US3340305A - Method of producing aryl alkyl aminoketones - Google Patents
Method of producing aryl alkyl aminoketones Download PDFInfo
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- US3340305A US3340305A US381945A US38194564A US3340305A US 3340305 A US3340305 A US 3340305A US 381945 A US381945 A US 381945A US 38194564 A US38194564 A US 38194564A US 3340305 A US3340305 A US 3340305A
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- 238000000034 method Methods 0.000 title claims description 39
- -1 aryl alkyl aminoketones Chemical class 0.000 title description 32
- 238000006243 chemical reaction Methods 0.000 claims description 70
- 150000001875 compounds Chemical class 0.000 claims description 33
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
- 229910052794 bromium Inorganic materials 0.000 claims description 18
- 239000011541 reaction mixture Substances 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 229910000039 hydrogen halide Inorganic materials 0.000 claims description 13
- 239000012433 hydrogen halide Substances 0.000 claims description 13
- 239000006227 byproduct Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 7
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 claims description 7
- BSMGLVDZZMBWQB-UHFFFAOYSA-N 2-methyl-1-phenylpropan-1-one Chemical compound CC(C)C(=O)C1=CC=CC=C1 BSMGLVDZZMBWQB-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- HEOVGVNITGAUKL-UHFFFAOYSA-N 3-Methyl-1-phenyl-1-butanone Chemical compound CC(C)CC(=O)C1=CC=CC=C1 HEOVGVNITGAUKL-UHFFFAOYSA-N 0.000 claims description 4
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical compound CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical class Cl* 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 1
- 238000005658 halogenation reaction Methods 0.000 description 13
- 230000026030 halogenation Effects 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000007795 chemical reaction product Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000005265 dialkylamine group Chemical group 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000005576 amination reaction Methods 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 238000013021 overheating Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000011437 continuous method Methods 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- 238000007872 degassing Methods 0.000 description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000009751 slip forming Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SFCCOHHWKRVDHH-UHFFFAOYSA-N 1-(2-bromophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC=C1Br SFCCOHHWKRVDHH-UHFFFAOYSA-N 0.000 description 1
- QMOSZSHTSOWPRX-UHFFFAOYSA-N 2-bromo-2-methyl-1-phenylpropan-1-one Chemical compound CC(C)(Br)C(=O)C1=CC=CC=C1 QMOSZSHTSOWPRX-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- JACMPVXHEARCBO-UHFFFAOYSA-N n-pentylpentan-1-amine Chemical compound CCCCCNCCCCC JACMPVXHEARCBO-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/18—Stationary reactors having moving elements inside
- B01J19/1868—Stationary reactors having moving elements inside resulting in a loop-type movement
- B01J19/1875—Stationary reactors having moving elements inside resulting in a loop-type movement internally, i.e. the mixture circulating inside the vessel such that the upwards stream is separated physically from the downwards stream(s)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/80—Ketones containing a keto group bound to a six-membered aromatic ring containing halogen
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00049—Controlling or regulating processes
- B01J2219/00051—Controlling the temperature
- B01J2219/00074—Controlling the temperature by indirect heating or cooling employing heat exchange fluids
- B01J2219/00076—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements inside the reactor
- B01J2219/00083—Coils
Definitions
- the present invention relates to a method of producing aryl alkyl aminoketones, and more particularly to the halogenation of aryl alkyl ketones so as to form the corresponding aryl alkyl haloketone, and to the amination of this aryl alkyl haloketone to the corresponding aryl alkyl aminoketone.
- the present invention mainly comprises the method of reacting a compound of the formula:
- R is selected from the group consisting of hydrogen and alkyl, wherein R is selected from the group consisting of alkyl and cycloalkyl, and wherein Y is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy and halogen, with a halogen in the absence of any solvent, thereby forming the corresponding hydrogen halide and the halogenated compound of the formula:
- X is the halogen and wherein R, R and Y have the'same definitions as above, whereby the halogenated compound is formed without any contaminating resinous side products.
- the thus formed halogenated compound of the second structural formula above is directly reacted without intermediate purification with a compound selected from the group consisting of primary and secondary dialkylamines and cycloaliphatic amines so as to form the corresponding aminated compound of the formula:
- Am is selected from the group consisting of secondary and tertiary dialkylamine and cycloaliphatic amine radicals and wherein R, R and Y have the same definitions as above.
- R, R and Y have the same definitions as above 7 is continuously introduced into a closed reaction vessel as is a halogen, both in the absence of any solvent, so as to continuously form in the reaction vessel the corresponding hydrogen halide and the halogenated compound of the formula:
- R may be hydrogen or an alkyl, and when an alkyl is preferably a lower alkyl for example of up to about carbon atoms.
- the substituent R which may be an alkyl or a cycloalkyl is preferably an alkyl of about 1-10 atoms, and most preferably a lower alkyl, and when a cycloalkyl is also preferably a lower cycloalkyl.
- the primary and secondary dialkylamines and the cycloaliphatic amines with which the halogenated aryl alkyl ketones are directly reacted, without intermediate purification, in accordance with the prescent invention are preferably lower dialkylamines and cycloaliphatic amines.
- the secondary and tertiary dialkylamine and cyclealiphatic amine radicals Am are preferably lower dialkylamine and cycloaliphatic amine radicals.
