase. After washing with water and evaporation to dryness, acetonitrile was recrystallized.
Utbytte: 6,3 g (29$), smp. 87-9O<0>Yield: 6.3 g ($29), m.p. 87-9O<0>
Analyse: C^H^NgO^ . (436»5)Analysis: C^H^NgO^ . (436»5)
Eksempel 162 N, N'- bis-( 2- hydroksyetyl)- M, N*- bis-( heptanoyl)- etylendiamin Example 162 N,N'-bis-(2-hydroxyethyl)-M,N*-bis-(heptanoyl)-ethylenediamine
ble fremstilt analogt Eksempel l6l av n-heptansyre og N,N'-bis-(2-hydroksyetyl)-etylendiamin. was prepared analogously to Example 16l from n-heptanoic acid and N,N'-bis-(2-hydroxyethyl)-ethylenediamine.
Utbytte: 48$, smp. 96-99° (eddikester/ligroin 2:1)Yield: 48$, m.p. 96-99° (acetic ester/ligroin 2:1)
Analyse: G20<H>40<N>2°4Analysis: G20<H>40<N>2°4
1 - Eksempel 163 N-( 2- hydroksyetyl)- N, N*- bis- jnonanoyl)- etylendiamin 1 - Example 163 N-(2-hydroxyethyl)-N,N*-bis-jnonanoyl)-ethylenediamine
Til den omrørte blanding av 10,4 g (0,1 mol) N-(2-hydroksyetyl)-etylendiamin, 20,2 g (0,2 mol) trietylamin og 350 ml abs. kloroform ble det ved 0°C dryppet 35 g (0,2 mol) pelargonsyreklorid. To the stirred mixture of 10.4 g (0.1 mol) of N-(2-hydroxyethyl)-ethylenediamine, 20.2 g (0.2 mol) of triethylamine and 350 ml of abs. chloroform, 35 g (0.2 mol) of pelargonic acid chloride were added dropwise at 0°C.
Man etteromrørte natten over, adskilte sjiktene og vasket den . organiske fase med vann. Etter fjerning av kloroformen ble det omkrystallisert fra ligroin. After stirring overnight, the layers were separated and washed. organic phase with water. After removal of the chloroform, it was recrystallized from ligroin.
Utbytte: 15,3 g (40$), smp. 71-72°Yield: 15.3 g ($40), m.p. 71-72°
Analyse: C22<H>44<N>2°3 ^84» 4)Analysis: C22<H>44<N>2°3 ^84» 4)
Eksempel 164 H, N*- bis-( 10- undecenoyl)- N , N*- difenyletylendiamin Example 164 H,N*-bis-(10-undecenoyl)-N,N*-diphenylethylenediamine
Syntesen av dette eksempel foregikk analogt Eksempel 16, idet det ble omsatt 10,5 g (0,05 mol) R,N<T->difenyletylendiamin. The synthesis of this example proceeded analogously to Example 16, in that 10.5 g (0.05 mol) of R,N<T->diphenylethylenediamine were reacted.
Utbytte: 8 g (29,4 %), smp. 59-6O0 (fra acetonitril) Analyse: C36H52<K>2°2<544.8) Yield: 8 g (29.4%), m.p. 59-6O0 (from acetonitrile) Analysis: C36H52<K>2°2<544.8)
Eksempel 165, N, N*-( p- tblylfenylacetyl)- piperazin Example 165, N,N*-(p-tblylphenylacetyl)-piperazine
30,0 g (0,2 mol) vannfritt p-tolyleddiksyre ble oppvarmet i 30.0 g (0.2 mol) of anhydrous p-tolylacetic acid was heated in
tilbakeløpskokende i J00 ml xylen og 8,6 g (0,1 mol) piperazin etter tilsetning av 0,5 g p-toluensulfonsyre under vannutskiller. Etter 48 timer avkjølte man, frasuget de utskilte krystaller og omkrystalliserte fra toluen. refluxing in 100 ml of xylene and 8.6 g (0.1 mol) of piperazine after adding 0.5 g of p-toluenesulfonic acid under a water separator. After 48 hours, the mixture was cooled, the precipitated crystals were filtered off with suction and recrystallized from toluene.
Bcsempel 166 N, N'- bis-( 5- fenoksypentanoyl)- piperazin ble fremstilt analogt Eksempel 16 av 5~fenoksypentansyre og piperasin. Eksempel 167 N, Nf- bis-( 9- undecenoyl)- 2, 5- dimetyl- piperazin kunne fås analogt Eksempel 16 av 9-undecensyre og piperazin. Example 166 N,N'-bis-(5-phenoxypentanoyl)-piperazine was prepared analogously to Example 16 from 5-phenoxypentanoic acid and piperazine. Example 167 N,Nf-bis-(9-undecenoyl)-2,5-dimethylpiperazine could be obtained analogously to Example 16 from 9-undecenoic acid and piperazine.
