Mechanochemical Thiocyanation of Aryl Compounds via C–H Functionalization

Abstract

Aryl thiocyanate compounds are important building blocks for the synthesis of bioactive compounds and intermediates for several functional groups. Reported thiocyanation reactions via C–H functionalization have limited substrate scope and low RME. The ball-milling method reported here uses ammonium persulfate and ammonium thiocyanate as reagents and silica as a grinding auxiliary. It afforded aryl thiocyanates with moderate to excellent yields for a wide variety of aryl compounds (36 examples, 8–96% yield), such as anilines, phenols, anisoles, thioanisole, and indole, thus tolerating substrates with sensitive functional groups. New products such as benzo[d][1,3]oxathiol-2-ones were obtained with C-4 substituted phenols. Thus, to our knowledge, we report, for the first time, aryl thiocyanation reaction by ball-milling at room temperature and solvent-free conditions, with short reaction times and no workup. Analysis of several mass-based green metrics indicates that it is an efficient greener method.

Introduction

Organosulfur compounds are common intermediates for target molecules in pharmaceuticals and materials science.¹ Aryl thiocyanates are particularly relevant because they can be converted into other useful functional groups, such as 1,2-thiobenzonitriles,¹ thiophenols,² trifluoromethyl thioethers,³ thioethers,⁴S-thiocarbamates,⁵ sulfonyl cyanides,⁵ disulfides,⁶ thioesters,⁷ or CN source, to benzonitrile formation (Scheme 1).⁸ They also function as versatile precursors for many bioactive compounds.^9,10

Scheme 1. Aryl Thiocyanate Compounds as Intermediates for Several Functional Groups.

Recently, aryl thiocyanate compounds were synthesized by directly introducing SCN moieties into aryl scaffolds as a convenient method for carbon–sulfur bond formation.^11,12 Some methods involve more than one step, long reaction times, costly, and tedious workup procedures (Scheme 2A).^3,13

Scheme 2. Representative Synthesis of Aryl Thiocyanate Compounds.

The C–H functionalization approaches for thiocyanation employ conventional solution (cs) reactions as well as alternative and greener methods such as microwave, electrochemical, and ultrasound (Scheme 2B).¹⁴ However, many of these methods still have some drawbacks and limitations, such as the use of metal catalysts, long reaction times, harsh reaction conditions, and mainly limited substrate scope.

During the last decade, chemical reactions induced or sustained by mechanical energy, so-called mechanochemistry, have gained significance substantially in several areas of chemical synthesis due to the drastic reduction or even elimination of reaction solvents, reaction times, and energy consumption. Additional advantages include stoichiometric control, the use of poorly soluble reactants, transformations, and reaction intermediates that are difficult or impossible to access in solution.¹⁵ The liquid-assisted grinding (LAG) and auxiliary grinding techniques, which use small amounts of additives, enable reactions that do not take place or are not efficient under neat grinding, thus expanding the application of mechanochemistry.¹⁶

It is shown in this work that thiocyanation reactions by ball milling (BM) afforded a wide variety of aryl thiocyanates under short reaction time and mild reaction conditions (Scheme 2C). In addition, an analysis of mass-based green parameters for thiocyanation reaction of aniline in solution and mechanical methods showed that the latter is greener, even though this reaction is one of the worst-case scenarios for mechanochemistry.

Results and Discussion

Initially, aniline (1a) was tested with ammonium thiocyanate (2a, 1.5 equiv) and ammonium persulfate (1.5 equiv), with 1a being consumed in 98%. However, 4-thiocyanatoaniline (3a) and azoxybenzene (4a) were isolated in 50% yield and traces, respectively (Table S1). The low yield is due to the polymerization of 1a, yielding polyaniline (5a), which competes with the thiocynation reaction. Syntheses of 4a and 5a were already reported via conventional and mechanochemical oxidation methods of aniline.^17,18 Also, LAG using MeOH (20 μL) and other milder oxidizing agents were tested (Tables S1 and S2), but in all cases, the yield of 3a was even lower and polyaniline was still present.

Therefore, 2-nitroaniline (1b), a substrate less prone to polymerization, was chosen as a model for optimization of thiocyanation reaction. The neat grinding reaction was performed using a Teflon jar at 0.5 mmol substrate scale and 30 min to yield 3b in 41% (Table 1, entry 1).

Table 1. Optimization of Thiocyanation Reaction with 1b^a.

entry	jar	2a (equiv)	time (min)	auxiliary	yield 3b [%]b
1	Teflon	1.5	30	-	41c
2	stainless-steel	3.0	60	SiO2	37c,d
3	stainless-steel	1.0	60	SiO2	69
4	stainless-steel	1.5	60	SiO2	92
5	Teflon	1.5	60	SiO2	72
6	stainless-steel	1.5	30	SiO2	82
7	stainless-steel	1.5	60	-	39

^aReaction conditions: 1b (0.2 mmol), mixer mill (RETSCH MM 200), jar (5 mL), and two stainless steel balls (7 mm). SiO₂ (230–400 or 70–230 mesh) was added as an auxiliary milling.

