NO139085B - PROCEDURE FOR THE PREPARATION OF 2-AMINO-BENZYLAMINES - Google Patents
PROCEDURE FOR THE PREPARATION OF 2-AMINO-BENZYLAMINES Download PDFInfo
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- NO139085B NO139085B NO742674A NO742674A NO139085B NO 139085 B NO139085 B NO 139085B NO 742674 A NO742674 A NO 742674A NO 742674 A NO742674 A NO 742674A NO 139085 B NO139085 B NO 139085B
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- Prior art keywords
- amino
- acid
- general formula
- dibromo
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- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title description 2
- 150000007524 organic acids Chemical class 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 7
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 6
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- -1 hydroxycyclohexyl residue Chemical group 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 235000005985 organic acids Nutrition 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 3
- GVOYKJPMUUJXBS-UHFFFAOYSA-N 2-(aminomethyl)aniline Chemical class NCC1=CC=CC=C1N GVOYKJPMUUJXBS-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 235000013832 Valeriana officinalis Nutrition 0.000 claims 1
- 244000126014 Valeriana officinalis Species 0.000 claims 1
- 235000016788 valerian Nutrition 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 9
- 238000000354 decomposition reaction Methods 0.000 description 9
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Substances OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 6
- GHUMSGGCKVMYGH-UHFFFAOYSA-N (2-amino-3,5-dibromophenyl)methanol Chemical compound NC1=C(Br)C=C(Br)C=C1CO GHUMSGGCKVMYGH-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 229940005605 valeric acid Drugs 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- QNVKOSLOVOTXKF-PFWPSKEQSA-N chembl1514634 Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 QNVKOSLOVOTXKF-PFWPSKEQSA-N 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- 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
- C07D295/04—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
I US-patenter 3.536.713 og 3.712.924 beskrives blant annet 2-amino-benzylaminer med den generelle formel I US patents 3,536,713 and 3,712,924 describe, among other things, 2-amino-benzylamines with the general formula I
hvor where
Hal betyr et klor- eller bromatom, Hal means a chlorine or bromine atom,
R^ betyr et hydrogen-, klor- eller bromatom, og R^ means a hydrogen, chlorine or bromine atom, and
R 3 betyr en hydroksycykloheksylrest, R 3 means a hydroxycyclohexyl residue,
deres fysiologisk forlikelige salter med uorganiske eller organiske syrer, og fremgangsmåter for fremstilling derav. Forbindelsene har verdifulle farmakologiske egenskaper, særlig sekretolytiske og/eller hostestillende virkninger. their physiologically compatible salts with inorganic or organic acids, and methods for their preparation. The compounds have valuable pharmacological properties, particularly secretolytic and/or antitussive effects.
Det er nu overraskende funnet at forbindelsene med den It is now surprisingly found that the connections with it
ovenstående generelle formel I kan fremstilles i gode utbytter ved følgende fremgangsmåte: the above general formula I can be prepared in good yields by the following procedure:
Omsetning av en forbindelse med den generelle formel II Reaction of a compound of the general formula II
hvor where
Hal og R-^ er som innledningsvis angitt, og Hal and R-^ are as indicated at the outset, and
R4 0<3 R5' som kan være like eller forskjellige, betyr hydrogenatomer eller organiske, acylrester, med et amin med den generelle formel III R4 0<3 R5' which may be the same or different, means hydrogen atoms or organic, acyl residues, with an amine of the general formula III
hvor where
1*2 er som innledningsvis angitt, i et oppløsningsmiddel og ved temperaturer mellom 100 og 220°C, i nærvær av en organisk syre hvis R. og betyr hydrogenatomer. 1*2 is, as indicated at the outset, in a solvent and at temperatures between 100 and 220°C, in the presence of an organic acid if R. and means hydrogen atoms.
