Synthesis and properties of dinitrobenzamido-TEMPO derivatives

4-Chloro-3,5-dinitrobenzoic acid ( 1a ) and 2-chloro-3,5-dinitrobenzoic acid ( 1b ) were converted into the corresponding acid chlorides ( 2a and 2b ) and these were reacted first with an equimolar amount of 4-amino-2,2,6,6-tetramethylpiperidine-N-oxyl radical (4-amino-TEMPO) to afford monoradicals 3a , 3b , 5a , and 5b and then either (i) with methoxyamine to yield hetero-diradicals 6a and 6b , or (ii) with a second mole of 4-amino-TEMPO to afford homo-diradicals 4a and 4b . The reaction of 3a with 1,3-bis(aminooxy)propane gave the homo-diradical 7a . These reaction products are stable mono-or di-radicals as evidenced by their ESR spectra at various temperatures. The above reaction products can participate as oxidizers in redox reactions, and they afford deep-colored anions with inorganic or organic bases.


Introduction
We designed a synthetic approach to stable monoradicals and diradicals starting from chlorodinitrobenzoic acid chlorides, which can undergo nucleophilic substitutions with markedly different rates allowing the selective preparation of target molecules.
The notation used in the following will denote the series of 2,6-dinitrophenyl compounds with letter a, and the 2,4-dinitrophenyl-substituted compounds with letter b.A TEMPO radical (2,2,6,6-tetramethylpiperidine-N-oxyl) will be denoted by the letter T with a dot above it, representing the odd electron.
A different type of homo-diradical (7a) was obtained from two moles of 3a by reaction with one mole of 1,3-bis(aminooxy)propane. 5 In principle, this compound could be oxidized to a hetero-tetra-radical but this reaction has not yet been tried.

Results and Discussion
The stability of nitroxides and of push-pull aminyls is nicely explained by Linnett's assumption 14,15 about a higher bond order than 1 between the two heteroatoms due to the presence of two opposite spins (α and β).As seen in Scheme 2, every atom has a closed electronic shell with opposite spins.Unlike the resonance-theoretical explanation, Linnett's theory implies a threeelectron bond between the two heteroatoms.Evidence for such a higher bond order was obtained by variable temperature ESR spectroscopy of 1-arenesulfonyl-2,2-bis(3,5-di-tertbutylphenyl)hydrazyl: the rotation barrier between the hydrazinic nitrogens was found to be substantial, leading to magnetic non-equivalence between the two 3,5-di-tert-butylphenyl groups. 16One should bear in mind that the polynitrophenyl-nitrogen bond in all neutral compounds (and even more in the corresponding anions, as will be discussed in one of the next sections) also has a partial double bond character.Mono-radicals 3a, 3b, 5a, 5b, and 6a present at room temperature the usual ESR triplet for TEMPO nitroxides as in Figure 1. 17 The homo-diradical 4b with ortho-connected TEMPO residues is the only one to show a difference in ESR coupling constants indicating spin interaction (Figure 2). 17At −153°C this frozen diradical shows line broadening (Figure 4), but no clear-cut evidence for a triplet state.The hetero-diradical 6a (Figure 3) also presents signs of spin interaction, but at room temperature the ESR spectrum changes during a few minutes into a normal triplet, probably due to the lower stability of oxyaminyl free radicals.In the ESR spectrum of the homo-diradical 7a at low temperature one observes a line broadening similar to that displayed in Figure 3.
One should note that we did not succeed to obtain ESR evidence for a hetero-diradical 6b.One can conjecture that it would cyclize intramolecularly to a benzopyrazolone.An analogous cyclization can be imagined for 6a yielding a benzofuroxan, explaining perhaps the unusual aspects of its ESR spectrum (Figure 3).
The paramagnetic and chromogenic properties of compounds 4a, 4b and 7a make them possible candidates for applications in analytical and bioanalytical chemistry.

Mass spectra
In the ESI mass spectra of compounds 3-5 one observes always the molecular peak as the base peak.An interesting observation was made for compounds 3a and 3b, namely that in addition to the molecular peak one observes the peaks due to the hydrochloride (M + 36).In the mass spectra of methoxyamino compounds 5a and 5b one observes low-intensity fragment peaks at m/z = M -15 due to loss of the methyl group.

Quenching effects and redox reactions
The substances described in this study (3-7) have a quenching effect on fluorescent compounds such as anthracene, carbazole, phenothiazine, tryptophan. 18,19Again, possible applications may be envisaged.

