Sulfuric acid, fuming chloro

Sulfonation or chlorosulfonation using fuming sulfuric acid or chloro-sulfonic acid are useful reactions. Sulfonations are often reversible and hence the sulfonate group may be used to protect a particular site on an aromatic ring. It can then be removed later in a synthetic sequence. 

Trinitrodipheny Isulfone, crysts (from glac acet ac), mp 196—97° was prepd by heating 4-chloro-rl,3-dinitrobenzene or 2,4-dinitrophenyl-p-toluenesulfonate with Na 3-nitrobenzene-l-sulfinate in aq ale (Refs 1 St 3) 3,5,4 TrinitrodiphenyIsulfone, ndls, mp 199° prepd by heating 3 nitrophenyI-(4-nitrophenyl)-sulfone with a mixt of fuming nitric acid 8c sulfuric acid at 150°(Refs 2St4)... 

Diphenyl-1,10-phenanthroline and 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline give disulfonic acids on reaction with chloro-sulfonic acid at 25°. The position of substitution was not established, but presumably it occurs in the two phenyl rings.281 An improved method of sulfonation utilizes hot fuming sulfuric acid.282... 

Apart from these synthetically impractical examples of hydrolysis of chloro-fluorocarbons, there are useful applications converting some chlorofluorocarbons to fluonnated carboxylic acids. As an alternative to the use of the highly corrosive fuming sulfuric acid, normally used in batch processes, a continuous hydrolytic process for converting 1,1,1-trichlorotrifluoroethane (CFC-113a), available by isomerization of CFC-113 [44], to trifluoroacetic acid has been developed [45] (equation 45). It uses metal chloride catalysts deposited on high-surface-area supports Unreacted CFC-113a can be recycled. 

To a solution of 2-(2-carboxy-4-chlorophenoxy)acetic acid in concentrated sulfuric acid is added dropwise a mixed liquid of fuming nitric acid and concentrated sulfuric acid under stirring with keeping at a temperature below 10°C. After the addition, the reaction mixture is stirred and poured into 10 L of ice-cold water. The precipitated crystals are collected by filtration, washed with 2 L of water four times and them dried to give 2-(2-carboxy-4-chloro-6-nitrophenoxy)acetic acid. 

The synthesis of pazopanib (1) involves sequential animation of 2,4-dichloropyrimidine 25 with 6-amino-2,3-dimethylindazole 24 and 5-amino-2-methyl-benzenesulfonamide 28. The 6-amino-2,3-dimethylindazole 24, on the other hand, was prepared from 2-ethylphenylamine 20 via 5-nitration with fuming nitric acid and concentrated sulfuric acid, followed by treatment with isoamyl nitrite and acetic acid to produce 6-nitro-3-methylindazole 22. The 6-nitro group was reduced with stannous chloride and concentrated HC1 in glyme and subsequently methylated at the C2 position of the indazole ring with trimethyloxonium tetrafluoroborate in acetone to produce 6-amino-2,3-dimethylindazole 24. The resultant indazole 24 was condensed with 2,4-dichloropyrimidine 25 in the presence of sodium bicarbonate in ethanol/THF and subsequent iV-methylation with iodomethane and cesium carbonate to produce 27. The 2-chloro group of pyrimidine was then allowed to react with 5-amino-2-methyl-benzenesulfonamide 28 in catalytic HCl/isopropanol and heated to reflux to deliver pazopanib hydrochloride (1) in good yield. 

Nitration of pyridazine 1-oxide (113, R = Rx = H) - and many of its 3- or 6-substituted and 3,6-disubstituted analogs (113, R and/or Rj= alkyl, alkoxy, or chloro) with a mixture of fuming nitric and concentrated sulfuric acid afforded the corresponding 4-nitro-pyridazine 1-oxide derivatives (114). Under similar reaction conditions nitration of 3-methylpyridazine 1-oxide could not be accomplished and even after 6 hours at 100° starting material was recovered, whereas 3-methylpyridazine 2-oxide is nitrated to give 3-methyl-5-nitropyridazine 2-oxide in excellent yield. ... 

The reaction of quinazolin-4(3i/)-one with chlorosulfonic acid gives the corresponding quin-azoline-6-sulfonyl chloride which can be characterized by conversion to 4-oxo-3,4-dihy-droquinazoline-6-sulfonamide (mp of hydrate 217-220°C). Sulfonation of 7-chloroquina-zolin-4(3 7)-one with fuming sulfuric acid in the presence of mercury(II) oxide affords a small amount of 7-chloro-4-oxo-3,4-dihydroquinazoline-6-sulfonic acid. ... 

Nitration of 2-chloro-6-methoxypyridine occurs in good yield at C-3 by treatment with fuming nitric acid and sulfuric acid at 20°C (84GEP3308449, 84JAP(K)59-33262). A convenient synthesis of 4-hydroxy-3-nitropyridine uses a nitration of 4-hydroxypyridinium nitrate (85OPP409). Nitration of... 

CHLORO-2-METHYLPROPENE (563-47-3) Forms explosive mixture with air (flash point 11°F/-12°C cc). Slowly hydrolyzes in water, forming methallyl alcohol and hydrochloric acid. Strong oxidizers may cause fire and explosions. Contact with acids or acid fumes produces highly toxic chloride fumes. Aqueous solution is incompatible with sulfuric acid, alkalis, ammonia, aliphatic amines, alkanolamines, alkylene oxides, amides, boranes, epichlorohydrin, nitromethane, organic anhydrides, isocyanates, vinyl acetate. In the presence of moisture, attacks metals can cause pitting and stress corrosion in austenitic stainless steels. 

DICHLOR-DIAETHYLAETHER (German) (111-44-4) Forms explosive mixture with air (flash point 131°F/55°C). Contact with water produces hydrogen chloride fumes. Forms unstable peroxides, unless inhibited. Violent reaction with strong oxidizers, chloro-sulfuric acid, metal powders, fuming sulfuric acid. Attacks iron, mild steel, aluminum. Attacks some plastics, rubber, and coatings. 

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