Photochemical Behaviour of Carbamates Structurally Related to Herbicides in Aqueous Media: Nucleophilic Solvent Trapping versus Radical Reactions

Irradiation of N -aryl O -aryl carbamates has been carried out in H 2 O/CH 3 CN (1: 1v/v) solutions at 𝜆 > 290 nm. When chlorine is on the N -aryl ring, halogen-substituted products are found. These photoproducts derive from the trapping of the intermediate radical cation by water and, even, by acetonitrile leading to phenols and N -arylacetamides (photo-Ritter products), respectively. Unsubstituted N -aryl carbamates slowly undergo photo-Fries reaction.


Introduction
Interaction of light with matter is one of the most important processes responsible for abiotic transformations of a xenobiotic in the environment, mainly in surface water [1][2][3].Often the transformation process forms products that are more toxic than the parent compound [4][5][6][7]; hence, there is a need to consider transformation products during the environmental risk assessment process [8].Although the photochemical behaviour of a molecule depends on the presence of peculiar functional groups, given the heterogeneity and, often, the structural complexity of these pollutants, it is frequently difficult to predict or rationalize their photochemical behavior.Carbamate function is present in a wide number of biologically active compounds.In particular, carbamate pesticides are an important group which are widely used through the world [9].Although weak, carbamates exhibit absorption of radiation present in sunlight (>290 nm), and this requires the understanding of their photochemical behaviour [10].The most general photochemical event, mainly observed in O-aryl derivatives, leads to rearranged products, via photo-Fries reaction and/or fragmentation [10,11].Less frequent is this type of photorearrangement in N-aryl carbamates [12,13].Recently, we studied the photochemical reactivity of two carbamate herbicides, chlorpropham, and phenisopham (Scheme 1) [14].
Irradiation of phenisopham in aqueous solution at 310 nm led to photo-Fries rearranged products involving the cleavage of O-aryl N-aryl carbamate function.As observed in other cases [12], the O-alkyl N-aryl carbamate was unreactive, and this result was also found in the irradiation of chlorpropham.In the latter case the N-aryl moiety reacted and gave isopropyl 3-hydroxycarbanilate by photosubstitution of aryl chlorine with a hydroxyl group [12,14].For the two pesticides different phototransformations were observed [14].These results induced us to gain more information about the photochemical reactivity of N-aryl O-aryl carbamates that combine functions present in the pesticides examined.In particular, we prepared six model compounds 1 (Figure 1) and focused our attention on the photoproducts formation in aqueous solution (H 2 O/CH 3 CN 1 : 1 v/v to have clear solutions) under UVB irradiation (>300 nm) in order that our investigation may be more relevant to environmental studies.

International Journal of Photoenergy
Figure 1: Synthetic carbamates investigated.

Analytical Instruments.
HPLC experiments were carried out on an Agilent 1100 HPLC system, equipped with an UV detector (set at 230 nm), using a RP-18 column (Gemini, 5 m, 110 A, 250 × 4.6 mm).A mixture of A (H 2 O containing 1% formic acid)/B (CH 3 CN) 1 : 1 (v/v) was used as mobile phase at a constant flow rate of 0.8 mL/min.Analytical and preparative TLC was made on Kieselgel 60 F 254 plates with 0.2 mm and 0.5 or 1 mm layer thickness, respectively (Merck).
Proton NMR spectra were recorded on a Varian Inova-500 instrument operating at 499.6 MHz and referenced with deuterated solvents (CDCl 3 ).Electronic impact mass spectra (EI-MS) were obtained with a GC-MS QP5050A (Shimadzu) equipped with a 70 eV EI detector.UV-Vis spectra were recorded with a Varian Cary 300 UV-Vis spectrophotometer.Melting point determinations were performed by a Gallenkamp melting point apparatus.

Synthesis of Diaryl Carbamates 1.
In a typical experimental procedure, to a solution of each aniline (15 mmol) in dry dichloromethane (26 mL), 1.6 mL of phenyl chloroformate (13 mmol) was added dropwise.The mixture was stirred at 0 ∘ C for 1 h and then it was kept at room temperature for 30 min.The reaction mixture was neutralized with a saturated solution of sodium hydrogen carbonate and extracted with CH 2 Cl 2 (3 × 50 mL).The combined organic layers were washed with brine, dried with anhydrous sodium sulfate, filtered and evaporated under reduced pressure.The residue was purified by silica gel column chromatography using light petroleum/diethyl ether 7 : 3 v/v (compounds 1c and 1e were purified using light petroleum/EtOAc 7 : 3 and 9 : 1 v/v, resp.) to give carbamic compounds 1 with yields generally >95%.Products 1a, 1c, 1e [15], and 1f [16] were identified by comparison of their NMR spectra with those reported in the literature.The new products 1b and 1d were characterized on the basis of their spectral data.

