DE1022223B - Process for the preparation of dicyclohexylcarbodiimide - Google Patents
Process for the preparation of dicyclohexylcarbodiimideInfo
- Publication number
- DE1022223B DE1022223B DEU4068A DEU0004068A DE1022223B DE 1022223 B DE1022223 B DE 1022223B DE U4068 A DEU4068 A DE U4068A DE U0004068 A DEU0004068 A DE U0004068A DE 1022223 B DE1022223 B DE 1022223B
- Authority
- DE
- Germany
- Prior art keywords
- dicyclohexylcarbodiimide
- acid chloride
- pyridine
- toluenesulfonic acid
- dicyclohexylurea
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 7
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000003208 petroleum Substances 0.000 claims description 5
- 150000003222 pyridines Chemical class 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims 1
- 238000004140 cleaning Methods 0.000 claims 1
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KAJICSGLHKRDLN-UHFFFAOYSA-N 1,3-dicyclohexylthiourea Chemical compound C1CCCCC1NC(=S)NC1CCCCC1 KAJICSGLHKRDLN-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ZZKDGABMFBCSRP-UHFFFAOYSA-N 3-ethyl-2-methylpyridine Chemical compound CCC1=CC=CN=C1C ZZKDGABMFBCSRP-UHFFFAOYSA-N 0.000 description 1
- XKPVWBSHARELAV-UHFFFAOYSA-N C1CCCCC1N=C=NC1CCCCC1.C1CCCCC1N=C=NC1CCCCC1 Chemical compound C1CCCCC1N=C=NC1CCCCC1.C1CCCCC1N=C=NC1CCCCC1 XKPVWBSHARELAV-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/02—Polymeric products of isocyanates or isothiocyanates of isocyanates or isothiocyanates only
- C08G18/025—Polymeric products of isocyanates or isothiocyanates of isocyanates or isothiocyanates only the polymeric products containing carbodiimide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von Dicyclohexylcarbodiimid Dicyclohexylcarbodiimid besitzt ein großes Interesse als Kondensationsmittel bei der Herstellung von Peptiden. Seine Verwendung (vergl. Sheehan und Heß, J. Am. Chem. Soc., Bd. 77, 1955, S. 1066) ermöglicht die direkte Verwendung einer Aminosäure, deren amphoterer Charakter durch Blockierung der Aminogruppe ausgeschaltet ist, ohne daß es nötig wäre, diese vorher in das Säurechlorid oder gemischte Anhydrid überzuführen. Diese Verbindung bindet das im Verlauf der Reaktion freigesetzte Wasser, und es wird fast vollständig in Form von Dicyclohexylharnstoff wieder zurückgewonnen.Process for the preparation of dicyclohexylcarbodiimide dicyclohexylcarbodiimide has great interest as a condensing agent in the production of peptides. Its use (cf. Sheehan and Heß, J. Am. Chem. Soc., Vol. 77, 1955, p. 1066) enables the direct use of an amino acid whose amphoteric character is eliminated by blocking the amino group, without it being necessary to convert this into the acid chloride or mixed anhydride beforehand. This compound binds the water released in the course of the reaction and it is almost completely recovered in the form of dicyclohexylurea.
Die vorliegende Erfindung betrifft nun ein Verfahren zur Herstellung von Dicyclohexylcarbodiimid aus Dicyclohexylharnstoff, wodurch es möglich ist, einen großen Teil des eingesetzten Kondensationsmittels wiederzugewinnen. Da außerdem der Dicyclohexylharnstoff sehr leicht durch Umsetzung von Cyclohexylamin mit Harnstoff erhältlich ist, ermöglicht das neue Verfahren diese Ausgangssubstanz direkt einzusetzen an Stelle vonDicyclohexylthioharnstoff, der bis jetzt verwendet wurde und bei dessen Herstellung von dem sehr brennbaren Schwefelkohlenstoff ausgegangen wird.The present invention now relates to a method of manufacture of dicyclohexylcarbodiimide from dicyclohexylurea, which makes it possible to produce a to recover a large part of the condensing agent used. Since also the dicyclohexylurea very easily by reacting cyclohexylamine with urea is available, the new process enables this starting substance to be used directly in place of the dicyclohexylthiourea which has been used heretofore and in its Production of the very flammable carbon disulfide is assumed.
Erfindungsgemäß dehydratisiert man Dixyclohexylharnstoff mittels p-Toluolsulfonsäurechlorid in Gegenwart einer tertiären Base, wie Pyridin oder Methyläthylpyridin bei etwa 70 bis 80°. Nach dem Abkühlen trennt man die gebildeten Pyridinsalze (Mischung des Chlorids und p-Toluolsulfonats) durch Zugabe eines Lösungsmittels, in welchem sie nicht löslich sind, wie Petroläther, ab, filtriert diese Salze ab, dampft das Lösungsmittel ein und rektifiziert das Dicyclohexylcarbodümid im Vakuum.According to the invention, dixyclohexylurea is dehydrated using p-toluenesulphonic acid chloride in the presence of a tertiary base such as pyridine or methylethylpyridine at about 70 to 80 °. After cooling, the pyridine salts formed (mixture of Chloride and p-toluenesulfonate) by adding a solvent in which they are not soluble, such as petroleum ether, these salts are filtered off and the solvent evaporates and rectifies the dicyclohexylcarbodiimide in vacuo.
