Anomalous addition of 2-cyanoprop-2-yl radicals to 2-(4-t -butyl-2-nitrosophenyl)-2-methylpropanoic acid

It has been reported that tertiary radicals like 2-cyanoprop-2-yl add to 1,4-di-t -butyl-2- nitrosobenzene 2 at the N and O atoms of the nitroso group. In contrast, treatment of the the analogous nitrosobenzene, 2-(4-t -butyl-2-nitrosophenyl)-2-methylpropanoic acid 12 , with azobisisobutyronitrile in boiling benzene afforded a 1,6-addition product, 2-[5-t -butyl-1-(1-cyano-1-methylethoxy)imino-4-(1-cyano-1-methylethyl)cyclohexa-2,5-dien-2-yl]-2-methyl- propanoic acid 16 as the sole isolable product.


Introduction
][3] A similar result has also been observed in a radical addition reaction using the moderately encumbered 1,4-di-t-butyl-2-nitrosobenzene 2 4 which is transformed into the N,O-adduct 3 upon treating with a 2.5 molar amount of azobisisobutyronitrile (AIBN) in boiling benzene for three hours 5 (Scheme 1).

Scheme 1
The same authors also investigated the behavior of the highly encumbered 1,3,5-tri-t-butyl-2nitrosobenzene 4 4 toward 2-cyanoprop-2-yl radicals and found an 'abnormal' reaction leading to the cross-conjugated adduct 6, the formation of which was rationalized with the intermediacy of the spin-delocalized anilino radical 5 (Scheme 2).

Scheme 2
A slightly less hindered nitrosobenzene, namely 2,4-di-t-butyl-6-methylnitrosobenzene 7, 4 shows a partitioning (1:3.6) between the 'normal' N,O-addition (generating product 8) and an 'abnormal' addition (generating a 2,4-cyclohexadieneimine 9) when subjected to t-butyl radicals generated by the photolysis of 2,2'-dimethyl-2,2'-azopropane. 6ther authors had earlier shown that tertiary alkyl radicals attack the nitroso group of 4 exclusively at the oxygen atom, whereas primary alkyl radicals attack the N atom giving exclusively nitroxides, and secondary radicals followed both options. 7Thus, both the nitroso compound and the nature of the radicals influence the course of radical additions to nitrosoarenes.The above mentioned findings are of relevance to the use of nitrosoarenes in general 8,9 and especially of 4 10,11 as spin traps.

Results and Discussion
We have earlier reported on a convenient photochemical access to 1-hydroxyindolin-2-ones, among them compound 10. 12 During the investigation of its reactions it was found that 10 could readily be transformed into the title compound 12 in 72% yield by treatment with a slight excess of potassium hexacyanoferrate(III) in alkaline solution followed by hydrolytic ring opening of the presumed oxoammonium intermediate 8a,13

Scheme 3
Compound 12 was characterized by its ready oxidation to the corresponding nitro compound 13 (80%) and spectroscopically (i) by its long wavelength absorption at λ max = 770 nm (log ε = 1.5) in methanol, and (ii) by its 1 H NMR spectrum: due to the diamagnetic anisotropy of the nitroso group 14 the proton vicinal to that group (3'-H) gives rise to a signal at δ = 6.15 ppm in CDCl 3 solution similar to δ = 5.85 ppm (3'-H, in CDCl 3 ) reported earlier 14 for compound 2. 1 H Chemical shifts in nitrosobenzenes are conformation-dependent: upfield shifts (compared to the parent compounds not bearing the nitroso group) are expected for protons or groups syn to the nitroso oxygen atom and shifts to lower field for protons or groups anti to the oxygen atom with the preferred coplanar arrangement of the N=O bond and the benzenoid ring. 14The δ value for 3'-H in 12 (6.15ppm) is 0.3 ppm to lower field compared to the corresponding value (5.85 ppm) for compound 2, which may be interpreted by a slight deviation from coplanarity of the benzenoid ring and the N=O bond.
Compound 12 can be regarded as a water-soluble analogue of 2. The carboxyl group might serve as an anchor to hook this potential spin trap to a substrate.We therefore wanted to test compound 12 in the addition reactions of 2-cyanoprop-2-yl radicals.When AIBN was thermolyzed in a benzene solution of 12 at reflux temperature for 30 minutes, to our surprise the sole product formed was not the trisubstituted hydroxylamine 15 (analogous to 3) but an 'abnormal' product 16 (31%) presumably via the delocalized aminyl radical 14 (Scheme 4).

Scheme 4
The six-membered ring in 16 clearly is not benzenoid, since in the 1 H NMR spectrum the AB subsystem originally present in 12 [δ A = 7.74 (5'-H), δ B = 7.67 ppm (6'-H), 3 J AB = 8.3 Hz] has been replaced by an AX system [δ A = 6.20 (3'-H), δ X = 3.69 ppm (4'-H), 3 J AX = 5.8 Hz], thus the second CMe 2 CN radical must have been connected to C-4' and not to C-2'.Further, while the chemical shift of the geminal 2-Me 2 in 12 is 1.86 (6H), the corresponding signal for 16 is split (δ = 1.48 and 1.49 for 3H each) which points to the presence of a distant chiral center (C-4').An analogous splitting for 2-Me 2 is observed in the 13 C NMR spectrum of 16.In the mass spectrum of 16 there is no indication of fragmentation of an O-atom from the molecular ion, which renders structure 17 highly unlikely in accord with the finding that only small and primary radicals are prone to be added at the nitrosoarene N atom. 7

Conclusions
In contrast to the N,O-bis-addition of 2-cyanoprop-2-yl radicals to 1,4-di-t-butyl-2nitrosobenzene 2, replacement of one methyl group in the ortho-t-butyl group as in 12 by carboxyl severely enhances the steric encumbrance of the nitroso group and thereby drives the bis-addition of the teriary radicals CMe 2 CN completely into the 'abnormal' mode.Whether this behaviour is (at least in part) due to the suspected non-coplanarity of the N=O bond and the benzenoid ring, or whether intramolecular OH … N hydrogen bonding impedes the normal addition, cannot be ascertained at present.

Experimental Section
General Procedures.Melting points were determined using a Kofler hot stage microscope "Reichert Thermovar".Elemental analyses were determined on a Carlo Erba model 1106 Elemental Analyzer.For EI mass spectra, an AMD 605 instrument was used in connection with a direct inlet system (inlet temperature given).IR spectra were recorded on a Perkin Elmer 285 instrument using KBr pellets.A Bruker WM 300 NMR spectrometer operating at 300 MHz for 1 H and at 75 MHz for 13 C was used on CDCl 3 solutions containing TMS as an internal standard.

2-(4-t-Butyl-2-nitrosophenyl)-2-methylpropanoic acid (12).
A sample of 10.1 g (43 mmol) of 6-t-butyl-1-hydroxy-3,3-dimethylindolin-2-one 12 10 was dissolved with gentle warming in 400 mL of 0.2 M aqueous NaOH.The mixture was then diluted with water to 1000 mL, a solution of 34.00 g (103 mmol) of potassium hexacyanoferrate(III) in 500 mL of 0.2 M NaOH was added all at once and the mixture was stirred at room temperature for 2 h.The resultant olive-green mixture was filtered.The filtrate was washed with diethyl ether (3 x 300 mL) to remove any neutral byproducts and acidified to pH 4-5 with dilute sulfuric acid.The green precipitate formed on standing for 24 h was collected by suction filtration to give 7.72 g (72%) of emerald-green crystals, mp 159 °C (with decomp., from ethyl acetate/cyclohexane); UV/Vis (methanol):