EP2285764A2 - Monoetherified diols of diamondoids - Google Patents
Monoetherified diols of diamondoidsInfo
- Publication number
- EP2285764A2 EP2285764A2 EP09757522A EP09757522A EP2285764A2 EP 2285764 A2 EP2285764 A2 EP 2285764A2 EP 09757522 A EP09757522 A EP 09757522A EP 09757522 A EP09757522 A EP 09757522A EP 2285764 A2 EP2285764 A2 EP 2285764A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- diamondoids
- acid
- diols
- reaction
- monoether
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000002009 diols Chemical class 0.000 title claims abstract description 47
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 239000002253 acid Substances 0.000 claims abstract description 26
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
- 125000006239 protecting group Chemical group 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 19
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims abstract description 18
- 150000001408 amides Chemical class 0.000 claims abstract description 16
- 150000001414 amino alcohols Chemical class 0.000 claims abstract description 16
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 16
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 13
- 235000019253 formic acid Nutrition 0.000 claims abstract description 13
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 11
- 150000001298 alcohols Chemical class 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 10
- 238000006434 Ritter amidation reaction Methods 0.000 claims abstract description 9
- 229960000583 acetic acid Drugs 0.000 claims abstract description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims abstract description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 8
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 48
- 238000002360 preparation method Methods 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000000460 chlorine Substances 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- ZICQBHNGXDOVJF-UHFFFAOYSA-N diamantane Chemical compound C1C2C3CC(C4)CC2C2C4C3CC1C2 ZICQBHNGXDOVJF-UHFFFAOYSA-N 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
- 238000000926 separation method Methods 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 239000007795 chemical reaction product Substances 0.000 claims description 7
- 150000002825 nitriles Chemical class 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- AMFOXYRZVYMNIR-UHFFFAOYSA-N ctk0i0750 Chemical compound C12CC(C3)CC(C45)C1CC1C4CC4CC1C2C53C4 AMFOXYRZVYMNIR-UHFFFAOYSA-N 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims 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 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 2
- 238000003776 cleavage reaction Methods 0.000 claims 1
- 238000007865 diluting Methods 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- 230000001376 precipitating effect Effects 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- -1 amino, hydroxy Chemical group 0.000 abstract description 25
- 125000000524 functional group Chemical group 0.000 abstract description 16
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 3
- 239000001117 sulphuric acid Substances 0.000 abstract 2
- 235000011149 sulphuric acid Nutrition 0.000 abstract 2
- 125000004423 acyloxy group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 19
- 238000004611 spectroscopical analysis Methods 0.000 description 18
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 17
- 238000004566 IR spectroscopy Methods 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 16
- 238000002844 melting Methods 0.000 description 16
- 230000008018 melting Effects 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- YOKBFUOPNPIXQC-UHFFFAOYSA-N anti-tetramantane Chemical compound C1C(CC2C3C45)CC6C2CC52CC5CC7C2C6C13CC7C4C5 YOKBFUOPNPIXQC-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 229910003460 diamond Inorganic materials 0.000 description 5
- 239000010432 diamond Substances 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 239000002274 desiccant Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000026030 halogenation Effects 0.000 description 4
- 238000005658 halogenation reaction Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 2
- KTPSMOFJKGGNKP-UHFFFAOYSA-N 3-(2,2,2-trifluoroethoxy)adamantan-1-ol Chemical compound C1C(C2)CC3CC1(O)CC2(OCC(F)(F)F)C3 KTPSMOFJKGGNKP-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 239000007848 Bronsted acid Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical class CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009435 amidation Effects 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000002704 decyl group Chemical class [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000003438 dodecyl group Chemical class [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000003187 heptyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004051 hexyl group Chemical class [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- VHRYZQNGTZXDNX-UHFFFAOYSA-N methacryloyl chloride Chemical compound CC(=C)C(Cl)=O VHRYZQNGTZXDNX-UHFFFAOYSA-N 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 238000004377 microelectronic Methods 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000001400 nonyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002347 octyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000003509 tertiary alcohols Chemical class 0.000 description 2
- HETFMJQWNWIBPN-MDZDMXLPSA-N (e)-undec-2-enenitrile Chemical compound CCCCCCCC\C=C\C#N HETFMJQWNWIBPN-MDZDMXLPSA-N 0.000 description 1