- the advantages of the present invention including the advantage and possibility of carrying out the method of the invention continuously from the aryl alkyl ketone through to the aryl alkyl aminoketone result from the discovery that not only is it possible to halogenate the aryl alkyl ketone to the corresponding halogenated compound without the presence of a solvent, but that atcually when such reaction is carried out in the absence of the solvent the desired final product is produced without any contaminating resinous side products so that the halogenated compound can be directly aminated without intermediate purification.
- the formation of the reaction mixture is continuously maintained by the continuous feed of the aryl alkyl ketone and the halogen in a rarified upper zone of the reaction chamber, and the maintaining of the reaction zone below this introduction zone.
- the pumping around of the reaction mixture is effected in the reaction zone and the finished halogenation product is continuously drawn off from the reaction vessel, which is preferably also provided with an agitator.
- the halogenation product is then led to the mixing vessel wherein it is aminated by means of an equivalent or excess amount of the selected amine. As noted above, this is accomplished without any intermediate purification or separation (except for the removal of the formed hydrogen halide from the reaction vessel).
- the reaction of amination is preferably carried out in the presence of an alkali, such as an alkali metal hydroxide, which may be introduced in an excess into the animation vessel, and the resulting aminated product may be continuously sepa-- rated from the reaction mass.
- the preferred device for carrying out the method of the present invention comprises a closed reaction chamber in which a jacketed vessel of smaller diameter is ar-- ranged, the inner jacketed space of which is provided with coolants which are circulated through by means of an agitating or pumping device, while the space between the jacketed vessel and the outer wall forms a circular flow conduit. It is advantageous for the carrying out of the method of the present invention to provide the opening of the feed pipe for the ketone in the reaction vessel above the opening of the feed pipe for the halogen.
- the reaction vessel is preferably extended above the lower rim of the open inner jacket and has connections for drawing oii of the halogenation product.
- a hollow cylindrical jacket 11 is arranged in a closed reaction vessel 10, the bottom of the jacket being open to accommodate the cooling system 12 and'an agitator 13 which acts in pump fashion.
- the diameter of the hollow cylindrical jacket 11 is less than that of the reaction vessel 10' so that there is a gap 14 inside the wall of the vessel 10.
- the head of the reaction vessel 10 is provided with two feed pipes 15, 16 for the introduction of the reaction components.
- the pipe 15,which is for the introduction of the halogen has its opening below that of the opening of the pipe 16 which is used for introduction of the aryl alkyl ketone into the reaction vessel.
- the inlets of the pipes are arranged in accordance with the course of the reaction desired.
- a discharge pipe 17 is provided for discharging of the formed gaseous hydrogen halide, and a discharge pipe 18 is provided at the bottom of the reaction vessel for discharging of the finished reaction product.
- Feed and discharge pipes, respectively, 19 and 20, are provided for the coolant liquid.
- Devices for the exposure to light of the reaction mass may advantageously be arranged inside the hollow cylindrical jacket 11.
- An upper reaction zone is formed substantially in the space between the terminal openings of pipes and 16, which open at different heights in the reaction vessel 10, and maintained by the continuous feeding of the halogen through the pipe 15 and of the ketone through the pipe 16.
- This reaction zone is located, based on the desired degree of filling of the container 10, in the vicinity of the upper rim of the open cylindrical jacket 11. The reaction is continuously maintained inside the jacket 11 by continuous cooling and under the action of the pump agitator 13.
- the finished halogenation product falls in the vessel 10, to the extent that it does not flow back into the interior of the hollow cylinder 11, and is fed through the pipe 18 to the further treatment stages, and particularly to a vessel in which the halongenated reaction product is aminated.
- the mixture gives off the greater portion of the hydrogen halide formed during the reaction, and this is continuously discharged through the outlet pipe 17 of the reaction vessel.
- the finished reaction product which is substantially free of contaminating resinous side products, but which may contain some dissolved hydrogen halide, is continuously fed into a further vessel, whose feed and discharge inlets can be opened or closed by means of control magnetic valves, for examples. If it is desired to-remove any residual hydrogen halide, this is accomplished by washing out with water or degasification at higher temperatures, preferably under vacuum.
- the amination vessel into which the halogenated reaction product is then pumped is preferably likewise formed as a mixing vessel provided with an agitator mechanism.
- the reaction is continuously maintained with an equivalent or excess amount of amine which is continously fed into the vessel.
- the aminated mixture is preferably further mixed in another vessel with an alkali, for example aqueous sodium hydroxide or sodium carbonate, the amine phase being continuously separated from the aqueous phase.
- the process of the present invention permits the production of the halogenated aryl alkyl ketone without the formation of any substantial contaminating resinous side products, and in addition it permits the production of the aryl alkyl aminoketone starting from the aryl alkyl ketone in a high degree of purity without any further recrystallization.
- the aryl alkyl aminoketones can be deposited directly as salts.
- the same may be directly used without any intermediate purification, these compounds being valuable therapeutic compounds which can be used, for example, as appetite reducing agents, and the compounds can also be used as intermediates in the production of other valuable compounds.
- aryl alkyl ketones are: diethylamine, dipropylamine, dibutylamine, diamylamine, piperidine, piperazine, pyrrolidine, and morpholine.
- Example 1 39.52 kg. of propiophenone and 46.6 kg. of bromine are continuously introduced into a reaction vessel of the type described above.
- the clear dark red reaction mixture is continuously freed of the hydrogen bromide and the halogenated reaction product is reacted with 60 kg. of diethylamine under constant stirring.
- 41 kg. of 34% aqueous sodium hydroxide are continuously fed into the continuously down flowing reaction mixture, the amine phase and aqueous phase being continuously separated.
