Ohm
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Help PLease!
Dear friends,
I am a newbie here..
I am planning to synthesize isothiazolinone based molecule (kindly see the attachment for structure and scheme). The rough scheme for synthesis is as
attached. Please go through the scheme and suggest any modifications / corrections in it...or entirely different scheme for the same molecule.
Thanks all..
Attachment: Scheme for isothiazolinone derivative.doc (31kB)
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bfesser
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No changes. Just a PDF exported from your .doc for sanity's sake.
Attachment: isothiazolinone.pdf (36kB)
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Dr.Bob
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I am pretty sure that SO2Cl2 WILL react with your double bond. But I am also pretty sure that it would react with the P(OH)2 also, in some manner,
depending on the conditions. I might try the left path but then leave the ethyls on the phosphate until after the ring closure with SO2@Cl2. There
might also be some other ways to remove the ethyl groups from the phosphate that are gentler, but not sure.
I might also try to build the phosphate first, then link a premade isothiazolinone via the bromide part of the molecule, then deprotect. You might
be able to couple the isothiazolinone via other methods as well, not sure if a Mitsunobu RNX will work from an alcohol to the isothiazolinone, but I
have done similar reactions a long time back.
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Asepsis
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I'd assume the isothiazolinone structure to be unstable to strong oxidizing agents (see MSDS for 2-Methyl-4-isothiazolin-3-one hydrochloride).
As for the first reaction, the halide is most likely to be alkylated by the thiol, followed by the amine, then the amide nitrogen. Were you planning
to protect the amine and thiol first?
The simplest way I can see to get around it would be to form isothiazolinone, deprotonate the amide nitrogen and use it as its own synthon. Tack it
onto the back end of the synthesis since it seems to be the most sensitive group to the other proposed manipulations. However, I'm not sure the
stability of isothiazolinone on its own.
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Ohm
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@ Dr.Bob-Thanks sir...(1) I just wished knowing how would SO2Cl2 reacts with P(OH)2 groups? do u mean it will react to give a four membered ring
comprising Of (p=O -O-O-SO2) and 2 mol HCl? but because of low stability of 4 membered rings it seems merely possible ..whats ur opinion?
(2) what if i plan to use Bulkier phosphite instead of diethyl phosphite so as to hydrolyse alkyl phosphite easily / at milder conditions? does this
makes sense that the use of bulkier /sterically hindered alkyl phosphite will be hydrolysed easily as compared to ethyl phosphite?
(3) I didnt get ur suggestion about Mitsonobu reaction..can you Please explain a bit?
@ Asepsis- Thank u ...talking about first reaction its reported one ....we do not need to protect thiol or amine...halide reacts with protons from
amide nitrogen as its directly linked to carbonyl carbon making it most labile.
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Nicodem
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Thread Moved
6-12-2013 at 07:44 |
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