Cyclopropanecarboxylic acid

Structural formula
General
Surname	Cyclopropanecarboxylic acid
other names	Cyclopropyl carboxylic acid Cyclopropanecarboxylic acid
Molecular formula	C 4 H 6 O 2
Brief description	colorless to light yellow liquid
External identifiers / databases
CAS number 1759-53-1 EC number 217-162-5 ECHA InfoCard 100.015.602 PubChem 15655 Wikidata Q2317381
properties
Molar mass	86.09 g mol −1
Physical state	liquid
density	1.087 g cm −3 at 20 ° C
Melting point	14-17 ° C 17-19 ° C
boiling point	182-184 ° C (1.013 hPa )
pK s value	4.83 (25 ° C )
solubility	Fully miscible with water, soluble in diethyl ether
Refractive index	1.4390 (20 ° C)
safety instructions
GHS labeling of hazardous substances danger H and P phrases H: 314 P: 280-301 + 330 + 331-305 + 351 + 338-309 + 310
Toxicological data	172 mg kg −1 ( LD 50 ,  mouse ,  ip )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . Refractive index: Na-D line , 20 ° C

Cyclopropanecarboxylic acid is the smallest cycloalkane that carries a carboxy group that is directly linked to the cyclopropyl group . The compound is the starting material for active pharmaceutical ingredients , pesticides and flavorings .

Natural occurrence and production

The structural element of (3-alkenyl-2,2-dimethyl-substituted) cyclopropanecarboxylic acid is found in the naturally occurring insecticidal pyrethrins and the synthetic pyrethroids derived from them , as well as in the non-proteinogenic amino acid aminocyclopropanecarboxylic acid .

The chemical synthesis of the cyclopropanecarboxylic acid takes place by complete hydrolysis of the nitrile group of the cyclopropanecarbonitrile with sulfuric acid via the intermediate stage of the carboxamide or biochemically with enzyme preparations from Rhodococcus strains and delivers the target product in 74 to 79% or approx. 90% yield.

In the air oxidation of cyclopropanecarboxaldehyde , yields of cyclopropanecarboxylic acid of up to 92% are achieved.

properties

Cyclopropane carboxylic acid is an organic carboxylic acid with a pungent odor and with the linear C ₃ acid propionic acid (pK _s = 4.87) almost identical acidity . In aqueous solution (10 g · l ⁻¹ at 22 ° C ) its pH value is 3. The compound dissolves in alcohols and in most organic solvents.

Applications

Under pressure (45 bar) and high temperatures (240 ° C.), cyclopropanecarboxylic acid and ammonia are converted into cyclopropanecarboxamide in 90% yield.

Cyclopropylamine can be obtained in 82% yield by reaction of cyclopropanecarboxylic acid with phosphorus trichloride to form cyclopropanecarbonyl chloride, its amidation with ammonia to form cyclopropanecarboxamide and further Hofmann rearrangement with bromine and sodium hydroxide solution (with formation of sodium hypobromite ).

The ethyl ester ethylcyclopropanecarboxylate, which can be obtained in 98% yield by esterification of cyclopropanecarboxylic acid with ethanol, is the starting material in the multi-stage synthesis of the antipsychotic pimozide .

Higher esters of cyclopropanecarboxylic acid are suitable as fragrances and flavors , such as. B. the cis -3-hexenol ester, to which a distinctive "rainforest" aroma is ascribed.

The reaction of the ethyl cyclopropylcarboxylate with toluene under Friedel-Crafts acylation conditions gives 2-methyl-1-indanone in 93% yield,

an intermediate stage for the ring-expanding synthesis (by reaction with n- butyl nitrite ) of isoquinolones (also known as isocarbostyrils), the basic structure of which is found in some alkaloids .

The hydrogenation of ethyl cyclopropanecarboxylate on a zinc oxide contact produces cyclopropylmethanol in almost quantitative yield, which can be rearranged to cyclobutanol in a one-pot reaction with hydrochloric acid with ring expansion and then oxidized to cyclobutanone with chromium (VI) oxide with yields of approx. 35% .

This synthetic route seems to offer a cheap and easy access to cyclobutanone.

That with thionyl chloride obtainable from cyclopropanecarboxylate cyclopropanecarbonyl is used in the synthesis of the opioid - analgesic buprenorphine , the opioid antagonist naltrexone and the benzodiazepine Prazepam . It is also a building block for the herbicides cyprazole, cypromid and cyclosulfamuron and the fungicide cyprofuram.