- PRJMANGDYDEYMM-UHFFFAOYSA-N 2-aminoadamantan-1-ol Chemical class C1C(C2)CC3CC1C(N)C2(O)C3 PRJMANGDYDEYMM-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical class CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- VXCUURYYWGCLIH-UHFFFAOYSA-N Dodecanenitrile Chemical compound CCCCCCCCCCCC#N VXCUURYYWGCLIH-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- RFFFKMOABOFIDF-UHFFFAOYSA-N Pentanenitrile Chemical compound CCCCC#N RFFFKMOABOFIDF-UHFFFAOYSA-N 0.000 description 1
- 150000007960 acetonitrile Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- MOLCWHCSXCKHAP-UHFFFAOYSA-N adamantane-1,3-diol Chemical compound C1C(C2)CC3CC1(O)CC2(O)C3 MOLCWHCSXCKHAP-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- WOLHOYHSEKDWQH-UHFFFAOYSA-N amantadine hydrochloride Chemical compound [Cl-].C1C(C2)CC3CC2CC1([NH3+])C3 WOLHOYHSEKDWQH-UHFFFAOYSA-N 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- SVPZJHKVRMRREG-UHFFFAOYSA-N cyclopentanecarbonitrile Chemical compound N#CC1CCCC1 SVPZJHKVRMRREG-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- HBZDPWBWBJMYRY-UHFFFAOYSA-N decanenitrile Chemical compound CCCCCCCCCC#N HBZDPWBWBJMYRY-UHFFFAOYSA-N 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000006251 dihalogenation reaction Methods 0.000 description 1
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
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- 125000002883 imidazolyl group Chemical group 0.000 description 1
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- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
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- 230000000873 masking effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
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- 238000006386 neutralization reaction Methods 0.000 description 1
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- 239000003208 petroleum Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
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- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 125000001935 tetracenyl group Chemical group C1(=CC=CC2=CC3=CC4=CC=CC=C4C=C3C=C12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/09—Preparation of ethers by dehydration of compounds containing hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/42—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/44—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton bound to carbon atoms of the same ring or condensed ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/52—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups or amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/46—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C229/50—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups and carboxyl groups bound to carbon atoms being part of the same condensed ring system
-
- 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
- C07C233/16—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 singly-bound oxygen atoms
- C07C233/23—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 singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/18—Ethers having an ether-oxygen atom bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C43/196—Ethers having an ether-oxygen atom bound to a carbon atom of a ring other than a six-membered aromatic ring containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/90—Ring systems containing bridged rings containing more than four rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- the present invention describes functionalized diols of the diamondoids in which one of the two hydroxy groups is masked by a protecting group, as well as methods for the preparation of these functionalized diols.
- the protecting group is a group -CHR 1 R 2 where R 1 is an alkyl group and R 2 is hydrogen or an alkyl group.
- the protecting group contains at least one halogen atom, preferably fluorine.
- the monoetheretherated diols allow the targeted production of derivatives of the diamondoids, for example the corresponding amino alcohols and aminocarboxylic acids.
- the present invention relates to functionalized diamondoids.
- These are monoetheretherated diols of the diamondoids, which may optionally have, in addition to the ether and the hydroxy group, further covalently bonded functional groups.
- Diamondoids are cage-like substituted and unsubstituted adamantane series compounds.
- the adamantane series includes adamantane, diamantane, triamane, tetramantane, pentamantane, hexamantane, heptamantane, octamantane, nomen- namane, decamantane, undecamantane and similar compounds as well as all isomers and stereoisomers.
- These compounds have a diamondoid topology, i.
- the arrangement of their carbon atoms can be aligned with a fragment of a FCC diamond lattice.
- higher diamondoids refers to all substituted and unsubstituted tetramantanes, pentamantanes, hexamantanes, heptamantanes, octamantanes, nonamantanes, decamantanes, undecamantanes, etc., and their isomers and stereoisomers.
- Adamantane is the smallest member of the Diamantoid series and consists of a single cage structure of the diamond crystal lattice.
- Diamantan consists of two Adamantane subunits condensed over the faces, triamantane of three, tetramantane of four, etc. While there is only one isomeric form of adamantane, diamantane, and triamantane, there are already four isomers of tetramantane, two of which form an enantiomeric pair. ie, four different possible arrangements of the adamantane subunits. The number of possible isomers increases nonlinearly with each higher member of the diamondoid series.
