Fery
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phenothiazine
C12H11N + 2 S -> C12H9NS + H2S
To 100 ml Erlenmayer flask was added 8,4 g diphenylamine (0,050 mol) + 3,2 g sulfur powder (0,100 mol) + 0,15 g iodine (catalyst). The content was
mixed and thermometer inserted, flask was put into oil bath outside (!!! H2S formation during following heating !!!). The mouth of the flask was
loosely covered with teflon tape to prevent air entering and oxidizing H2S back to S (excess of S would contaminate the product). H2S evolution
observed at 170 C inside flask and perhaps very slow evolution even already at 150 C. The T was kept at 190-200 C (thermometer readings in melted
reaction mixture) for 30 minutes so the content in the flask was liquid. Then cooled down, content broken into very small pieces (without this it
dissolves very slowly!!!). Dissolved in 150 ml of isopropanol on boiling (150 ml total volume of all isopropanol used, smaller volumes used 5 times
until everything dissolved, first portion served to detach the mass from the flask, only then it was possible to crush it into small pieces). Filtered
hot into heated flask from which boiling isopropanol vapor heated the funnel in the mouth of the flask. Slowly cooled down to room temperature - at
first small crystals observed, but later something like yellow eyes with green center appeared, finally the content solidified into thick paste so
almost no solvent visible. Put into a fridge to +4 C. Sucked on Buchner funnel, washed with 15 ml of cold isopropanol (+4 C from fridge) on filter
paper and sucked for 30 minutes. Only circa 75 ml of mother liquor obtained, something stayed adhering on product and something evaporated at reduced
pressure (that's the reason to chill everything to +4 C before vacuum filtration and to use only vacuum level of water aspirator pump to reduce
evaporation of solvent).
43,6 g of wet product obtained so at least 33,6 g of solvent (cca 25%) trapped in the product !!! because theoretical 100% yield 0,05 mol * 199,27
g/mol = 10 g.
Air dried for 3 days in dark. Last 3rd day only 0,1 g lost on last traces of solvent evaporation. Weight 8,2 g. Yield 82%. It is very fine pale
yellow-green powder or better to say it is a dust (like crushed chalk, just yellow-green color, it is not toxic, substituted phenothiazines were used
as 1st generation of antipsychotics).
m.p. 176-179 C (perhaps it requires another recrystallization, wikipedia 185 C, Systematic organic chemistry, by W. M. Cumming 180 C)
reagents
reagents in flask after addition and after mixing
thermometer inserted to read temperature of reaction mixture and mouth of flask loosely covered with teflon tape to prevent oxidation of H2S back to
S, flask heated in oil bath, reaction performed outside because of toxic H2S formed
H2S evolution observed as very weak fumes from the flask at the temperature of the mixture 170 C (the fumes are not visible on photo due to photo
limitation)
the content in flask after heating
content crushed into small pieces (otherwise it dissolves very slowly, first small portion of isopropanol helped to detach the product from flask
walls), filtered hot into a heated flask in which solvent slowly boiled and heated the funnel in the mouth of the flask
dissolved product in isopropanol, after filtration
content in flask during crystallization (click on pictures to see more details, this is quite interesting)
vacuum filtration
product is very fine dust
product in a dish on the left and mother liquor in a beaker on the right
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Fery
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useful info gathered from net:
Possible solvents:
Acetone, but high solubility at room temperature 25,4 g phenothiazine for 100 g of solvent. Here they used it for recrystallization:
https://sci-hub.ee/10.1021/je2001649
ethyl acetate here they used it for 2-chlorophenothiazine:
https://www.sciencedirect.com/science/article/abs/pii/S00219...
http://www.seiko-chem.co.jp/us/products/2011/05/phenothiazin...
Solubility g/100g solv./25 C
Water:Insoluble
Acetone:25.4
Ethanol:3.4
Benzene:3.2
n-Hexane:Insoluble
Trichlene:1.4
Appearance:Yellow to greenish powder or prills
Purity:99.7%
Melting Point:183 C
https://sci-hub.ee/10.1107/s0567740876002215
...crystals of higher quality were subsequently grown by heating 1 g of the substance dissolved in 50 cm 3 methyl alcohol in a reflux condenser for 20
min and allowing to evaporate slowly for a period of three weeks.
The pale yellow needle-shaped crystals turned brown slowly on exposure to light, but they proved to be stable over a period of years.
https://en.wikipedia.org/wiki/Phenothiazine
Appearance greenish-yellow rhombic leaflets or diamond-shaped plates
Melting point 185 °C (365 °F; 458 K)
Boiling point 371 °C (700 °F; 644 K)
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Boffis
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Hi Fery,
I missed this post somehow when you originally posted it, but its an excellent piece of work and an interesting synthesis. I have been considering
trying to synthesis this compound as an intermediate to some redox-type metallochromic reagents.
I wonder what functional groups on the benzene nuclei will withstand this reaction? I presume halo-groups, chloro and bromo, but what about a nitro
hydroxy or methoxy groups; if I wanted to prepare nuclear substituted phenothiazines.
Somewhere I have a paper that describes the condensation of acrylonitrile with the hydrogen on the NH group to give N(2-cyanoethyl)-phenothiazine, the
starting material for the compounds I am interested in.
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Fery
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Hi Boffis, sometimes the ring could be synthesized in different way, e.g. for methylene blue the sulfur is introduced into the heterocycle by Na2S2O3
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