Eksempel 168 Example 168
N, N'- bis-( oktyloksyacetyl)- piperazinN,N'-bis-(octyloxyacetyl)-piperazine
Dette stoff ble dannet analogt Eksempel 1§ fra oktyloksyeddik-syre og piperazin. Utbytte: 72$, smp. 37-38° (petroleter) Analyse: C24<H>4<6N>2°4(426,6) This substance was formed analogously to Example 1§ from octyloxyacetic acid and piperazine. Yield: 72$, m.p. 37-38° (petroleum ether) Analysis: C24<H>4<6N>2°4(426.6)
Eksempel 169 Example 169
N, N'- bis-( N- pentanoyl- alanyl)- 2, 5- dimetylpiperazinN,N'-bis-(N-pentanoyl-alanyl)-2,5-dimethylpiperazine
ble fremstilt analogt Eksempel 16 av N-pentanoyl-alanin og 2,5-^dimetylpiperazin. was prepared analogously to Example 16 from N-pentanoyl-alanine and 2,5-β-dimethylpiperazine.
Utbytte: 28$, smp. 176-l80°C (eddikester)Yield: 28$, m.p. 176-180°C (acetic acid)
Analyse: G^H^N^ (424,5) Analysis: G^H^N^ (424.5)
Eksempel 170 Example 170
H, H'- bis-( 2- klorfenoksyacetyl)- piperazin. H,H'-bis-(2-chlorophenoxyacetyl)-piperazine.
ble fremstilt analogt Eksempel 165 av 8,6 g (0,1 mol) vannfri piperazin, 37,3 g (0,2 mol) 2-klorfenoksyeddiksyre. was prepared analogously to Example 165 from 8.6 g (0.1 mol) of anhydrous piperazine, 37.3 g (0.2 mol) of 2-chlorophenoxyacetic acid.
Utbytte: 26,4 g (62$), smp. 234-236°C (av nitrometan) Analyse: C20<H>20C12N2°4<423>3) Yield: 26.4 g ($62), m.p. 234-236°C (of nitromethane) Analysis: C20<H>20C12N2°4<423>3)
Eksempel 171- 175 (Tabell 13) "Eksempléné 17I-I75 bl®fremstilt analogt Eksempel 16, idet det blandede ahhydrid, tilberedt av 18,4 g (0,1 mol) undecylensyre, 10,1 g (0,1 mol) trietylamin og 10,8 g (0,1 mol) klormaursyreetylestér, ble omsatt med 0,05 mol av.det i Tabell 13 nevnte diamin. Dannede oljer ble renset ved søylekromato-grafi (nøytralt Al^, eluerlng med .petroleter). Eksempel 177 W , N .* - bis-( 4- N- metylanilinokarbonylbutyryl) - piperazin 4,9 g (O.O25 mol) piperazin-hexahydrat ble kokt i 300 ml sylen med 11 g (0,05 mol) 4-N-metylanilinokarbonylsmØrsyre under tilsetning av en spatelspiss p-toluensulfonsyre under vannutskiller, inntil tynnsj ikt kromat ografisk ikke mer kunne påvises utgangs-materialer (24 timer). Etter fjerning av xylen ble det ora-' krystallisert fra acetonitril. Utbytte: 5,1 g (41,5$), smp. 142-143° Analyse: C28H36N4°4 $ (492,6) Eksempel 178 N, N'- bis-( 10- undecenoyl)- 1, 2-( N, N'- dimetyl- amino)- cyklohexan Til 7,1 g (0,05 mol) 1,2-{K,N'-dimetylamino)-cyklohexan i 150 ml abs. tetrahydrofuran ble det sått 18,4 g (0,1 mol) undecylensyre. Iløpet av 30 min. ble det tildryppet 21,4 g (0,1 moi) dicyklo-héxylkarbodiimid i 100 ml abs. tetrahydrofuran. Man omrørte enda" natten over, frasuget dicyklohexylurinstoff, vasket godt med tetrahydrofuran og fjernet oppløsningmidlet. Ovennevnte residu ble kromatografert på nøytralt aluminiumoksyd, eluert med petrol eter. (forts.side 77) Examples 171-175 (Table 13) "Examples 17I-175 were prepared analogously to Example 16, in that the mixed hydride, prepared from 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine and 10.8 g (0.1 mol) of chloroformic acid ethyl ester, were reacted with 0.05 mol of the diamine mentioned in Table 13. Formed oils were purified by column chromatography (neutral Al^, elution with petroleum ether). Example 177 W , N .