DE935127C - Process for the preparation of N-aryl-N'-aminoalkylureas - Google Patents
Process for the preparation of N-aryl-N'-aminoalkylureasInfo
- Publication number
- DE935127C DE935127C DEG11942A DEG0011942A DE935127C DE 935127 C DE935127 C DE 935127C DE G11942 A DEG11942 A DE G11942A DE G0011942 A DEG0011942 A DE G0011942A DE 935127 C DE935127 C DE 935127C
- Authority
- DE
- Germany
- Prior art keywords
- general formula
- alkylene
- urea
- parts
- dimethyl
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- HJHZRZFONUPQAA-UHFFFAOYSA-N 2-isocyanato-1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=C(N=C=O)C(C)=C1 HJHZRZFONUPQAA-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- KNTSDSCGWPXOEN-UHFFFAOYSA-N (2,4,6-trimethylphenyl)carbamic acid Chemical compound CC1=CC(C)=C(NC(O)=O)C(C)=C1 KNTSDSCGWPXOEN-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000002994 raw material Substances 0.000 claims 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
- 230000003442 weekly effect Effects 0.000 claims 1
- -1 alkylene radical Chemical class 0.000 description 27
- 239000004202 carbamide Substances 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 125000005853 β-dimethylaminoethyl group Chemical group 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 235000013877 carbamide Nutrition 0.000 description 5
- 239000000155 melt Substances 0.000 description 5
- 238000009835 boiling Methods 0.000 description 4
- YQLRKXVEALTVCZ-UHFFFAOYSA-N 2-isocyanato-1,3-dimethylbenzene Chemical compound CC1=CC=CC(C)=C1N=C=O YQLRKXVEALTVCZ-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
- QSACPWSIIRFHHR-UHFFFAOYSA-N dimethylphenyl isocyanide Natural products CC1=CC=CC(C)=C1C#N QSACPWSIIRFHHR-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- WUYJXWRFOUCHEB-UHFFFAOYSA-N (2,4,6-trimethylphenyl)azanium;chloride Chemical compound [Cl-].CC1=CC(C)=C([NH3+])C(C)=C1 WUYJXWRFOUCHEB-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UFFBMTHBGFGIHF-UHFFFAOYSA-N 2,6-dimethylaniline Chemical group CC1=CC=CC(C)=C1N UFFBMTHBGFGIHF-UHFFFAOYSA-N 0.000 description 1
- QNWMFJDRMZWZNN-UHFFFAOYSA-N 2,6-dimethylaniline;hydron;chloride Chemical compound Cl.CC1=CC=CC(C)=C1N QNWMFJDRMZWZNN-UHFFFAOYSA-N 0.000 description 1
- IZQAUUVBKYXMET-UHFFFAOYSA-N 2-bromoethanamine Chemical compound NCCBr IZQAUUVBKYXMET-UHFFFAOYSA-N 0.000 description 1
- WJAXXWSZNSFVNG-UHFFFAOYSA-N 2-bromoethanamine;hydron;bromide Chemical compound [Br-].[NH3+]CCBr WJAXXWSZNSFVNG-UHFFFAOYSA-N 0.000 description 1
- LQMMFVPUIVBYII-UHFFFAOYSA-N 2-methylmorpholine Chemical compound CC1CNCCO1 LQMMFVPUIVBYII-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000004965 chloroalkyl group Chemical group 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- IJAQDOIKWBEHFN-UHFFFAOYSA-N ethyl n-(2,6-dimethylphenyl)carbamate Chemical compound CCOC(=O)NC1=C(C)C=CC=C1C IJAQDOIKWBEHFN-UHFFFAOYSA-N 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- MKDYQLJYEBWUIG-UHFFFAOYSA-N n',n'-diethyl-n-methylethane-1,2-diamine Chemical compound CCN(CC)CCNC MKDYQLJYEBWUIG-UHFFFAOYSA-N 0.000 description 1
- QXPRMANJAMOFLQ-UHFFFAOYSA-N n',n'-dimethyl-n-propan-2-ylethane-1,2-diamine Chemical compound CC(C)NCCN(C)C QXPRMANJAMOFLQ-UHFFFAOYSA-N 0.000 description 1
- SORARJZLMNRBAQ-UHFFFAOYSA-N n,n',n'-trimethylpropane-1,3-diamine Chemical compound CNCCCN(C)C SORARJZLMNRBAQ-UHFFFAOYSA-N 0.000 description 1
- WLNSKTSWPYTNLY-UHFFFAOYSA-N n-ethyl-n',n'-dimethylethane-1,2-diamine Chemical compound CCNCCN(C)C WLNSKTSWPYTNLY-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 229940072358 xylocaine Drugs 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