- the excess diethylamine is distilled off from the crude base and Washed with water, and the crude base thus purified is continuously distilled.
- the yield of pure base is 51.8 kg.
- the pure base can be reacted with hydrochloric acid to form the hydrogen chloride salt which melts at 172174 C.
- the chlorine content is 14.58%.
- Example 2 Example 3 2.81 kg. (5% excess) of propiophenone are introduced into a reaction vessel of the type described above provided with cooling coils and mechanical stirrer, and with hollowed blades and impeller elements. A few grams of o -bromopropiophenone, previously prepared, are added to catalyze the reaction. 3.19 kg. of bromine are slowly added under careful cooling to maintain the temperature at about 10 C.
- This phase of the operation is conducted discontinuously in order to fill the apparatus up to the point of overflow of the smaller inner vessel. Then 143.5 kg. of propiophenone and 287.8 kg. of bromine are continuously added, at the rate respectively of 0.03 mol per minute for the ketone and 0.027 mol per minute for the halogen. The bromine immediately reacts and no excss of unreacted bromine is present in the reaction mixture throughout the operation. The residence time is 2 minutes.
- Hydrogen bromide continuously formed is permitted to escape through the outlet of conduit 17.
- the oc-blOlTlO- propiophenone is continuously removed from the lower outlet and led into another vessel where it is continuously washed with water.
- the product is then distilled, giving 88% yield of pure a-bromopropiophenone.
- the direct reaction of the undistilled reaction product exhibits a considerably higher yield of about 96%.
- the above reaction can be continued by the continued addition of propiophenone and bromine in the above in dicated ratio.
- Example 4 3.108 kg. (5% excess) of n-butyrophenone are introduced into the same reaction vessel as above with the slow addition of 3.19 kg. of bromine discontinuously until the apparatus is filled to the desired level.
- 299.0 kg. of n-butyrophenone and 3.19 kg. of bromine are added to the reaction vessel in constant ratio, and the reaction product is continuously withdrawn.
- the yield of u-bromo-n-butyrophenone is above 96%, and upon distillation of the crude product a yield of the pure product is obtained in an amount of 7 90%.
- the reaction temperature is maintained by cooling at below 20 C.
- Example 3.11 kg. (5% excess) of isobutyrophenone are discontinuously reacted as in Example 4 with 3.19 kg. of bromine and then 29.9 kg. of isobutyrophenone are continuously brominated with 31.9 kg. of bromine.
- the reaction temperature is maintained between 05 C.
- the yield of a-bromo-isobutyrophenone is above 95%.
- Example 6 3.11 kg. of isobutyrophenone and 42 kg. of chlorine are reacted in the above described halogenating apparatus. There is subsequently continuously added 22.9 kg. of isobutyrophenone and 14.2 kg. of chlorine. The reaction is carried out at about 20 C. The obtained a-chloroisobutyrophenone boils under 2 mm. Hg at 76-79 C., and is so pure that it can be used without distillation.
- Example 7 3.4 kg. of isovalerophenone are reacted with 3.19 kg. of bromine and then 29.7 kg. of isovalerophenone and 28.8 kg. of bromine are continuously reacted.
- the yield of a-bromo-isovalerophenone is above 90%.
- Example 8 3.4 kg. of n-valerophenone and 3.19 kg. of bromine are introduced into the above described apparatus to fill the same, and the reaction is then continuously carried out with 29.8 kg. of n-valerophenone and 28.8 kg. of bromine. After removal of the hydrogen bromide, the oc-blOIIlO-Ilvalerophenone crystallizes out.
- the chlorination and bromination takes place on the alpha carbon of the alkyl group of the carbonyl group.
- the method which comprises continuously introducing into the upper portion of a closed reaction vessel a liquid compound selected from the group consisting of propiophenone, n-bu-tyrophenone, isobutyrophenone, nvalerophenone and isovalerophenone, and also continuously introducing into the upper portion of said reaction vessel at a level below the level of introduction of said liquid compound a halogen selected from the group consisting of chlorine and bromine, so as to form in the upper portion of said reaction vessel in a reaction zone substantially located between the levels of introduction of said compound and said halogen a reaction mixture, the latter being free of any solvent, and continuously agitating said reaction mixture and circulating the same between the upper and lower portion of the reaction vessel so as to continuously form in said reaction vessel the corresponding hydrogen halide and.
- a liquid compound selected from the group consisting of propiophenone, n-bu-tyrophenone, isobutyrophenone, nvalerophenone and isovalerophenone
- the method as defined in claim compound is propiophenone.
- reaction mixture is cooled so as to be maintained at a temperature below 20 C.
- reaction mixture is circulated in said reaction vessel so as to move downwardly through the peripheral portion of the reaction vessel and upwardly through the center portion thereof.
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Description
Sept. 5, 1967 u. J AHN METHOD OF PRODUCING ARYL ALKYL AMINOKETONES Filed July '7, 1964 wssw u United States Patent T 20 Claims. (Cl. 260592) This application is a continuation-in-part of my copending application Ser. No. 852,237, filed Nov. 12, 1959, and now abandoned, for Preparation of Aryl Alkyl Aminoketones.
The present invention relates to a method of producing aryl alkyl aminoketones, and more particularly to the halogenation of aryl alkyl ketones so as to form the corresponding aryl alkyl haloketone, and to the amination of this aryl alkyl haloketone to the corresponding aryl alkyl aminoketone.
