An environment-friendly Beckmann rearrangement: The diazotisation of ketoxime carbamates

Article abstract of DOI:10.1016/S0040-4039(00)01243-0

The titled reaction was effected with iso-amyl nitrite or sodium nitrite, both in conc. H₂SO₄ at 0-25°C in excellent yields (55-98%). Apart from the mild temperatures employed, organic solvents and reagents can be avoided, and the by-products are CO₂ and N₂, so the conditions are environment-friendly. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01243-0

Tetrahedron Letters 41 (2000) 7235±7237
An environment-friendly Beckmann rearrangement:
the diazotisation of ketoxime carbamates
R. Anilkumar and Sosale Chandrasekhar*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 7 July 2000; accepted 20 July 2000
Abstract
The titled reaction was e€ected with iso-amyl nitrite or sodium nitrite, both in conc. H2SO4 at 0±25ꢀC in
excellent yields (55±98%). Apart from the mild temperatures employed, organic solvents and reagents can
be avoided, and the by-products are CO2 and N2, so the conditions are environment-friendly. # 2000
Elsevier Science Ltd. All rights reserved.
Keywords: Beckmann rearrangement; environment-friendly; oxime carbamates.
The historic Beckmann rearrangment has retained its practical importance to this day, with
improved variants and ever milder conditions still being sought.1 We have previously reported2
the BF3 induced Beckmann rearrangement of oxime carbonates, and herein report our results on
the transformation of ketoxime carbamates.
In principle, the Beckmann rearrangement can be induced in the oxime carbamates 2 by the
diazotisation of the carbamate amine function: the resulting diazonium compound 3 is expected
to be unstable and to fragment with loss of carbon dioxide and nitrogen (Scheme 1), thus
`triggering' the migration of an alkyl or aryl group of the oxime moiety; the resulting nitrilium
species 4 is hydrated to the ®nal amide or lactam product 5 in the usual way. Although oxime
carbamates were being prepared as early as in 1906, their structure had been misassigned as an
oxaziridine and as a nitrone;3 6 Exner and Horak5 suggested the correct structure in 1959, which
has been con®rmed by recent spectroscopic work.6 The oxime carbamates are readily prepared by
the reaction of the corresponding oxime 1 with an excess of sodium cyanate, in the presence of a
strong acid in an organic solvent3,4 (tri¯uoroacetic acid in dichloromethane in the present study);
the direct preparation3,4 from the carbonyl compound is far less satisfactory.
The diazotisation of benzophenone oxime carbamate 2a under a variety of aqueous and non-
aqueous conditions, was explored in the present study. The diazotising agent was generally iso-
amyl nitrite in the presence of sulphuric acid, tri¯uoroacetic acid, p-toluenesulphonic acid or
boron tri¯uoride etherate, in dioxane, THF or water as appropriate at 0ꢀC. Thereafter, the
* Corresponding author. Fax: +91-80 3600 529; e-mail: sosale@orgchem.iisc.ernet.in
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01243-0

7236
Scheme 1.
reaction mixture needed to be stirred at 25ꢀC for several hoursÐwhich presumably facilitated the
decomposition of 3Ðto e€ect the rearrangement. Although the formation of the expected
benzanilide 5a was observed under many of the above conditions, the yields were variable, with
benzophenone as a by-product. The best conditions were determined to be concentrated sulphuric
acid (12±14 equiv.) at 0ꢀC, with either iso-amyl nitrite or sodium nitrite as the diazotising agent,
followed by stirring at 25ꢀC for 6 h.y (A control experiment con®rmed that the diazotising agent
was necessary.) The scope of the reaction was also determined to be wide, as seen in Table 1.
A related method for the Beckmann rearrangement, via the diazotisation of ketone
hydrazones7 under similar conditions to the above, must be mentioned. However, the above
hydrazones were apparently unstable to geometrical isomerisation under the reaction conditions,7
which clearly limits the scope of the method. In the present methodology, such isomerisation is
apparently not a problem, as seen in the reactions of the three unsymmetrical ketoxime
carbamates 2e±2g, each of which furnished only one of the two possible rearrangement products
(5e±5g, respectively, Table 1) in excellent yields. (A recent report8 on the conversion of aldoximes
to nitriles via the O-phenylcarbamoyl derivatives is of some relevance to the present work and
also bears mention.)
In the present methodÐapart from the mild temperatures employedÐthe rearrangement step
per se possesses two important advantages: (i) no organic reagent or solvent is employed (when
sodium nitrite is the diazotising agent); and (ii) the only by-products are the relatively harmless
gases nitrogen and carbon dioxide (apart from sodium sulphate and ammonium sulphate). Thus,
the conditions are environment-friendly and would be valuable for scale-up. Further work is
planned.
Typical procedure for the rearrangement: Conc. H2SO4 (7 mmol) at 0ꢀC was stirred and treated portion-wise with
y
either NaNO2 (2.5 mmol) or iso-amyl nitrite (5 mmol), followed by the oxime carbamate 2 (0.5 mmol) portion-wise
over 0.5 h. After another 0.5 h at 0ꢀC, the mixture was stirred at 25ꢀC for the speci®ed time, and poured into cold
NH4OH (5 ml). The amide/lactam 5 was generally ®ltered o€, recrystallised and characterised by mp comparison with
reported values; 5c and 5e were isolated via ether extraction and characterised spectroscopically. The ketoxime carbamates 2
were prepared and characterised spectroscopically and by mp comparison,3 6 with the new ones furnishing satisfactory
elemental analysis for C, H and N.

7237
Table 1
The preparation of the oxime carbamates 2 and their Beckmann rearrangement to the amides/lactams 5: yields
and the duration of the rearrangement
Acknowledgements
UGC and CSIR (N. Delhi) are thanked for generous ®nancial support.
References
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