- adamantane subunits From five adamantane subunits, i. from pentamantane, structures with different molecular formulas exist for a given number of adamantane subunits. These different molecular formulas result from special arrangements of the adamantane subunits.
- the four different structures of the tetramantane are isotetramantanes [1 (2) 3], anti-tetramantanes [121] and the two enantiomeric skew tetramantanes [123]. All four tetramantanes have the molecular formula C22H28 (molecular weight 292).
- pentamantanes There are ten different pentamantanes, of which nine have the molecular formula C 26 H 32 (molecular weight 344). Among these nine pentamantanes, there are three pairs of enantiomers generally depicted as [12 (1) 3)], [1234] and [1213], with the remaining three pentamantanes containing [12 (3) 4], [1212] and [1 (2,3) 4]. Furthermore, there is a pentamantane [1231] with the molecular formula C25H30 (molecular weight 330).
- Hexamantanes can be present in thirty-nine possible structures, of which twenty-eight have the molecular formula C 30 H 36 (molecular weight 396). Ten hexamantanes have the molecular formula C 2 gH 34 (molecular weight 382), and the remaining hexamantane [13212] has the molecular formula C 26 H 30 (molecular weight 342). It is postulated that heptamantanes can be present in 160 possible structures, of which 85 have the molecular formula C 34 H 40 (molecular weight 448) and of which seven are achiral.
- Octamantanes have eight adamantane subunits and exist in structures with five different molecular weights. Of the octamantanes, 18 have the molecular formula C 43 H 38 (molecular weight 446). Octamantanes also have the empirical formulas C 38 H 44 (molecular weight 500), C 37 H 42 (molecular weight 486), C 36 H 40 (molecular weight 472) and C 33 H 36 (molecular weight 432).
- the nonamantanes have six families with different molecular weights and the following structural formulas: C 42 H 48 (molecular weight 552), C 4 -IH 46 (molecular weight 538), C 40 H 44 (molecular weight 498), C 37 H 40 (molecular weight 484 ) and C 34 H 36 (molecular weight 444).
- the decamantans have seven families with different molecular weights. Among the decamantanes there is a single compound with the molecular formula C 35 H 36 (molecular weight 456) which is structurally compact compared to the other decamantanes.
- the other families of decamantane have the following molecular formulas: C 46 H 52 (molecular weight 604), C 45 H 50 (molecular weight 590), C 44 H 48 (molecular weight 576), C 42 H 46 (molecular weight 550), C 41 H 44 (Molecular weight 536) and C 38 H 40 (molecular weight 496).
- Undecamantans have families of eight different molecular weights. Among the undecanantanes there are two compounds with the sum formal C 39 H 40 (molecular weight 508), which are structurally compact compared to the other undecamantanes.
- the other undecamantane families have the following molecular formulas: C 4 -
- diamondoids are found in petroleum, natural gas and other materials rich in hydrocarbon compounds. Among the naturally occurring diamondoids are also alkyl-substituted compounds.
- Diamantoids are of interest as starting materials for microelectronics, pharmacy, nanotechnology and materials science. Potential applications of diamondoids and their derivatives include, for example, the production of temperature-stable plastics, coatings with tailored conductivities for LEDs and transistors, nanoelectronics, and their use in pharmaceuticals against viral and neurodegenerative diseases.
- diamantanes having hydroxyl, carbonyl, carboxyl, amino and / or aminocarbonyl groups, since they are important intermediates for the preparation of oligomeric and polymeric diamantanes.
- the abovementioned functional groups can be substituted by other functional groups, so that substituted diamantanes in this way represent important starting materials for the preparation of further substituted diamantanes.
- WO 00/342141 A1 describes aminohydroxyadamantane derivatives and their use as dipeptidyl peptidase IV inhibitors, for example for the treatment of diabetes.
- the methods presented for the preparation of these adamantane deities do not permit, in the case of two identical functional groups, only one of them to be converted into another functional group.
- WO 2007/069656 A1 describes a process for preparing a polymerizable hydroxydiamantyl ester compound.
- a 4,9-Diamantandiol prepared by dihalogenation and subsequent hydrolysis with water.
- the 4,9-diamondediol is esterified with a mixture of an unsaturated carboxylic acid and an anhydride of an unsaturated carboxylic acid in the presence of a polymerization inhibitor and an acidic catalyst
- halogen niches are used, a haloalkanoyl group is introduced, which is then split off again by reaction with thiourea.