The halogenation of aryl alkyl ketones to the corresponding halogenated compound is known, reactions to achieve this having been carried out in solvent mediums such as glacial acetic acid, water, aqueous solutions or the like. However, great difiiculties arise in carrying out this method in practice, particularly if it is attempted to use the method commercially, due to the fact that the resulting halogenated ketone is contaminated to a great extent with resinous side products. Consequently, the resulting halogenated ketone cannot directly be used for any purpose whatsoever, not even for further reaction with aminating agents, without a time consuming and expensive purification for removal of the contaminating resinous side products.
' Attempts to avoid this difliculty by increasing the ketone excess have been unsatisfactory, as have been attempts to avoid the difiiculty by increasing the amount of solvent. As a matter of fact, the use of a considerable excess of either makes the time consuming purification steps even more difldcult.
If it is attempted to use the impure halogenated ketones for reaction with amines to corresponding aminoketones, then a series of additional undesired side products is formed, which requires extremely laborious and expensive purification steps in order to try to separate the same from the desired aminoketones. If it is attempted to achieve such separation by means of distillation, this results in partial decomposition and transposition of the amines, with resultant considerable loss of desired final product. Consequently, the only practical method of puritying the resulting aminoketones is by repeated recrystallizations, which is obviously rather expensive and time consuming.
Another disadvantage of the known methods is that the same could only be carried out discontinuously, i.e. in batch processing. This is due not only to the high percentage of undesired impurities which are formed, which necessarily prevents continuous operation, but in addition, during the halogenation reaction a strong local overheating occurs in the mixing Zones, and this also makes a continuous reaction difficult. Vigorous cooling and irradiation are not advantageous because the conduction of heat from the small reaction zones, despite vigorous stirring, is relatively slow. Attempts to minimize the overheating by the addition of solvents results in an increase in the undesired resinous side products due to over halogenation and condensation and the participation of the solvent in the reaction. Furthermore, although the reaction temperature falls with further halogenation, to-
wards the close of the reaction it again rises quite sharply because of side reactions.
It is accordingly a primary object of the present invention to provide a method of halogenating aryl alkyl ketones whereby the desired halogenated compound is produced without the production of any contaminating resinous side products.
It is another object of the present invention to provide a method of producing halogenated aryl alkyl ketones of such degree of purity that the same can be directly aminated, without inter-mediate purification, to the desired aryl alkyl aminoketone.
It is yet another object of the present invention to provide a continuous method of converting aryl alkyl ketones to aryl alkyl aminoketones by way of intermediate halogenation of the aryl alkyl ketone and amination of the halogenated compound without any need for separation and/ or purification steps.
It is yet another object of the present invention to provide for the halogenation of aryl alkyl ketones in high yield, and to provide for the production of aryl alkyl aminoketones in high yield.
Other objects and advantages of the present invention will be apparent (from a further reading of the specification and of the appended claims.
With the above and other objects in view, the present invention mainly comprises the method of reacting a compound of the formula:
wherein R is selected from the group consisting of hydrogen and alkyl, wherein R is selected from the group consisting of alkyl and cycloalkyl, and wherein Y is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy and halogen, with a halogen in the absence of any solvent, thereby forming the corresponding hydrogen halide and the halogenated compound of the formula:
wherein X is the halogen and wherein R, R and Y have the'same definitions as above, whereby the halogenated compound is formed without any contaminating resinous side products.
In accordance with a further embodiment of the present invention, the thus formed halogenated compound of the second structural formula above is directly reacted without intermediate purification with a compound selected from the group consisting of primary and secondary dialkylamines and cycloaliphatic amines so as to form the corresponding aminated compound of the formula:
wherein Am is selected from the group consisting of secondary and tertiary dialkylamine and cycloaliphatic amine radicals and wherein R, R and Y have the same definitions as above.
'3 In accordance with still another embodiment of the present invention a compound of the formula:
wherein R, R and Y have the same definitions as above 7 is continuously introduced into a closed reaction vessel as is a halogen, both in the absence of any solvent, so as to continuously form in the reaction vessel the corresponding hydrogen halide and the halogenated compound of the formula:
wherein Am, R, R and Y have the same definitions as above, and the thus formed aryl alkyl aminoketone is continuously recovered. Thus, according to this embodiment of the present invention the aryl alkyl aminoketone can be continuously formed and recovered from the aryl alkyl ketone.
Despite the fact that it would ordinarily be assumed that the attempts to carry out a discontinuous process in a continuous manner would result in the same difficulties as the continuous process, however to an even higher degree, by making the changes in the overall process which have been described above, it is most surprising to find that it is possible in accordance with the present invention to continuously produce aryl alkyl aminoketones in greater yield and far more simply than could be achieved by the older known processes.
It is advantageous in carrying out the continuous method of the present invention to pump the reaction mixture around in the cooled interior of a jacketed vessel under the action of light, and to discharge the halogenation product at the outside of the jacketed vessel.
The preferred halogens in carrying out the halogenation reaction of the present invention are bromine and chlorine. In the formulae above R may be hydrogen or an alkyl, and when an alkyl is preferably a lower alkyl for example of up to about carbon atoms. The substituent R which may be an alkyl or a cycloalkyl is preferably an alkyl of about 1-10 atoms, and most preferably a lower alkyl, and when a cycloalkyl is also preferably a lower cycloalkyl.