^bIsolated yields.

^c0.5 mmol scale of 1b.

^d0.3 g of SiO₂ (230–400 mesh).

Most importantly, no polymerization or side products were observed, and the starting material was recovered by chromatography. It is also noteworthy that the reaction mixture became sticky and adhered to the bottom of the jar during the reaction, which prevented efficient mass and energy transfer. In order to prevent this, silica (SiO₂) was used as a grinding auxiliary to homogenize the reaction mixture, since the LAG experiment with aniline did not improve the reaction yield (Table S1). This provided an additional feature because the reaction protocol was simplified by eliminating a workup step and allowing the ground sample to be directly purified by column chromatography.

Nonetheless, the reaction with 0.30 g of SiO₂ as a grinding auxiliary afforded 3b in only 37% yield (Table 1, entry 2) and occupied almost half of the volume of the jar. This high load hindered the motion of the balls and reduced the generated mechanical energy.¹⁹ Indeed, the yield of 3b increased to 69% when the mass of SiO₂ (0.15 g), 2-nitroaniline (0.2 mmol), and NH₄SCN (0.2 mmol) was reduced, resulting in 1/3 occupation of the jar (Table 1, entry 3). The yield increased to 92% (Table 1, entry 4) using an excess of NH₄SCN (1.5 equiv). On the other hand, variations such as using a Teflon jar (Table 2, entry 5), reducing the grinding time to 30 min (entry 6, Table 1), or not adding SiO₂ as the grinding auxiliary (Table 1, entry 7) decreased the yield of 3b.

Table 2. Scope of Thiocyanation with C-2, C-3, and C-4-Substituted Anilines^a.

^aIsolated yields.

The effects of the oxidants were tested using Oxone (Table S3, entry 2) and iodine (Table S3, entry 3), which resulted in conversion yields of 60 and 25%, respectively. Another oxidizing agent 2,4,6-trichloro-1,3,5-triazine (TCTA) led to complete consumption of 2-nitroaniline. However, instead of the thiocyanate product observed under solution conditions,²⁰ only the monosubstituted TCTA product, 4,6-dichloro-N-(2-nitrophenyl)-1,3,5-triazin-2-amine, was isolated in 49% yield (3b″, Scheme S1). The substitution reaction of a chlorine atom of TCTA by 2-nitroaniline (1b) was confirmed by milling these two compounds without NH₄SCN.

These yields were significantly lower than persulfate, which afforded 92% isolated yield of 3b (Table 1, entry 4) under the same reaction conditions, thus showing the strong dependence in the strength of the oxidizing agent.

As a result, the best reaction conditions were aryl compound (0.2 mmol scale), ammonium thiocyanate (1.5 equiv), ammonium persulfate (1.5 equiv), and silica (0.15 g) milling at 25 Hz for 1 h, using a 5.0 mL stainless steel jar and two 7 mm stainless steel balls. These conditions were applied to other substrates (Table 2).

Aniline (1a) tested under these conditions yielded 3a in 67% (Table 2, entry 1) and other substituted anilines with an electron withdrawing group (EWG) at C-2, such as nitro-, cyano-, and chloro-, afforded products 3b–d in excellent yields (Table 2, entries 2–4).

Substrate 1e, with a larger phenyl group at the ortho-position, afforded 3e in 73% (entry 5, Table 2). Only one aniline with EDG afforded exclusively product 3f in good yield (61%, Table 2, entry 6), whereas complex mixtures of by-products were observed by GC–MS with benzene-1,2-diamine and 2-aminophenol as substrates. Subsequently, three substituted anilines on C-3, one with EWG and two with EDG, were investigated. Only 3-aminobenzonitrile (1g) and 3-methylaniline (1h) provided the products 3g and 3h in 45% and 65% yield, respectively (Table 2, entries 7 and 8). On the other hand, 3-aminophenol (1i) generated an unexpected cyclic compound (3i′) in 15% isolated yield (Table 2, entry 9). Most likely, thiocyanation occurs at para- to the −NH₂ group, followed by attack of the −OH group onto the −SCN group. This leads to a 2-iminobenzo[d][1,3]oxathiol-6-amine, which undergoes hydrolysis in situ to afford 6-aminobenzo[d][1,3]oxathiol-2-one (3i′) (Table 2, entry 9).

Anilines substituted at C-4 were employed to complete the scope investigation (Table 2). As expected, the C-2 thiocyanation product underwent an in situ cyclization through an attack of the −NH₂ group onto −SCN generating 1,3-benzothiazole-2-amines.

Products 3j through 3n were obtained in 18–71% reaction yields (Table 2, entries 10–14), with the best results obtained with anilines containing EWGs. The reaction with 4-aminophenol afforded a complex mixture of products, in which the product of thiocyanation ortho- to the NH₂ group and cyclization was not observed by GC–MS. Substituted 1,3-benzothiazol-2-amines have been reported^14j in thiocyanation reactions of C-4-substituted anilines.

