2,6-Dichloroisonicotinic acid

off-white to beige or light brownish powder

2,6-dichloroisonicotinic acid is a member of the class of pyridines that is isonicotinic acid which is substituted by chlorine at positions 2 and 6. It has a role as an EC 1.11.1.11 (L-ascorbate peroxidase) inhibitor. It is an organochlorine compound, a monocarboxylic acid and a member of pyridines.

Citrazinic acid (10.35 g, 66.7 mmol) and tetraethylammonium chloride (11.05 g, 66.7 mmol) were suspended in phosphoroxychloride (20 mL, excess) and heated at 130 °C for 18 h and then at 145 °C for 2 h. The reaction mixture was allowed to cool to RT and poured onto crushed ice (150 g). Extraction of ethyl acetate (3 x 100 mL), drying of the combined organic layers (MGS04) and evaporation in vacuo gave 11. 34 g (89 percent) of a white solid. IH NMR (400 MHz, DMSO-d6) 8 7.85 (s, 2H) 13.90 (br s, OH).Citrazinic acid 1 (20.0 g, 129 mmol) and benzyltriethylammonium chloride (32.3 g, 142 mmol) in 40 ml of POClReagents and conditions: a) n-BuLi, ArBr; ZINC12 ; then 2, 6- dibromopyridine and cat. Pd (PPH3) 4 (95percent); b) LiOH, THF/H2O (100percent); C) (COCI) 2; NaN3 ; TFA; d) K2CO3, CH30H (78percent); e) HCI, CH3CN, NAN02 ; KI (52percent); f) n-BuLi, ArBr; ZINC12 ; then 13 and cat. Pd (PPh3) 4 (98percent); g) ArB (OH} 2, cat. Pd2 (dba) 3, cat. P (T-BU) 3, CS2CO3, (82percent); h) as (F) (71percent) ; i) as (g) (31percent) ; j) n-BuLi, ArBr; ZINC12 ; then 12 (80percent) ; k) 2- aminophenol, EDCI (97percent); 1) 230°C (87percent); m) ArB (OH) 2, cat. Pd2 (dba) 3, cat. [HP (T-BU) 3] BF4, CS2CO3 (78percent). Synthesis of 4 begins with pyridine derivative citrazinic acid. Treatment with POC13 at elevated temperature afforded the corresponding 2-6, dichloroisonicotinoyl chloride. To facilitate purification, the reaction was quenched with methanol; methyl ester 1 was isolated in 76percent yield after passage through a plug of silica gel to remove colored impurities. Saponification then provided acid 2 in quantitative yield without purification. Transformation to 3 was effected by conversion to the acyl azide, thermal Curtius rearrangement, and hydrolysis of the resulting trifluoroacetamide to provide 2, 6-DICHLORO-4-AMINOPYRIDINE (3), (Pfister, J. R. , Wymann, W. E. Synthesis 1983, 38). While this method for converting 2 to 3 is nominally 3 steps, it requires only a single extractive workup and the steps can thus be carried out in rapid succession. 3 was converted directly to 4 by diazotization and reaction with potassium iodide (it is necessary to stir 3 in cold hydrochloric acid for several hours prior to diazotization in order to obtain an acceptable yield) providing 4 in reasonable yield and excellent purity after trituration with acetone. This short sequence of reactions allows preparation of 4 IN-35percent overall yield, requires no chromatography beyond a single filtration through a plug of silica gel, and has allowed the routine preparation of 5-10 g quantities of this intermediate. Unlike many 4-halopyridines, 4 is stable for several months at room temperature if protected from light. 4 can be ready transformation to fluorophores of the present invention.

It is used to study the effects of exogenous treatment on plant disease resistance and secondary metabolites.

Molecular Weight:192.00
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:190.9540837
Monoisotopic Mass:190.9540837
Topological Polar Surface Area:50.2
Heavy Atom Count:11
Complexity:155
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes