Phenothiazine 5-oxides

The formation of adduct is followed by fragmentation and subsequent H-atom abstraction reaction from the sulfinic acid produced. Strong acid solutions of aromatic sulfoxides like thianthrene 5-oxide (7) or phenothiazine 5-oxide (8) gives rise to ESR signals, which... 

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]... 

Our hypothesis is based on the observation that the photooxidation upon direct excitation of F yields G as well as a hydroxylated sulfone, too (28). Again, this reaction must involve oxidants other than singlet oxygen, for no reaction has been observed between the latter and ground state 10-methyl-phenothiazine-5-oxide (F). 

SO that passing through T+ and the intermediates 20 and 18 one gets This explains why identical solutions may be obtained starting with phenothiazine or phenothiazine-5-oxide, as mentioned above. 

Formation of S" " is revealed by an orange coloration of the solutions when phenothiazine is electrochemically oxidized in acetonitrile and by a golden color when sulfuric acid is used as an oxidant. Characteristic absorption maxima located at 271, 437 and 515 my. were assigned to this species.The same spectrum is recorded when equivalent quantities of phenothiazine and phenothiazine-5-oxide are dissolved in 66% perchloric acid, " the sulfoxide being first converted by the acid into T+ (see Scheme 2, Section IV,B,2), then reduced to S" " by phenothiazine (R) as shown by Eq. (3) (Section IV,B,1). 

Another characteristic spectrum with absorption maxima at 281 and 420 is displayed by solutions containing T+, obtained either on further electrochemical oxidation or on treating phenothiazine-5-oxide with perchloric acid. ... 

With these spectral assignments, one is able to follow the kinetics of oxidized forms. An example is provided by the processes which take place when phenothiazine-5-oxide is dissolved in 97% formic acid. The characteristic absorption pattern with four maxima (225, 270, 302, and 336 my) of the sulfoxide may be observed for a short time. This spectrum is then replaced by that of T+, which undergoes slow... 

Particularly valuable for S " are the ESR data. This method directly demonstrated the monoelectronic character of the first oxidation step, excluding the quinhydrone forms, and showed that R may be quantitatively converted into S+. Second, since identical ESR signals were obtained in all the four cases so far mentioned—namely (i) the first step of electrochemical oxidation, (m) the action of sulfuric acid and of other chemical oxidants, (in) the treatment of phenothiazine-5-oxide with phenothiazine in perchloric acid, and (iv) in the other reductive processes involving T in acid media—it may be considered as demonstrated that S " is formed in all these reactions. Third, the features of the ESR spectrum demonstrate that a proton is attached to the heterocyclic nitrogen, both in acid and neutral media. Hence S ", unlike TH +, is a weak acid, and the different behavior of the two oxidation potentials corresponding to S+ and T+ is thus better understood. 

Another instance of transformation of the phenazathionium cation with hydroxylation in position 3 is encountered in the reaction of phenothiazine-5-oxide with 59% H2SO4. Shine and Mach found that a mixture of radical species S+ and 3-hydroxy-S+ is formed by dismutation and hydrolysis. 

Another interesting reaction, for which a similar mechanism was invoked, is the action of halogenacids on phenothiazine-5-oxides, the... 

A particular instance of reductive bromination has been reported by Bodea and Terdic. They brominated phenothiazine-5-oxide with elementary bromine and found that bromophenothiazines are formed, containing one bromine atom more than expected on the basis of the utilized molar ratio. Thus, starting with phenothiazine-5-oxide, on treatment with 1 mole of bromine one obtains 3,7-dibromophenothiazine, with 2 moles of bromine 1,3,7-tribromopheno-thiazine, and with 3 moles of bromine 1,3,7,9-tetrabromophenothia-zine. It was therefore assumed that the first step consists of an electrophilic substitution, leading to 3-bromophenothiazine-5-oxide (54), which immediately undergoes reductive bromination with the hydrobromic acid formed in the first reaction to give 3,7-dibromo-phenothiazine (55). If more bromine is used, 55 is further brominated to the tri- or tetrabromo derivative. 

The chlorination of phenothiazine-5-oxide, proceeds similarly to that of phenothiazine the sulfoxide oxygen is lost and 1,3,7,9-tetrachlorophenothiazine (2a) is formed. 

The bromination of phenothiazine-5-oxide probably proceeds via the phenazathionium cation and was therefore discussed in Section IV, G, 4. 

The use of SOCI2 as a chlorinating agent for phenothiazine and for some of its derivatives has been reported in several papers. Eupprecht cites unpublished work describing the preparation of 1,3,7,9-tetrachlorophenothiazine by the action of thionyl chloride on phenothiazine. Kano and Fujimoto confirmed this result, showing also that phenothiazine-5-oxide yields the same product, with loss of the sulfoxide oxygen. Phenothiazine-5,5-dioxide does not react with thionyl chloride. 

There is lack in agreement over the use of sulfuryl chloride as a chlorinating agent. Fujimoto stated that tetrachlorophenazathio-nium chloride is obtained from phenothiazine, phenothiazine-5-oxide, and the tetrachlorophenothiazine. However, Spasov and Panov prepared tetrachlorophenothiazine from phenothiazine-5-oxide, and octachlorophenothiazine from tetrachlorophenothiazine. Surprisingly,... 

The thiocyanation of phenothiazine-5-oxide, both with thiocyanogen and by Kaufmann s method, yielded only 3,7-dithiocyanato-phenothiazine (83b), with removal of the oxygen from sulfur. 

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. 

Pure 3,7-dinitrophenothiazine is obtained on treating phenothiazine with sodium nitrite and acetic acid in chloroform phenothiazine-5-oxide does not react under these conditions,. 

There are many cleavage reactions of the phenothiazine heterocycle which may be interpreted as substitutions at the carbon atom adjacent to sulfur. These reactions depend to a great extent upon the oxidation state of sulfur they occur with phenothiazines and phenothiazine-5-oxides, but not with the 5,5-dioxides. In structure proofs such cleavage reactions are of particular importance, because they often lead to diphenylamines with known structimes. 

The preparation of 10-(2-hydroxyalkyl)phenothiazines from alkene oxides and phenothiazines in the presence of bases is described in a patent. Conditions were subsequently found under which N-polyoxyalkylene derivatives of phenothiazine and phenothiazine-5-oxide may be obtained using the same reagents. 

Particular difficulties were encountered in the preparation of unsubstituted phenothiazine-5-oxide and phenothiazine-5,5-dioxide,... 

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