- tertiary alcohols can be converted into the corresponding tertiary amino compounds, see A Jirgensons, V Kauss, I KaIvinsh, MR Gold: "A Practical Synthesis of tert-Alkylamines via the Ritter Reaction with Chloroacetonitriles.” Synthesis 2000, 12, 1709-1712.
- US 2002/0177743 A1 describes derivatives of higher diamondoids which have one or two polymerisable functional groups, as well as intermediates which are useful for the synthesis of the polymerizable higher diamondoids.
- Both the intermediates and the polymerizable higher diamondoids include, for example, derivatives having hydroxyl, amino and carbonyl functions. Also, production methods for substituted higher diamondoids are proposed. However, all of the processes proposed in US 2002/0177743 A1 use educt mixtures, so that product mixtures are formed. The processes proposed in this document would also yield product mixtures when using pure starting materials, and it is not possible to introduce certain functional groups in a regio- and / or stereoselective manner.
- EP 1 453 777 B1 describes similar functionalized higher diamond oxides as described in US 2002/0177743 A1.
- EP 1 453 777 B1 states that diamondoids react in nucleophilic substitutions to S N 1, resulting in stable diamondoid carbocations. Such stable diamondoid carbocations can be generated, for example, from hydroxylated diamondoids.
- " Eur J Org Chem 2007, 4738-4745 describes how diamondoids react to the corresponding nitroxylated derivatives. The nitroxy groups can then be converted into hydroxy groups.
- halogenation is usually a bromination. Therefore, production methods are desirable in which the smallest possible number of different products is produced and the least possible without bromination (or generally without halogenation). Preferred are those processes in which only a single substance is produced as the main product.
- the present invention for the first time provides derivatives of diamondoids which have two hydroxy groups, one of which is masked by a protective group.
- the derivatives of the diamondoids according to the invention therefore permit the selective conversion of one hydroxy group into another functional group, with the second, masked hydroxy group subsequently being released again and optionally subsequently being converted into another functional group as well.
- the object of the present invention is to provide functionalized diols of the diamondoids in which one of the two hydroxyl groups is masked by a protective group, and to provide processes for their preparation.
- R 1 is a linear or branched alkyl group -C n H p X q ,
- n is a natural number from 1 to 25,
- ⁇ p is an integer between O and 50 and q is a natural number between 1 and 51, ⁇ and the sum of q and p (2n + 1) gives,
- R 2 is hydrogen or a linear or branched alkyl group -C m H 1 -X 3 ,
- n is a natural number from 1 to 25,
- ⁇ r and s are integers between 0 and 51, ⁇ and the sum of r and s (2m + 1) gives,
- X is a halogen selected from fluorine, chlorine or bromine
- R 3 , R 4 , R 5 and R 6 independently of one another represent hydrogen, a linear or branched alkyl group having 1 to 20 carbon atoms, a cyclic alkyl group having 3 to 20 carbon atoms, an aryl group having 6 to 18 carbon atoms, a heteroaryl group having 5 to 18 ring atoms, of which 1 or 2
- Atoms are heteroatoms selected from nitrogen, oxygen,
- Sulfur, and the remaining ring atoms are carbon atoms.
- R 1 and R 2 are defined as described above.
- diamondoid refers to the substituted and unsubstituted caged compounds of the adamantane series described at the beginning, ie it comprises, for example, but not exhaustively substituted and unsubstituted adamantane, diamantane, theamantane, tetramantane, pentamantane, hexamantane, heptamantane, Octamantane, nonamantane, decamantane, undecamantane, etc.
- Substituted diamondoids carry substituents R 3 , R 4 , R 5 and R 6 according to formula (I). "Diamondoid” or “diamondoids” further includes homologous, analogous and isomeric compounds.
- “Homologous” diamondoids are understood to mean a series of compounds which can be represented by a general empirical formula and in which a compound of this series from the previous substance is formed by "adding" another "chain member.”
- the chain link is formally a C 4 H 4 unit: formally adamantane is obtained by adding a C 4 H 4 unit diamantane, then by adding a C 4 H 4 unit thamantane, etc.
- “Analogous” diamondoids are compounds with the same number of adamantane subunits, but different molecular formulas and different molecular weights Analogs, as described above, exist for diamondoids containing at least five adamantane subunits, ie, from pentamantane.
