106131-61-7

Basic information

• Product Name: 3,6-Dichloro-1,2,4,5-tetrazine
• Synonyms: 3,6-Dichloro-1,2,4,5-tetrazine;3,6-Dichloro-s-tetrazine;Dichloro-s-tetrazine;dichloro-1,2,4,5-tetrazine
• CAS NO: 106131-61-7
• Molecular Formula: C₂Cl₂N₄
• Molecular Weight: 150.9542
• Mol File: 106131-61-7.mol
• Article Data: 11

Chemical Properties

• Melting Point: 148℃
• Boiling Point: 331.0±25.0 °C(Predicted)
• Appearance: /
• Density: 1.750±0.06 g/cm3(Predicted)
• Storage Temp.: 2-8°C
• PKA: -5.54±0.10(Predicted)
• CAS DataBase Reference: 3,6-Dichloro-1,2,4,5-tetrazine(CAS DataBase Reference)
• NIST Chemistry Reference: 3,6-Dichloro-1,2,4,5-tetrazine(106131-61-7)
• EPA Substance Registry System: 3,6-Dichloro-1,2,4,5-tetrazine(106131-61-7)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26
• WGK Germany: 3
• Hazardous Substances Data: 106131-61-7(Hazardous Substances Data)

Usage

Description

3,6-Dichloro-1,2,4,5-tetrazine is a chemical compound characterized by the presence of two chlorine atoms at the 3rd and 6th positions on a tetrazine ring. It is known for its unique photochemical properties and has been utilized in various applications due to its reactive nature.

Uses

Used in Stapling of Complex Peptides:
3,6-Dichloro-1,2,4,5-tetrazine is used as a photochemical trigger for the stapling of complex peptides. This innovative application has been demonstrated by Professor Amos Smith and his team in several recent reports. The stapling process involves the use of this compound to covalently link peptide chains, enhancing their stability and bioactivity. This technique has significant implications in the development of therapeutic peptides and drug delivery systems.

Synthetic route

3,6-dihydrazinyl-1,2,4,5-tetrazine (5940-53-4) → 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7)

Conditions	Yield
With trichloroisocyanuric acid In acetonirile at 0 - 20℃;	81%
With trichloroisocyanuric acid In acetonitrile at 0 - 20℃; for 0.833333h; Inert atmosphere;	68%
With trichloroisocyanuric acid In acetonitrile at 0 - 20℃; for 0.333333h;	67%

3,6-dimethylthio-1,2,4,5-tetrazine (1672-34-0) → 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7)

Conditions	Yield
	68%

3,6-bis-(3,5-dimethyl-pyrazol-1-yl)-1,2,4,5-tetrazine (30169-25-6) → 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7)

Conditions	Yield
Stage #1: 3,6-bis-(3,5-dimethyl-pyrazol-1-yl)-1,2,4,5-tetrazine With hydrazine Stage #2: With chlorine

[1,2,4,5]tetrazinane-3,6-dione dihydrazone (5940-11-4) → 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7)

Conditions	Yield
With trichloroisocyanuric acid In acetonitrile at 0 - 20℃; for 0.333333h;

N,N-bis(4-bromophenyl)-4-hydroxyphenylamine (336619-79-5) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3-{4-[bis(4-bromophenyl)amino]phenoxy}-6-chloro-1,2,4,5-tetrazine (1374356-14-5)

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃; for 1h;	100%

N-aminopyridin-1-ium iodide (6295-87-0) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → (6-chloro-1,2,4,5-tetrazin-3-yl)(pyridin-1-ium-1-yl)amide

Conditions	Yield
With potassium carbonate In acetonitrile at 23℃; for 3h;	99%

9-methoxy-7H-furo[3,2-g][1]benzopyran-7-one (298-81-7) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 2-chloro-6-methoxypyridazino[4,3-h]psoralen (647021-08-7)

Conditions	Yield
Stage #1: 9-methoxy-7H-furo[3,2-g][1]benzopyran-7-one; 3,6-dichloro-1,2,4,5-tetrazine In dichloromethane at 140℃; Stage #2: With N-ethyl-N,N-diisopropylamine	98%

morpholine (110-91-8) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 4-(6-chloro-1,2,4,5-tetrazin-3-yl)morpholine (106131-66-2)