* - bis-(4-N-methylanilinocarbonylbutyryl)-piperazine 4.9 g (0.025 mol) of piperazine hexahydrate was boiled in 300 ml of silane with 11 g (0.05 mol) of 4-N-methylanilinocarbonylbutyric acid while adding a spatula tip of p-toluenesulfonic acid under a water separator, until starting materials could no longer be detected by thin-layer chromatography (24 hours). After removal of the xylene, it was ora-' crystallized from acetonitrile. Yield: 5.1 g (41, 5$), mp 142-143° Analysis: C28H36N4°4$ (492.6) Example 178 N,N'-bis-(10-undecenoyl)-1,2-(N,N'-dimethylamino) - cyclohexane To 7.1 g (0.05 mol) 1,2-{K,N'-dimethylamino)- cyclohexane in 150 ml abs. tetrahydrofuran, 18.4 g (0.1 mol) of undecylenic acid were added. Within 30 min. 21.4 g (0.1 moi) of dicyclohexylcarbodiimide was added dropwise in 100 ml abs. tetrahydrofuran. It was stirred again overnight, dicyclohexylurea was sucked off, washed well with tetrahydrofuran and the solvent removed. The above-mentioned residue was chromatographed on neutral aluminum oxide, eluted with petroleum ether. (cont. page 77)
Utbytte: '3.6 g (15.298),* n<22>I.4B38 Yield: '3.6 g (15.298),* n<22>I.4B38
D D
Analyse: C30H54N2°2 <474,8) Analysis: C30H54N2°2 <474.8)
Eksempel 179 N fN*- di- acetyl- N, NT- bis-( 1- cyanoetyl)- trimetylendiamin 90,0 g (0,5 mol) N,N'-bis-(1-cyanoetyl)-trimetylendiamin ble oppløst i eter og man tildryppet 112,2 g (1,1 mol) acetanhydrid. Etter henstand natten over ble flyktige deler fjernet med olje-pumpe og det viskose residu ble kromatografert over aluminiumoksyd (nøytralt). Det ble eluert med petroleter/eddikester 1:1. Olje; n<22>1,4<8>45 D Analyse: ci3H20II402(2o4»2) Det som utgangsmateriale anvendte N,N<*->bis-(1-cyanoetyl)-tri-met ylendiamin fremstilles som følger: Til 74 g (1 mol) 1,3-di-amindpropan i 200 ml alkohol dryppet man under isavkjøling 142 g (2 mol) melkesyrenltril. Etter omrøring natten over ble opp-løsn ingsmidlet fullstendig fjernet. Man fikk som residu en olje. Analyse: coHi6<N>2 (l80»2) Example 179 N fN*-di-acetyl-N,NT-bis-(1-cyanoethyl)-trimethylenediamine 90.0 g (0.5 mol) N,N'-bis-(1-cyanoethyl)-trimethylenediamine was dissolved in ether and 112.2 g (1.1 mol) of acetic anhydride were added dropwise. After standing overnight, volatile parts were removed with an oil pump and the viscous residue was chromatographed over aluminum oxide (neutral). It was eluted with petroleum ether/acetic acid 1:1. Oil; n<22>1,4<8>45 D Analysis: ci3H20II4O2(2o4»2) The N,N<*->bis-(1-cyanoethyl)-trimethylenediamine used as starting material is prepared as follows: To 74 g (1 mol) of 1,3-diaminepropane in 200 ml of alcohol was added dropwise under ice cooling to 142 g (2 mol) of lactic acid nitrile. After stirring overnight, the solvent was completely removed. An oil was obtained as a residue. Analysis: coHi6<N>2 (l80»2)
Eksempel l80 Example l80
N * N *- bis-( 10- undecenoyl)- N, NT- bis-( 1- etoksvkarbonvletvl)- trimetylendiamin N * N *- bis-( 10- undecenoyl)- N, NT- bis-( 1- ethoxycarbonyl)- trimethylenediamine
Fremstillingen foregikk analogt Eksempel 12 fra l8,4 g (0,1 mol) undecylensyre, 10,1 g (0,1 mol) trietylamin, 10,8 g (0,1 mol) klormaursyreétylester og 13»7g (0,05 mol) N,N<?->bis-(1-etoksy-karbonyletyl ) -trimetylendiamin . Det dannede råprodukt ble renset ved kromatografering (AlgO^, nøytral; eluering med petroleter) . The preparation proceeded analogously to Example 12 from 18.4 g (0.1 mol) undecylenic acid, 10.1 g (0.1 mol) triethylamine, 10.8 g (0.1 mol) chloroformic acid ethyl ester and 13.7 g (0.05 mol ) N,N<?->bis-(1-ethoxy-carbonylethyl )-trimethylenediamine . The crude product formed was purified by chromatography (AlgO 4 , neutral; elution with petroleum ether).
