Dicyclohexylcarbodiimide

Structural formula
General
Surname	N , N '-dicyclohexylcarbodiimide
other names	Dicyclohexylcarbodiimide DCC Carbodiimidyl dicyclohexane
Molecular formula	C 13 H 22 N 2
Brief description	colorless solid with a characteristic odor
External identifiers / databases
CAS number 538-75-0 EC number 208-704-1 ECHA InfoCard 100.007.914 PubChem 10868 Wikidata Q306565
properties
Molar mass	206.33 g mol −1
Physical state	firmly
density	0.95 g cm −3 (40 ° C)
Melting point	35-36 ° C
boiling point	154–156 ° C (at 15 h Pa )
solubility	almost insoluble in water
safety instructions
GHS hazard labeling from  Regulation (EC) No. 1272/2008 (CLP) , expanded if necessary danger H and P phrases H: 302-311-317-318 P: 280-301 + 312 + 330-302 + 352 + 312-305 + 351 + 338 + 310
Toxicological data	1110 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

N , N '-Dicyclohexylcarbodiimid (abbreviated DCC , also N , N ' -Dicyclohexylmethandiimin) is a reactive organic compound from the group of the carbodiimides , which is often used in synthetic chemistry . Under standard conditions, DCC is a colorless solid with a weak, characteristic odor.

Presentation and extraction

One illustration is based on dicyclohexylthiourea, the reaction with mercury (II) oxide via a sulfur-oxygen exchange producing the corresponding urea derivative as an intermediate and, after subsequent dehydration, the target compound.

In a similar synthesis route, dicyclohexylurea is dehydrated in the presence of a sulfonic acid chloride (e.g. TsCl ) and potassium carbonate as the base or triphenylphosphine and triethylamine as the base.

properties

Dicyclohexylcarbodiimide is a low melting solid with a melting point of 34-35 ° C. At colder ambient temperatures, the substance can also be in liquid form as a supercooled melt. Since the compound tends to polymerize and decompose at higher temperatures, distillation can only take place under reduced pressure. The boiling point is 148–152 ° C at a pressure of 15 mbar. The flash point is relatively high at 113 ° C. The connection is thermally unstable. A DSC measurement shows an exothermic decomposition reaction from 254 ° C with an exothermicity of −269 kJ kg ⁻¹ or −55.5 kJ mol ⁻¹ .

use

DCC is mainly used in the synthesis of organic esters and amides . In particular with sterically demanding starting materials , there are significant increases in yield. In addition, in contrast to Fischer esterification , it enables esterifications and amidations under very mild conditions, which is of interest for acid-labile starting materials such as tert-butyl alcohol . Therefore, DCC also plays an important role in in vitro peptide synthesis and in the introduction of protective groups .

Esterification and amidation with DCC

Carboxy groups add rapidly to a C = N double bond of the DCC, with the corresponding O- acylisourea being formed. This ester is very reactive (comparable to an acid anhydride), so that it is easily converted from amines to amide. An acyl group transfer agent such as DMAP is also required for the reaction with alcohols and this is known as a Steglich esterification . In total, the water resulting from the condensation of the acid with the alcohol / amine is absorbed by the DCC and this is converted into N , N '-dicyclohexylurea.

In esterifications, a 1,3-rearrangement often occurs as a competing reaction, in which the O -acylisourea reacts irreversibly to form the N -acylurea. Both acyl group transfer agents and acid catalysis can suppress this reaction, but both are still the subject of current research. Further problems of these reactions result in particular in the purification of the product from the N , N '-dicyclohexylurea obtained or from acid anhydrides that are also formed.

DCC- activated esterifications are usually carried out at 0 to 25 ° C and in dry (DCC is water-sensitive) dichloromethane , as this has been used to achieve the best yields in the past. The urea derivative that forms is also insoluble in dichloromethane and thus precipitates out of the reaction solution.

Other carbodiimides and the standard protective group reagent di- tert-butyl dicarbonate (Boc ₂ O) have been proposed as alternatives to DCC .

safety instructions

DCC can be toxic even after skin contact, but it can also cause severe irritation of the respiratory tract or eye damage. DCC has a sensitizing effect .