- “Isomeric” diamondoids in the sense of the present invention have the same empirical formula but a different arrangement of the adamantane subunits and / or the substituents R 3 , R 4 , R 5 and R 6 .
- “Lower diamondoids” are understood to mean all substituted and / or unsubstituted adamantanes, diamantanes and triamantanes and their derivatives and isomers Substituted and / or unsubstituted tetramantanes, pentamantanes, hexamantanes, heptamantanes, octamantanes, nonamantanes, decamantanes, undecamantanes (elev Adamantane subunits) and all other diamondoids containing more than eleven adamantane subunits and their derivatives, analogs and isomers are referred to as "higher diamondoids”.
- the present invention relates to all lower, higher, substituted, unsubstituted, homologous, analogous and / or isomeric diamondoids according to the above definitions.
- substituents R 3 , R 4 , R 5 and R 6 are bonded to the functionalized diols of the diamondoids according to the invention. These substituents are, as defined above, independently of one another hydrogen, a linear or branched alkyl group, a cyclic alkyl group, an aryl or a heteroaryl group.
- each of these alkyl groups independently contains 1 to 20 carbon atoms.
- These alkyl groups are, for example, methyl, ethyl, n-propyl, isopropyl, 1-butyl, 2-butyl, tert-butyl, 1-pentyl, 2-pentyl, 3-pentyl, 3-methylbutyl, 2,2-dimethylpropyl, and all isomers of hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl.
- R 3 , R 4 , R 5 and / or R 6 are a cyclic alkyl group having 3 to 20 carbon atoms, this is preferably selected from cyclopentyl, cyclohexyl, cycloheptyl.
- R 3 , R 4 , R 5 and / or R 6 is an aryl group having 6 to 18 carbon atoms, it is selected from phenyl, naphthyl, anthracenyl, phenanthrenyl, tetracenyl.
- R 3 , R 4 , R 5 and / or R 6 may further be a heteroaryl group having from 5 to 18 ring atoms, of which 1 or 2 atoms are heteroatoms selected from nitrogen, oxygen and sulfur, which include the remaining ring atoms are carbon atoms.
- the heteroaryl group is selected from furanyl, benzofuranyl, isobenzofuranyl, pyrrolyl, indolyl, isoindolyl, thiophenyl, benzothiophenyl, benzo [c] thiophenyl, imidazolyl, benzimidazolyl, pyrazolyl, indazolyl, oxazolyl, benzoxycolyl, isoxazolyl, benzisoxazolyl, thiazolyl, benzothiazolyl, pyridinyl , Quinolinyl, isoquinolinyl, pyrazinyl, quinoxalinyl, acridinyl, pyrimidinyl, quinazolinyl, pyridazinyl, cinnolinyl.
- R 1 is a linear or branched alkyl group -C n H p X q .
- n is a natural number from 1 to 25
- p is an integer between 0 and 50
- q is a natural number between 1 and 51.
- the sum of p and q is (2n + 1).
- R 2 is hydrogen or a linear or branched alkyl group -C m H 1 -X 3 .
- m is a natural number from 1 to 25, and r and s are integers between 0 and 51. The sum of r and s is (2m + 1).
- the halogen atom X in R 1 and R 2 is selected from fluorine, chlorine and bromine.
- R 1 is formally an alkyl group -C n H 2n + I, in which at least one and at most all hydrogen atoms are replaced by a halogen atom X.
- R 2 is an alkyl group -C m H 2 m + i, in which no one to all hydrogen atoms are replaced by a halogen atom X, unless R 2 is a hydrogen atom.
- R 1 or R 2 are at least monohydrogenated and perhalogenated alkyl groups -C n H 2n + I or -C m H 2m + 1 , these are, for example, halogenated methyl groups as defined above. , Ethyl, n-propyl, isopropyl, 1-butyl, 2-butyl, tert-butyl, 1-pentyl, 2-pentyl, 3-pentyl, 3-methylbutyl, 2, 2-dimethylpropyl groups and to all isomers of the above definition halogenated hexyl, heptyl, octyl, nonyl, decyl, decode, and dodecyl groups. Analogously, R 2 may also be the corresponding non-halogenated alkyl groups.
- n and m are natural numbers between 1 and 25.
- the protective group -CHR 1 R 2 according to the invention therefore contains at least two and a maximum of 26 carbon atoms.
