Regioselective Thiocyanation of Aromatic and Heteroaromatic Compounds by Using Boron Sulfonic Acid as a New , Efficient , and Cheap Catalyst inWater

e electrophilic thiocyanation of aromatics and heteroaromatics is an important carbon-heteroatom bond formation reaction in organic synthesis [1–3]. iocyanate is a versatile synthon which can be readily transferred to other functional groups such as sul�de [4–7], aryl nitrile [8], thiocarbamate [9], and thionitrile [10]. erefore, it is important to �nd the new and fast methods for synthesis of thiocyanate group containing aromatic systems [11]. In view of the versatility of thiocyanate group in heterocyclic construction [3], it will be important to probe the thiocyanation of aromatic and heteroaromatic compounds. Several methods have been developed for the thiocyanation of arenes by using various reagents under certain conditions [12–21]. Yet, only a limited number of reagents, such as bromine/potassium thiocyanate (only for indoles) [18], N-thiocyanatosuccinimide (only for 5-methoxy-2-methylindole and accompanied by two bisthiocyanates) [19], ceric ammonium nitrate (CAN) [20], acidic mont K10 clay [21], iodine/methanol, oxone [22], diethyl azodicarboxylate [23], IL-OPPh2 [24], potassium peroxydisulfate-copper(II) [25], and HCl/H2O2 [26] have been applied to the thiocyanation of aromatic and heteroaromatic systems. However, these methodologies suffer from one or more drawbacks such as the low availability or hard preparation of starting materials [18, 19], the requirement of large excess of strong oxidizing reagents, low yields for some compounds [20], and performances under certain special conditions [21]. Hence, a requirement for developing alternative synthesis routines accessible to the thiocyanation of aromatic and heteroaromatic compounds is in high demand. ere is an increasing interest in the use of environmentally benign reagents and procedures. Aqueousmediated reactions have received considerable attention in organic synthesis due to the environmentally safety reasons. Water is a desirable solvent for chemical reactions because it is safe, nontoxic, environmentally friendly, readily available, and inexpensive compared to organic solvents [27–29].erefore, the development of an efficient and convenient thiocyanation synthetic methodology in aqueous medium is an important research area [30, 31]. Boron sulfonic acid (BSA) as acidic catalyst was introduced by Kiasat and Fallah-Mehrjardi and used for the regioselective conversion of epoxides to thiocyanohydrins under solvent-free reaction conditions (Scheme 1) [32].

ere is an increasing interest in the use of environmentally benign reagents and procedures.Aqueous mediated reactions have received considerable attention in organic synthesis due to the environmentally safety reasons.Water is a desirable solvent for chemical reactions because it is safe, nontoxic, environmentally friendly, readily available, and inexpensive compared to organic solvents [27][28][29].erefore, the development of an efficient and convenient thiocyanation synthetic methodology in aqueous medium is an important research area [30,31].
Boron sulfonic acid (BSA) as acidic catalyst was introduced by Kiasat and Fallah-Mehrjardi and used for the regioselective conversion of epoxides to thiocyanohydrins under solvent-free reaction conditions (Scheme 1) [32].

Experimental
S 1: Boron sulfonic acid synthesis under nitrogen atmosphere at room temperature.
S 2: e solvent effect on product yields was investigated using 1a as a substrate.Both the yields and reaction times listed in Table 1 suggest that water appears to be very favorable for thiocyanations in presence of BSA (as a strong and new catalyst).
a Shimadzu IR-435 spectrometer using a KBr disk.e 1 H NMR spectra were recorded on a Bruker AQS 300 Avance instrument at 300 MHz in dimethyl sulfoxide (DMSO- 6 ) as solvent and tetramethylsilane (TMS) as an internal standard.e progress of reaction was followed with TLC using silica gel SILG/UV 254 and 365 plates.All products are known compounds and were characterized by comparing the IR, 1 H, and 13 C NMR spectroscopic data, and their melting points with the literature values.All yields refer to isolated products.