Web links

• DCC in peptide synthesis
• Reaction mechanism of a DCC coupling

Individual evidence

1. ↑ ^{a b c d e} data sheet dicyclohexylcarbodiimide (PDF) from Merck , accessed on January 19, 2011.
2. ↑ ^{a b c} Entry on dicyclohexylcarbodiimide in the GESTIS substance database of the IFA , accessed on January 8, 2020(JavaScript required) .
3. ↑ Günter Losse, Werner Zönnchen: The formyl group, an oxidative removable protecting group for peptide synthesis. In: Justus Liebig's Annals of Chemistry. 636, 1960, pp. 140-143, doi : 10.1002 / jlac.19606360113 .
4. ↑ Entry on dicyclohexylcarbodiimide in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), accessed on February 1, 2016. Manufacturers or distributors can expand the harmonized classification and labeling .
5. ^ S. Hauptmann, J. Graefe, H. Remane: Textbook of organic chemistry , Deutscher Verlag für Grundstoffindustrie, Leipzig 1976, p. 433.
6. ↑ ZM Jászay; I. Petneházy; L. Töke; B. Szajáni: Preparation of Carbodiimides Using Phase-Transfer Catalysis . In: Synthesis 1987, 520-523. doi : 10.1055 / s-1987-27992 .
7. ↑ R. Appel; R. Kleinstück; K.-D. Ziehn: About the joint action of phosphines and carbon tetrachloride on ammonia (derivatives), IV note about a new carbodiimide synthesis . In: Chem. Ber. 104 (1971) 1335-1336. doi : 10.1002 / cber.19711040438 .
8. ↑ ^{a b c} Sorbe: Safety characteristics of chemical substances. 130. Supplementary delivery 6/2009, ecomed-Verlag.
9. ↑ Sperry, JB; Minteer, CJ; Tao, J .; Johnson, R .; Duzguner, R .; Hawksworth, M .; Oke, S .; Richardson, PF; Barnhart, R .; Bill, DR; Giusto, RA; Weaver, JD: Thermal Stability Assessment of Peptide Coupling Reagents Commonly Used in Pharmaceutical Manufacturing in Org. Process Res. Dev. 22 (2018) 1262-1275, doi : 10.1021 / acs.oprd.8b00193 .
10. ↑ Harold Wiener, Chaim Gilon: An improved method for the catalytic preparation of t-butyl esters of carboxylic and fatty acids. In: Journal of Molecular Catalysis. 37, 1986, pp. 45-52, doi : 10.1016 / 0304-5102 (86) 85136-7 .
11. ↑ Bernhard Neises, Wolfgang Steglich: Simple Method for the Esterification of Carboxylic Acids. In: Angewandte Chemie International Edition in English. 17, 1978, pp. 522-524, doi : 10.1002 / anie.197805221 .
12. ↑ Eric FV Scriven: 4-Dialkylaminopyridines: super acylation and alkylation catalysts. In: Chemical Society Reviews. 12, 1983, p. 129, doi : 10.1039 / CS9831200129 .
13. ↑ K. Holmberg, B. Hansen: Ester Synthesis with Dicyclohexylcarbodiimide Improved by Acid Catalysts . In: Acta Chem. Scand. 1979, B33, 410-412, doi : 10.3891 / acta.chem.scand.33b-0410 , PDF .
14. ^ ^{A b} Jeffrey S. Moore, Samuel I. Stupp: Room temperature polyesterification. In: Macromolecules. 23, 1990, pp. 65-70, doi : 10.1021 / ma00203a013 .
15. ↑ EP Boden, GE Keck: Proton-transfer steps in Steglich esterification: a very practical new method for macrolactonization in J. Org. Chem. 1985, 50, 2394-2395, doi : 10.1021 / jo00213a044 .
16. ↑ Lukas J. Goossen, Arno Döhring: A Convenient Protocol for the Esterification of Carboxylic Acids with Alcohols in the Presence of di-t-Butyl Dicarbonate. In: Synlett. 2004, p. 0263, doi : 10.1055 / s-2003-44986 .