- R 1 or R 2 can only be branched if n or m is at least equal to 3.
- the halogen atom X is fluorine.
- radicals R 3 and R 4 each represent a hydrogen atom and the radicals R 5 and R 6 each represent a linear or branched alkyl group having 1 to 20 carbon atoms.
- R 3 and R 4 are hydrogen and R 5 and R 6 are identical.
- R 5 and R 6 are identical.
- R 5 and R 6 are a linear or branched alkyl group having 1 to 20 carbon atoms.
- the functionalized diols of the diamondoids according to the invention are compounds in which the protective group of the formula (II)
- the protecting group of the formula (II) contains a total of 2 to 12 carbon atoms, and the halogen atom X is fluorine.
- protecting groups -CHR 1 R 2 selected from -O-CH 2 -CF 3 , -O-CH 2 -CF 2 H, -O-CH 2 -CF 2 -CF 3 , -O-CH 2 - CF 2 -CF 2 H, -O-CH- (CF 3 ) 2 , -O-CH 2 - (CF 2 ) 2 -CF 3 , -O-CH 2 - (CF 2 ) 2 -CF 2 H, - O-CH 2 - (CF 2 ) 3 -CF 3 , -O-CH 2 - (CF 2 ) 3 -CF 2 H.
- the functionalized diols of the diamondoids according to the invention are prepared by reacting a diamondoid diol (III) with a halogenated alcohol (IV) in the presence of a Bronsted or Lewis acid catalyst according to
- R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined above.
- the process according to the invention for the preparation of the functionalized diols of the diamondoids comprises the following steps: a) mixing a diamondoid diol DR 3 R 4 R 5 R 6 (OH) 2 with a halogenated alcohol CHOHR 1 R 2 , where D, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined above, b) adding a catalyst acid, c) stirring at -20 ° C to 100 ° C, d) terminating the reaction by adding an amine or water, e ) Isolating the crude end product, f) purifying the crude end product.
- the mixing ratio of diamondoid diol and halogenated alcohol plays no role in the success of the reaction, ie for the successful formation of the monoether according to the invention. Accordingly, the mixture of diamondoid diol and halogenated alcohol may be concentrated or dilute solutions or suspensions.
- Fluorinated alcohols are preferably used, for example HO-CH 2 -CF 3 , HO-CH 2 -CF 2 H, HO-CH 2 -CF 2 -CF 3 , HO-CH 2 -CF 2 -CF 2 H, HO-CH - (CF 3 ) 2 , HO-CH 2 - (CF 2 ) 2 -CF 3 , HO-CH 2 - (CF 2 ) 2 -CF 2 H, HO-CH 2 - (CF 2 ) 3 -CF 3 , HO-CH 2 - (CF 2 ) S -CF 2 H.
- the use of fluorinated alcohols is particularly advantageous because of their low boiling points compared to the non-fluorinated analogs.
- catalyst acid a Bronsted or Lewis acid is selected.
- Suitable catalyst acids are, for example, CF 3 SO 3 H and p-toluenesulfonic acid. It will be advantageous 10 ⁇ 5 vol% to 10% by volume of catalyst acid, preferably about 0.1% by volume, based on the volume of the solution of the diamondoid diol added.
- reaction mixture After addition of the catalyst acid, the reaction mixture is stirred at about -20.degree. C. to 100.degree. Preferred is a reaction temperature of 25 ° C to about 40 ° C.
- Halogenated alcohols are compounds HO-CHR 1 R 2 , which according to the above definition of the protecting group -CHR 1 R 2, at least one halogen atom X selected from fluorine, chlorine and bromine.
- higher diamondoids are more reactive than their lower homologues and analogues in terms of the required reaction time and temperature.
- OH groups are more reactive in medial positions of the diamondoid than in apical ones.
- the etherification reaction between diamondoid diol and halogenated alcohol can be terminated by adding an amine or by adding water.
- an amine By adding an amine, the catalyst acid is neutralized.
- Suitable amines are, for example, thethylamine and diisopropylethylamine (DIPEA).
- DIPEA diisopropylethylamine
- reaction can be stopped by adding water.
- crude end product is isolated by extraction from the reaction mixture, for example with chloroform.
- the crude end product is purified by methods known to those skilled in the art, for example by column chromatography. Cleaning methods for diamondoid derivatives are known to those skilled in the art and may be used without departing from the scope of the claims.
- the monoethers of the diamondoids according to the invention can be used for the specific preparation of further diamondoid derivatives.
- Particularly advantageous is the Ritter reaction of the free hydroxy group with a halogenated bonklarenitril to an amide according to
- R 1 to R 6 are as defined above, R 7 is a linear, branched or cyclic alkylene group -C 1 H 2 T, wherein t is a natural number of 1 to 1 1, and Y is a halogen atom selected from fluorine , Chlorine, bromine, iodine.
- the monoether (I) is dissolved in glacial acetic acid and the halogenated nitrile is added at room temperature. Subsequently, concentrated sulfuric acid is added. The reaction is stopped by adding water. Suitable nitriles for the Ritter reaction and the required reaction conditions are known to the person skilled in the art and can be used without departing from the scope of the patent claims.
- the nitriles are selected, for example, from halogenated acetonitrile, propionitrile, butyronitrile, valeronitrile, capronitrile, heptanoic acid nitrile, octanoic acid nitrile, Nonanoic nitrile, decanoic acid nitrile, undecenonitrile, lauric acid nitrile and cyclopentanecarbonitrile. Preference is given to using chlorinated nitriles.
- the amides of the monoethers formed in this reaction are referred to below as "monoether amides".
- the monoether amides thus formed can be used to prepare amino alcohols or aminocarboxylic acids of the diamondoids.
- a hydroxy group of a diamantane diol having a protecting group -CHR 1 R 2 is masked in the first step.
- both alkanoyl groups (-OC-CF 3 and -COR 7 Y) are removed by heating with thiourea, ethanol and glacial acetic acid, and then the reaction solution is made alkaline with an aqueous alkali, for example NaOH or KOH. Finally, the crude aminoalcohol is isolated from the reaction mixture and purified. This is exemplified in Example 7 for the preparation of 4-amino-diamantane-9-ol 9 from 4-trifluoroacetoxy-9- (2-chloroacetylamino) -diamantane 8.
- aminocarboxylic acid From this amino alcohol can be produced the corresponding aminocarboxylic acid.
- the aminoalcohol is reacted with a mixture of oleum and 100% formic acid at temperatures between -20 ° C and 0 ° C.
- an alkali is added, for example, NaOH or KOH to precipitate the crude aminocarboxylic acid salt.
- the aminocarboxylic acid salt is then separated, purified and dried. It is then reacted with thionyl chloride / methanol to give the corresponding aminocarboxylic acid methyl ester. This is then isolated and purified.
- Example 10 This is exemplified in Example 10 for the preparation of 4-amino-9-diamantancarbon Vietnamese-ol 9.
- the ester By adding a strong mineral acid and heating, the ester can be saponified to give the carboxylic acid hydrochloride, which is finally separated, purified and dried, as shown in Example 11 for the preparation of 4-amino-9-diamantancarbonklarehydrochlorid 12 from 4-amino-9-diamantancarbonklamethylester 11 ,
- aminocarboxylic acids of the diamondoids can be prepared by heating a monoether amide with thiourea, ethanol and glacial acetic acid. Subsequently, the reaction solution is diluted with water and made alkaline with an alkali, for example NaOH or KOH, then the resulting monoether-amine is isolated and purified. This is exemplified in Example 4 for the preparation of 9- (2,2,2-trifluoroethoxy) -diamantane-4-amine 6 from 2-chloro-N- [9- (2,2,2-trifluoroethoxy) -diamantane. 4-yl] -acetamide 5.
- the monoether-amine is reacted with a mixture of concentrated sulfuric acid and 100% formic acid at temperatures between -20 ° C and 0 ° C.
- the mixture is then placed on ice and the amino carboxylic acid isolated and purified. This is shown by way of example in Example 5 for the reaction of 9- (2,2,2-trifluoroethoxy) diamantane-4-amine 6 to 4-amino-9-diamantane carboxylic acid 7.
- Amino alcohols and aminocarboxylic acids of the diamondoids are particularly well suited to selectively introduce other functional groups. This is below for the preparation of nitro alcohols of the diamondoids from the corresponding aminoalcohols.
- the corresponding nitro alcohols can be prepared, for example by reaction with meta-alcohols.
- Chloroperbenzoic acid mCPBA
- the protective group -CHR 1 R 2 according to the invention can be converted back into an OH group by treatment with a strong acid, for example CF 3 COOH or H 2 SO 4 , and subsequent neutralization with an alkali, for example NaOH or KOH.
