Benoxinate Hydrochloride Chemical Properties

Melting point:

157-160 C

storage temp. 

2-8°C

solubility 

Very soluble in water, freely soluble in ethanol (96 per cent).

color 

White to Off-White

Merck 

13,1045

InChI

InChI=1S/C17H28N2O3.ClH/c1-4-7-11-21-16-13-14(8-9-15(16)18)17(20)22-12-10-19(5-2)6-3;/h8-9,13H,4-7,10-12,18H2,1-3H3;1H

InChIKey

PRGUDWLMFLCODA-UHFFFAOYSA-N

SMILES

C1(C(=O)OCCN(CC)CC)=CC=C(N)C(OCCCC)=C1.Cl

CAS DataBase Reference

5987-82-6(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi,Xn

Risk Statements 

36/37/38-20/21/22

Safety Statements 

22-26-36

RIDADR 

UN 1544PSN2 6.1 / PGIII

WGK Germany 

3

RTECS 

DG1502900

HS Code 

29225000

Toxicity

LD50 scu-rat: 60 mg/kg NIIRDN 6,154,82

Benoxinate Hydrochloride Usage And Synthesis

Chemical Properties

White or almost white, crystalline powder or colourless crystals.

Originator

Dorsacaine HCl,Dorsey,US,1953

Uses

antibacterial, coccidiostat

Uses

Benoxinate Hydrochloride is a local anesthetic used in ophthalmology to numb the surface of the eye for a variety of procedures.

Uses

anticonvulsant

Definition

ChEBI: The monohydrochloride salt of oxybuprocaine.

Manufacturing Process

25 grams of 3-oxy-4-nitrobenzoic acid are esterified (ethyl ester) and 26 grams of the ester are dissolved in 200 cc of absolute ether and treated with 7 grams of caustic potash in 20 cc of absolute methanol. The red potassium phenolate with 7 grams of pure butyl bromide and 7 grams of absolute alcohol are heated for 5 hours in the oven to 150°C. When cool, the alcohol is evaporated in vacuo and the butoxy-nitrobenzoic acid ethyl ester is precipitated with water. The substance is sucked off and saponified for 15 minutes with a solution of 2.5 grams of caustic potash in 30 cc of alcohol on a water bath. The alcohol is evaporated in vacuo and the 3-butoxy-4- nitrobenzoic acid is precipitated with hydrochloric acid. It forms needles which melt at 174°C. 7.9 grams of dry acid are boiled for 45 minutes under a reflux condenser with 25 cc of thionyl chloride. The excess of thionyl chloride is then removed in vacuo, and the oil is distilled. The acid chloride has a yellow color and solidifies.
7.3 grams of the acid chloride are treated with 6.6 grams of diethyl-aminoethanol in 20 cc of absolute benzene. The mixture is then warmed for 1 hour on a water bath. When cold, it is treated with a solution of soda and washed with ether. After drying over potash, the ether and benzene are removed by distillation and 3-butoxy-4-nitrobenzoic acid diethylamino-ethyl ester is obtained, having a BP 215°C/2.5 mm.
5.0 grams of this product are hydrogenated in absolute alcohol solution with fresh Raney nickel. When the absorption of hydrogen ceases (5 hours), the solution is filtered and the alcohol evaporated in vacuo. The 3-butoxy-4- aminobenzoic acid diethyl-amino-ethyl ester boils at 215°-218°C at 2 mm pressure; it is an almost colorless oil.
By precipitation of a solution of the ester in absolute ether with hydrogen chloride gas, the dihydrochloride is obtained; upon recrystallization from alcohol/ether, it forms crystals which melt at 196°-197°C.

brand name

Dorsacaine (Novartis).

Therapeutic Function

Local anesthetic

Clinical Use

Benoxinate hydrochloride is a topical anesthetic. Benoxinate hydrochloride ophthalmic solution, 0.4%, was originally permitted in 1953 as Dorsacaine under NDA 08-729. The product was reviewed as part of the Drug Efficacy Study Implementation (DESI), found to be effective, approved and marketed by Dorsey until 1980. An abbreviated new drug application (ANDA) was also approved [Sola Barnes Hind (ANDA 84-149)] and marketed until 1991.

Safety Profile

Poison by subcutaneous route. A topical anesthetic. When heated to decomposition it emits toxic fumes of NOx and HCl.

structure and hydrogen bonding

Oxybuprocaine hydrochloride acts as a local anesthetic and is used in eye drop formulations. Mod. II, the stable polymorphic form, contains two molecules with markedly different conformations (stretched and bent). The 13C CPMAS NMR spectrum of this sample12 showed crystallographic splittings arising from the fact that there are two molecules in the asymmetric unit. An INADEQUATE two-dimensional experiment was used to link signals for the same independent molecule. Of the four ethyl groups attached to NHt nitrogens, one gives rise to unusually low chemical shifts, very different from those of the other three groups. This was attributed to gamma-gauche conformational effects, and confirmed by shielding computations. The oxybuprocaine system is too large for computations performed on the crystallographic unit and the intermolecular shielding effects have to be neglected. Nevertheless, the computed shifts do match the order of the experimental ones. The assignment of 13C signals to specific carbons in the two crystallographically inequivalent molecules of oxybuprocaine polymorph showed the power of NMR crystallography.

Benoxinate Hydrochloride(5987-82-6)Related Product Information

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