- C07D295/04—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
- C07D295/125—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 with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—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 with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/18—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
- C07C273/1809—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas with formation of the N-C(O)-N moiety
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/18—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
- C07C273/1854—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas by reactions not involving the formation of the N-C(O)-N- moiety
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von N-Aryl-N'-aminoalkylharnstoffen N-Aryl-N'-aminoalkylharnstoffe der allgemeinen Formel alkylen - Am worin R1 Wasserstoff oder die Methylgruppe, R2 Wasserstoff oder - eine niedermolekulare Alkylgruppe, alkylen eine Alkylenrest mit 2 bis 3 Kohlenstoffatomen und Am eine niedermolekulare Dialkylaminogruppe, eine Alkyleniminogruppe mit 5 bis 6 Ringgliedern oder die Morpholinogruppe bedeutet, sind bisher nicht bekanntgeworden.Process for the preparation of N-aryl-N'-aminoalkylureas N-aryl-N'-aminoalkylureas of the general formula alkylene - Am in which R1 is hydrogen or the methyl group, R2 is hydrogen or - a low molecular weight alkyl group, alkylene is an alkylene radical with 2 to 3 carbon atoms and Am is a low molecular weight dialkylamino group, an alkyleneimino group with 5 to 6 ring members or the morpholino group, have not yet become known.
Wie nun gefunden wurde, besitzen diese Verbindungen eine ausgezeichnete lokalanästhetische Wirksamkeit. Sie sind zufolge ihrer Beständigkeit gegenüber schwachen Alkalien auch in Injektionslösungen von Arzneimitteln mit schwach alkalischer Reaktion verwendbar. Gegenüber dem bekannten c,)-Diäthylaminoessigsäure-2, 6-xylidid (»Xylocain«) zeichnen sie sich durch eine bedeutend stärkere lokalanästhetische Wirksamkeit, bestimmt an der Kaninchencornea in Anlehnung an die Methode von Régnier, aus. Trotz höherer Toxizität (Ratte und Maus i. v.) ist ihre therapeutische Breite deutlich, d. h. I,5- bis 4,5mal größer. As has now been found, these compounds are excellent local anesthetic effectiveness. They are weak as a result of their persistence Alkalis also in injection solutions of drugs with a weakly alkaline reaction usable. Compared to the well-known c,) - diethylaminoacetic acid-2,6-xylidide ("xylocaine") they are characterized by a significantly stronger local anesthetic effectiveness, determined on the rabbit cornea based on the Régnier method. Despite higher toxicity (rat and mouse IV), its therapeutic range is clear, d. H. I, 5 to 4.5 times larger.
Man kann die neuen Verbindungen herstellen, indem man ein reaktionsfähiges, funktionelles Derivat der 6-Dimethyl- bzw. der 2, , 6-Trimethyl-carbanil- säure, worunter deren Alkyl-, Arylester- oder ihre Amide verstanden werden, oder das 2, 6-Dimethyl-und das 2, 4, 6-Trimethyl-phenylisocyanat mit einem Diaminoalkan der allgemeinen Formel worin R2, alkylen und Am die oben angegebene Bedeutung haben, umsetzt.The new compounds can be prepared by adding a reactive, functional derivative of 6-dimethyl or 2, 6-trimethyl-carbanilic acid, which is understood to mean their alkyl, aryl ester or their amides, or the 2, 6-Dimethyl and 2,4,6-trimethyl phenyl isocyanate with a diaminoalkane of the general formula in which R2, alkylene and Am have the meaning given above.