Conclusions
The stable monoradicals 3a,b formed from 4-amino-TEMPO and dinitrobenzoyl chlorides 2a,b have a reactive chloro substituent that can be substituted by nucleophiles.Reaction of 3a with methoxyamine yields the monoradical 4a which can be oxidized to the hetero-diradical 6a.Reaction of 3a,b with 4-amino-TEMPO affords the homo-diradicals 4a,b.Another homodiradical, 7a, was formed from 3a and 1,3-bis(aminooxy)propane.Whereas most of the compounds described in the present study exhibit three lines in their ESR spectra, the homodiradical 4b with ortho-connected chains ending in TEMPO groups presents a 5-line ESR spectrum that broadens at low temperature.
Compounds 4a and 7a yield blue anions on treatment with inorganic or organic bases, whereas compound 4b affords a red anion under the same conditions.Compounds 3-7 quench the fluorescence of aromatic compounds and oxidize push-pull hydrazinic derivatives such as 2,2-diphenyl-1-picrylhydrazine.

Experimental Section
General Procedures.NMR Spectra were recorded with a Varian Gemini 300 MHz instrument.Electronic absorption spectra were obtained with a UV-Vi Hitachi U-3000.IR spectra were obtained with a Paragon 1000 FT-IR and EPR spectra were recorded with a Jeol Jes-RE1X or Bruker ESP-300E instrument.Electrospray ionization mass spectra (ESI-MS) were recorded on a Finnigan LCQ mass spectrometer.
Commercially available starting materials were the two 4-and 2-chloro-3,5-dinitrobenzoic acids (1a and 1b, respectively) from Aldrich, 4-amino-TEMPO (Aldrich), DPPH (Aldrich) and N-methoxyamine or O-methylhydroxylamine (Merck).Silica gel glass plates 60F 254 (Merck) were employed for TLC separations.The preparation of DPPH 2 (15, R= H), of compounds 13af, 23,24 and of 1,3-bis(aminooxy)propane dihydrochloride was prepared as described earlier. 5and 2-Chloro-3,5-dinitrobenzoyl chloride (2a and 2b, respectively) were prepared from the corresponding acids in benzene (5 mL/g of acid) with thionyl chloride (0.8 ml/g) and N,Ndimethylformamide (DMF, 2 drops/g).After refluxing for 1 h the volatile products were evaporated under reduced pressure leaving the crystalline products in quantitative yield: pale yellow solids, easily soluble in chloroform or dichloromethane, in which the acids are insoluble.2a. 1 and 3b, respectively).were obtained similarly to ref. 31 from an ice-cold solution of 4-amino-TEMPO (1g in 10 mL water) into which an ice-cold solution of acid chloride (1 g in 2.5 mL of acetone) was added in one portion under strong stirring in an ice-salt cooling bath.After 45 seconds, 50 mL of 1M hydrochloric acid was added in a single portion and the stirring was continued for 30min.keeping the cooling bath.The yellow-orange solid was filtered off through a G 3 sintered glass filter, washed with 1M cold hydrochloric acid and then with water, suspended in 30 mL of 10% aqueous sodium hydrogen carbonate, stirred for 30 min., filtered off and washed with water.After 24 h drying in a desiccator over anhydrous calcium chloride the crude product was dissolved in methylene chloride, alumina (Merck, Brockmann activity I) was added, the suspension was stirred for 30 min.and filtered.The solvent was removed under vacuum, and the purity (determined by TLC on silicxa gelGF254 glass plates with CH 2 Cl 2 -diethyl ether 8:2 v/v) was satisfactory for further use.For higher purity, preparative TLC was used under similar conditions, the product was extracted in a Soxhlet apparatus, and the solvent was removed under vacuum.3a.yield 44%; mp.236-37ºC (lit. 13 Variant A. To the acid chloride 3 in methylene chloride (5 mL/g), triethylamine and 4-amino-TEMPO (in methylene chloride, 5 mL/g) were added in molar ratios 1:3: 2. The mixture became red and was stirred at room temperature for 3 days.Then the mixture was shaken sequentially (three times each) in a separatory funnel with 1M hydrochloric acid, aqueous NaHCO 3 , and water.After drying over anhydrous Na 2 SO 4 , the organic phase was evaporated under vacuum and the products were purified by preparative TLC as described above.
Variant B. The monoradicals 3a or 3b were converted into diradicals by treatment with with triethylamine and 4-amino-TEMPO (molar ratio 1:2.5:1.(5a and 5b).respectively, were obtained by stirring the monoradicals 3 in methylene chloride (25 mL/g) with triethylamine and solid methoxyamine hydrochloride in molar ratio 1:4:3 at room temperature for 5 days.The solution becomes rapidly blue for 5a and red for 5b.On washing twice with 1M hydrochloric acid the solutions became yellow.The product was extracted into aqueous sodium hydroxide which became colored as described above.Then the aqueous layer was acidified rapidly with 1M hydrochloric acid and the product was extracted into methylene chloride.After drying over anhydrous Na 2 SO 4 , the organic phase was evaporated under vacuum and the products were purified by preparative TLC as described above.Product detection can be performed either by detection with UV light at 254 nm, or by exposure to ammonia vapor when the two products become colored as indicated above.

Figure 4 .
Figure 4. Low temperature experimental ESR spectra of compound 4b at 120 K.

Table 1 .
Hyperfine coupling constants (a N ) for