Omsetningen utføres hensiktsmessig i et høytkokende opp-løsningsmiddel så som tetralin eller xylen ved temperaturer mellom 100 og 220°C og i nærvær av en organisk syre, som samtidig kan tjene som oppløsningsmiddel, hvis R^ og R^ betyr hydrogenatomer. Ved omsetningen kan imidlertid også et overskudd av det anvendte amin med den generelle formel III anvendes som oppløsningsmiddel. The reaction is conveniently carried out in a high-boiling solvent such as tetralin or xylene at temperatures between 100 and 220°C and in the presence of an organic acid, which can also serve as a solvent, if R^ and R^ mean hydrogen atoms. During the reaction, however, an excess of the amine used with the general formula III can also be used as a solvent.
Hvis R^ og Rj. i en forbindelse med den generelle formel If R^ and Rj. in connection with the general formula
II betyr hydrogenatomer, utføres omsetningen fortrinnsvis ved temperaturer mellom 140 og 180°C, eller hvis R^ og/eller R,, betyr acylrester, utføres omsetningen fortrinnsvis ved temperaturer mellom 120 og 190°C. II means hydrogen atoms, the reaction is preferably carried out at temperatures between 140 and 180°C, or if R^ and/or R,, means acyl residues, the reaction is preferably carried out at temperatures between 120 and 190°C.
Ved omsetningen har det som organiske syrer vist seg særlig hensiktsmessig å anvende alifatiske syrer så som eddiksyre, smørsyre, valeriansyre, trimetyleddiksyre eller kapronsyre. During the reaction, it has proven particularly appropriate to use aliphatic acids such as acetic acid, butyric acid, valeric acid, trimethylacetic acid or caproic acid as organic acids.
Som organiske acylrester, som er nevnt ovenfor som definisjon på restene R^ og R^, kommer særlig i betraktning acetyl, butyryl, benzoyl eller p-klorbenzoyl. As organic acyl residues, which are mentioned above as a definition of the residues R^ and R^, acetyl, butyryl, benzoyl or p-chlorobenzoyl come into particular consideration.
De erholdte forbindelser med den generelle formel I kan eventuelt overføres til sine fysiologisk forlikelige salter med uorganiske eller organiske syrer. Som syrer anvendes hensiktsmessig saltsyre, bromhydrogensyre, svovelsyre, fosforsyre, melke-syre, sitronsyre eller maleinsyre. The obtained compounds of the general formula I can optionally be transferred to their physiologically compatible salts with inorganic or organic acids. Suitable acids are hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, lactic acid, citric acid or maleic acid.
De som utgangsstoffer anvendte forbindelser med den generelle formel II kan fremstilles fra de tilsvarende benzyl-alkoholer, som på sin side fremstilles ved reduksjon av de tilsvarende aldehyder med natriumborhydrid, og eventuelt påfølgende acylering med de tilsvarende acylhalogenider i nærvær av pyridin, og de derved samtidig dannede estere forsepes alkalisk. De erholdte utgangsstoffer med den generelle formel II kan imidlertid også omsettes uten forutgående isolering. The compounds with the general formula II used as starting materials can be prepared from the corresponding benzyl alcohols, which in turn are prepared by reduction of the corresponding aldehydes with sodium borohydride, and possibly subsequent acylation with the corresponding acyl halides in the presence of pyridine, and thereby simultaneously formed esters are saponified alkaline. However, the obtained starting materials with the general formula II can also be reacted without prior isolation.
En utgangsforbindelse med formel II inneholder samtidig A starting compound of formula II simultaneously contains
en amino- og en hydroksylgruppe. Det er derfor overraskende at disse to grupper ikke reagerer med hverandre ved f-remgangsmåten ifølge oppfinnelsen under dannelse av tilsvarende polymerer, an amino and a hydroxyl group. It is therefore surprising that these two groups do not react with each other in the process according to the invention to form corresponding polymers,
selv om det er kjent at aromatiske aminogrupper alkyleres lettere med alkoholer enn hva tilfellet er med alifatiske aminogrupper (se Houben-Weyl, bind XI/1, side 134). although it is known that aromatic amino groups are alkylated more easily with alcohols than is the case with aliphatic amino groups (see Houben-Weyl, vol. XI/1, page 134).