Man kann auch einen N-Aryl-N'-halogenalkylharnstoff der allgemeinen Formel worin R1, R2 und alkylen die oben angegebenen Bedeutungen haben und Hal Chlor oder Brom bedeutet, mit einem sekundären Amin der allgemeinen Formel Am - H, mit Am gemäß oben angegebener Bedeutung, umsetzen.One can also use an N-aryl-N'-haloalkylurea of the general formula in which R1, R2 and alkylene have the meanings given above and Hal is chlorine or bromine, with a secondary amine of the general formula Am - H, with Am as defined above, to react.
Als Diaminoalkane zur Verwendung im erstgenannten Verfahren seien N- (fl-Amino-äthyl) N-(ß-Amino-propyl)-, N-(ß-Amino-isopropyl)-, N-(y-Aminopropyl)-, N-(ß-Methylamino-äthyl)-, N-(ß-Äthylaminoäthyl)-, N - (ß -Methylamino -propyl)-, N - (ß -Methyl-Beispiel I In eine Suspension von 43 Teilen Mesidin-hydrochlorid in 450 Volumteilen absolutem Toluol wird bei einer Temperatur von go bis 1000 unter starkem Rühren so lange Phosgen eingeleitet, bis alles in Lösung gegangen ist. Darauf wird das Toluol abdestilliert und der Rückstand im Vakuum fraktioniert. Man erhält 37 Teile 2, 4, 6-Trimethyl-phenylisocyanat vom Siedepunkt II5° unter I2 mm Druck.As diaminoalkanes for use in the first-mentioned process are N- (fl-amino-ethyl) N- (ß-amino-propyl) -, N- (ß-amino-isopropyl) -, N- (γ-aminopropyl) -, N- (ß-methylaminoethyl) -, N- (ß-ethylaminoethyl) -, N - (ß-methylamino-propyl) -, N - (ß -methyl example I Phosgene is introduced into a suspension of 43 parts of mesidine hydrochloride in 450 parts by volume of absolute toluene at a temperature of from 0 to 1000 with vigorous stirring until everything has dissolved. The toluene is then distilled off and the residue is fractionated in vacuo. 37 parts of 2, 4, 6-trimethylphenyl isocyanate with a boiling point of II5 ° under I2 mm pressure are obtained.
Die Harnstoffverbindung wird dargestellt, indem man in eine Lösung von 9,8 Teilen N, N-Diäthyl-N'-methyl-äthylendiamin in 25 Volumteilen absolutem Beispiel 2 In eine Lösung von 9,2 Teilen 2, 4, 6-Trimethylphenylisocyanat in 20 Volumteilen absolutem Äther wird eine Lösung von 6,6 Teilen N, N-Dimethyl-N'-äthvl-äthvlendiamin eingetropft; nach dem Abklinamino-isopropyl)- und N- (y -Methylamino-propyl)-dimethylamin, -methyläthylamin, -diäthylamin, -dipropylamin, -dibutylamin, -pyrrolidin, -piperidin, -2-methyl-piperidin und -morpholin genannt.The urea compound is prepared by adding absolute Example 2 to a solution of 9.8 parts of N, N-diethyl-N'-methyl-ethylenediamine in 25 parts by volume A solution of 6.6 parts of N, N-dimethyl-N'-ethyl-ethylenediamine is added dropwise to a solution of 9.2 parts of 2,4,6-trimethylphenyl isocyanate in 20 parts by volume of absolute ether; named after the Abklinamino-isopropyl) - and N- (γ-methylamino-propyl) -dimethylamine, -methylethylamine, -diethylamine, -dipropylamine, -dibutylamine, -pyrrolidine, -piperidine, -2-methyl-piperidine and -morpholine.