The primary and secondary dialkylamines and the cycloaliphatic amines with which the halogenated aryl alkyl ketones are directly reacted, without intermediate purification, in accordance with the prescent invention are preferably lower dialkylamines and cycloaliphatic amines. Thus, the secondary and tertiary dialkylamine and cyclealiphatic amine radicals Am are preferably lower dialkylamine and cycloaliphatic amine radicals. As is clear from the above, the advantages of the present invention, including the advantage and possibility of carrying out the method of the invention continuously from the aryl alkyl ketone through to the aryl alkyl aminoketone result from the discovery that not only is it possible to halogenate the aryl alkyl ketone to the corresponding halogenated compound without the presence of a solvent, but that atcually when such reaction is carried out in the absence of the solvent the desired final product is produced without any contaminating resinous side products so that the halogenated compound can be directly aminated without intermediate purification.
It has been found that in practical carrying forth of this method in technical, commercialyield, that it is best to do the same in apparatus specially designed therefor. Such apparatus, which will be described in greater detail below, permits the utilization of certain processing expedients which provide further advantages in carrying out the method of the present invention.
Thus, in accordance with the method of the invention, the formation of the reaction mixture is continuously maintained by the continuous feed of the aryl alkyl ketone and the halogen in a rarified upper zone of the reaction chamber, and the maintaining of the reaction zone below this introduction zone. The pumping around of the reaction mixture is effected in the reaction zone and the finished halogenation product is continuously drawn off from the reaction vessel, which is preferably also provided with an agitator.
The halogenation product is then led to the mixing vessel wherein it is aminated by means of an equivalent or excess amount of the selected amine. As noted above, this is accomplished without any intermediate purification or separation (except for the removal of the formed hydrogen halide from the reaction vessel). The reaction of amination is preferably carried out in the presence of an alkali, such as an alkali metal hydroxide, which may be introduced in an excess into the animation vessel, and the resulting aminated product may be continuously sepa-- rated from the reaction mass.
The preferred device for carrying out the method of the present invention comprises a closed reaction chamber in which a jacketed vessel of smaller diameter is ar-- ranged, the inner jacketed space of which is provided with coolants which are circulated through by means of an agitating or pumping device, while the space between the jacketed vessel and the outer wall forms a circular flow conduit. It is advantageous for the carrying out of the method of the present invention to provide the opening of the feed pipe for the ketone in the reaction vessel above the opening of the feed pipe for the halogen. The reaction vessel is preferably extended above the lower rim of the open inner jacket and has connections for drawing oii of the halogenation product.
The novel features which are considered characteristic for the invention are set forth in particular in the appended claims. The invention itself, however, both as to its method of operation and apparatus then may be used in advantageously carrying out the method, together with additional objects and advantages of the invention, would be best understood from the following description of the single figure of the drawing, described in'connc ction with the carrying out of the method of the present invention.
Referring more particularly to the drawing, a hollow cylindrical jacket 11 is arranged in a closed reaction vessel 10, the bottom of the jacket being open to accommodate the cooling system 12 and'an agitator 13 which acts in pump fashion. The diameter of the hollow cylindrical jacket 11 is less than that of the reaction vessel 10' so that there is a gap 14 inside the wall of the vessel 10. The head of the reaction vessel 10 is provided with two feed pipes 15, 16 for the introduction of the reaction components. The pipe 15,which is for the introduction of the halogen has its opening below that of the opening of the pipe 16 which is used for introduction of the aryl alkyl ketone into the reaction vessel. The inlets of the pipes are arranged in accordance with the course of the reaction desired. A discharge pipe 17 is provided for discharging of the formed gaseous hydrogen halide, and a discharge pipe 18 is provided at the bottom of the reaction vessel for discharging of the finished reaction product. Feed and discharge pipes, respectively, 19 and 20, are provided for the coolant liquid. Devices for the exposure to light of the reaction mass may advantageously be arranged inside the hollow cylindrical jacket 11.
An upper reaction zone is formed substantially in the space between the terminal openings of pipes and 16, which open at different heights in the reaction vessel 10, and maintained by the continuous feeding of the halogen through the pipe 15 and of the ketone through the pipe 16. This reaction zone is located, based on the desired degree of filling of the container 10, in the vicinity of the upper rim of the open cylindrical jacket 11. The reaction is continuously maintained inside the jacket 11 by continuous cooling and under the action of the pump agitator 13.
A cycle simultaneously exists in which the reaction mixture flows over the upper edge of the hollow cylinder 11 into the gap 14 and flows back at the lower rim of the cylinder 11 in the direction shown by the arrow in the drawing, partly into the interior of the jacket 11, the reaction mixture forceably flowing around the cooling surfaces 12. The finished halogenation product falls in the vessel 10, to the extent that it does not flow back into the interior of the hollow cylinder 11, and is fed through the pipe 18 to the further treatment stages, and particularly to a vessel in which the halongenated reaction product is aminated.
During the cycle of the reaction the mixture gives off the greater portion of the hydrogen halide formed during the reaction, and this is continuously discharged through the outlet pipe 17 of the reaction vessel. The finished reaction product, which is substantially free of contaminating resinous side products, but which may contain some dissolved hydrogen halide, is continuously fed into a further vessel, whose feed and discharge inlets can be opened or closed by means of control magnetic valves, for examples. If it is desired to-remove any residual hydrogen halide, this is accomplished by washing out with water or degasification at higher temperatures, preferably under vacuum.