Typical Procedure for 3-iocyanato Indole Synthesis.
A suspension of indole 1a (0.117 g, 1 mmol), potassium thiocyanate (0.294 g, 3 mmol), and BSA/SiO 2 (0.05 g, 5%) in H 2 O (7-10 mL) was stirred at room temperature for 5-10 min.Aer that period H 2 O 2 (30%, 0.45 mL) was dropwisely added (2-5 min).e progress of the reaction was monitored by TLC (ethyl acetate: n-hexane, 1 : 10).Aer completion of the reaction, the reaction mixture was extracted with CHCl 3 (3 × 20 mL), dried with Na 2 SO 4 (5 g) for 20 min, �ltered, and chloroform removed.Yield 0.167 g (96%); dark brown solid; mp 71-73 ∘ C (1b) [2,22,33].FT-IR (KBr,):  (cm  [26,32].A 50 mL suction �ask was equipped with a constant pressure dropping funnel.e gas outlet was connected to a vacuum system through an adsorbing solution (water) and an alkali trap.Boric acid (1.55 g, 25 mmol) was charged in the �ask and chlorosulfonic acid (8.74 g, ca. 5 mL, 75 mmol in 5 mL CH 2 Cl 2 ) was added dropwise over a period of 1 h at room temperature under N 2 gas.HCl evolved immediately.Aer completion of the addition, the mixture was shaken for 85 min, while the residual HCl was eliminated by suction.e mixture was washed with diethyl ether to remove the unreacted chlorosulfonic acid ( 1 H NMR spectrum of BSA in acetone- 6 showed absorption at 12.22 ppm) and then 14.4 g SiO 2 was added and mixed.Finally, dried and a grayish solid material was obtained in 95.6% yield (21.6 g).

Results and Discussion
e thiocyanation was investigated at various conditions.In the absence of BSA, reaction was not accomplished, but in the presence of 5% BSA (0.05 g BSA equal 0.15 mmol H + ) the reaction took place with best result.We have found that BSA is active as a catalyst towards the thiocyanation of aromatic and heteroaromatic compounds using H 2 O 2 as an oxidant (Scheme 2).To identify optimal conditions for the synthesis of aryl thiocyanates, we began with an investigation of the conversion of indole into the corresponding indole thiocyanate using BSA/H 2 O 2 /KSCN in water as a model reaction (Scheme 2).e stoichiometry of the reactants was also varied.A ratio of 1 : 4 : 3 (indole : H 2 O 2 : KSCN) was found to be the most suitable, and decreasing the amount of H 2 O 2 or potassium thiocyanate increased the reaction time and lowered the yield.e scope of this reaction was further examined using various arenes under optimized conditions (Table 2).
As shown in Table 2, indole and electron-rich indoles gave the desired products in excellent yields (Table 2, entries 1-3).Also, electron-de�cient indoles such as 5-bromoindole reacted with potassium thiocyanate and BSA/H 2 O 2 to afford the corresponding 5-bromo-3-thiocyanatoindole in good yield, but required longer reaction time (Table 2, entry 4).is observation can be attributed to the lower electron density of such substrates.e lower yield is probably attributed to the steric hindrance of 2-substituted indole (Table 2, entry 3).e addition was highly regioselective occurring at the 3-position of the indole ring [25].Various N,N-disubstituted aromatic amines were converted into the respective 4-thiocyanato amines in high to excellent overall yields (Table 2, entries 5-10).e reactions were clean and the products were obtained with high-paraselectivity (Table 2, entries 9, 10).However, in the case of parasubstituted amine, ortho-thiocyanation did not occur (Table 2, entry 14).
In comparison with other reported methods using other reagents which require re�uxing conditions, the assistance of ultrasonic irradiation, toxic solvent, or oxidant, this method works under milder and greener reaction conditions.e proposed reaction mechanism is shown in Scheme 3. In the �rst step, H 2 O 2 reacts with BSA(H+) to presumably in situ form hydrogen peroxonium ion (H 3 O 2 + ) [34].We have shown that the counter ion of an acid did not have any role in the course of the reaction and H 2 SO 4 acts the same as HCl.Subsequently, reaction of hydrogen peroxonium ion with SCN − generates HOSCN, which is in the presence of H + able to produce thiocyanium ion + SCN 35 and H 2 O.In the last step of the reaction electrophilic substitution of thiocyanium ion + SCN with indole will generate the corresponding indole thiocyanate.

Conclusions
We have developed an efficient, simple, and green thiocyanation of aromatic and heteroaromatic compounds using BSA/H 2 O 2 /KSCN in water as solvent, which takes place with high regioselectivity.is procedure offers advantages such as simple workup, short reaction time, low cost of reagents, mild reaction conditions, and clean formation of the desired products in high yields.

S 3 :
e proposed mechanism for the thiocyanation of indoles and N,N-dialkylanilines.T 1: Solvent effects on the thiocyanation of 1a. .b Isolated yield of the products aer column chromatography.