Utbytte: 15,8 g (52$) av en olje n<21>1.4753Yield: 15.8 g ($52) of an oil n<21>1.4753
D D
Det som utgangsmateriale anvendte N,N<*->bis-(1-etoksy-karbonyletyl) -trimetylendiamin ble fremstilt som følger: 36O g (2 mol) N,N'-bis-(1-cyanoetyl)-trimetylendiamin ble lang-somt under avkjøling og omrøring dryppet i 2,3 1 konsentrert saltsyre. Deretter kokte man 6 timer under tilbakeløp, fjernet salt-syren fullstendig i vakuum, opptok residuet i metanol, frasuget det uoppløselige og inndampet igjen til tørrhet. Residuet ble opp-tatt i metanol, fejen filtrert og blandet med dietylamin til svak, basisk reaksjon. Etter henstand natten over i kjøleskap, ble det faste stoff suget fra og vasket godt med alkohol og tørket ved f0°G\Utbytte: 168 g (60$), smp. > 250°C. The N,N<*->bis-(1-ethoxy-carbonylethyl)-trimethylenediamine used as starting material was prepared as follows: 360 g (2 mol) N,N'-bis-(1-cyanoethyl)-trimethylenediamine was long- which, while cooling and stirring, is dripped into 2.3 1 concentrated hydrochloric acid. It was then boiled for 6 hours under reflux, the hydrochloric acid was completely removed in vacuo, the residue was taken up in methanol, the insoluble matter was filtered off with suction and evaporated again to dryness. The residue was taken up in methanol, the residue filtered and mixed with diethylamine to a weak, basic reaction. After standing overnight in a refrigerator, the solid was suctioned off and washed well with alcohol and dried at f0°G\Yield: 168 g (60$), m.p. > 250°C.
Den således dannede aminosyre ble oppslemmet I 1 liter abs. etanol. Ved 15-20° innførte man HCl-gass til metning. The amino acid thus formed was suspended in 1 liter of abs. ethanol. At 15-20°, HCl gas was introduced to saturation.
Etter henstand natten over fjernet man oppløsningsmidlet i vakuum, oppløste residuet i 300 ml isvann og tilsatte 800 ml eter. Ved avkjøling holder man temperaturen rundt 0°, mens man med 3°$-ig vandig NaOH-oppløsning innstilte alkalisk. Etter tilsetning av fast KgCO^til fjerning av en halvfast vandig faee, helte man av etéroppløsningen, behandlet den vandige fase enda 3 ganger med 200 ml eter, forenet eteroppløsningene , tørket godt med Na2S0^After standing overnight, the solvent was removed in vacuo, the residue was dissolved in 300 ml of ice water and 800 ml of ether was added. During cooling, the temperature is kept around 0°, while alkaline was set with a 3°$-ig aqueous NaOH solution. After addition of solid KgCO^ to remove a semi-solid aqueous phase, the ether solution was poured off, the aqueous phase was treated 3 more times with 200 ml of ether, the ether solutions were combined, dried well with Na2SO^
og destillerte. Kokepunkt 128-132°/0,6 mm. and distilled. Boiling point 128-132°/0.6 mm.
Utbytte: 79<g=>(37,4$)-; Dividend: 79<g=>(37.4$)-;
Analyse: CI3H26W2°4 (274.4) Analysis: CI3H26W2°4 (274.4)
Beregnet: C 56,9 H 9,6 N 10,2 Funnet: C 56,7 H 9,7 N 10,3 Calculated: C 56.9 H 9.6 N 10.2 Found: C 56.7 H 9.7 N 10.3
Eksempel l8l Example l8l
RtN*- bis-( dodecanoyl)- R, R'- bis-( 1- etoksykarbonyletyl)- trimetylendiamin RtN*- bis-(dodecanoyl)- R, R'- bis-(1- ethoxycarbonylethyl)- trimethylenediamine
ble fremstilt analogt Eksempel 16 resp. Eks. l8o under anvendelse av 20,0 g (0,1 mol) dodekansyre. was produced analogously to Example 16 or Ex. l8o using 20.0 g (0.1 mol) of dodecanoic acid.