The method was tested with phenol (6a), affording 7a in excellent yield (96%, Table 3, entry 1), and then extended to substituted phenols. However, the initial yields with substrates 6b and 6c, containing EWG at C-2, were very low: 8 and 34% (Table 3, entries 2–3). Therefore, a two-step procedure was employed, in which the substrates 6b and 6c with 1.5 equivalent of (NH₄)₂S₂O₈ and NH₄SCN were milled for 45 min, followed by the addition of another 1.0 equivalent of both reagents and milling for another 45 min. This increased the yields to 15% for 7b and 47% for 7c. It is noteworthy that a solution method¹⁴ⁱ for 6c afforded 7c in 40%, while 2-nitrophenol (6b) did not react under those conditions. Higher isolated yields were observed for phenols containing EDG, ranging from 54 to 94%, 7d–g (Table 3, entries 4–7), indicating an important electronic effect of C-2 substituents.

Table 3. Scope of Thiocyanation with C-2, C-3, and C-4-Substituted Phenols^a.

^aIsolated yields.

^bThiocyanation by two sequential millings of 45 min each, with addition of 1.5 and 1.0 equiv, in each step, of (NH₄)₂S₂O₈ and NH₄SCN.

Substituted phenols at C-3 with -Me or -OMe groups were also tested and afforded the para-thiocyanated product, 7i or 7j, in 85 and 52% yield, respectively (entries 9 and 10, Table 3). The lower yield of the latter reaction can be explained by the directing effect of the -OMe group which leads to ortho-thiocyanation to the OH-group (Table 3, entry 10) and affords compound 8j′ in 14% yield, thus showing competition of donor groups. The formation 8j′ can be explained by the cyclization of 3-methoxy-2-thiocyanatophenol, which generates 6-methoxybenzo[d][1,3]oxathiol-2-one after hydrolysis. The cyclization and hydrolysis were also observed with 3-hydroxyphenol, affording 7k′ in 22% yield (Table 3, entry 11). An unexpected product, 8h, from the ortho-thiocyanation of 3-hydroxybenzaldehyde, was isolated in 28% yield (Table 3, entry 8). In reactions with substituted C-4 phenols (Table 3, entries 12–15), benzo[d][1,3]oxathiol-2-ones were obtained as products (7l–o) in 14–30% isolated yield. This class of compounds arouses interest due to their biological properties, such as antibacterial²¹ and antioxidant.²² To our knowledge, these compounds have not been prepared directly by one-pot thiocyanation reaction. 4-Substituted-2-thiocyanatophenols^20,23 or benzo[d][1,3]oxathiol-2-imines^14k were reported as products in the few examples of thiocyanation of C-4 substituted phenols described in the literature.

Control experiments without silica (SiO₂) were performed with resorcinol (6k) and 4-methylphenol (6n) as substrates to ascertain the role of the grinding auxiliary in the in situ hydrolysis of benzo[d][1,3]oxathiol-2-imines. In fact, analysis of the crude sample showed the starting material and products but no indication of benzo[d][1,3]oxathiol-2-ones. Only after the workup (extraction AcOEt/H₂O), the hydrolyzed products were detected (Schemes S2 and S3, Figures S2 and S3). Therefore, thiocyanation of substituted phenols at C-4 will be further studied under silica-free conditions.

The selectivity of the mechanochemical thiocyanation reaction of aniline and phenol was exclusively at the para-position, as also observed for most solution methods.¹⁴ Exceptions observed for solution methods included ortho-thiocynation of phenol²⁰ and aniline²⁴ as well as ortho- and para-mixtures.²³

The scope for aromatic substrates containing EDG and EWG as a directing group was also explored; however, only N,N-dimethylaniline, anisoles, thioanisole, 1-naphthol, and indole afforded the products in 33–96% isolated yields (Table 4). Even after doubling the milling time (2 h) and the amount of ammonium thiocyanate (3.0 equiv), the yield of the reaction with anisole increased by only 6% (Table 4, entry 2).

Table 4. Scope of Thiocyanation with Aromatic Substrates Containing EDG as a Directing Group and N-Heteroaromatic Compound^a.

^aIsolated yields.

^b2 h.

^c3.0 equiv of NH₄SCN.

Unfortunately, the reaction failed for aryl compounds with EWGs, such as bromobenzene, iodobenzene, and nitrobenzene, as well as other N-heteroaromatic compounds such as pyridine and quinoxaline, which agrees with the literature.^14j Toluene also failed, while acetanilide afforded just traces of the desired product observed by GC–MS. A complex mixture of products was obtained when the reaction was carried out with nitrosobenzene (19), in which the desired product was not observed by GC–MS and di-para-thiocyanate azoxybenzene (20) was isolated in 5% yield (Scheme S4).