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃; for 1h;	97%
With N-ethyl-N,N-diisopropylamine In tert-butyl methyl ether at 20℃; for 21h; Inert atmosphere;	87%
In various solvent(s) at 20℃;	83%

(4-(di-tert-butylfluorosilyl)phenyl)methanol (1146956-36-6) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3-chloro-6-((4-(di-tert-butylfluorosilyl)-benzyl)oxy)-1,2,4,5-tetrazine

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃; for 0.666667h; Inert atmosphere;	95%
With 2,4,6-trimethyl-pyridine In dichloromethane for 0.583333h; Inert atmosphere;	95%

[18F]-SiFA-OH + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → C17H24Cl(18)FN4OSi

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane for 0.25h;	95%

N-acetylcystein (616-91-1) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3,6-bis-S,S'-(NHAc-Cys-OH)tetrazine (1234326-41-0)

Conditions	Yield
With ammonium bicarbonate In 1,4-dioxane; water for 1h; Inert atmosphere; Darkness;	93%
In acetonitrile at 80℃; for 24h; Kinetics; Solvent; pH-value; Temperature; Inert atmosphere;	49%

4-(di-tert-butylfluorosilanyl)benzenethiol (1112840-20-6) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3-chloro-6-((4-(di-tert-butylfluorosilyl)phenyl)-thio)-1,2,4,5-tetrazine

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃; for 0.666667h; Inert atmosphere;	93%

1-ferrocenylmethanol (1273-86-5) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3-chloro-6-(ferrocenemethoxy)-1,2,4,5-tetrazine

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane for 0.666667h; Inert atmosphere;	93%

4,4'-(s-tetrazine-3,6-diyl)bis(oxy)dibutan-1-ol (907560-43-4) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3,6-bis(4-(6-chloro-1,2,4,5-tetrazin-3-yloxy)butoxy)-1,2,4,5-s-tetrazine (1040376-29-1)

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane Inert atmosphere;	92%

1,2,4-Triazole (288-88-0) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3,6-bis(1,2,4-triazolyl-1-yl)1,2,4,5-tetrazine (1612764-65-4)

Conditions	Yield
With 2,4,6-trimethyl-pyridine In acetonitrile at 0 - 20℃; for 1h;	92%
In acetone; acetonitrile for 20h; Reflux;	83%

C17H30N4O7S + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → (R)-2,2'-(7-(1-carboxy-4-((2-((6-chloro-1,2,4,5-tetrazin-3-yl)thio)ethyl)amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 0.5h;	91%

(2-aminomethylpyridine) (3731-51-9) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → C8H7ClN6

Conditions	Yield
In tert-butyl methyl ether at 20℃; for 12h;	91%

(S)-2,2'-(7-(1-carboxy-4-((2-mercaptoethyl)amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → (S)-2,2'-(7-(1-carboxy-4-((2-((6-chloro-1,2,4,5-tetrazin-3-yl)thio)ethyl)amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 0.166667h;	91%

2',3'-O-isopropylideneuridine (362-43-6) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 5′-O-(6-chloro-1,2,4,5-tetrazin-3-yl)-2′,3′-O-isopropylideneuridine

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃; for 16.5h;	90%

3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) + diethylamine (109-89-7) → 3-chloro-6-diethylaminotetrazine (614756-32-0)

Conditions	Yield
In various solvent(s) at 20℃;	89%

t-butyl mercaptoacetate (20291-99-0) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 1,2,4,5-tetrazine-3,6-di-tert-butyldithioglycolic ester

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃;	89%

3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) + thioredoxin → tetrazine Stapled thioredoxin