- a strong acid for example CF 3 COOH or H 2 SO 4
- an alkali for example NaOH or KOH.
- the monoethers of the diamantides described in the present invention allow medicinally relevant diamondoids in a targeted manner and in higher yield and purity than hitherto.
- the monoethers according to the invention allow the electron exit behavior of the diamondoids to be controlled by targeted introduction of groups which emit good or poor electron.
- the monoethers of the invention and the process for their preparation are useful in the production of Diamantoiddehvaten for electronic components.
- Aminocarboxylic acids and aminoalcohols of the diamondoids also allow the introduction of functional groups for the polycondensation and also for the production of peptides.
- Embodiment 1 Preparation of 3- (2,2,2-trifluoroethoxy) -adamantan-1-ol
- Embodiment 5 Preparation of 4-amino-9-diamantanecarboxylic acid from 9- (2,2,2-trifluoroethoxy) diamantan-4-amine
- Embodiment 6 Preparation of 4-trifluoroacetoxy-9- (2-chloroacetylamino) -diamantane from 2-chloro- / V- [9- (2,2,2-trifluoroethoxy) -diamantan-4-yl] -acetamide
- Embodiment 7 Preparation of 4-aminodiamantan-9-ol from 4-trifluoroacetoxy-9- (2-chloroacetylamino) diamantane
- Embodiment 8 is a diagrammatic representation of Embodiment 8
- Exemplary embodiment 9 Preparation of 4-amino-9-diamantanecarboxylic acid from 4-aminodiamantan-9-ol
- Embodiment 10 is a diagrammatic representation of Embodiment 10:
- Embodiment 11 is a diagrammatic representation of Embodiment 11:
- Embodiment 13 is a diagrammatic representation of Embodiment 13:
- Embodiment 14 is a diagrammatic representation of Embodiment 14:
- Embodiment 15 is a diagrammatic representation of Embodiment 15:
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Abstract
Description
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Application Number | Priority Date | Filing Date | Title |
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DE102008027341A DE102008027341A1 (en) | 2008-06-07 | 2008-06-07 | Mono-etherified diols of the diamondoids |
PCT/EP2009/056746 WO2009147141A2 (en) | 2008-06-07 | 2009-06-02 | Monoetherified diols of diamondoids |
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EP2285764A2 true EP2285764A2 (en) | 2011-02-23 |
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EP09757522A Withdrawn EP2285764A2 (en) | 2008-06-07 | 2009-06-02 | Monoetherified diols of diamondoids |
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US (1) | US20110124912A1 (en) |
EP (1) | EP2285764A2 (en) |
DE (1) | DE102008027341A1 (en) |
WO (1) | WO2009147141A2 (en) |
Family Cites Families (6)
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WO1998040337A1 (en) * | 1997-03-11 | 1998-09-17 | Daicel Chemical Industries, Ltd. | Adamantane derivatives and process for producing them |
US6858700B2 (en) | 2001-01-19 | 2005-02-22 | Chervon U.S.A. Inc. | Polymerizable higher diamondoid derivatives |
JP2005511730A (en) | 2001-12-07 | 2005-04-28 | シェブロン ユー.エス.エー. インコーポレイテッド | Functionalized high-grade diamondoid |
EP1789380A1 (en) | 2004-07-23 | 2007-05-30 | Justus-Liebig-Universität Giessen | Amino adamantane derivatives, methods for the production and use thereof |
DE102005058357A1 (en) | 2005-12-06 | 2007-06-28 | Justus-Liebig-Universität Giessen | Process for the preparation of substituted diamantanes |
CN101321721B (en) | 2005-12-16 | 2012-05-02 | 株式会社德山 | Method for producing polymerizable hydroxydiamantyl ester compound |
-
2008
- 2008-06-07 DE DE102008027341A patent/DE102008027341A1/en not_active Withdrawn
-
2009
- 2009-06-02 EP EP09757522A patent/EP2285764A2/en not_active Withdrawn
- 2009-06-02 WO PCT/EP2009/056746 patent/WO2009147141A2/en active Application Filing
- 2009-06-02 US US12/996,399 patent/US20110124912A1/en not_active Abandoned
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DE102008027341A1 (en) | 2009-12-10 |
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WO2009147141A3 (en) | 2010-07-22 |
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