Utbytte: 48 g (69$), oljen<21>I.47O<O>Yield: 48 g ($69), the oil<21>I.47O<O>
D D
Analyse: C32<H>6<0N>2°6(568,7):Analysis: C32<H>6<0N>2°6(568.7):
Beregnet: C 69,2 H 10,9 N £,5 0 15,4Calculated: C 69.2 H 10.9 N £.5 0 15.4
Funnet: C 69,6 H 10,6 N 4,7 0 15.4 Found: C 69.6 H 10.6 N 4.7 0 15.4
Eksempel 182 Example 182
R;, M ' - bis- ( dodecanoyl) - N yN' - bis-( 1-^ hydroksykarbonyletyl) - trimetylendiamin R;, M' - bis-( dodecanoyl) - N yN' - bis-( 1-^ hydroxycarbonylethyl) - trimethylenediamine
Til en isavkjølt og godt opprørt blanding av 21,8 g (0,1 mol) N,R'-bis-(1-hydroksykarbonyletyl)-trimetylendiamin (se Eks. l80), 250 ml av en 1 N vandig NaOH-oppløsning, 200 ml benzen og 100 ml eter dryppet man rundt 0° 48,2 g (0,22 mol) dodecansyreklorid. Etter omrøring natten over ble det surgjort, den organiske fase - ble adskilt, vasket med vann og oppløsningsmidlet fjernet. Det oljeaktige residu ble omkrystallisert fra metanol. To an ice-cooled and well-stirred mixture of 21.8 g (0.1 mol) of N,R'-bis-(1-hydroxycarbonylethyl)-trimethylenediamine (see Ex. l80), 250 ml of a 1 N aqueous NaOH solution, At around 0°, 48.2 g (0.22 mol) of dodecanoic acid chloride were added dropwise to 200 ml of benzene and 100 ml of ether. After stirring overnight it was acidified, the organic phase was separated, washed with water and the solvent removed. The oily residue was recrystallized from methanol.
[Jtbytte; 41,2 g (72,5$), smp. 36-38°.[Jtchange; 41.2 g ($72.5), m.p. 36-38°.
Analyse: . C^HgøNgOg (568,7) Analysis: . C^HgøNgOg (568.7)
Eksempel 183- 184 (Tabell 14) Example 183-184 (Table 14)
Syntesen av.disse forbindelser foregikk analogt Eksempel l8 ved omsetning av 0,05 mol av det tilsvarende amin ned 17,7 g (0,1 mol),, nonansyrekljsrid i kloroform som oppløsnings-niddel. The synthesis of these compounds proceeded analogously to Example 18 by reacting 0.05 mol of the corresponding amine with 17.7 g (0.1 mol) of nonanoic acid chloride in chloroform as a solvent.
Eksempel 185 Example 185
g~ 2- kloretyl- H, NT- bis-( nonanoyl)- etylendiamin g~ 2- chloroethyl- H, NT- bis-(nonanoyl)- ethylenediamine
2,8 g,(0,05 mol) N-p-kloretyl-etylendiamin x 2 HC1 ble oppløst i 200 ml isvann. Under avlkjøling med is tildryppet man ved 0°3amtidig 17,7 g (0,11 mol) nonansyreklorid og .2 N vandig NaOH-Dppløsning, således at oppløsningen forble nmtrent nøytral. Vatten over ble det omrørt Ved værelsetemperatur og reaksjonsproduktet ble ekstrahert med kloroform. Det ble etter vasking med rann og fjerning av oppløsningsmidlet dannet 14,6 g rått diamid. 2.8 g (0.05 mol) of N-p-chloroethyl-ethylenediamine x 2 HCl was dissolved in 200 ml of ice water. While cooling with ice, 17.7 g (0.11 mol) of nonanoic acid chloride and .2 N aqueous NaOH solution were added dropwise at 0°3, so that the solution remained practically neutral. The water above was stirred at room temperature and the reaction product was extracted with chloroform. After washing with running water and removal of the solvent, 14.6 g of crude diamide were formed.
Analyse- C22P43C1N202(403,06) Analysis- C22P43C1N202(403.06)
Eksempel l8# i M, N*- bis-( dodecanoyl)-N-( g- dodecanoyloksyetyl)- etylendiamin 10,4 g (0,1 mol) W-(3-hydroksyetyl)-etylendiamin ble oppløst i 200 ml abs. tetrahydrofuran. Etter tilsetning av 3°»3g (°»3mol) trietylamin ble det under isavkjøling tildryppet 46 g (°>3 mol) dodecansyreklorid. Etter at man enda hadde etteromrørt i 2 timer ved værelsetemperatur oppvarmet man 2 timer ved ca. 50 » avkjølte og helte I vann. Reaksjonsproduktet ble ekstrahert med kloroform. Etter vasking med vann cg inndamping til tørrhet, Example 18# in M, N*-bis-(dodecanoyl)-N-(g-dodecanoyloxyethyl)-ethylenediamine 10.4 g (0.1 mol) of W-(3-hydroxyethyl)-ethylenediamine were dissolved in 200 ml of abs. tetrahydrofuran. After the addition of 3°»3g (°»3mol) of triethylamine, 46 g (°>3mol) of dodecanoic acid chloride were added dropwise under ice-cooling. After still stirring for 2 hours at room temperature, it was heated for 2 hours at approx. 50 » cooled and poured into water. The reaction product was extracted with chloroform. After washing with water and evaporation to dryness,
ble det omkrystallisert fra ligroin og fra acetonitril. was recrystallized from naphtha and from acetonitrile.