The amination vessel into which the halogenated reaction product is then pumped, is preferably likewise formed as a mixing vessel provided with an agitator mechanism. The reaction is continuously maintained with an equivalent or excess amount of amine which is continously fed into the vessel. The aminated mixture is preferably further mixed in another vessel with an alkali, for example aqueous sodium hydroxide or sodium carbonate, the amine phase being continuously separated from the aqueous phase.
The process of the present invention permits the production of the halogenated aryl alkyl ketone without the formation of any substantial contaminating resinous side products, and in addition it permits the production of the aryl alkyl aminoketone starting from the aryl alkyl ketone in a high degree of purity without any further recrystallization. The aryl alkyl aminoketones can be deposited directly as salts.
By carrying out the method of the present invention in the preferred device described herein it is possible to carry out the method without the use of any excess of ketone, which would result in considerable losses. Local overheating is also avoided and by carrying out the reaction in accordance with the present invention the production of resinified side products is avoided.
Because of the high degree of purity of the aryl alkyl aminoketones produced in accordance with the method of the present invention, the same may be directly used without any intermediate purification, these compounds being valuable therapeutic compounds which can be used, for example, as appetite reducing agents, and the compounds can also be used as intermediates in the production of other valuable compounds.
Among the preferred amines with which the halogenated aryl alkyl ketones can be reacted for the production of aryl alkyl aminoketones are: diethylamine, dipropylamine, dibutylamine, diamylamine, piperidine, piperazine, pyrrolidine, and morpholine.
The following examples are given to further illustrate the present invention. The scope of the invention is not, however, meant to be limited to the specific details of the examples:
Example 1 39.52 kg. of propiophenone and 46.6 kg. of bromine are continuously introduced into a reaction vessel of the type described above. The clear dark red reaction mixture is continuously freed of the hydrogen bromide and the halogenated reaction product is reacted with 60 kg. of diethylamine under constant stirring. 41 kg. of 34% aqueous sodium hydroxide are continuously fed into the continuously down flowing reaction mixture, the amine phase and aqueous phase being continuously separated. The excess diethylamine is distilled off from the crude base and Washed with water, and the crude base thus purified is continuously distilled. The yield of pure base is 51.8 kg. The pure base can be reacted with hydrochloric acid to form the hydrogen chloride salt which melts at 172174 C. The chlorine content is 14.58%.
Example 2 Example 3 2.81 kg. (5% excess) of propiophenone are introduced into a reaction vessel of the type described above provided with cooling coils and mechanical stirrer, and with hollowed blades and impeller elements. A few grams of o -bromopropiophenone, previously prepared, are added to catalyze the reaction. 3.19 kg. of bromine are slowly added under careful cooling to maintain the temperature at about 10 C.
This phase of the operation is conducted discontinuously in order to fill the apparatus up to the point of overflow of the smaller inner vessel. Then 143.5 kg. of propiophenone and 287.8 kg. of bromine are continuously added, at the rate respectively of 0.03 mol per minute for the ketone and 0.027 mol per minute for the halogen. The bromine immediately reacts and no excss of unreacted bromine is present in the reaction mixture throughout the operation. The residence time is 2 minutes.
Hydrogen bromide continuously formed is permitted to escape through the outlet of conduit 17. The oc-blOlTlO- propiophenone is continuously removed from the lower outlet and led into another vessel where it is continuously washed with water. The product is then distilled, giving 88% yield of pure a-bromopropiophenone. The direct reaction of the undistilled reaction product, however, exhibits a considerably higher yield of about 96%.
The above reaction can be continued by the continued addition of propiophenone and bromine in the above in dicated ratio.
Example 4 3.108 kg. (5% excess) of n-butyrophenone are introduced into the same reaction vessel as above with the slow addition of 3.19 kg. of bromine discontinuously until the apparatus is filled to the desired level. By means of an adjusted dosing pump, 299.0 kg. of n-butyrophenone and 3.19 kg. of bromine are added to the reaction vessel in constant ratio, and the reaction product is continuously withdrawn. The yield of u-bromo-n-butyrophenone is above 96%, and upon distillation of the crude product a yield of the pure product is obtained in an amount of 7 90%. The reaction temperature is maintained by cooling at below 20 C.
Example 3.11 kg. (5% excess) of isobutyrophenone are discontinuously reacted as in Example 4 with 3.19 kg. of bromine and then 29.9 kg. of isobutyrophenone are continuously brominated with 31.9 kg. of bromine. The reaction temperature is maintained between 05 C. The yield of a-bromo-isobutyrophenone is above 95%.
Example 6 3.11 kg. of isobutyrophenone and 42 kg. of chlorine are reacted in the above described halogenating apparatus. There is subsequently continuously added 22.9 kg. of isobutyrophenone and 14.2 kg. of chlorine. The reaction is carried out at about 20 C. The obtained a-chloroisobutyrophenone boils under 2 mm. Hg at 76-79 C., and is so pure that it can be used without distillation.
Example 7 3.4 kg. of isovalerophenone are reacted with 3.19 kg. of bromine and then 29.7 kg. of isovalerophenone and 28.8 kg. of bromine are continuously reacted. The yield of a-bromo-isovalerophenone is above 90%.
Example 8 3.4 kg. of n-valerophenone and 3.19 kg. of bromine are introduced into the above described apparatus to fill the same, and the reaction is then continuously carried out with 29.8 kg. of n-valerophenone and 28.8 kg. of bromine. After removal of the hydrogen bromide, the oc-blOIIlO-Ilvalerophenone crystallizes out.
