2-Isopropyl-N,2,3-trimethylbutyramide

2-Isopropyl-N,2,3-trimethylbutyramide Property

Melting point:

58-61 °C

Boiling point:

bp0.35mm 83-85°

Density 

0.9419 (rough estimate)

vapor pressure 

0.3-0.32Pa at 25℃

refractive index 

1.4621 (estimate)

FEMA 

3804 | 2-ISOPROPYL-N,2,3-TRIMETHYLBUTYRAMIDE

storage temp. 

Sealed in dry,Room Temperature

pka

16.46±0.46(Predicted)

form 

Solid

color 

White to Almost white

Odor

at 25.00 % in dipropylene glycol. mild cooling mentholic minty

Odor Type

minty

JECFA Number

1595

Merck 

14,9716

LogP

2.5 at 25℃ and pH7

CAS DataBase Reference

51115-67-4(CAS DataBase Reference)

EPA Substance Registry System

Butanamide, N,2,3-trimethyl-2-(1-methylethyl)- (51115-67-4)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38-52/53

Safety Statements 

37/39-26

HS Code 

29242990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H319Causes serious eye irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P330Rinse mouth.

P501Dispose of contents/container to..…

2-Isopropyl-N,2,3-trimethylbutyramide Chemical Properties,Usage,Production

Description

2-isopropyl-N,2,3-trimethylbutyramide is one nearly odorless white crystalline powder widely used as a coolant in medicinal preparations, oral care products, foodstuffs, cosmetics, and confection-eye products. It is an artificial synthesis cooling agent and could be synthesized by the Ritter reaction of 2,2-diisopropylpropionitrile (DIPPN) with methanol in the presence of acid. Compared with menthol, WS-23 is characterized by a continuous and long-lasting cooling and refreshing effect with no side effects of burning or stinging sensations. As an important additive in menthol cigarettes, WS-23 can cover up the bitter and astringent taste of cigarettes, make the cigarette feel fresh, improve the coordination and softness of cigarette smoke, and reduce the thorn in the mouth and throat. WS-23 is also compatible with other flavors and cooling agents[1].

Chemical Properties

N,2,3-Trimethyl-2-isopropylbutanamide is a white, crystalline powder,which gives a physiological cooling sensation on skin or mucosa. It is mainly used to create cooling and freshness in oral care preparations.
The material can be prepared by a Ritter reaction using N,2,3-trimethyl-2- isopropylbutyronitrile as the starting material and alkylating agents such as, for example, borates, carbonates, or phosphates.

Chemical Properties

2-Isopropyl-N-2,3-trimethylbutyramide has a cool, mint–menthol-type odor

Uses

2-Isopropyl-N,2,3-trimethylbutanamide is flavored compound and comprising the recount flavored compound for electronic cigarette liquid.

Uses

Physiological coolant in foods, beverages, tobacco products, toiletries, cosmetics and pharmaceuticals.

Definition

ChEBI: N,2,3-Trimethyl-2-(1-methylethyl)butanamide is a fatty amide.

Aroma threshold values

Aroma characteristics at 5.0%: slight cooling impact with little character.

Taste threshold values

Taste characteristics at 20 ppm: high-impacting cooling that lasts on the tongue and palate.

Trade name

Winsense WS-23 (Renessenz).

Synthesis

Step 3: 3-isopropyl-4-methyl-2-pentanone (128 g, 0.82 mol) obtained above was dissolved in tetrahydrofuran, followed by the addition of hydroxylamine hydrochloride (1.2 equiv.) and potassium carbonate and the reaction was stirred. The progress of the reaction was monitored by TLC and after confirming that the reaction was complete, water was added to the reaction mixture and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 135 g of crude product. The crude product was dissolved in polyphosphonic acid and heated to 100 °C for 3-8 hours. After the reaction was completed, the reaction solution was neutralized with alkali, extracted again with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate and then distilled under reduced pressure to remove the solvent. Finally, it was purified by recrystallization to obtain N,2,3-trimethyl-2-isopropylbutyramide 85 g with 99% purity and 49.7% combined yield.

References

[1] Ze-Hong Wu. “Acute and subacute inhalation toxicity assessment of WS-23 in Sprague-Dawley rats.” Journal of Applied Toxicology (2021): 1826–1838.