Individual evidence

1. ↑ ^{a b c d e f g} Data sheet cyclopropanecarboxylic acid for synthesis (PDF) from Merck , accessed on January 28, 2018.
2. ↑ ^{a b c} data sheet cyclopropanecarboxylic acid from Sigma-Aldrich , accessed on January 28, 2018 ( PDF ).
3. ^ William M. Haynes: CRC Handbook of Chemistry and Physics, 97th Edition . CRC Press, Boca Raton, FL, USA 2017, ISBN 978-1-4987-5429-3 , pp. 5-90 .
4. ↑ ^{a b} Datasheet Cyclopropanecarboxylic acid, 98% from AlfaAesar, accessed on January 28, 2018 ( PDF )(JavaScript required) .
5. ^ CM McCloskey, GH Coleman: Cyclopropanecarboxylic acid In: Organic Syntheses . 24, 1944, p. 36, doi : 10.15227 / orgsyn.024.0036 ; Coll. Vol. 3, 1955, p. 221 ( PDF ).
6. ↑ N. Matsuo, T. Mori (Eds.): Pyrethroids, From Chrysanthemum to Modern Industrial Insecticide, Topics in Current Chemistry 314 . Springer, Berlin 2007, ISBN 978-3-642-27345-2 .
7. ↑ F. Brackmann, A. de Meijere: Natural occurrence, syntheses, and applications of cyclopropyl-group-containing α-amino acids. 1. 1-Aminocyclopropanecarboxylic acid and other 2,3-methanoamino acids . In: Chem. Rev. Band 107 , no. 11 , 2007, p. 4493-4537 , doi : 10.1021 / cr078376j .
8. ^ CM McCloskey, GH Coleman: Cyclopropanecarboxylic acid In: Organic Syntheses . 24, 1944, p. 36, doi : 10.15227 / orgsyn.024.0036 ; Coll. Vol. 3, 1955, p. 221 ( PDF ).
9. ↑ MA Cohen, J. Sawden, NJ Turner: Selective hydrolysis of nitriles under mild conditions by on enzymes . In: Tetrahedron Lett. tape 31 , no. 49 , 1990, pp. 7223-7226 , doi : 10.1016 / S0040-4039 (00) 97285-X .
10. ↑ ^{a b c d} Patent US5663418 : Process for the preparation of cyclopropanecarboxylic acid and derivatives thereof. Applied on November 27, 1995 , published on September 2, 1997 , Applicant: Eastman Chemical Co., Inventor: S. Liang, TW Price. ‌
11. ↑ W. Kirmse, O. Schnurr, H. Jendralla: Deamination reactions, 33. Reactions of aliphatic diazonium ions with lithium azide . In: Chem. Ber. tape 112 , no. 6 , 1979, pp. 2120-2144 , doi : 10.1002 / cber.19791120621 .
12. ^ R. Vardanyan, V. Hruby: Synthesis of Essential Drugs . Elsevier BV, Amsterdam 2006, ISBN 978-0-444-52166-8 , pp. 96 .
13. ↑ Patent EP0869111A1 : Cyclopropyl carboxylic acid ester and uses thereof in imparting, augmenting and enhancing aromas. Filed February 6, 1998 , published October 7, 1998 , Applicant: International Flavors & Fragrances, Inc., Inventors: MG Monteleone, GI Malcolm, MR Hanna, MD Evans. ‌
14. ↑ HW Pinnick, SP Brown, EA McLean, LW Zoller III: Friedel-Crafts reactions of ethyl cyclopropane carboxylate . In: J. Org. Chem. Band 46 , no. 18 , 1981, p. 3758-3760 , doi : 10.1021 / jo00331a046 .
15. ↑ EJ Moriconi, FJ Creegan: 2-Hydroxy-2-methylisocarbostyril In: Organic Syntheses . 48, 1968, p. 90, doi : 10.15227 / orgsyn.048.0090 ; Coll. Vol. 5, 1973, p. 63 ( PDF ).
16. ↑ Patent EP0728722A1 : Process for the production of hydroxymethyl-cyclopropane. Applied on February 8, 1996 , published on August 28, 1996 , Applicant: Bayer AG, Inventors: L. Frohn, R. Langer, G. Darsow, E. Zirngiebl, J.-D. Jentsch, B. Pennemann, C. Tiburtius. ‌
17. ↑ M. Krumpolc, J. Rocek: Cyclobutanone In: Organic Syntheses . 60, 1981, p. 20, doi : 10.15227 / orgsyn.060.0020 ; Coll. Vol. 7, 1990, p. 114 ( PDF ).
18. ↑ Compendium of Pesticide Common Names, http://www.alanwood.net/pesticides/index.html