Die für das dritte Verfahren benötigten N-Aryl-N'-halogenalkylharnstoffe kann man z. B. durch Umsetzung von 2, 6-Dimethyl- bzw. 2, 4, 6-Trimethylphenylisocyanat mit Chloralkyl- oder Bromalkylaminen herstellen. Als einzelne N-Aryl-N'-halogenalkylharnstoffe seien beispielsweise N-(2, 6-Dimethylphenyl)- und N-(2, 4, 6-Trimethyl-phenyl)-N'-(fl-chloräthyl) -harnstoff, - N' - (fl-brom-propyl) -harnstoff, -N'-(y-brom-propyl)-harnstoff und -N'-(ß-cblor-äthyl)-N'-methylharnstoff genannt. Diese Harnstoffverbindungen können mit beliebigen, der allgemeinen Formel Am - H entsprechenden sekundären Aminen, wie Dimethylamin, Diäthylamin, Piperidin und Morpholin, umgesetzt werden. The N-aryl-N'-haloalkylureas required for the third method you can z. B. by reacting 2, 6-dimethyl or 2, 4, 6-trimethylphenyl isocyanate prepare with chloroalkyl or bromoalkylamines. As individual N-aryl-N'-haloalkyl ureas are for example N- (2, 6-dimethylphenyl) - and N- (2, 4, 6-trimethyl-phenyl) -N '- (fl-chloroethyl) -urea, -N '- (fl-bromo-propyl) -urea, -N' - (y-bromo-propyl) -urea and -N '- (ß-cblor-ethyl) -N'-methylurea called. These urea compounds can with any secondary amines corresponding to the general formula Am - H, such as dimethylamine, diethylamine, piperidine and morpholine are implemented.
Mit anorganischen oder organischen Säuren, wie Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Methansulfonsäure, Äpfelsäure, Berusteinsäure, Weinsäure, Benzoesäure, Phthalsäure, bilden die neuen N-Aryl-N'-aminoalkylharnstoffe Salze, die in Wasser mit annähernd neutraler Reaktion löslich sind. With inorganic or organic acids such as hydrochloric acid, hydrobromic acid, Sulfuric acid, phosphoric acid, methanesulfonic acid, malic acid, succinic acid, tartaric acid, Benzoic acid, phthalic acid, form the new N-aryl-N'-aminoalkylureas salts, which are soluble in water with an approximately neutral reaction.
Die nachfolgenden Beispiele erläutern die Herstellung der neuen Verbindungen. Teile bedeuten darin Gewichtsteile, diese verhalten sich zu Volumteilen wie g zu cm3. Die Temperaturen sind in Centigraden angegeben. The following examples explain the preparation of the new compounds. In this, parts mean parts by weight; these relate to parts by volume like g cm3. Temperatures are given in centigrades.
Äther eine ätherische Lösung von I2 Teilen 2, 4, 6-Trimethyl-phenylisocyanat eintropfen läßt. Es tritt eine starke Reaktion ein, so daß der Äther ins Sieden kommt. Ist alles Isocyanat zugegeben, so wird noch 1½ Stunden unter Rückfluß zum Kochen erwärmt und dami der Äther abdestilliert. Gibt man zum öligen Rückstand ein wenig Pentan, so tritt bald eine Kristallisation des N-(2, 4, 6-Trimethyl-phenyl) N'-methyl-N'-(ß-diäthylamino-äthyl)-harnstoffs ein.Ether an ethereal solution of I2 parts 2, 4, 6-trimethyl-phenyl isocyanate lets drip in. A strong reaction occurs, causing the ether to boil comes. When all the isocyanate has been added, the reflux is continued for 1½ hours Boiling warms up and the ether is distilled off. Enter to the oily residue little pentane, then crystallization of the N- (2, 4, 6-trimethyl-phenyl) N'-methyl-N '- (ß-diethylamino-ethyl) urea.
Man kristallisiert aus Pentan um, F. 68°, Hydrochlorid F. I86 bis 187°. gen der exothermen Reaktion wird noch rl/2 Stunden unter Rückfluß gekocht. Hierauf werden die basischen Anteile mit verdünnter Salzsäure extrahiert, die klare, saure, wäßrige Phase mit konzentrierter Kaliumcarbonatlösung alkalisch gestellt und mit Äther ausgeschüttelt. Nach dem Trocknen über N atriumsulfat wird eingedampft und der Rüclistand aus Pentan umkristallisiert. Der N-(2,4,6-Trimethylphenyl)-N'-äthyl-N'-(ß-dimethylamino-äthyl)-harnstoff schmilzt bei 55', sein Hydrochlorid bei 174 bis 175°. Analog können dargestellt werden: N-(2,4,6-Trimethyl-phenyl)-N'-ispropyl-N'-(ß-dimethylamino-äthyl)-harnstof, F. 79 bis 80°, N-(2,4,6-Trimethyl-phenyl)-N'-n-propyl-N'-(ß-dimethylamino-äthyl)-harnstoff. F. 81 bis 82°, N-(2,4,6-Trimethyl-phenyl)-N'-äthyl-N'-(ß-diäthylamino-äthyl)-harnstoff, F. 48°, und N-(2,4,6-Trimethyl-phenyl)-N'-(ß-diäthylaminoäthyl)-harnstoff, F. 130°, N-(2,4,6-Trimethyl-phenyl)-N'-(ß-pyrrolidino-äthyl)-harnstoff, N-(2,4,6-Trimethyl-phenyl)-N'-(γ-dimethylaminopropyl) -harnstoff, N-(2,4,6-Trimethyl-phenyl)-N'-n-propyl-N'-(ß-dimethylamino-propyl)-harnstoff.It is recrystallized from pentane, mp 68 °, hydrochloride mp 186 bis 187 °. The exothermic reaction is refluxed for a further 1/2 hour. The basic components are then extracted with dilute hydrochloric acid, the clear, acidic, aqueous phase with concentrated Potassium carbonate solution alkaline placed and shaken out with ether. After drying over sodium sulphate it becomes evaporated and the Rüclistand recrystallized from pentane. The N- (2,4,6-trimethylphenyl) -N'-ethyl-N '- (ß-dimethylamino-ethyl) -urea melts at 55 ', its hydrochloride at 174 to 175 °. Analog can be shown are: N- (2,4,6-trimethyl-phenyl) -N'-ispropyl-N '- (ß-dimethylamino-ethyl) -urea, F. 79 to 80 °, N- (2,4,6-trimethyl-phenyl) -N'-n-propyl-N '- (ß-dimethylamino-ethyl) -urea. F. 81 to 82 °, N- (2,4,6-trimethyl-phenyl) -N'-ethyl-N '- (ß-diethylamino-ethyl) -urea, 48 °, and N- (2,4,6-trimethyl-phenyl) -N '- (ß-diethylaminoethyl) urea, 130 °, N- (2,4,6-trimethyl-phenyl) -N '- (ß-pyrrolidino-ethyl) -urea, N- (2,4,6-trimethyl-phenyl) -N' - (γ-dimethylaminopropyl) -urea, N- (2,4,6-trimethyl-phenyl) -N'-n-propyl-N '- (ß-dimethylamino-propyl) -urea.
Beispiel 3 In eine Suspension von 50 Teilen 2,6-Xylidinhydrochlorid in 250 Volumteilen siedendem Toluol wird so lange Phosgen eingeleitet, bis alles in Lösung gegangen ist. Dann wird das Toluol abdestilliert und der Rückstand im Vakuum fraktioniert, wobei das 2,6-Dimethyl-phenylisocyanat unter 13 mm Druck bei 91 bis 92° übergeht.Example 3 Phosgene is passed into a suspension of 50 parts of 2,6-xylidine hydrochloride in 250 parts by volume of boiling toluene until everything has dissolved. The toluene is then distilled off and the residue is fractionated in vacuo, the 2,6-dimethylphenyl isocyanate passing over under 13 mm pressure at 91 to 92 °.