Videre er det overraskende at et fremstilt sekundært Furthermore, it is surprising that a produced secondary
amin med formel I ikke overføres til et tilsvarende tertiært amin med den 2-amino-halogen-benzylalkohol med formel II som er til stede i reaksjonsblandingen, selv om 2-amino-halogen-benzylalkoholen er meget reaktiv. amine of formula I is not transferred to a corresponding tertiary amine with the 2-amino-halo-benzyl alcohol of formula II present in the reaction mixture, even though the 2-amino-halo-benzyl alcohol is very reactive.
De følgende eksempler skai tjene til å illustrere oppfinnelsen ytterligere. The following examples shall serve to further illustrate the invention.
Eksempel 1 Example 1
2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin 2- amino- 3, 5- dibromo- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine
5,8 g (0,018 mol) 2-acetylamino-3,5-dibrom-benzylalkohol omrøres sammen med 2,3 g (0,020 mol) trans-4-amino-cykloheksanol i 20 ml tetralin i 4 timer ved 175°C. Derefter inndamper man opp-løsningen ved 120°C i vannstrålevakuum, opptar residuet i eter, utryster 3 ganger med vann, tørrer den organiske fase med natriumsulfat og inndamper den til tørrhet. Residuet oppløser man i absolutt etanol, surgjør med etanolisk saltsyre og bringer 2-amino-3,5-dibrom-N-(trans-4-hydroksy-cykloheksyl)-benzylamin-hydroklorid til krystallisasjon ved tilsetning av eter. Utbytte: 4,4.g (59,0% av det teoretiske). Efter omkrystallisasjon fra absolutt etanol smelter forbindelsen ved 233-234,5°C under spaltning. 5.8 g (0.018 mol) of 2-acetylamino-3,5-dibromo-benzyl alcohol are stirred together with 2.3 g (0.020 mol) of trans-4-amino-cyclohexanol in 20 ml of tetralin for 4 hours at 175°C. The solution is then evaporated at 120°C in a water jet vacuum, the residue is taken up in ether, shaken 3 times with water, the organic phase is dried with sodium sulphate and evaporated to dryness. The residue is dissolved in absolute ethanol, acidified with ethanolic hydrochloric acid and 2-amino-3,5-dibromo-N-(trans-4-hydroxy-cyclohexyl)-benzylamine hydrochloride is brought to crystallization by addition of ether. Yield: 4.4 g (59.0% of the theoretical). After recrystallization from absolute ethanol, the compound melts at 233-234.5°C during decomposition.
Eksempel 2 Example 2
2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin , 2-amino-3,5-dibromo-N-(trans-4-hydroxy-cyclohexyl)-benzylamine,
Smeltepunkt for hydrokloridet: 233-234,5°C (spaltning). Melting point of the hydrochloride: 233-234.5°C (decomposition).
Fremstilt fra 2-diacetylamino-3,5-dibrom-benzylalkohol og trans-4-amino-cykloheksanol analogt med eksempel 1. Prepared from 2-diacetylamino-3,5-dibromo-benzyl alcohol and trans-4-amino-cyclohexanol analogously to example 1.
Eksempel 3 Example 3
2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin 2- amino- 3, 5- dibromo- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine
5,6 g (0,02 mol) 2-amino-3,5-dibrom-benzylalkohol omrøres sammen med 11,5 g (0,10 mol) trans-4-amino-cykloheksanol og 8,8 g 5.6 g (0.02 mol) of 2-amino-3,5-dibromo-benzyl alcohol are stirred together with 11.5 g (0.10 mol) of trans-4-amino-cyclohexanol and 8.8 g
(0,10 mol) smørsyre i 10 timer ved 165°C. Derefter opptar man reaksjonsoppløsningen i .eter, utryster to ganger med vann, tørrer den organiske fase med natriumsulfat og inndamper den til tørrhet. Residuet oppløser man i absolutt etanol og eter (1:1) og surgjør (0.10 mol) butyric acid for 10 hours at 165°C. The reaction solution is then taken up in ether, shaken twice with water, the organic phase is dried with sodium sulphate and evaporated to dryness. The residue is dissolved in absolute ethanol and ether (1:1) and acidified
med etanolisk saltsyre. Det krystalliserer først 1,5 g av et bi-produkt, og efter ytterligere tilsetning av eter 3,5 g (42% av det teoretiske) 2-amino-3,5-dibrom-N-(trans-4-hydroksy-cykloheksyl)-benzylamin-hydroklorid med smeltepunkt 233-234,5°C (spaltning). with ethanolic hydrochloric acid. First 1.5 g of a by-product crystallizes, and after further addition of ether 3.5 g (42% of the theoretical) 2-amino-3,5-dibromo-N-(trans-4-hydroxy-cyclohexyl) )-benzylamine hydrochloride with melting point 233-234.5°C (decomposition).