Utbytte: 44,1 g (68$), smp. 62T64°Yield: 44.1 g ($68), m.p. 62T64°
Analyse: C4o<H>78<N>2°4(651,0)Analysis: C4o<H>78<N>2°4(651.0)
Eksempel l8' 7 Dietyleddiksyre-/ N, N *- bis-( 1, 3- dietvlacetylamino)- 2- propyléster/ Example 18' 7 Diethylacetic acid-/N,N*-bis-(1,3-diethylacetylamino)-2-propyl ester/
Til 4,5 g (0,05 mol) l,3-diamino-2-hydroksypropan i 100 ml abs. To 4.5 g (0.05 mol) of 1,3-diamino-2-hydroxypropane in 100 ml of abs.
kloroform og 16,7 g (0,165 mol) trietylamin ble det under is-avkjøling tildryppet 22,2 g (0,165 mol) dietyleddiksyreklorid. Man omrørte enda 2 timer ved værelsetemperatur og deretter enda 2 timer ved ca. 40°C. Etter avkjøling vasket man i rekkefølge chloroform and 16.7 g (0.165 mol) of triethylamine, 22.2 g (0.165 mol) of diethylacetic acid chloride were added dropwise under ice-cooling. It was stirred for another 2 hours at room temperature and then another 2 hours at approx. 40°C. After cooling, they were washed in sequence
med vann, 1 N vandig NaOH og vann. Etter fjerning av kloroform ble det omkrystallisert to ganger fra ligroin. with water, 1 N aqueous NaOH and water. After removal of chloroform, it was recrystallized twice from ligroin.
Utbytte: 12,6 g (66$), smp. II4-II5<0>Yield: 12.6 g ($66), m.p. II4-II5<0>
?Eksempel 188 N, N*- bis-( 8- dodecanoyloksyetvl)- N, N *- bis-( dodecanoyl)- etylendiamin ?Example 188 N,N*-bis-(8-dodecanoyloxyethyl)-N,N*-bis-(dodecanoyl)-ethylenediamine
7,4 g (0,05 mol) N ,N *-di-(Ø-hydroksyetyl)-etylendiamin ble opp-løst i 200 ml isvann. Etter tilsetning av 300 ml kloroform tilsatte man 20 g (0,25 mol) etznatron. Ved ca. 0° tildryppet man 44,0 g (0,2 mol) dodekansyreklorid under god omrøring. Ved is-badtemperatur ble det omrørt enda i 3.timer, og etter omrøring 7.4 g (0.05 mol) of N,N*-di-(O-hydroxyethyl)-ethylenediamine was dissolved in 200 ml of ice water. After the addition of 300 ml of chloroform, 20 g (0.25 mol) of caustic soda were added. At approx. 0°, 44.0 g (0.2 mol) of dodecanoic acid chloride were added dropwise with good stirring. At ice-bath temperature, it was stirred for a further 3 hours, and after stirring
natten over adskilte man den organiske fase ved å vaske den med vann og fjernet kloroformen i vakuum. Residuet ble omkrystallisert fra etanol og fra metanol. overnight, the organic phase was separated by washing with water and the chloroform was removed in vacuo. The residue was recrystallized from ethanol and from methanol.
Utbytte: 43,8 g (6,2$), . smp. 69<->7I<0>Yield: 43.8 g ($6.2), . m.p. 69<->7I<0>
Analyse: C54<H>104<N>2°6<<8>?7,4) Analysis: C54<H>104<N>2°6<<8>?7,4)
Eksempel 18Q- 193 Example 18Q- 193
Fremstillingen av disse eksempler foregikk analogt Eksempel 16 ved omsetning av 18,4 g (0,1 mol) undecylensyre med 0,05 mol av den angitte diamino-forbindelse over det blandede anhydrid.i tetrahydrofuran som oppløsnlngsmiddel. The preparation of these examples proceeded analogously to Example 16 by reacting 18.4 g (0.1 mol) of undecylenic acid with 0.05 mol of the specified diamino compound over the mixed anhydride in tetrahydrofuran as solvent.
