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Synthesis 2005(1): 19-21  
DOI: 10.1055/s-2004-834928
SHORTPAPER
© Georg Thieme Verlag Stuttgart · New York

An Improved Synthesis of N-Isocyanoiminotriphenylphosphorane and Its Use in the Preparation of Diazoketones

Matthew M. Bio*, Gary Javadi, Zhiguo Jake Song
Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA
Fax: +1(732)5941499; e-Mail: matthew_bio@merck.com;
Further Information

Publication History

Received 13 July 2004
Publication Date:
08 December 2004 (online)

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Abstract

An improved synthesis of N-isocyanoiminotriphenylphosphorane is reported. This reagent is a safe, stable, solid alternative to diazomethane and TMS-diazomethane in the Arndt-Eistert synthesis of diazoketones.

Key words

diazoketone - diazomethane - isonitrile - iminophosphorane

    References

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  • 7a Aller and co-workers reference the following paper for the synthesis of 1: Weinberger B. Fehlhammer WP. Chem. Ber.  1985,  118:  42 
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  • 7b

    To the best of our knowledge no other syntheses of 1 have been reported.
    Crossref
  • 8 Appel has studied the reaction of tertiary phosphoranes and CCl4 in detail and notes the acceleration of the reaction in MeCN specifically: Appel R. Angew. Chem., Int. Ed. Engl.  1975,  14:  801 
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  • 13 For a review see: Ye T. McKervey A. Chem. Rev.  1994,  94:  1091 
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  • 14 Aside from the papers mentioned in ref., we have found only a single additional mention of this compound in the literature: Zinner G. Beck G. Fehlhammer WP. Wilberg N. J. Organomet. Chem.  1989,  368:  23 
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5

It should be noted that diazoketones themselves are often unstable compounds, thus great care should be taken whenever diazoketones or diazoalkanes are being formed.

6

A further advantage of Aller’s procedure is that the isolation of pure diazoketones from reaction is often simpler than from reactions using TMSCHN2 or CH2N2. Diazoketones formed from both diazo reagents invariably are contaminated with α-chloroketones and, in the case of TMSCHN2, the α-TMS ketone, both of which are difficult to remove because they usually impart a polarity similar to that of the diazoketone functionality. Using 1 to form diazoketones gives none of these difficult to remove impurities. In our experience in using 1, the overall yield of diazoketone from acid is consistently higher than when TMSCHN2 or CH2N2 is used.

9

Compound 1 showed no degradation by HPLC analysis after more than 3 d in MeCN-H2O (1:1) or in MeCN-0.01% K2HPO3 (1:1) aqueous solution.

10

The addition of more water anti-solvent led to high isolated yield but lower quality material.

11

The synthesis of 6 will be published at a later date.

12

A cursory cost calculation based on quotes obtained for bulk quantities of formic hydrazide, PPh3, CCl4 and DBU give a raw material cost of $0.54/gram N-isocyanotriphenyl-iminophosphorane.

15

Adding seed to the reaction is necessary only if no crystalline material has precipitated upon cooling to 35 °C. The initial seed may be obtained by removing a few millilitres of the reaction solution and cooling it to r.t.

16

After 40 min the reaction was complete by HPLC assay; a reaction sample quenched into MeOH show ca 99% conversion to the methyl ester.

17

Concentration and flush with fresh DCE removes excess oxalyl chloride.