Eksempel 4 - 2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin Smeltepunkt for hydrokloridet: 233-234,5°C(spaltning). Example 4 - 2-amino-3,5-dibromo-N-(trans-4-hydroxy-cyclohexyl)-benzylamine Melting point for the hydrochloride: 233-234.5°C (decomposition).
Fremstilt fra 2-butyrylamino-3,5-dibrom-benzylalkohol og trans-4-amino-cykloheksanol analogt med eksempel 1;. Prepared from 2-butyrylamino-3,5-dibromo-benzyl alcohol and trans-4-amino-cyclohexanol analogously to example 1;.
Eksempel 5 Example 5
2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin Smeltepunkt for hydrokloridet: 233-234,5°C (spaltning). Fremstilt fra 2-p-klorbenzoylamino-3,5-dibrom-benzylalkohol og trans-4-amino-cykloheksanol analogt med eksempel 1. 2- amino- 3, 5- dibromo- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point for the hydrochloride: 233-234.5°C (decomposition). Prepared from 2-p-chlorobenzoylamino-3,5-dibromo-benzyl alcohol and trans-4-amino-cyclohexanol analogously to example 1.
Eksempel 6 Example 6
2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin Smeltepunkt for hydrokloridet: 233-234,5°C (spaltning). Fremstilt fra 2-amino-3,5-dibrom-benzylalkohol, trans-4-amino-cykloheksanol og eddiksyre analogt med eksempel 3. 2- amino- 3, 5- dibromo- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point for the hydrochloride: 233-234.5°C (decomposition). Prepared from 2-amino-3,5-dibromo-benzyl alcohol, trans-4-amino-cyclohexanol and acetic acid analogously to example 3.
Eksempel 7 Example 7
2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin Smeltepunkt for hydrokloridet: 233-234,5°C (spaltning). Fremstilt fra 2-amino-3,5-dibrom-benzylalkohol, trans-4-amino-cykloheksanol og valeriansyre analogt med eksempel 3. 2- amino- 3, 5- dibromo- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point for the hydrochloride: 233-234.5°C (decomposition). Prepared from 2-amino-3,5-dibromo-benzyl alcohol, trans-4-amino-cyclohexanol and valeric acid analogously to example 3.
Eksempel 8 Example 8
2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin Smeltepunkt for hydrokloridet: 233-234,5°C (spaltning). Fremstilt fra 2-amino-3,5-dibrom-benzylalkohol, trans-4-amino-cykloheksanol og kapronsyre analogt med eksempel 3. 2- amino- 3, 5- dibromo- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point for the hydrochloride: 233-234.5°C (decomposition). Prepared from 2-amino-3,5-dibromo-benzyl alcohol, trans-4-amino-cyclohexanol and caproic acid analogously to example 3.
