2,6-dichloro,3-nitropyridine

Dichloro-3-nitropyridine Acetic anhydride Tetrafluoroboric acid Diethyl ethoxymethylenemalonate Thionyl chloride Ethyl iodide... 

Dichloro-3-nitropyridine was reacted with N-ethoxycarbonylpiperazine to give 6-chloro-2-(4-ethoxycarbonyl-l-piperazinyl)-3-nitropyridine. The product, without purification, was heated with ethanolic ammonia in a sealed tube at 120°-125°C to give 6-amino-2-(4-ethoxycarbonyl-l-piperazinyl)-3-nitropyridine (mp 132°-134°C), which was treated with acetic anhydride in acetic acid to give 6-acetylamino-2-(4-ethoxycarbonyl-l-piperazinyl)-3-nitropyridine (mp 168°-169°C). This compound was catalytically hydrogenated in the presence of 5% palladium-carbon in acetic acid to yield 3-amino-6-acetylamino-2-(4-ethoxycarbonyl-l-piperazinyl)pyridine. The obtained 3-amino derivative, without further purification, was dissolved in a mixture of ethanol and 42% tetrafluoroboric acid, and to this solution was added a solution of isoamyl nitrite in ethanol at below 0°C with stirring 20 minutes later, ether was added to the solution. The resulting precipitate was collected by filtration and washed with a mixture of methanol and ether and then with chloroform to yield 6-acetylamino-2-(4-ethoxycarbonyl-l-piperazinyl)-3-pyridine diazonium tetrafluoroborate mp 117°-117.5°C (dec.). 

Pyridine itself can be converted into 3-nitropyridine only inefficiently by direct nitration even with vigorous conditions, however a pair of methyl groups facilitate electrophilic substitution sufficiently to allow nitration to compete with side-chain oxidation. Steric or/and inductive inhibition of A-nitration allows C-substitution using nitronium tetrafluoroborate, an example is 2,6-dichloropy-ridine dehalogenation of 2,6-dichloro-3-nitropyridine provides a practicable preparation of 3-nitropyridine. ... 

Halopyridines such as 2,5-dichloro-3-nitropyridine undergo regioselective nucleophilic displacement at the 2-position in high yield with the sodium salt of diethyl malonate in DME at room temperature (Equation 106). 

Pyridine /V-oxide is nitrated in the 4-position as the free base (9.81) [64CI(L)1577] and/p has been estimated as between 2.1 x 10"3 and 4 x 10"6 [66JCS(B)870 67JCS(B)1213], up to 95% yields of 4-nitropyridine N-oxide have been reported (51RTC581). 4-Nitration on the free base also occurs for the 3,5-dimethyl and 2,6- and 3,5-dichloro derivatives (9.82-9.84) [67JCS(B)1213]. 

The monochlorobenzosultam carbanion, generated through symproportionation of an equimolar mixture of benzosultam and its dichloro derivative, is capable of addition to 2-chloro-3-nitropyridine. Subsequent elimination of HCl from the intermediate adduct affords 3-(pyridin-2-yl)-substituted benzosultam according to the VNS mechanism (Scheme 35) [129]. 

Ompoimd (13) has been prepared ftom 2-chloro-3-nitropyridine by a four-step sequence (treatment with NaHS, reduction with tin(Q)chloride, diazotization with nitrous acid and treatment with carbon disulfide at 220°Q[72],[85]. Compound (14) has been prepared by treatment of disodium 5-cyanoisotiilaz-oledithiolate with thiophosgene [83], [86]. Con unds (15)-(17) have beai prepared by a two-step sequence (treatment with KHS or NaHSe and reaction with thiophosgene) [78],[82]. Reactions with phosgene yielded the corresponding -2-ones [78],[82],[83],[86]. Compounds (15),(17) have been prepared also by treatment of 2,3-dichloropyrazine and 2,3-dichloro-5,6-dimethylpyrazine respe vely, with potassium tiithiocarbonate [78]. 

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