Das folgende Beispiel soll die Erfindung erläutern. Die Herstellung der Ausgangssubstanz dient nur zur Veranschaulichung; Schutz wird dafür im Rahmen der vorliegenden Erfindung nicht beansprucht.The following example is intended to illustrate the invention. The production the starting substance is for illustration purposes only; Protection is provided for this in the framework of the present invention not claimed.
Beispiel 30 g Harnstoff und 120 g Cyclohexylamin werden unter Rückfluß erhitzt. Es bildet sich zuerst ein voluminöser Niederschlag, dann entstehen zwei Schichten, und schließlich wird die Lösung nach 10 Minuten homogen. Nach Maßgabe des Erhitzens steigt die Temperatur der Reaktionsmischung, die anfänglich durch den Rückfluß des Cyclohexylamins begrenzt ist, an und erreicht nach 2 Stunden 160`. In diesem Moment beobachtet man eine plötzliche Niederschlagsbildung. Man bricht das Erhitzen ab, nimmt das Reaktionsgemisch in salzsäurehaltigem Wasser auf, filtriert es und wäscht den gewonnenen Dicyclohexylharnstoff mit Wasser, Alkohol und Äther. Nach dem Trocknen kristallisiert man ihn aus 100 ccm absolutem Alkohol um und erhält schließlich 54 g Dicyclohexylharnstoff in farblosen Nadeln. F. = 234 bis 235°.Example 30 g of urea and 120 g of cyclohexylamine are refluxed heated. One voluminous precipitate forms first, then two Layers, and finally after 10 minutes the solution becomes homogeneous. In accordance with As the heating rises, the temperature of the reaction mixture initially increases the reflux of the cyclohexylamine is limited and reaches 160 'after 2 hours. At this moment a sudden formation of precipitation can be observed. One breaks the heating is off, the reaction mixture is taken up in hydrochloric acid-containing water and filtered it and washes the obtained dicyclohexylurea with water, alcohol and ether. After drying, it is recrystallized from 100 cc of absolute alcohol and obtained finally 54 g of dicyclohexylurea in colorless needles. F. = 234 to 235 °.
33,6 g des erhaltenen Dicyclohexylharnstoffs, 50 ccm Pyridin und 28,5 g p-Toluolsulfonsäurechlorid werden 11I2 Stunden unter Rühren auf 70 bis 75° erhitzt. Nach dem Abkühlen trennt sich die Mischung in zwei stark gefärbte Schichten. Man versetzt die Reaktionsmasse mit 300 ccm Petroläther, worauf das Py ridinhydrochlorid und -p-toluolsulfonat auskristallisieren. Man saugt die Pyridinsalze ab und wäscht sie auf dem Filter mit Petroläther. Die Petrolätherlösungen werden mit Wasser gewaschen und dann über Magnesiumsulfat getrocknet. Zur Zerstörung des nicht umgesetzten p-Toluolsulfonsäurechlorids setzt man 2 ccm Diäthylamin zu und kocht das Gemisch ',',Stunde in Gegenwart von Aktivkohle. Man filtriert die Aktivkohle ab und dampft das Filtrat zur Trockne ein. Der ölige Rückstand wird im Vakuum rektifiziert. Man erhält 20 g rohes Dicyclohexylcarbodiimid, das bei Kp.3_4 = 130 bis 136' übergeht. Eine erneute Rektifikation liefert das reine Produkt. Kp.3_4 = 131'-; F. = etwa 35`; Ausbeute 15 g (50°'o der Theorie).33.6 g of the dicyclohexylurea obtained, 50 cc of pyridine and 28.5 g of p-toluenesulphonic acid chloride are heated to 70 to 75 ° for 1112 hours with stirring. After cooling, the mixture separates into two strongly colored layers. Man the reaction mass is mixed with 300 cc of petroleum ether, whereupon the pyridine hydrochloride and -p-toluenesulfonate crystallize out. The pyridine salts are suctioned off and washed them on the filter with petroleum ether. The petroleum ether solutions are washed with water and then dried over magnesium sulfate. To destroy the unreacted p-toluenesulfonic acid chloride 2 cc of diethylamine are added and the mixture is boiled for ',', hour in the presence of Activated carbon. The activated charcoal is filtered off and the filtrate is evaporated to dryness. The oily residue is rectified in vacuo. 20 g of crude dicyclohexylcarbodiimide are obtained, which passes over at Kp.3_4 = 130 to 136 '. Another rectification delivers the pure Product. Bp.3_4 = 131'-; F. = about 35 '; Yield 15 g (50% of theory).
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1022223X | 1955-09-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1022223B true DE1022223B (en) | 1958-01-09 |
Family
ID=9577491
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEU4068A Pending DE1022223B (en) | 1955-09-15 | 1956-08-16 | Process for the preparation of dicyclohexylcarbodiimide |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1022223B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1230791B (en) * | 1962-10-13 | 1966-12-22 | Hoechst Ag | Process for the preparation of carbodiimides |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2536079A (en) * | 1946-07-23 | 1951-01-02 | Schering Corp | Alkyl-substituted carbamates |
| DE823445C (en) * | 1950-01-05 | 1951-12-03 | Bayer Ag | Process for the preparation of carbodiimides |
-
1956
- 1956-08-16 DE DEU4068A patent/DE1022223B/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2536079A (en) * | 1946-07-23 | 1951-01-02 | Schering Corp | Alkyl-substituted carbamates |
| DE823445C (en) * | 1950-01-05 | 1951-12-03 | Bayer Ag | Process for the preparation of carbodiimides |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1230791B (en) * | 1962-10-13 | 1966-12-22 | Hoechst Ag | Process for the preparation of carbodiimides |
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