Eksempel 194 N- dodecanoyl- NI- fg- decanoylaminoetyl) - piperazin Example 194 N-dodecanoyl-NI-fg-decanoylaminoethyl)-piperazine
■6,5 g (0,05 mol) R-(3-aminoetyl)-piperazin og 10,1 g (0,1 mol) trietylamin ble oppløst i 100 ml abs. kloroform. 21,8 g (0,1 mol) laurinsyreklorid ble tildryppet, oppløst i 5° ml abs. CHCl^, omrørt 1 3 timer ved værelsetemperstur og 2 timer ved 5°°c« Deretter ble det utrystet med vann, kloroformen ble fjernet og residuet ;ble omkrystallisert fra alkohol. ■6.5 g (0.05 mol) of R-(3-aminoethyl)-piperazine and 10.1 g (0.1 mol) of triethylamine were dissolved in 100 ml of abs. chloroform. 21.8 g (0.1 mol) lauric acid chloride was added dropwise, dissolved in 5° ml abs. CHCl^, stirred for 13 hours at room temperature and 2 hours at 5°°c. Then it was shaken out with water, the chloroform was removed and the residue was recrystallized from alcohol.
Utbytte: 17,7 g (72$), smp. 87-88°Yield: 17.7 g ($72), m.p. 87-88°
Analyse: C^H^N^Og (493*7)Analysis: C^H^N^Og (493*7)
Eksempel 195 .■■■'• . Example 195 .■■■'• .
N, N*- bis-( decanoyl)- 2- aminométyl- pyrrolidinN,N*-bis-(decanoyl)-2-aminomethyl-pyrrolidine
Fremstillingen foregikk analogt Eksempel 194* Det ble omsatt 5 g (0,1 mol) 2-aminoraetylpyrrolidin med 19,0 g (0,1 mol) kaprinsyreklorid. Utbytte: 11,5 g { 56.5$). smp. 55-56° (fra ligroin) Analyse: C25H48N2°2 <408,5) Eksempel 19& tø , N'- bis-(decanoyi)- 2- aminometyl- piperidin The preparation proceeded analogously to Example 194* 5 g (0.1 mol) of 2-aminoraethylpyrrolidine was reacted with 19.0 g (0.1 mol) of capric acid chloride. Yield: 11.5 g { 56.5$). m.p. 55-56° (from ligroin) Analysis: C25H48N2°2 <408.5) Example 19& tø , N'-bis-(decanoyi)-2-aminomethyl- piperidine
Denne forbindelse ble fremstilt analogt Eksempel I64 under anvendelse av 5,7 g (0,05 mol) 2-aminometyl-piperidin og 19,0g (0,1 mol) decansyreklorid. This compound was prepared analogously to Example I64 using 5.7 g (0.05 mol) of 2-aminomethylpiperidine and 19.0 g (0.1 mol) of decanoic acid chloride.
Utbytte: 9,2 g (43,6$), smp. 45-47° :.(fra litt petroleter) Analyse: C26<H>5<0N>2°2(422,6) Yield: 9.2 g ($43.6), m.p. 45-47° :.(from a little petroleum ether) Analysis: C26<H>5<0N>2°2(422.6)
Eksempel 197 N. NVbis-( 2- etyl- eb. éxanoyl)- 2- aminometyl- hexametylenimin Example 197 N.NVbis-(2-ethyl-eb.hexanoyl)-2-aminomethyl-hexamethyleneimine
fremstilles analogt .Eksempel I64 av 6,4 g (0,05 mol) 2-aminometyl-cyklohexanimin og 16,2 g (0,1 mol) etyl-propyl-eddlksyre-klorid. Etter kromatografering over aluminiumoksyd (nøytral) og eluering med petroleter ble det dannet en olje. is prepared analogously to Example I64 from 6.4 g (0.05 mol) of 2-aminomethyl-cyclohexanimine and 16.2 g (0.1 mol) of ethyl-propyl-acetic acid chloride. After chromatography over alumina (neutral) and elution with petroleum ether, an oil was formed.
Utbytte: 9,3 g (52,8$), n<2>° I.4840Yield: 9.3 g ($52.8), n<2>° I.4840
D D
Analyse: CgoH.iNgOg . (380,6)......Analysis: CgoH.iNgOg . (380.6)......
