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Hriss
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| Joined: 16 Apr 2005 |
| Posts: 10 |
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321.50 Points
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Idea for p2p rote
Tue Sep 06, 2005 10:27 pm |
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Hi
Is possible this following rote of P2P starting from citric acid:
1 citric acid + H2SO4conc = 3-oxo pentanedioic acid
2 Esterification the product with EtOH
3 Enolization with 1 mol EtO:Na
4 Adition of Ph-Br to obtain COCH2CH(Ph)(COOEt)2 and after heating with NaOH/H2O cleavage to P2P ??
Thanks |
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Lego
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| Joined: 15 Apr 2005 |
| Posts: 52 |
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2408.30 Points
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re: Idea for p2p rote
Tue Sep 06, 2005 10:45 pm |
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| No, because phenylbromide is no alkylating agent, unlike benzylbromide, therefore it will not react. Check SN1/SN2 reactions.... |
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Hriss
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| Joined: 16 Apr 2005 |
| Posts: 10 |
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321.50 Points
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re: Idea for p2p rote
Tue Sep 06, 2005 11:03 pm |
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| Sorry my mistake: Benzylbromide insted PhBr:) |
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Lego
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| Joined: 15 Apr 2005 |
| Posts: 52 |
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2408.30 Points
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Re: re: Idea for p2p rote
Wed Sep 07, 2005 5:05 am |
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| Hriss wrote: |
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Sorry my mistake: Benzylbromide insted PhBr:)
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Should work, perhaps not with NaH.....
But then you get 4-phenyl-2-butanone, simply count the atoms:
you use pentan-3-one (5 Cs)
and benzylbromide (ring + 1 C)
--> ring + C6
minus two carboxylic acids: C4
you end up with a nice molecule without any use to drug synthesis, but it should work 
Chemo-Enzymatic Method for the Synthesis of Statine, Phenylstatine and Analogues
Spiros Kambourakis, J. David Rozzell
Adv. Synth. Cat., 2003, 345(6-7), 699-706
http://dx.doi.org/10.1002/adsc.200303048
Synthesis of Diethyl 2-Alkyl-3-ketoglutarates
A typical protocol for the synthesis of both diethyl 2-phenyl and 2-isopropyl-3-ketoglutarates is described. Under a nitrogen atmosphere diethyl 1,3-acetone-dicarboxylate (15 mL, 0.072mol) was dissolved in tetrahydrofuran (60 mL) and the mixture was cooled at -18 °C(ice/NaCl) for 10 minutes before lithium diisopropylamine (74 mL, 2M in hexane, 0.148 mol) was slowly added over a period of 20minutes. After stirring the solution at -18 °C for 10 minutes, a THF solution (20 mL) containing benzyl bromide (9.5 mL, 0.080 mol) or 1-iodo-2-
methylpropane (0.08 mol) was slowly added, and the solution was stirred for another 2.5 h (temperature was slowly increased to -10 °C) and 2more hours at room temperature before complete reaction was observed by thin layer chromatography analysis of reaction aliquots. The reaction mixture was then poured into an ice-cold aqueous hydrochloric acid solution (100 mL of2M HCl) and was extracted twice with ethyl acetate (200 mL x 2). The combined organic layers were back-extracted with brine (50 mL), dried over Na2SO4, and evaporated to dryness giving 25 g of an oily product. This product can be enzymatically reduced to the alcohol without any further purification. Pure diethyl 2-benzyl- or 2-isobutyl-3-ketoglutarates were obtained using silica gel chromatography (hexane/EtOAc, v/v, 8/2, 70% to 85% isolated yield). |
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Hriss
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| Joined: 16 Apr 2005 |
| Posts: 10 |
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321.50 Points
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re: Idea for p2p rote
Wed Sep 07, 2005 9:36 pm |
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Haha i made two mistakes in one forum..hmm i should be inloved
Bromobenzene is the right reagent for sure!But yes may be i should work with other alkilation agent to not to obtain P2P this is danderous chemical for some reasons you know  ) Lithium diisopropilamine is a fine reagent used in the paper synthesis Lego. |
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Hriss
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| Joined: 16 Apr 2005 |
| Posts: 10 |
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321.50 Points
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re: Idea for p2p rote
Thu Sep 08, 2005 1:36 am |
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Its me again..Lego you are right that bromobenzene wouldnt react easily with my enolate:( I red this in my oganic book:"Unactivated aryl halides may react with enolates under more vigorous conditions, particularly sodium amide in liquid ammonia. Under these conditions, the reaction of bromobenzene with diethylmalonate, for example, takes place by an elimination–addition sequence in which benzyne is an intermediate" But i think this is hard to be done in case with my synthesis. Any good idea for arylation of diethyl 1,3-acetone-dicarboxylate??
I think about bromination of it and then arylation by Zandmayer with phenyldiazonium bromide/CuBr but may be this is too shed Continue thinking... |
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