In eine Lösung von S Teilen N, N-Dimethyl-N'-isopropyl-äthylendiamin in 40 Volumteilen absolutem Äther werden innerhalb 10 Minuten 9 Teile 2,6-Dimethyl-phenylisocyanat eingetropft, das Ganze noch I Stunde unter Rückfluß gekocht und anschließend der ether abdestilliert. Der ölige Rückstand kann lurch Zusatz von Petroläther zur Kristallisation gelaracht werden. Der N-(2, 6-Dimethyl-phenyl)-N'-isopropyl-N'-(ß-dimethylamino-äthyl)-harnstoff schmilzt bei 89 bis 90°. In analoger Weise können hergestellt werden: N-(2,6-Dimethyl-phenyl)-N'-n-propyl-N'-(ß-dimethylamino-äthyl)-harnstoff, F. 83 bis 84°, N-(2,6-Dimethyl-phenyl)-N'-äthyl-N'-(ß-dimethylamino-äthyl)-harnstoff, F. 6s bis 69°, N-(2,6-Dimethyl-phenyl)-N'-methyl-N'-(ß-dimethylamino-äthyl)-harnstoff, F. 130°, N-(2,6-Dimethyl-phenyl)-N'-äthyl-N'-(ß-diäthylamino-äthyl)-harnstoff, F. 55°, N-(2,6-Dimethyl-phenyl)-N'-methyl-N'-(γ-morpholino-propyl)-harnstoff, N-(2,6-Dimethyl-phenyl)-N'-(ß-piperidino-äthyl)-harnstoff, F. 158°, N-(2,6-Dimethyl-phenyl)-N'-methyl-N'-(ß-diäthylamino-äthyl)-harnstoff, F. 81,5 bis 82°, usm. In a solution of S parts of N, N-dimethyl-N'-isopropyl-ethylenediamine in 40 parts by volume of absolute ether, 9 parts of 2,6-dimethylphenyl isocyanate are obtained within 10 minutes added dropwise, the whole thing refluxed for another hour and then the ether distilled off. The oily residue can be crystallized by adding petroleum ether to be laughed at. The N- (2,6-dimethyl-phenyl) -N'-isopropyl-N '- (ß-dimethylamino-ethyl) -urea melts at 89 to 90 °. The following can be prepared in an analogous manner: N- (2,6-dimethyl-phenyl) -N'-n-propyl-N '- (ß-dimethylamino-ethyl) -urea, F. 83 to 84 °, N- (2,6-dimethyl-phenyl) -N'-ethyl-N '- (ß-dimethylamino-ethyl) -urea, F. 6s to 69 °, N- (2,6-dimethyl-phenyl) -N'-methyl-N '- (ß-dimethylamino-ethyl) -urea, F. 130 °, N- (2,6-dimethyl-phenyl) -N'-ethyl-N '- (ß-diethylamino-ethyl) -urea, F. 55 °, N- (2,6-dimethyl-phenyl) -N'-methyl-N '- (γ-morpholino-propyl) -urea, N- (2,6-Dimethyl-phenyl) -N '- (ß-piperidino-ethyl) -urea, mp 158 °, N- (2,6-dimethyl-phenyl) -N'-methyl-N'- (ß-diethylamino-ethyl) -urea, F. 81.5 to 82 °, etc.
Beispiel 4 24,2 Teile 2, 6-Xylidin werden in einer Lösung von 10,6 Teilen Natriumcarbonat in 100 Teilen Wasser unter starkem Rühren suspendiert, dann bei o bis 5 langsam innerhalb I Stunde 7I,6 Teile Chlorameisensäure-äthylester eingetropft und anschließend noch 2 Stunden bei dieser Temperatur weitergerührt.Example 4 24.2 parts of 2,6-xylidine are suspended in a solution of 10.6 parts of sodium carbonate in 100 parts of water with vigorous stirring, then 7I, 6 parts of ethyl chloroformate are slowly added dropwise at 0 to 5 within 1 hour and then for a further 2 hours stirred further at this temperature.
Heirauf wird abgesaugt und mit wenig Eiswasser gewaschen. Nach dem Umkristallisieren aus sehr wenig absolutem Alkohol schmilzt das erhaltene 2,6-Dimethyl-phenylurethan bei F. 82 bis 83@.It is filtered off with suction and washed with a little ice water. After this Recrystallization from very little absolute alcohol melts the 2,6-dimethylphenyl urethane obtained at F. 82 to 83 @.
