Hello everyone! I am a biotech student but for some reasons I am doing an internship in a chemical companyz. As one of my tasks I had to design a synthesis for isotopically labeled octahydrophenazine using relatively cheap labeled precursor, easy procedure without using any “fancy” equipment and of course good yelds. I did some research and I came up with a 5 step route starting with deuterated cyclohexane. I had shown this to my supervisor, he looked at it for like a minute and said – "Ok, it is fine." Next day he told me he had ordered 1g of deuterated cyclohexane lol. I came here for some help because I feel like my supervisor doesn’t care about my success or failure in synthesizing this compound and also seems busy and don’t pay much attention when I have some questions. Our conversations usually took like 2minutes. But I care about this little project and want to get it done so here I am =]
The synthesis I designed goes like this
1) Selective chlorination of cyclohexane with cobalt(II) porphiryn complex
Source Khanna, V., Tamilselvan, P., Jeet Singh Kalra, S., & Iqbal, J. (1994). Cobalt(II)-porphyrin catalyzed selective functionalization of alkanes with sulfurylchloride: A remarkable substituent effect. Tetrahedron Letters, 35(32), 5935–5938. https://doi.org/10.1016/S0040-4039(00)78223-2
2) Elimination reaction to get cyclohexene
3) Selective oxidation to cyclohexanone
4) Bromination with NBS to 2-bromocyclohexanone
As described in this paper Zhang, G., Wang, F., Du, J., Qu, H., Ma, X., Wei, M., & Wang, C. (n.d.). Supporting Information Towards the Total Synthesis of Palhinine A : Expedient Assembly of Multifunctionalized Isotwistane Ring System with Contiguous Quaternary Stereocenters.
5) Condensation with ammonia to octahydrophenazine using microvawe or just heating it in a flask for some time
Utsukihara, T., Nakamura, H., Watanabe, M., & Horiuchi, C. A. (2006). Microwave-assisted synthesis of a -hydroxy ketone and a -diketone and pyrazine derivatives from a -halo and a , a 0 -dibromo ketone, 47, 9359–9364. https://doi.org/10.1016/j.tetlet.2006.10.087
I am testing this procedure using normal reagents and I failed at step 1. I used a 3,5ml of cyclohexane, 10ml of benzene, 5ml of sulfuryl chloride and 34mg of porphiryn. I had a problem with a temperature sensor so the temperature so for some time was too high(110°C). I didn't get any mono or disubstituted halogenes. After about 15hrs of refluxing the mixture at 85 I transfered it to another flask suitable to distillation in small scale. In the first(refluxing flask) remained a lot of black tarry solid which was unexpected. The liquid in a second flask had dark brow/oragne colour which makes me think that due to overheating porphiryn decomposed but I found some paper and If I understood it correctly it should be stable at this temperaturehttps://www.researchgate.net/publication/260261591_Spectral_and_thermal_investigations_of_porphyrin_and_phthalocyanine_nanomaterials
Another thing that may cause the failiure may be the porphirin itself. Some time ago my supervisor gave me a mini jar with label "tetrakis(4-methoxyphenyl)porphyrin". It is purple compact pieces but not shiny, I forgot to take picture.
The procedure he told me to make cobalt complex from it is:
"Dissolve (200mg) porphiryn in chloroform
Dissolve (1g) cobalt acetate in methanol
Mix it and add about 5g of sodium carbonate as a base to get protons from porphiryn
Heat under reflux for 2 to 4h
Filtrate and evaporate solvents under reduced pressure"
I am not sure if using sodium carbonate is really necessary because
1) It poorly disolves in that solvents
2) I found a paper describing the synthesis of porphpiryn and no such thing was usedhttps://www.tandfonline.com/doi/pdf/10.1080/00397910802574617
3) I think that it reacts with cobalt acetate
I checked cobalt carbonate in google images and it looks so simillar to some of the solid that stays on the filter after filtration of reaction mixture that I am almost sure it does react and really no cobalt gets built into porphiryn.
What do you think? Should sodium carbonate be used in this reaction or is he just trolling me?
I was promised to do an UV-VIS spectra to confirm if the product is really the porphiryn Co complex but it was not done. Instead he looked at the small purple shiny crystals I got after the reaction and said "Ok, It looks fine, this is it".
Also I have a quick question about elimination reaction. I couldn't find conditions for it but i think that dissolving some base (I have KOH, NaOH, t-BuONa) in propanole(because it has higher boiling point than cyclohexene i want to get) and refluxing it for couple hours is the right approach to it.
Besides what do you guys think about this synthesis route? Can I improve it to get the desired product in faster and more efficient way starting with cyclohexane? Someone on other forum suggested using TsNBr2
to convert cyclohexene to bromocyclohexanone in one step but I would have to make it from p-TsOH and it seems like a lot of work.
PS English isn't my native language so sorry for any grammar mistakes ;p