Being a mild, fast, and solvent-free methodology, the present mechanochemical thiocyanation method is potentially green. To ascertain and quantify the green aspects of this method and to compare it with a solution approach, mass-based green metrics²⁵ such as the Environmental Impact Factor (E-Factor or E_m),²⁶ atom economy (AE),²⁷ and reaction mass efficiency (RME)²⁸ can be used. The RME is factored into four independent parameters: reaction yield (ε), AE, inverse of the stoichiometric factor (SF), and material recovery parameter (MRP), which would ideally be 1. The mathematical expression for each parameter and their relationships were demonstrated by Andraos^28b (equations in Supporting Information).

The solution method described by Mete et al.(14i) also employs a thiocyanate ion and persulfate as the oxidizing agent, and it was chosen to compare the impact of performing the reaction without a solvent. Only the reaction step was evaluated in mass-based green metrics because both methods do not employ a workup step and have similar chromatographic purification. All reaction auxiliary materials (e.g., solvent, grinding auxiliary) were considered as unrecovered and any post-reaction materials as fully recovered.

The reaction with aniline (1a) was used to determine the green parameters for both methods, and the results are presented in Table 5 (Excel spreadsheet²⁹ is available in the Supporting Information).

Table 5. Values of Some Green Parameters Obtained for the Thiocyanation of Aniline Employing BM (This Work) and CS Methods.

method	AE	yield	1/SF	MRP	RME	E-factor	ref
BM	0.38	0.67	0.72	0.42	0.077	12.0	this work
CS	0.34	0.90	0.59	0.23	0.042	22.8	(14i)

It is noteworthy that the atomic efficiency (AE) values for these two methods are similar, as expected, but the reaction yield was lower for the BM method. Nevertheless, the 1/SF, MRP, RME, and E-factor parameters of the mechanochemical method are significantly better than the CS method. These results indicate the importance of developing reactions without a solvent as well as decreasing the excess of the oxidizing agent (persulfate). It is worthy of mention that the green parameters employed have some limitations because they are mass-based only, so relevant green aspects such as energy efficiency and toxicities of materials are not considered. Nonetheless, it is well-established that mechanochemical methods are more energy efficient than CS methods.^16g

In conclusion, a green mechanochemical method of thiocyanation was successfully developed for a wide range of substrates, including anilines, phenols, anisoles, thioanisole and indole, which resulted in a total of 36 aryl thiocyanates with yields in the range of 8–96%. It is a simple, mild, and solvent-free method, which tolerates substrates with sensitive functional groups, such as nitro, aldehyde, and nitrile. Anilines and phenols with a substituent at C-4 afforded cyclic compounds: 1,3-benzothiazol-2-amines and benzo[d][1,3]oxathiol-2-ones, respectively. The presence of two strong electron-donating substituents in phenols led to low regioselectivity, since both can act as a directing group. Distinct reactivity for anilines C-2 substituted was observed when compared to the solution method, which added some complementarity between these methods.

Experimental Section

General Information

The experiments were performed with the vibratory mill MM200 model obtained from Retsch (Haan, Germany) at 25 Hz using 5 mL stainless-steel grinding jars (Form-Tech Scientific) and 7 mm diameter (1.3 g) stainless-steel balls. All known compounds were characterized by ¹H and ¹³C NMR, melting point, infrared (IR), and GC–MS and compared to literature values. All new compounds were also characterized by high-resolution mass spectrometry (HRMS). The solvents, except hexane and cyclohexane, were used without previous purification. Thin-layer chromatography was performed using silica gel MACHEREY-NAGEL, with detection by UV-absorption (254 nm). Column chromatography was performed using silica gel 230–400 Mesh (Merck) or 70–230 Mesh (Sigma-Aldrich). Melting points were obtained in a MEL-TEMP equipment. ¹H and ¹³C NMR experiments were recorded on Varian Unitty Plus 300 MHz or Varian UNMRS 400 MHz with chemical shifts (δ) given in parts per million (ppm). All NMR analyses were recorded using CDCl₃ (δH = 7.26 ppm and δC = 77 ppm) or DMSO-d₆ (δH = 2.5 ppm and δC = 40 ppm) as a solvent. IR spectra were recorded on a Bruker FT-IR VERTEX 70 apparatus (UFRN), PerkinElmer Spectrum 400 (LAC—UFPE), and BRUKER IFS66 with KBr (UFPE). GC–MS analyses were performed on a Thermo Scientific Quadrupole (Trace 1300—ISQ). HRMS analyses were performed on a high-performance liquid chromatography–QTOF Bruker Daltonics model (USP).

General Procedures for Mechanosynthesis of Aryl or N-heteroaromatic Thiocyanates

Aryl compound or indole (0.2 mmol scale) was added to a 5.0 mL stainless-steel jar charged with a pair of stainless-steel ball bearings (7 mm diameter, 1.3 g) and 0.15 g of SiO₂ (230–400 mesh or 70–230 mesh), where the mixture was milled at 25 Hz for 2.0 min. After, ammonium thiocyanate (1.5 equiv, 0.3 mmol, 0.023 g) and ammonium persulfate (1.5 equiv, 0.3 mmol, 0.068 g) were added to the mixture on a jar and milled for more 1.0 h at 25 Hz. After milling, the crude mixture was transferred to column chromatography to be purified.

