A NEW WAY FOR SYNTHETIZING ( E )-METHYL METHYLSULFANYL ( PHENYLAMINO ) METHYLENE CARBAMATES VIA BECKMANN TRANSPOSITION IN TRIFLIC ACID

At low temperature in triflic acid, nitroketene S,N-acetals with a tethered phenyl ring react to form the corresponding hydroxynitrilium ions. Quenching with methanol leads to the formation of dications which undergo an unexpected Beckmann transposition affording new (E)-methyl methylsulfanyl(phenylamino) methylene carbamates.


INTRODUCTION
Nitroethene compounds are well-known synthons in organic chemistry.For instance, they are used in the field of drug synthesis [1,2] and for intramolecular cyclizations involving nitrile oxides (INOC reactions) [2,3].In superacids, non-tethered phenyl ring substrates, such as alkyl or aryl amines derivatives are polyprotonated to lead to multicharged species that can be trapped by suitable nucleophiles [4,5].
We have previously described the behaviour and the reactivity of 1-benzylamino-1methylsulfanyl-2-nitroethylene derivatives 1 in triflic acid.It was shown that these compounds are firstly C,O-diprotonated to give hydroxynitrilium ions 2. By quenching with water, these ions were transformed into a reactive nitrile oxide 3, which undergoes an intramolecular-1,3dipolar cyclization to afford cyclic products 4 (Scheme 1) [6].In the present paper, we report the synthesis of new (E)-methyl methylsulfanyl (phenylamino)methylene carbamates via Beckmann transposition in triflic acid from nitroketene S,N-acetals with a tethered phenyl ring.
Compounds 10a-e were characterized from their 1 H and 13 C NMR spectra, with vinylic and amino protons respectively in the range of δ H 6.47-6.58ppm and 10.32-10.52 ppm.The C-1 and C-2 carbons resonate at δ C 165.0-165.5 ppm and 106.5-106.7 ppm, respectively.
In organic solvent, compounds 10a-e exist as a sole isomer as shown by a single set of signals in the 13 C NMR spectra.They are probably all (E)-isomers because this conformation allows formation of an intramolecular hydrogen bond between the N-H and one of the oxygen atoms of -NO 2 group, as previously reported for the 1-arylamino-1-methylthio-2-nitroethenes 10a [8].

Reactions in triflic acid
In the present study, the reactions were carried out in triflic acid at low temperature between -5 to 0 °C and under nitrogen atmosphere.The molar ratio of triflic acid/starting compounds 10a-e was 50:1.The starting materials were fully transformed within 1 to 5 h of reaction time, depending on the substituent.The observed reaction, reported in Scheme 4, was generally clean with yields varying from 18 to 50% (Table 2) except for 10e, because of degradation reactions leading to the formation of dark polar products which has not been identified by NMR study.The yields of isolated products 11a-d were low, probably because the formed hydroxynitrilium ions can either react (i) to afford degradation products or (ii) with triflate anion to form the nucleophilic addition, that easily decomposed during the hydrolysis step of the reaction medium, as previously observed in situ with 1-amino-2-nitroethylene derivatives [4].The structure of compounds 11a-d was determined by NMR and HRMS spectroscopy.The CH 3 O protons appear in the range of δ H 3.64-3.71ppm and the NH proton as a broad singlet in the range of δ H 9.80-10.07ppm.Methoxy, imine and carbamate carbons resonate respectively at δ C 52.95-53.00ppm, δ C 163.12-163.14ppm and 174.43-174.50ppm.The structure of compounds 11 was corroborated by X-ray crystallographic analysis of 11a [10][11][12] (Figure 1).The X-ray analysis indicated the trapping of a methoxy group, the loss of oxime group and the formation of carbamate derivatives.
Compounds 11a-d are presumably (E)-isomers because this conformation allows formation of intramolecular hydrogen bond between the N-H and O=C-OMe groups.The formation of compounds 11 may be explained by the mechanism described in Scheme 5.In this mechanism, starting materials 10a-e undergo a protonation on the carbon bearing the nitro group and an Oprotonation of the nitro group.This last O-protonation occurred through a fast proton exchange process with the acidic medium, as demonstrated in fluorosulfonic acid at -80 o C [13,14].Prototropic exchanges and the formal loss of a molecule of water lead to the formation of the reacting conjugated hydroxynitrilium ion 12.Such hydroxynitrilium cations were previously observed with 1,1-heterodisubstitud-2-nitroethylene derivatives by NMR experiments [4][5][6][15][16][17].They are electrophilic species which can react in situ with aromatic ring [7,[15][16][17][18][19][20].In the present case, starting compounds 10a-e lead to hydroxynitrilium ions 12 which do not react through an intramolecular process, probably because of the excessively high activation energy of the reaction at this low temperature or the length of alkyl chain between the aryl and the NH.In agreement with this hypothesis is the fact that with the 10a, hydroxynitrilium ion formed reacts with the tethered phenyl ring by way of an electrophilic aromatic substitution mechanism to give a cyclic subproduct 16 [5].By quenching with a cold mixture of CH 2 Cl 2 /MeOH, hydroxynitrilium ions 12a-d are trapped with MeOH to give dications13, which undergo an Beckmann transposition via dications 14, followed by prototropic exchanges [13][14][15][16][17][18][19][20] to afford carbamic esters compounds 11.

CONCLUSION
New (E)-methyl methylsulfanyl(phenylamino)methylene carbamates have been easily prepared via Beckmann transposition in triflic acid.The mechanism of the reaction implies the formation of a stable hydroxynitrilium ion which was trapped by methanol leading to a reactive dication.A Beckmann transposition of this dication leads to the methyl carbamate derivatives.The present study constitutes an extension of the transformation of nitroketene S,N-acetals with a tethered phenyl ring in triflic acid.

General remarks
Melting points were determined with a Büchi Melting point B545 apparatus using capillary tubes (temperature rate 2 o C/min) and were not corrected.A Bruker DPX 300 spectrometer, equipped with a low temperature probe, was used for 1 H-and 13 C-NMR spectra recorded at 300 and 75 MHz, respectively.NMR spectra were recorded at room temperature and chemical shifts reported relative to Me 4 Si.The reproducibility of 13 C NMR shift was about 0.05 ppm, depending on cell and concentration.Chemical assignments were made using DEPT-135 techniques and usual chemical shift assignments rules.Electron-impact ionization (70 eV) mass spectra were obtained with a FinniganIncos 500 Instrument.High resolution mass spectrometry was performed by the "Centre Régional de Mesures Physiques de l'Ouest -Université de Rennes, France".Flash chromatography was achieved on silica gel (20 to 45 m particle size).Triflic acid was purchased from Acros and 1,1-bis(methylthio)-2-nitroethene from Lancaster and were used without further purification.No attempt was made to optimize the yields.

Figure 1 .
Figure 1.The X-ray analysis of compound 11a.