Photolysis Experiments.
Irradiation was conducted in a Helios Italquartz multirays merry-go-round photoreactor equipped with six 15 W UV-B lamps with a maximal output at ca. 310 nm (1 mW cm −2 ).Samples were irradiated in quartz tubes (20 × 1 cm, 25 mL). 1 × 10 −3 M solutions of each carbamate 1 (50-90 mg) in H 2 O/CH 3 CN 1 : 1 v/v were irradiated and analyzed by HPLC and 1 H NMR at different times.The irradiation experiments were not stopped until starting compound was degraded at least for 20-30%.The content of all tubes was collected and evaporated.The residue was analyzed by 1 H NMR and then chromatographed using light petroleum/Et 2 O 6 : 4 v/v.Percentages of photoproducts in the irradiation mixtures were deduced by integration of isolated NMR signals and confirmed by chromatography.Compounds 2a [17] and 5c (=1e) [15] were identified by comparison of their NMR spectra with those reported in the literature while compounds 2c, 3c, 8f, 9f, and 4hydroxybenzoic acid (7) were identified by comparison of their proton NMR spectra with those of authentic samples (Aurora Building Blocks and Aldrich).

Results and Discussion
Phenyl meta-chlorophenyl carbamates 1a,b can be distinguished by the presence of chlorine on the N-aryl group (function present in chlorpropham) and by the different substitution on nitrogen (function present in phenisopham) (Figure 2).Irradiation was followed by HPLC and interrupted at a conversion of ca.20-40%.Compound 1a was converted for 30% after 2 h.Preparative TLC chromatography led to isolation of unreacted 1a (71%), hydroxy derivative 2a (14%), and a product (15%) to which structure 3a was assigned by spectroscopic means (Figure 2).In particular, mass spectrum of 3a showed the absence of isotopic chlorine peaks and a peak at 270 / indicating the presence of another nitrogen.Moreover, in the proton spectrum a typical singlet at  2.16 associated to a methyl linked to a carbonyl group and in the 13 C NMR a quaternary low-field signal at  168.4 indicated the substitution of chlorine with NHCOCH 3 group.The percentages of photoproducts were deduced by integration of selected signals in the proton NMR of the irradiation mixture and confirmed by chromatography.
The different photodegradation rates of 1a and 1b could be due to the different intensities of UV absorptions.Indeed, as shown in Figure 3, the N-monosubstituted carbamate 1a exhibits stronger absorption bands than the N-ethyl analogue 1b, even in 280-300 nm range.
Despite the presence of the O-aryl moiety, the photoinduced carbamate cleavage was not observed and only dehalogenated products, phenols 2a,b, and acetamides 3a,b, were isolated.Photohydrolysis to give phenols is the most frequent photoreaction of halogenated aromatic compounds in water and is reported to occur by a photoionization  process, favoured by the medium, [18,19].Accordingly, phenols 2a,b should derive from the radical cation 4 that can be trapped by water (pathway a, Figure 4) [18,19].The attack on the radical cation 4 by nitrogen of acetonitrile and subsequent hydrolysis should give compounds 3a,b (pathway b, Figure 4).Compounds 2 and 3 can also be formed by nucleophilic solvent trapping of an aryl cation deriving from homolysis, followed by in-cage electron transfer [18].Acetamides as 3 have been found by irradiating halogenated compounds [20] or dienes [21] in aqueous acetonitrile, and it has been shown that this solvent is involved in their formation in a so-called photo-Ritter reaction [20,21].Control experiments showed that, as expected, the amounts of photo-Ritter products 3a,b decreased with increasing the water content in the reaction medium.For example, amount of 3a decreased from 15% to 5% when the acetonitrile amount decreased from 50% to 30%.It is interesting to note that the conversion of 1c is accelerated (30% after only 1 h) by water increase in the reaction medium, because the first photochemical event is the photoionization that is favoured by the aqueous medium.
Photoreduction has been sometimes observed in the irradiation of halogenated aromatic compounds, mainly in para-substituted derivatives [18].A radical mechanism has been proposed so that formation of 5c should occur probably via intermediate 6c (Figure 6).It is also plausible that, as suggested in similar cases [19], a carbene intermediate 6  c is involved in the formation of 5c and also 2c, thus justifying the absence of similar compounds for 1d (Figure 6).
Structures 8f and 9f derive by a typical photo-Fries rearrangement.As well known [22], this reaction occurs via homolytic cleavage of the carbonyl-heteroatom single bond giving the caged radical pair 10 (Figure 8).In-cage recombination in para and/or ortho-position affords the acyl migration products as 8f and 9f, respectively.para-Hydroxybenzoic acid 7 could be formed by hydrolysis of 8 due to the long water contact for the prolonged irradiation.Stabilization of radicals by substitution could account for the breakage less difficult in N-ethyl compound 1f than 1e.

Conclusions
Our results show that the N-aryl O-aryl substitution is not a sufficient condition to have a photo-induced breaking of  the carbamate bond.This process is completely overcome in the presence of other photosensitive functions as chlorine on the N-aryl ring.In the latter case photosolvolysis or photoreduction occurs depending on the halogen position on the ring.
The N-substitution does not affect the product formation but influences the degradation rate due to radical stabilization or to a lower absorption of UVB radiation.
An interesting result is the obtaining of the photo-Ritter products derived from the nucleophilic trapping of radical cations by acetonitrile.We proved that when the pesticide chlorpropham was irradiated in H 2 O/acetonitrile 1 : 1 v/v, a product with similar spectroscopic data as 3c,d was formed.
Acetonitrile is generally used in environmental investigation as cosolvent to have clear aqueous solutions of compounds slightly soluble in water.The U.S. Environmental Protection Agency in the Fate and Transformation of chemicals Test Guidelines [23] suggests that the use of acetonitrile should be preferably not exceeding 1%, but cosolvent percentages up to 10% are allowed.Hence, to avoid mistakes, characterization of photoproducts is necessary.