As noted in the above examples, the chlorination and bromination takes place on the alpha carbon of the alkyl group of the carbonyl group.
Withoutfurther analysis, the foregoing will so fully reveal the gist of the present invention that others can by applying current knowledge readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention and, therefore, such adaptations should and are intended to be comprehended within the meaning and range of equivalence of the following claims.
What is claimed as new and desired to be secured by Letters Patent is:
1. The method which comprises continuously introducing into the upper portion of a closed reaction vessel a liquid compound selected from the group consisting of propiophenone, n-bu-tyrophenone, isobutyrophenone, nvalerophenone and isovalerophenone, and also continuously introducing into the upper portion of said reaction vessel at a level below the level of introduction of said liquid compound a halogen selected from the group consisting of chlorine and bromine, so as to form in the upper portion of said reaction vessel in a reaction zone substantially located between the levels of introduction of said compound and said halogen a reaction mixture, the latter being free of any solvent, and continuously agitating said reaction mixture and circulating the same between the upper and lower portion of the reaction vessel so as to continuously form in said reaction vessel the corresponding hydrogen halide and. the corresponding alpha chloro or alpha bromo halogenated compound, whereby said halogenated compound is formed in the absence of a solvent and without any contaminating resinous side products; continuously removing hydrogen ha- 8 lide from the reaction vessel; andv continuously. withdrawing halogenated compound from the lower portion of said reaction vessel.
2. The method as defined in claim compound is propiophenone.
1, wherein said halogen is bromine. I
9. The method as defined in claim 1, wherein said reaction mixture in said reaction vessel is exposed to light.
10. The method as defined in claim 1, wherein the residence time of said reaction mixture in said reaction vessel is about 2 minutes.
11. The method as defined in claim 1, and including removal of residual hydrogen halide from said withdrawn halogenated compound.
12. The method as defined in claim 11, wherein said residual hydrogen halide is removed by washing said withdrawn halogenated compound with water.
13. The method as defined in claim 11, wherein said residual hydrogen halide is removed by degasification under reduced pressure of said withdrawn halogenated compound.
14. The method as defined in claim 1, wherein said reaction mixture is cooled during circulation of the same between the upper and lower portion of the reaction vessel.
15. The method as defined in claim 14, wherein said reaction mixture is cooled so as to be maintained at a temperature below 20 C.
16. The method as defined in claim 15, wherein said reaction mixture is cooled so as to be maintained at a temperature between about 0 and 5 C.
17. The method as defined in claim 1, wherein said reaction mixture is circulated in said reaction vessel so as to move downwardly through the peripheral portion of the reaction vessel and upwardly through the center portion thereof.
18. The method as defined in claim 17, wherein said References Cited UNITED STATES PATENTS 2,107,905 2/1938 Ralston et al. 260592 2,116,893 5/1938 Heisel 260592 2,155,194 4/1939 Kamlet 260577 2,784,193 3/1957 Schultz 260-570.5 X 2,827,460 3/ 8 Stein etal 260570 X CHARLES B. PARKER, Primary Examiner.
ROBERT V. HINES, Assistant Examiner,
Claims (1)
1. THE METHOD WHICH COMPRISES CONTINUOUSLY INTRODUCING INTO THE UPPER PORTION OF A CLOSED REACTION VESSEL A LIQUID COMPOUND SELECTED FROM THE GROUP CONSISTING OF PROPIOPHENONE, N-BUTYROPHENONE, ISOBUTYROPHENONE, NVALEROPHENONE AND ISOVALEROPHENONE, AND ALSO CONTINUOUSLY INTRODUCING INTO THE UPPER PORTION OF SAID REACTION VESSEL AT A LEVEL BELOW THE LEVEL OF INTRODUCTION OF SAID LIQUID COMPOUND A HALOGEN SELECTED FROM THE GROUP CONSISTING OF CHLORINE AND BROMINE, SO AS TO FORM IN THE UPPER PORTION OF SAID REACTION VESSEL IN A REACTION ZNE SUBSTANTIALLY LOCATED BETWEEN THE LEVELS OF INTRODUCTION OF SAID COMPOUND AND SAID HALOGEN A REACTION MIXTURE, THE LATTER BEING FREE OF ANY SOLVENT, AND CONTINUOUSLY AGITATING SAID REACTION MIXTURE AND CIRCULATING THE SAME BETWEEN THE UPPER AND LOWER PORTION OF THE REACTION VESSEL SO AS TO CONTINUOUSLY FORM IN SAID REACTION VESSEL THE CORRESPONDING HYDROGEN HALIDE AND THE CORRESPONDING ALPHA CHLORO OR ALPHA BROMO HALOGENATED COMPOUND, WHEREBY SAID HALOGENATED COMPOUND IS FORMED IN THE ABSENCE OF A SOLVENT AND WITHOUT ANY CONTAMINATING RESINOUS SIDE PRODUCTS; CONTINUOUSLY REMOVING HYDROGEN HALIDE FROM THE REACTION VESSEL; AND CONTINUOUSLY WITHDRAWING HALOGENATED COMPOUND FROM THE LOWER PORTION OF SAID REACTION VESSEL.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DET16340A DE1164388B (en) | 1959-03-02 | 1959-03-02 | Process and apparatus for the production of aryl alkyl bromoketones |