4-Thiocyanatoaniline (3a)^14l

Brown solid (20 mg, 67%), mp 52–54 °C. R_f = 0.22 (Hex/AcOEt 3:1). ¹H NMR (300 MHz, CDCl₃): δ 3.96 (s, 2H, NH), 6.67 (H_2,6: d, J = 8 Hz, 2H), 7.35 (H_3,5: d, J = 8 Hz, 2H). ¹³C NMR (75 MHz, CDCl₃): δ 109.6 (C₄), 112.3 (SCN), 116 (C_2,6), 134.4 (C_3,5), 148.8 (C₁). IR (neat, cm^–1): 820, 1083, 1177, 2145, 3345, 3415. MS (EI, 70 eV) m/z (%): 150 [M⁺], 124, 118, 58.

2-Nitro-4-thiocyanatoaniline (3b)³⁰

Yellow solid (36 mg, 92%), mp 108–110 °C. R_f = 0.17 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 6.38 (s, 2H, NH), 6.91 (H₆: d, J = 8.8 Hz, 2H), 7.56 (H₅: dd, J = 8.8, 2.4 Hz, 2H), 8.40 (H₃: d, J = 2.4 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃): δ 109.6 (C₄), 110.7 (SCN), 120.8 (C₆), 131.3 (C₃), 132.1 (C₂), 138.8 (C₅), 145.7 (C₁). IR (neat, cm^–1): 822, 893, 1340, 1505, 2152, 3361, 3477. MS (EI, 70 eV) m/z (%): 195 [M⁺], 169, 149, 137, 122, 105.

2-Cyano-4-thiocyanatoaniline (3c)^14j,14n

Yellow solid (30 mg, 87%), mp 113–115 °C. R_f = 0.29 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 4.80 (s, 2H, NH), 6.81 (H₆: d, J = 8.8 Hz, 1H), 7.53 (H₅: dd, J = 8.8, 2.4 Hz, 1H), 7.63 (H₃: d, J = 2.4 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 97.3 (C₂), 110.3 (C₄), 110.9 (SCN), 115.7 (CN), 116.7 (C₆), 137.1 (C₃), 138.2 (C₅), 151.2 (C₁). IR (neat, cm^–1): 825, 905, 2155, 2225, 2925, 3360, 3440. MS (EI, 70 eV) m/z (%): 175 [M⁺], 148, 121, 105, 90, 78, 63, 52.

2-Chloro-4-thiocyanatoaniline (3d)^14i,14j

Yellow solid (33 mg, 89%), mp 45–47 °C. R_f = 0.35 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 4.15 (s, 2H, NH), 6.70 (H₆: d, J = 8 Hz, 1H), 7.21 (H₅: dd, J = 8, 4 Hz, 1H), 7.42 (H₃: d, J = 4 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 110.1 (C₄), 111.5 (SCN), 116.4 (C₆), 119.7 (C₂), 132.6 (C₅), 133.7 (C₃), 145.2 (C₁). IR (neat, cm^–1): 825, 855, 870, 2155, 3300, 3430. MS (EI, 70 eV) m/z (%): 184 [M⁺], 158, 152, 149, 122, 105, 90, 78, 63.

2-Phenyl-4-thiocyanatoaniline (3e)³¹

Brown solid (33 mg, 73%), mp 56–58 °C. R_f = 0.50 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 6.79 (H₃: d, J = 8 Hz, 1H), 7.34–7.47 (H_{4,6,2′,3′,4′,5′,6′}: m, 7H). ¹³C NMR (101 MHz, CDCl₃): δ 110.1 (C₅), 112.2 (SCN), 116.8 (C₃), 128 (C_4′), 129 (C_2′,6′), 129.1 (C_3′,5′), 133.2 (C₆), 135 (C₄), 137.5 (C_1′), 145.6 (C₁), 153.5 (C₂). IR (neat, cm^–1): 815, 860, 2153, 3330, 3415.

2-Methoxy-4-thiocyanatoaniline (3f)^14h

Yellow solid (22 mg, 61%), mp 44–46 °C. R_f = 0.33 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 3.88 (s, 3H, OCH₃), 6.67 (H₆: d, J = 8 Hz, 1H), 6.95 (H₃: d, J = 2 Hz, 1H), 7.02 (H₅: dd, J = 8, J = 2 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 55.7 (OCH₃), 109 (C₄), 112.3 (SCN), 114.5 (C₃), 114.9 (C₆), 126.7 (C₅), 138.9 (C₁), 147.6 (C₂). IR (neat, cm^–1): 810, 833, 1028, 2145, 3341, 3370. MS (EI, 70 eV) m/z (%): 180 [M⁺], 165, 154, 137, 122, 110, 93, 78, 67, 52.

