2,3,5,6-tetramethyl pyrazine

2,3,5,6-tetramethyl pyrazine, also known by names including tetramethylpyrazine, chuanxingzine, and ligustrazine, is a heterocyclic aromatic organic compound with the molecular formula C₈H₁₂N₂. It appears as a crystalline solid with a melting range of 85 to 90°C and exhibits distinctive nutty, cocoa, and coffee aroma characteristics. This compound is naturally found in various roasted and fermented foods such as coffee, cocoa, roasted beef, green tea, soy products, and certain nuts. It can be sourced through natural extraction or produced synthetically for use in flavor and fragrance applications. Detailed chemical and safety data for this compound are available via links such as PubChem, facilitating further research and formulation.

2,3,5,6-tetramethyl pyrazine naturally occurs in a diverse array of foods including coffee, cocoa products, roasted beef, dairy products, green tea, peanuts, macadamia nuts, cheese, rum, and soybeans. Its presence contributes nutty, cocoa, coffee, and roasted notes to these matrices. It is applied widely as a flavor and fragrance ingredient, enhancing chocolate, coffee, nutty, and green aroma profiles. Beyond food flavoring, it is utilized in cosmetic formulations as a perfuming agent. Its use is regulated under FEMA (US) guidelines among others, supporting safe inclusion levels in various consumer products.

This compound is a crystalline solid with melting points between 85 and 90°C at 760 mmHg. It exhibits a vapor pressure of approximately 0.671 mmHg at 25°C, indicating moderate volatility. The flash point is around 93°C (200°F), signifying a moderate flammability hazard. With a logP value near 1.28, it has moderate lipophilicity, enabling solubility in alcohol, fixed oils, propylene glycol, and water at roughly 7007 mg/L at 25°C. Stability is classified as good in alcoholic fine fragrances, antiperspirants, detergents, soaps, and fabric softeners but poor in hypochlorite bleach. These physicochemical traits influence its formulation behavior, handling, and application in flavor and fragrance products.

	2,3,5,6-tetramethylpyrazine
NIST Chemistry WebBook:	Search Inchi
Canada Domestic Sub. List:	1124-11-4
Pubchem (cid):	14296
Pubchem (sid):	134980455
Pherobase:	View

(IUPAC):	Atomic Weights of the Elements 2011 (pdf)
Videos:	The Periodic Table of Videos
tgsc:	Atomic Weights use for this web site
(IUPAC):	Periodic Table of the Elements
FDA Substances Added to Food (formerly EAFUS):	View
CHEMBL:	View
HMDB (The Human Metabolome Database):	HMDB36584
FooDB:	FDB015495
Export Tariff Code:	2933.99.9700
VCF-Online:	VCF Volatile Compounds in Food
ChemSpider:	View

Safety information

Preferred SDS: View
European information :
Most important hazard(s):
Xn - Harmful.
R 22 - Harmful if swallowed. R 36/37/38 - Irritating to eyes, respiratory system, and skin. R 41 - Risk of serious damage to eyes. S 02 - Keep out of the reach of children. S 20/21 - When using do not eat, drink or smoke. S 24/25 - Avoid contact with skin and eyes. S 26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S 37/39 - Wear suitable gloves and eye/face protection.
Hazards identification
Classification of the substance or mixture
GHS Classification in accordance with 29 CFR 1910 (OSHA HCS)
None found.
GHS Label elements, including precautionary statements
Pictogram
Hazard statement(s)
None found.
Precautionary statement(s)
None found.
Oral/Parenteral Toxicity:
gavage-rat LD50 1910 mg/kg (Oser, 1969g) intravenous-mouse LD50 239 mg/kg Chinese Medical Journal Vol. 4, Pg. 319, 1978. intraperitoneal-mouse LD50 800 ug/kg International Journal of Crude Drug Research. Vol. 23, Pg. 119, 1985. oral-rat LD50 1910 mg/kg Drug and Chemical Toxicology. Vol. 3, Pg. 249, 1980.
Dermal Toxicity:
Not determined
Inhalation Toxicity:
Not determined