Publications (1)
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US3340305A true US3340305A (en) | 1967-09-05 |
Family
ID=7548212
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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US381945A Expired - Lifetime US3340305A (en) | 1959-03-02 | 1964-07-07 | Method of producing aryl alkyl aminoketones |
Country Status (3)
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US (1) | US3340305A (en) |
DE (1) | DE1164388B (en) |
GB (1) | GB945162A (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3492351A (en) * | 1964-04-08 | 1970-01-27 | Boehringer Sohn Ingelheim | 1-(lower alkoxy-phenyl)-2-(lower alkyl-amino)- alkanones-(1) and salts |
US4308400A (en) * | 1977-12-22 | 1981-12-29 | Ciba-Geigy A.G. | Sensitizers for photopolymerization |
WO2000075094A2 (en) * | 1999-06-03 | 2000-12-14 | Ishihara Sangyo Kaisha, Ltd. | Method for producing a halogenated acetophenone |
US20090012328A1 (en) * | 2007-07-06 | 2009-01-08 | Chaogang Wu | Process for preparing bupropion hydrochloride |
CN106268567A (en) * | 2016-09-27 | 2017-01-04 | 冀州天大天久精细化工科技有限公司 | A kind of enamel reaction still |
CN111545131A (en) * | 2020-04-29 | 2020-08-18 | 北京航空航天大学 | Waste heat recovery type sealed hydrothermal reaction kettle |
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Publication number | Priority date | Publication date | Assignee | Title |
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DE1270022B (en) * | 1966-08-26 | 1968-06-12 | Kalk Chemische Fabrik Gmbh | Process for the preparation of alpha-bromoalkylaryl ketones |
US20030225179A1 (en) * | 2002-04-26 | 2003-12-04 | Chiu Chingfan Chris | Novel morpholinoketone derivatives, and preparation process and uses of the same |
CN104741062A (en) * | 2014-07-09 | 2015-07-01 | 季永东 | Heat resistant type electrical heating reaction vessel |
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US2107905A (en) * | 1937-03-09 | 1938-02-08 | Armour & Co | Chlorinated aralkyl ketones |
US2116893A (en) * | 1935-11-05 | 1938-05-10 | Ig Farbenindustrie Ag | Process of chlorinating and brominating carbonyl compounds |
US2155194A (en) * | 1938-10-27 | 1939-04-18 | Kamlet Jonas | Preparation of alpha-alkylaminoacylophenones |
US2784193A (en) * | 1955-01-19 | 1957-03-05 | Merck & Co Inc | Phenalkylamines |
US2827460A (en) * | 1954-10-23 | 1958-03-18 | Hoechst Ag | Alpha, alpha-diphenyl-beta-amino-propanols |
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DE696772C (en) * | 1935-11-06 | 1940-09-28 | I G Farbenindustrie Akt Ges | Process for the chlorination or bromination of ketones |
DE859146C (en) * | 1943-11-19 | 1952-12-11 | Temmler Werke | Process for the production of ª ‡ -bromopropiophenone |
-
1959
- 1959-03-02 DE DET16340A patent/DE1164388B/en active Pending
- 1959-10-09 GB GB34326/59A patent/GB945162A/en not_active Expired
-
1964
- 1964-07-07 US US381945A patent/US3340305A/en not_active Expired - Lifetime
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
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US2116893A (en) * | 1935-11-05 | 1938-05-10 | Ig Farbenindustrie Ag | Process of chlorinating and brominating carbonyl compounds |
US2107905A (en) * | 1937-03-09 | 1938-02-08 | Armour & Co | Chlorinated aralkyl ketones |
US2155194A (en) * | 1938-10-27 | 1939-04-18 | Kamlet Jonas | Preparation of alpha-alkylaminoacylophenones |
US2827460A (en) * | 1954-10-23 | 1958-03-18 | Hoechst Ag | Alpha, alpha-diphenyl-beta-amino-propanols |
US2784193A (en) * | 1955-01-19 | 1957-03-05 | Merck & Co Inc | Phenalkylamines |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3492351A (en) * | 1964-04-08 | 1970-01-27 | Boehringer Sohn Ingelheim | 1-(lower alkoxy-phenyl)-2-(lower alkyl-amino)- alkanones-(1) and salts |
US4308400A (en) * | 1977-12-22 | 1981-12-29 | Ciba-Geigy A.G. | Sensitizers for photopolymerization |
WO2000075094A2 (en) * | 1999-06-03 | 2000-12-14 | Ishihara Sangyo Kaisha, Ltd. | Method for producing a halogenated acetophenone |
WO2000075094A3 (en) * | 1999-06-03 | 2001-02-15 | Ishihara Sangyo Kaisha | Method for producing a halogenated acetophenone |
US20090012328A1 (en) * | 2007-07-06 | 2009-01-08 | Chaogang Wu | Process for preparing bupropion hydrochloride |
US7737302B2 (en) * | 2007-07-06 | 2010-06-15 | Zhejiang Apeloa Medical Technology Co., Ltd. | Process for preparing bupropion hydrochloride |
CN106268567A (en) * | 2016-09-27 | 2017-01-04 | 冀州天大天久精细化工科技有限公司 | A kind of enamel reaction still |
CN111545131A (en) * | 2020-04-29 | 2020-08-18 | 北京航空航天大学 | Waste heat recovery type sealed hydrothermal reaction kettle |
CN111545131B (en) * | 2020-04-29 | 2021-10-08 | 北京航空航天大学 | Control method of waste heat recovery type sealed hydrothermal reaction kettle |
Also Published As
Publication number | Publication date |
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GB945162A (en) | 1963-12-23 |
DE1164388B (en) | 1964-03-05 |
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