3-Cyano-4-thiocyanatoaniline (3g)

Yellow solid (16 mg, 45%), mp 108–110 °C. R_f = 0.59 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, CDCl₃): δ 4.26 (s, 2H, NH), 6.87 (H₆: dd, J = 8.4, 2.8 Hz, 1H), 7.00 (H₂: d, J = 2.8 Hz, 1H), 7.55 (H₅: d, J = 8.4 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 109.9 (SCN), 112 (C₄), 115.8 (CN), 118.4 (C₃), 119.5 (C_2,6), 136.3 (C₅), 149.2 (C₁). IR (KBr, cm^–1): 833, 860, 2162, 2234, 3363, 3466. MS (EI, 70 eV) m/z (%): 175 [M⁺], 148, 143, 131, 121, 116, 105, 99, 90, 78, 63. HRMS (ESI, m/z): [M + H]⁺ calculated for C₈H₆N₃S, 176.0204; found, 176.0279.

3-Methyl-4-thiocyanatoaniline (3h)^14h

Brown solid (21 mg, 65%), mp 82–84 °C. R_f = 0.21 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 2.45 (s, 3 H, CH₃), 3.81 (s, 2H, NH), 6.50 (H₆: dd, J = 8.4, 2.4 Hz, 1H), 6.59 (H₂: d, J = 2.4, 1H), 7.36 (H₅: d, J = 8.4 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 20.9 (CH₃), 109.1 (C₄), 111.9 (SCN), 113.7 (C6), 117.2 (C2), 136.2 (C5), 143 (C3), 149.3 (C1). IR (KBr, cm^–1): 815, 862, 2146, 3341, 3429. MS (EI, 70 eV) m/z (%): 164 [M⁺], 149, 131, 119, 104, 94, 77.

6-Aminobenzo[d][1,3]oxathiol-2-one (3i′)

Brown solid (5.0 mg, 15%), mp 100–102 °C. R_f = 0.61 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, CDCl₃): δ 3.85 (s, 2 H, NH), 6.57 (H₅: d, J = 8 Hz, 1H), 6.63 (H₇: s, 1H), 7.11 (H₄: d, J = 8 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 98.9 (C₇), 110.5 (C_3a), 112.4 (C₅), 122.7 (C₄), 146.7 (C₆), 149.2 (C_7a), 170 (C₂). IR (neat, cm^–1): 821, 963, 1013, 1100, 1735, 3356, 3465. MS (EI, 70 eV) m/z (%): 167 [M⁺], 139, 123, 111, 96, 84, 79, 67, 61. HRMS (ESI, m/z): [M + H]⁺ calculated for C₇H₆NO₂S, 168.0041; found, 168.0113.

6-Cyano-1,3-benzothiazol-2-amine (3j)^14j,32

Yellow solid (25 mg, 71%), mp 185–187 °C. R_f = 0.50 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, CDCl₃): δ 5.62 (s, 2H, NH), 7.54–7.59 (H_4,5: m, 2H), 7.88 (H₇: s, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 105.2 (C₆), 119.2 (CN), 119.5 (C₄), 125.1 (C₇), 130 (C₅), 132.2 (C_7a), 155.4 (C_3a), 168.6 (C₂). IR (KBr, cm^–1): 810, 820, 1318, 1458, 1524, 1635, 2224, 2850, 2925, 3318. MS (EI, 70 eV) m/z (%): 175 [M⁺], 148, 121, 96, 69.

6-Nitro-1,3-benzothiazol-2-amine (3k)^24,32

Yellow solid (16 mg, 41%), mp 223–225 °C. R_f = 0.38 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, DMSO-d₆): δ 7.41 (H₄: d, J = 8 Hz, 1H), 8.09 (H₅: dd, J = 8 Hz, J = 2 Hz, 1H), 8.23 (s, 2H, NH), 8.67 (H₇: d, J = 2 Hz, 1H). ¹³C NMR (101 MHz, DMSO-d₆): δ 116.8 (C₄), 117.7 (C₇), 122 (C₅), 131.6 (C_7a), 140.7 (C₆), 158.5 (C_3a), 171.7 (C₂). IR (KBr, cm^–1): 748, 1125, 1287, 1324, 1450, 1481, 1517, 1634, 3280, 3401.

6-Fluoro-1,3-benzothiazol-2-amine (3l)^14j

Green solid (20 mg, 59%), mp 153–155 °C. R_f = 0.44 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, DMSO-d₆): δ 7.03 (H₅: td, J = 8 Hz, J = 4 Hz, 1H), 7.29 (H₄: dd, J = 8 Hz, J = 4 Hz, 1H), 7.45 (s, 2H, NH), 7.57 (H₇: dd, J = 8, 4 Hz, 1H). ¹³C NMR (101 MHz, DMSO-d₆): δ 107.7 (C₇: d, J = 27.3 Hz), 112.6 (C₅: d, J = 24.2 Hz), 118 (C₄: d, J = 8.1 Hz), 131.8 (C_7a: d, J = 11.1 Hz), 149.3 (C_3a), 156.5 (C₆: d, J = 236.3 Hz), 166.3 (C₂). IR (neat, cm^–1): 809, 853, 921, 1464, 1541, 1640, 2921, 3269, 3384. MS (EI, 70 eV) m/z (%): 168 [M⁺], 141, 114, 84, 69, 57.

6-Chloro-1,3-benzothiazol-2-amine (3m)^14j,24

Brown solid (19 mg, 51%), mp 158–160 °C. R_f = 0.45 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, DMSO-d₆): δ 7.22 (H₅: d, J = 8 Hz, 1 H), 7.30 (H₄: d, J = 8 Hz, 1H), 7.66 (s, 2H, NH), 7.77 (H7: s, 1H). ¹³C NMR (101 MHz, DMSO-d₆): δ 118.4 (C₄), 120.5 (C₇), 124.5 (C_7a), 125.5 (C₅), 132.3 (C₆), 151.2 (C_3a), 167.1 (C₂). IR (KBr, cm^–1): 762, 812, 1446, 1534, 1633, 2070, 3380, 3456. MS (EI, 70 eV) m/z (%): 184 [M⁺], 157, 149, 130, 122, 95, 63.

6-Methoxy-1,3-benzothiazol-2-amine (3n):^14j,24

Black solid (7.0 mg, 18%), mp 130–132 °C. R_f = 0.44 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, DMSO-d₆): δ 3.73 (s, 3 H, OCH₃), 6.81 (H₅: d, J = 8 Hz, 1 H), 7.23 (H₄: d, J = 8 Hz, 1H), 7.30 (NH + H7: s, 3H, NH). ¹³C NMR (101 MHz, DMSO-d₆): δ 55.5 (OCH₃), 105.6 (C₇), 112.9 (C₅), 117.9 (C₄), 131.6 (C_7a), 146.2 (C_3a), 154.3 (C₆), 164.8 (C₂). IR (neat, cm^–1): 806, 846, 1053, 1641, 3294, 3387. MS (EI, 70 eV) m/z (%): 180 [M⁺], 165, 149, 137, 110, 80, 69.

(Z)-1,2-Diphenyldiazene Oxide (4b)³³

Trace (<5.0%). R_f = 0.7 (Hex/AcOEt 3:1). ¹H NMR (300 MHz, CDCl₃): δ 7.37–7.42 (H_4′: m, 1H), 7.46–7.57 (H_{3,4,5,3′,5′}: m, 5H), 8.14–8.18 (H_2′,6′: m, 2H), 8.30–8.33 (H_2,6: m, 2H). ¹³C NMR (75 MHz, CDCl₃): δ 122.3 (C_2,6), 125.5 (C_2′,6′), 128.7 (C_3′,5′), 128.8 (C_3,5), 129.6 (C_4′), 131.6 (C₄), 144 (C_1′). MS (EI, 70 eV) m/z (%): 198 [M⁺], 182, 169, 152, 141, 115, 105, 91, 77, 64, 51.

4-Thiocyanatophenol (7a)¹⁴ⁱ

White solid (29 mg, 96%), mp 46–48 °C. R_f = 0.47 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 5.89 (s, 1H, OH), 6.88 (H_2,6: d, J = 8 Hz, 2H), 7.44 (H_3,5: d, J = 8 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃): δ 112.1 (SCN), 113.4 (C₄), 117.4 (C_2,6), 134.2 (C_3,5), 157.9 (C₁). IR (neat, cm^–1): 832, 1100, 1170, 2161, 3420. MS (EI, 70 eV) m/z (%): 151 [M⁺], 122, 96, 81, 70, 65.

2-Nitro-4-thiocyanatophenol (7b)³⁴

Yellow solid (6.0 mg, 15%), mp 72–73 °C. R_f = 0.38 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 7.30 (H₆: d, J = 8.8 Hz, 1H), 7.79 (H₅: dd, J = 8.8, 2.4 Hz, 1 H), 8.37 (H₃: d, J = 2,4 Hz, 1H), 10.71 (s, 1H, OH). ¹³C NMR (101 MHz, CDCl₃): δ 109.6 (SCN), 115.2 (C₄), 122.6 (C₆), 128.5 (C₃), 133.9 (C₂), 139.9 (C₅), 156.2 (C₁). IR (KBr, cm^–1): 848, 892, 1253, 1416, 1523, 2156, 3266. MS (EI, 70 eV) m/z (%): 196 [M⁺], 179, 169, 150, 138, 123. HRMS (ESI, m/z): [M + H]⁺ calculated for C₇H₅N₂O₃S, 196.9943; found, 197.0028.