19,3 Teile dieser Verbindung und 32 Volumteile N,N-Diäthyl-äthylendiamin werden 18 Stunden unter Rückfluß gekocht. Der Überschuß an N,N-Diäthyläthylendiamin wird im Vakuum abdestilliert und der Rückstand aus wenig absolutem Alkohol umkristallisiert. Der N-(2,6-Dimethyl-phenyl)-N-(ß-diäthylamino-äthyl)-harnstoff schmilzt bei 106°. 19.3 parts of this compound and 32 parts by volume of N, N-diethylethylenediamine are refluxed for 18 hours. The excess of N, N-diethylethylenediamine is distilled off in vacuo and the residue is recrystallized from a little absolute alcohol. The N- (2,6-dimethyl-phenyl) -N- (ß-diethylamino-ethyl) -urea melts at 106 °.
Beispiel 5 14,7 Teile 2,6-Dimethyl-phenylisocyanat werden zu einer benzolischen Lösung von ß-Brom-äthylamin (die Base wird aus 22 Teilen ß-Brom-äthylaminhydrobromid freigesetzt) zugetropft. Die Abscheidung des N-(2,6-Dimethyl-phenyl)-N'-(ß-brom-äthyl)-harnstoffs beginnt sofort; sie wird durch einhalbstündiges Kochen beendigt. Dann wird stark abgekühlt und abgesaugt, F. 138 bis 139°. Example 5 14.7 parts of 2,6-dimethylphenyl isocyanate become one Benzene solution of ß-bromo-ethylamine (the base is made from 22 parts of ß-bromo-ethylamine hydrobromide released) was added dropwise. The deposition of N- (2,6-dimethyl-phenyl) -N '- (ß-bromo-ethyl) -urea starts immediately; it is ended by boiling for an hour and a half. Then get strong cooled and sucked off, mp 138 to 139 °.
I5 Teile dieser Harnstoffverbindung werden mit 40 Volumteilen Diäthylamin 3 Stunden unter Rückfluß gekocht, dann der Überschuß an Diäthylamin abdestilliert, der Rückstand in Äther aufgenommen und die ätherische Lösung mit Wasser gründlich gewaschen. 15 parts of this urea compound are combined with 40 parts by volume of diethylamine Boiled under reflux for 3 hours, then the excess of diethylamine is distilled off, the residue taken up in ether and the ethereal solution with water thoroughly washed.
Dann wird diese mit verdünnter Salzsäure ausgeschüttelt und der salzsaure Auszug alkalisch gestellt, worauf die ausgeschiedenen basischen Anteile in Äther aufgenommen werden. Durch Verjagen des Lösungsmittels erhält man den N-(2,6-Dimethylphenyl)-N'-(ß-diäthylamino-äthyl)-harnstoff, der nach Umkristallisieren aus absolutem Alkohol bei 106 bis 1070 schmilzt. Eine Mischung mit einer Probe der Verbindung gemäß Beispiel 4 besitzt den gleichen Schmelzpunkt.Then this is shaken out with dilute hydrochloric acid and the hydrochloric acid Extract made alkaline, whereupon the precipitated basic components in ether be included. By driving off the solvent, N- (2,6-dimethylphenyl) -N '- (ß-diethylamino-ethyl) -urea is obtained, which melts at 106 to 1070 after recrystallization from absolute alcohol. One Mixture with a sample of the compound according to Example 4 has the same melting point.
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DE1196640B (en) * | 1961-11-18 | 1965-07-15 | Dehydag Gmbh | Process for the production of biocidal urea or urethane compounds |
EP0007184A1 (en) * | 1978-07-03 | 1980-01-23 | American Home Products Corporation | Urea derivatives, processes for preparing them and compositions containing them |
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1953
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DE1196640B (en) * | 1961-11-18 | 1965-07-15 | Dehydag Gmbh | Process for the production of biocidal urea or urethane compounds |
EP0007184A1 (en) * | 1978-07-03 | 1980-01-23 | American Home Products Corporation | Urea derivatives, processes for preparing them and compositions containing them |
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