Eksempel 198 H, Nt- bis-( 2- etyl- hexanoyl)- 2- metylaminometyi- piperidin Example 198 H, Nt-bis-(2-ethyl-hexanoyl)-2-methylaminomethyl-piperidine
fremstilles analogt Eksempel 194 idet det gås ut fra 3,4 g is prepared analogously to Example 194, starting from 3.4 g
(0,026 mol) 2-metyiaminometyl-piperidin, 5,3 g (0,052 mol) trietylamin og 8,4 g'{0,052 mol) 2-etylpentansyreklorid i kloroform. Olje (etter kromatograf ering over AlgO^, nøytralt, og eluering med petroleter). (0.026 mol) of 2-methylaminomethyl-piperidine, 5.3 g (0.052 mol) of triethylamine and 8.4 g (0.052 mol) of 2-ethylpentanoic acid chloride in chloroform. Oil (after chromatography over AlgO^, neutral, and elution with petroleum ether).
Utbytte: 4,5 g (53$), n<21>I.481OYield: 4.5 g ($53), n<21>I.481O
D D
Analyse: C<g>^<H>^NgOg (380,6)Analysis: C<g>^<H>^NgOg (380.6)
Claims (1)
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DE19752515146 DE2515146A1 (en) | 1975-04-08 | 1975-04-08 | Hypolipemic carboxylic-amides - such as N-isovaleryl N,N'-bis-(10-undecenoyl) ethylene-diamine |
DE19752551483 DE2551483A1 (en) | 1975-11-17 | 1975-11-17 | Hypolipemic carboxylic-amides - such as N-isovaleryl N,N'-bis-(10-undecenoyl) ethylene-diamine |
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AU (1) | AU1271476A (en) |
DK (1) | DK164176A (en) |
FI (1) | FI760919A (en) |
FR (1) | FR2306683A1 (en) |
IL (1) | IL49352A0 (en) |
LU (1) | LU74709A1 (en) |
NL (1) | NL7603594A (en) |
NO (1) | NO761050L (en) |
PT (1) | PT64980B (en) |
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FR2642422A1 (en) * | 1988-12-22 | 1990-08-03 | Roussel Uclaf | NOVEL ACYLATED POLYAMINES, PROCESS FOR PREPARING THEM AND THEIR APPLICATION AS FUNGICIDES |
DE59005853D1 (en) * | 1989-03-03 | 1994-07-07 | Moeller Willi Ag | Carboxamides that form lipophilic complexes with magnesium ions, process for producing the lipophilic magnesium complexes and ion-selective parts. |
AU708115B2 (en) * | 1991-10-04 | 1999-07-29 | Sloan-Kettering Institute For Cancer Research | Novel potent inducers of terminal differentiation and methods of use thereof |
TWI238068B (en) | 2001-03-06 | 2005-08-21 | Kao Corp | Composition for external application |
GB0425556D0 (en) * | 2004-11-19 | 2004-12-22 | Glaxo Group Ltd | Novel compounds |
JP5406870B2 (en) * | 2010-03-11 | 2014-02-05 | 株式会社クラレ | Cross-linking agent, cross-linkable composition, cross-linked product, compound and method for producing the same |
KR101187064B1 (en) * | 2010-07-18 | 2012-09-28 | 주식회사 바이오폴리메드 | Cationic lipid, method for manufacturing the same and delivery system comprising the same |
DE102011080131A1 (en) | 2011-07-29 | 2013-01-31 | Evonik Degussa Gmbh | Low molecular weight products, and their use as reversible or permanent low temperature crosslinkers in Diels-Alder reactions |
WO2014148136A1 (en) * | 2013-03-19 | 2014-09-25 | 岐阜市 | Compound having anti-allergic activity and use of same |
WO2018198523A1 (en) * | 2017-04-28 | 2018-11-01 | 味の素株式会社 | N-acylamino acid derivative |
-
1976
- 1976-02-27 SE SE7602707A patent/SE7602707L/en unknown
- 1976-03-25 NO NO761050A patent/NO761050L/no unknown
- 1976-04-05 IL IL49352A patent/IL49352A0/en unknown
- 1976-04-06 FI FI760919A patent/FI760919A/fi not_active Application Discontinuation
- 1976-04-06 AU AU12714/76A patent/AU1271476A/en not_active Expired
- 1976-04-06 NL NL7603594A patent/NL7603594A/en unknown
- 1976-04-06 PT PT64980A patent/PT64980B/en unknown
- 1976-04-06 LU LU74709A patent/LU74709A1/xx unknown
- 1976-04-07 DK DK164176A patent/DK164176A/en unknown
- 1976-04-07 JP JP51038348A patent/JPS51127002A/en active Pending
- 1976-04-08 FR FR7610309A patent/FR2306683A1/en not_active Withdrawn
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NL7603594A (en) | 1976-10-12 |
PT64980A (en) | 1976-05-01 |
FR2306683A1 (en) | 1976-11-05 |
SE7602707L (en) | 1976-10-09 |
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FI760919A (en) | 1976-10-09 |
PT64980B (en) | 1977-09-07 |
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