Safety in use information

Category:
cosmetic, flavor and fragrance agents
RIFM Fragrance Material Safety Assessment: Search
IFRA Code of Practice Notification of the 49th Amendment to the IFRA Code of Practice
Recommendation for 2,3,5,6-tetramethyl pyrazine usage levels up to:
	0.6000 % in the fragrance concentrate.
Maximised Survey-derived Daily Intakes (MSDI-EU):		6.70 (μg/capita/day)
Maximised Survey-derived Daily Intakes (MSDI-USA):		19.00 (μg/capita/day)
Structure Class:		II
Use levels for FEMA GRAS flavoring substances on which the FEMA Expert Panel based its judgments that the substances are generally recognized as safe (GRAS).
The Expert Panel also publishes separate extensive reviews of scientific information on all FEMA GRAS flavoring substances and can be found at FEMA Flavor Ingredient Library
publication number: 4
Click here to view publication 4
		average usual ppm	average maximum ppm
baked goods:		-	5.00000
beverages(nonalcoholic):		-	5.00000
beverages(alcoholic):		-	-
breakfast cereal:		-	-
cheese:		-	-
chewing gum:		-	-
condiments / relishes:		-	10.00000
confectionery froastings:		-	-
egg products:		-	-
fats / oils:		-	-
fish products:		-	-
frozen dairy:		-	-
fruit ices:		-	-
gelatins / puddings:		-	-
granulated sugar:		-	-
gravies:		-	10.00000
hard candy:		-	5.00000
imitation dairy:		-	-
instant coffee / tea:		-	-
jams / jellies:		-	-
meat products:		-	10.00000
milk products:		-	5.00000
nut products:		-	-
other grains:		-	-
poultry:		-	-
processed fruits:		-	-
processed vegetables:		-	-
reconstituted vegetables:		-	-
seasonings / flavors:		-	-
snack foods:		-	-
soft candy:		-	-
soups:		-	10.00000
sugar substitutes:		-	-
sweet sauces:		-	-

Safety references

European Food Safety Athority(EFSA):Flavor usage levels; Subacute, Subchronic, Chronic and Carcinogenicity Studies; Developmental / Reproductive Toxicity Studies; Genotoxicity Studies...

European Food Safety Authority (EFSA) reference(s):

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to Flavouring Group Evaluation 17 (FGE.17): Pyrazine derivatives from chemical group 24 (Commission Regulation (EC) No 1565/2000 of 18 July 2000) View page or View pdf

Flavouring Group Evaluation 50 (FGE.50): Consideration of pyrazine derivatives evaluated by JECFA (57th meeting) structurally related to pyrazine derivatives evaluated by EFSA in FGE.17 (2005) (Commission Regulation (EC) No 1565/2000 of 18 July 2000) - Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC) View page or View pdf

Flavouring Group Evaluation 17, Revision 1 (FGE.17Rev1): Pyrazine derivatives from chemical group 24 - Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with Food (AFC) [1] View page or View pdf

Scientific Opinion on Flavouring Group Evaluation 17, Revision 2 (FGE.17Rev2): Pyrazine derivatives from chemical group 24 View page or View pdf

Scientific Opinion on Flavouring Group Evaluation 50, Revision 1 (FGE.50Rev1): Consideration of pyrazine derivatives evaluated by JECFA (57th meeting) structurally related to pyrazine derivatives evaluated by EFSA in FGE.17Rev2 (2010) View page or View pdf

Safety and efficacy of pyrazine derivatives including saturated ones belonging to chemical group 24 when used as flavourings for all animal species View page or View pdf

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EPA Substance Registry Services (TSCA):1124-11-4

EPA ACToR:Toxicology Data

EPA Substance Registry Services (SRS):Registry

Laboratory Chemical Safety Summary :14296

National Institute of Allergy and Infectious Diseases:Data

WGK Germany:3

2,3,5,6-tetramethylpyrazine

Chemidplus:0001124114

RTECS:UQ3905000 for cas# 1124-11-4