Conditions	Yield
Stage #1: thioredoxin With tris(2-carboxyethyl)phosphine immobilized on agrose at 20℃; for 2h; pH=5; Inert atmosphere; Stage #2: 3,6-dichloro-1,2,4,5-tetrazine In dimethyl sulfoxide pH=5; Inert atmosphere;	88%

piperidine (110-89-4) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3-chloro-6-(piperidin-1-yl)-1,2,4,5-tetrazine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tert-butyl methyl ether at 20℃; for 21h; Inert atmosphere;	88%

4-hydroxyltriphenylamine (25069-86-7) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3-chloro-6-[4-(diphenylamino)phenoxy]-1,2,4,5-tetrazine (1374356-15-6)

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃; for 1h;	87%

tetraethylene glycol monomethyl ether (23783-42-8) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → C11H19ClN4O5

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 3h;	87%

3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) + 4,4,5,5-tetramethyl-2-trimethylsilanylethynyl-[1,3,2]dioxaborolane (159087-46-4) → 3,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trimethylsilyl)pyridazine (919197-91-4)

Conditions	Yield
In xylene for 24h; Heating;	86%
In xylene 3,6-dichlorotetrazine reacted with B compd. in xylenes under reflux for 24 h;	86%

di(d5-phenyl)acetylene-1,2-13C2 + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3,6-dichloro-4,5-di(d5-phenyl)pyridazine-4,5-13C2

Conditions	Yield
In toluene at 180℃; for 6h; Microwave irradiation;	86%

4-(2-aminoethyl)-1-(phenylmethyl)piperidine (86945-25-7) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → N-(2-(1-benzylpiperidin-4-yl)ethyl)-6-chloro-1,2,4,5-tetrazin-3-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tert-butyl methyl ether at 20℃; for 21h; Inert atmosphere;	86%

1-(cyclopent-2-en-1-yl)pyrrolidine + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 1,4-dichloro-6,7-dihydro-5H-cyclopenta[d]pyridazine (91846-80-9)

Conditions	Yield
In dichloromethane for 0.0833333h;	86%

methanol (67-56-1) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3,6-bis(methoxy)-1,2,4,5-tetrazine (81930-31-6)

Conditions	Yield
With hydrogen carbonate Heating;	85%
With sodium carbonate; magnesium sulfate at 25 - 65℃;	30.8%

methanol (67-56-1) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3-chloro-6-methoxy-1,2,4,5-tetrazine

Conditions	Yield
at 20℃; for 1h;	85%
at 20℃; for 1h;	82%
at 20℃; for 1h;	75%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;	70%

guanazole (1455-77-2) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 1,1′-(1,2,4,5-tetrazine-3,6-diyl)-bis(1H-1,2,4-triazole-3,5-di-amine) (1612764-66-5)

Conditions	Yield
In N,N-dimethyl-formamide; acetonitrile at 20℃; for 2h;	85%
In acetonitrile

N-benzyltryptamine (4307-98-6) + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → N10-[6-chloro-3-(1,2,4,5-tetrazinyl)]-N1-benzyltryptamine (264619-99-0)

Conditions	Yield
In dichloromethane for 2h; Substitution; Heating;	83%

N,N-di-(4-methoxy-1',1''-biphenyl)-N-(4-[2'-ethanol]biphenyl)amine + 3,6-dichloro-1,2,4,5-tetrazine (106131-61-7) → 3-chloro-6-([4''-([4'''-(dimethoxy)-1,1'-biphenyl]amine)-1',1''-biphenyl]ethoxy)-1,2,4,5-tetrazine

Conditions	Yield
With 2,4,6-trimethyl-pyridine In dichloromethane at 20℃;	83%

Upstream product

• 5940-53-4 3,6-dihydrazinyl-1,2,4,5-tetrazine 
• 1672-34-0 3,6-dimethylthio-1,2,4,5-tetrazine 
• 30169-25-6 3,6-bis-(3,5-dimethyl-pyrazol-1-yl)-1,2,4,5-tetrazine 
• 5940-11-4 [1,2,4,5]tetrazinane-3,6-dione dihydrazone 

