Nitration of phenothiazines

The compound may be prepared in 70% yield by the nitration of phenothiazine with a mixture of 98% nitric acid and anhydrous sulphuric acid at 60°C. In addition to nitration, oxidation of the sulphur atom also takes place, resulting in the formation of the sulphoxide. 

Recently the nitration of phenothiazine has been clarified and most of the controversy in the early literature over the structure and... 

Nitration of phenothiazine-5-oxide has not been thoroughly investigated however, using HNO3 d. 1.42, pure 3-nitropheno-thiazine-5-oxide can be obtained in good yield. 

A few more examples of nitration by nitrous acid should be mentioned the nitration of m-fluoro-A -dimethylaniline [88], nitration of phenothiazine-3 [89] and phenothiazine-5-oxide [90]. They also should be rationalized by formulae (5a) and (5b). 

Authors are designed row sensitive and selective test-systems for analysis of heavy metals, active chlorine, phenols, nitrates, nitrites, phosphate etc. for analysis of objects of an environment and for control of ions Ee contents in the technological solutions of KH PO, as well as for testing some of pharmacological psychotropic daigs alkaloids (including opiates), cannabis as well as pharmaceutical preparations of phenothiazines, barbiturates and 1,4-benzodiazepines series too. 

Even the comparatively unreactive phenoxazine and phenothiazine systems undergo halogenation and nitration with ease and it is normal to prepare monosubstituted derivatives by stepwise procedures rather than by direct electrophilic attack. Indeed, the nitration of phenoxazine is uncontrollable and even N-acylphenoxazines afford a mixture of di- and tetra-nitro products (03CB475). Similarly phenothiazine and nitric acid produce a complex mixture of nitrated sulfoxides and sulfones. Chlorine in DMSO at 40 °C reacts with phenothiazine to yield 3,7-dichlorophenothiazine, whereas cupric chloride gives the 1,7-isomer (76JPR353). Direct bromination of phenoxazine produces a mixture of 3-bromo- and 3,7-dibromo-phenoxazines, while thionyl chloride affords the 1,3,7,9-tetrachloro derivative (60ZOB1893). 

An interesting oxidative nitration of 10-dialkylaminoalkyI-phenothiazine-5,5-dioxides, (99), involving the concomitant introduction of a nitrogroup (in position 3) and a hydroxyl (in position 7), (100), was reported recently by Wunderlich and Stark. ... 

Although many early reports of oxidation of phenothiazines to 5-oxides and 5,5-dioxides may be found, efficient preparative methods for these compounds have been elaborated only in recent years. Oxidation at the sulfur bridge improves the stability of some ring-substituted derivatives (e.g., amines. Section VI,C, 1). Such oxidations often accompany ring substitution (e.g., nitration, see Section V,A,2) or reactions involving functional groups on the ring (e.g., haloform oxidation of C-acetylphenothiazines, see Section VI,B, 2). 

The intervention of a SET path in (hetero)aromatic nitration has been the subject of an extended debate [65]. The evidence is usually based either on the detection of intermediates or on the regioselectivity of the attack in relation to the spin and charge density on the radical cation. Limiting the attention to heteroaromatic substrates, it should be noted that the radical cations were detected spectroscopically [66] or even isolated as a salt [67] during nitration of, e.g., phenothiazine, phenox-... 

PHENOTHIAZINE (92-84-2) Combustible solid. Mixture with acids or acid fumes causes decomposition and formation of sulfur dioxide and nitrogen oxides. Incompatible with aldehydes, cellulose nitrate (of high surface area), organic anhydrides, isocyanates, nitrates. 

Filiala Cluj. Studii Cercecari Chim 8, 303 (1957) St CA 54, 22657(1960) [Prepn of 1,3,7,9-Tetranitro phenothiazine-5-oxide, yel-orn ndls (from Nttrobenz), mp 354—55°, by. nitrating phenothiazine with a mixt of ni trie acid (d 1.50) St 20% oleum and heating on a w-bath for 20 mins]... 

Phenothiazine nitrated to its tetranitro derivative was used by the Germans during World War II as a component of a non-fusible explosive composition known under the name of Pressling . Monard, Ficheroulle and Fournier [45] found the compound to be phenothiazine tetranitrosulphoxide (I) (m. p. 368°C) ... 

Bemthsen [46], Kehrmann and co-workers [47] and Gilman and Shirley [48] also observed similar oxidation of the sulphur atom when nitrating phenothiazine... 

ANTIPSYCHOTICS-PHENOTHIAZINE, CLOZAPINE, PIMOZIDE NITRATES 1. T risk of antimuscarinic side-effects when isosorbide dinitrate is co administered with these drugs. 2.1 efficacy of sublingual nitrate tablets 1. Additive effect both of these drugs cause antimuscarinic side-effects 2. Antimuscarinic effects i saliva production, which i dissolution of the tablet 1. Warn patient of these effects 2. Consider changing the formulation to a sublingual nitrate spray... 

ANTIHISTAMINES-CHLORPHENAMINE, CYPROHEPTADINE, HYDROXYZINE 1. ANALGESICS - nefopam 2. ANTIARRHYTHMICS-disopyramide, propafenone 3. ANTIDEPRESSANTS-TCAs 4. ANTIMUSCARINICS - atropine, benzatropine, cydopentolate, dicydoverine, flavoxate, homat-ropine, hyosdne, orphenadrine, oxybutynin, procydidine, propantheline, tolterodine, trihexyphenidyl, tropicamide 5. ANTI PARKINSON S DRUGS -dopaminergics 6. ANTIPSY-CHOTICS - phenothiazines, dozapine, pimozide 7. MUSCLE RELAXANTS - baclofen 8. NITRATES - isosorbide dinitrate t risk of antimuscarinic side-effects. NB i efficacy of sublingual nitrate tablets... 

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