Eksempel 9 Example 9
2- amino- 3, 5- dibrom- N-( trans- 4- hydroksy- cykloheksyl)- benzylamin Smeltepunkt for hydrokloridet: 233-234,5°C (spaltning). Fremstilt fra 2-amino-3,5-dibrom-benzylalkohol, trans-4-amino-cykloheksanol og trimetyleddiksyre analogt med eksempel 3. 2- amino- 3, 5- dibromo- N-( trans- 4- hydroxy- cyclohexyl)- benzylamine Melting point for the hydrochloride: 233-234.5°C (decomposition). Prepared from 2-amino-3,5-dibromo-benzyl alcohol, trans-4-amino-cyclohexanol and trimethylacetic acid analogously to example 3.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19732337334 DE2337334A1 (en) | 1973-07-23 | 1973-07-23 | Anti-tussive secretolytic 2-aminobenzylamines prepn. - by reaction of 2-acylaminobenzyl alcohols and amines |
| DE19732337363 DE2337363A1 (en) | 1973-07-23 | 1973-07-23 | Anti-tussive secretolytic 2-aminobenzylamines prepn. - by reaction of 2-acylaminobenzyl alcohols and amines |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO742674L NO742674L (en) | 1975-02-17 |
| NO139085B true NO139085B (en) | 1978-09-25 |
| NO139085C NO139085C (en) | 1979-01-03 |
Family
ID=25765536
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO742674A NO139085C (en) | 1973-07-23 | 1974-07-22 | PROCEDURE FOR THE PREPARATION OF 2-AMINO-BENZYLAMINES |
Country Status (13)
| Country | Link |
|---|---|
| JP (1) | JPS57303B2 (en) |
| AT (1) | AT331779B (en) |
| CA (1) | CA1052790A (en) |
| CH (2) | CH605614A5 (en) |
| DK (1) | DK137952C (en) |
| ES (1) | ES427622A1 (en) |
| FI (1) | FI61700C (en) |
| HU (1) | HU168702B (en) |
| NL (1) | NL7409043A (en) |
| NO (1) | NO139085C (en) |
| PL (1) | PL91508B1 (en) |
| SE (1) | SE418178B (en) |
| YU (1) | YU36917B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ2017775A3 (en) * | 2017-12-04 | 2019-08-21 | Vysoká Škola Báňská-Technická Univerzita Ostrava | Device for reducing the abrasive effects of flowing bulk material |
-
1974
- 1974-06-11 FI FI1773/74A patent/FI61700C/en active
- 1974-06-18 YU YU1705/74A patent/YU36917B/en unknown
- 1974-06-20 AT AT510374A patent/AT331779B/en active
- 1974-06-25 ES ES427622A patent/ES427622A1/en not_active Expired
- 1974-07-04 NL NL7409043A patent/NL7409043A/en not_active Application Discontinuation
- 1974-07-19 CH CH1001574A patent/CH605614A5/en not_active IP Right Cessation
- 1974-07-19 PL PL1974172883A patent/PL91508B1/pl unknown
- 1974-07-22 HU HUTO969A patent/HU168702B/hu unknown
- 1974-07-22 NO NO742674A patent/NO139085C/en unknown
- 1974-07-22 CA CA205,312A patent/CA1052790A/en not_active Expired
- 1974-07-22 JP JP8405974A patent/JPS57303B2/ja not_active Expired
- 1974-07-22 DK DK394674A patent/DK137952C/en not_active IP Right Cessation
- 1974-07-22 SE SE7409535A patent/SE418178B/en not_active IP Right Cessation
-
1977
- 1977-11-21 CH CH1420477A patent/CH620668A5/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE7409535L (en) | 1975-01-24 |
| HU168702B (en) | 1976-06-28 |
| YU36917B (en) | 1984-08-31 |
| YU170574A (en) | 1982-06-18 |
| JPS57303B2 (en) | 1982-01-06 |
| JPS5047946A (en) | 1975-04-28 |
| FI61700C (en) | 1982-09-10 |
| PL91508B1 (en) | 1977-02-28 |
| FI61700B (en) | 1982-05-31 |
| ATA510374A (en) | 1975-12-15 |
| DK137952C (en) | 1978-11-06 |
| ES427622A1 (en) | 1976-08-01 |
| NO139085C (en) | 1979-01-03 |
| DK394674A (en) | 1975-03-10 |
| NL7409043A (en) | 1975-01-27 |
| DK137952B (en) | 1978-06-12 |
| CH620668A5 (en) | 1980-12-15 |
| NO742674L (en) | 1975-02-17 |
| AT331779B (en) | 1976-08-25 |
| FI177374A (en) | 1975-01-24 |
| SE418178B (en) | 1981-05-11 |
| CA1052790A (en) | 1979-04-17 |
| CH605614A5 (en) | 1978-09-29 |
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