Downstream Products

• 91846-80-9 1,4-dichloro-6,7-dihydro-5H-cyclopenta[d]pyridazine 
• 67279-24-7 1,4-dichloro-5,6,7,8-tetrahydrophthalazine 
• 264619-99-0 N¹⁰-[6-chloro-3-(1,2,4,5-tetrazinyl)]-N¹-benzyltryptamine 
• 919197-90-3 3,6-dichloro-4-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridazine 
• 919197-88-9 3,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridazine 
• 1174415-69-0 3-chloro-6-(2,3-diphenylaziridin-1-yl)-s-tetrazine 
• 1234326-38-5 3,6-dicysteine S,S-tetrazine 
• 1234326-44-3 C₄₇H₆₈N₁₆O₁₃S₂ 
• 1230026-50-2 8-[p-(p-chloro-s-tetrazinyloxy)phenyl]-2,6-diethyl-4,4-difluoro-1,3,5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene 
• 1230026-54-6 8-[o-(p-chloro-s-tetrazinyloxy)phenyl]-2,6-diethyl-4,4-difluoro-1,3,5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene 
• 1230026-38-6 8-[m-(p-chloro-s-tetrazinyloxy)-p-methoxyphenyl]-2,6-diethyl-4,4-difluoro-1,3,5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene 
• 1230026-42-2 8-[m-(p-chloro-s-tetrazinyloxy)phenyl]-2,6-diethyl-4,4-difluoro-1,3,5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene 
• 1230026-46-6 C₄₈H₅₂B₂F₄N₈O₂ 
• 1374356-14-5 3-{4-[bis(4-bromophenyl)amino]phenoxy}-6-chloro-1,2,4,5-tetrazine 

Relevant articles and documents

Hydrolytic stability of nitrogenous-heteroaryltrifluoroborates under aqueous conditions at near neutral pH

The hydrolytic stability of heteroaryltrifluoroborates under physiological conditions has been analyzed by 19F NMR spectroscopy and is found to be greatly enhanced by the presence of endocyclic ring nitrogens. Stability is further enhanced by the presence of exocyclic electron withdrawing substituents. As with aryltrifluoroborates, NMR analysis suggests that the hydrolysis proceeds via single rate-determining step reflecting loss of the first fluoride atom. The stability of these complexes is significant both in terms of metal catalyzed cross-coupling reactions as well as the potential for generating boronic acid based 18F-PET imaging agents.

A tetrazine templated method for the synthesis of ternary conjugates

Conjugation is an important reaction that enables coupling of molecules. Many protocols exist for the synthesis of binary conjugates from two different molecules or for the polyvalent display of a single molecule. There aren't many methods for the synthesis of ternary conjugates. However, methods for ternary conjugation are important for understanding the interplay of interactions between three biomolecules (or any three molecules per se). A strategy for ternary bioconjugation using inverse electron demand Diels-Alder reaction with tetrazine is studied. Ternary conjugation was demonstrated by the reaction of a model glyco-peptide binary conjugate with a fluorescent tagged olefin. The Royal Society of Chemistry 2013.

Chemical modification of single walled carbon nanotubes with tetrazine-tethered gold nanoparticles via a Diels-Alder reaction

A versatile methodology for the modification of single walled carbon nanotubes (SWCNTs) through an inverse electron demand Diels-Alder reaction with tetrazine-AuNPs (1-AuNPs) under ambient conditions is described. A robust covalently bonded hybrid nanocomposite is formed.

s-Tetrazines as a New Electrode-Active Material for Secondary Batteries

Because of the limitations of conventional metal-oxide-based electrodes, studies on organic redox-active materials as alternative electrodes for secondary batteries are emerging. However, reported organic electrode materials are still limited to a few kinds of organic redox groups. Therefore, the development of new redox-active groups for high-performance electrode materials is indispensable. Here, we evaluate s-tetrazine derivatives as a new electrode material in Li-ion batteries and study their charge/discharge mechanisms by ex situ XPS measurements. The porous carbon CMK-3 was introduced to encapsulate the s-tetrazines, which allowed 100 % utilization of the theoretical capacity and stable cycle performance of the s-tetrazines by preventing dissolution of the molecules into the electrolytes. This new class of redox-active group can pave the way for the next-generation of energy storage systems.