2-Formyl-4-thiocyanatophenol (7c)¹⁴ⁱ

White solid (17 mg, 47%). mp 89–90 °C. R_f = 0.41 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 7.08 (H₆: d, J = 8 Hz, 1H), 7.70 (H₅: dd, J = 8.0, 4.0 Hz, 1H), 7.83 (H₃: d, J = 4 Hz, 1 H), 9.90 (s, 1H, OH), 11.21 (s, 1H, CHO). ¹³C NMR (101 MHz, CDCl₃): δ 110.5 (SCN), 113.8 (C₄), 120.3 (C₆), 121.5 (C₂), 137.5 (C₃), 140 (C₅), 163 (C₁), 195.3 (CHO). IR (neat, cm^–1): 845, 900, 1575, 1655, 2155, 3300. MS (EI, 70 eV) m/z (%): 179 [M⁺], 161, 151, 133, 123.

2-Methyl-4-thiocyanatophenol (7d)^14i,14l

Yellow solid (31 mg, 94%). mp 64–66 °C. R_f = 0.39 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 2.22 (s, 3H, CH₃), 6.65 (s, 1H, OH), 6.79 (H₆: d, J = 8.4 Hz, 1H), 7.23 (H₅: dd, J = 8.4, 2.8 Hz, 1H), 7.31 (H₃: d, J = 2.8 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 15.7 (CH₃), 112.2 (C₄), 112.6 (SCN), 116.6 (C₆), 127.1 (C₂), 131.4 (C₅), 135 (C₃), 156.5 (C1). IR (KBr, cm^–1): 816, 884, 1589, 2161, 3373. MS (EI, 70 eV) m/z (%): 165 [M⁺], 146, 137, 122, 107, 77, 59.

2-Methoxy-4-thiocyanatophenol (7e)^14k

White solid (26 mg, 70%), mp 99–101 °C. R_f = 0.33 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 3.93 (s, 3H, OCH₃), 5.88 (s, 1H, OH), 6.95 (H₆: d, J = 8 Hz, 1 H), 7.05 (H₃: d, J = 4 Hz, 1H), 7.10 (H₅: dd, J = 8.0, 4.0 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 56.2 (OCH₃), 111.6 (SCN), 113 (C₄), 114.4 (C₃), 115.8 (C₆), 126.2 (C₅), 147.5 (C₂), 147.8 (C₁). IR (KBr, cm^–1): 806, 926, 1028, 2160, 3356. MS (EI, 70 eV) m/z (%): 181 [M⁺], 166, 155, 138, 123, 111, 95, 79, 69.

4-Thiocyanatobenzene-1,2-diol (7f)¹⁴ⁱ

Pale yellow solid (19.5 mg, 58%), mp 140–142 °C. R_f = 0.38 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, DMSO-d₆): δ 6.84 (H₆: d, J = 8 Hz, 1H), 6.94 (H₅: dd, J = 8.0, 4.0 Hz, 1H), 7.00 (H₃: d, J = 4 Hz, 1H), 9.55 (s, 2H, OH). ¹³C NMR (101 MHz, DMSO-d₆): δ 110.9 (C₄), 112.5 (SCN), 117 (C₆), 118.9 (C₃), 123.9 (C₅), 146.8 (C₂), 147.9 (C₁). IR (KBr, cm^–1): 1281, 1510, 2165, 3297. MS (EI, 70 eV) m/z (%): 167 [M⁺], 141, 134, 121, 111, 95, 84, 69, 51.

2,6-Dimethyl-4-thiocyanatophenol (7g)¹⁴ⁱ

Brown solid (19 mg, 54%), mp 97–99 °C. R_f = 0.55 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 2.24 (s, 6H, CH₃), 5.07 (s, 1H, OH), 7.20 (H_3,5: s, 2H). ¹³C NMR (101 MHz, CDCl₃): δ 15.8 (CH₃), 112.1 (SCN), 112.6 (C₄), 125.5 (C_2,6), 132.4 (C_3,5), 154.2 (C₁). IR (neat, cm^–1): 2155, 3453. MS (EI, 70 eV) m/z (%): 179 [M⁺], 164, 146, 136, 121, 91, 77, 65, 59.

5-Formyl-2-thiocyanatoaniline (8h)

Light yellow solid (10 mg, 28%), mp 180–182 °C. R_f = 0.17 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, DMSO-d₆): δ 7.27 (H₄: dd, J = 8.0, 4.0 Hz, 1H), 7.52 (H₆: d, J = 4 Hz, 1H), 7.62 (H₃: d, J = 8 Hz, 1H), 10.01 (s, 1H, OH), 10.50 (s, 1H, CHO). ¹³C NMR (101 MHz, DMSO-d₆): δ 111.6 (SCN), 114.6 (C₂), 122.2 (C₆), 122.8 (C₄), 130.1 (C₃), 133.6 (C₁), 158 (C₅), 193.3 (CHO). IR (KBr, cm^–1): 829, 870, 1665, 2157, 3298. MS (EI, 70 eV) m/z (%): 179 [M⁺], 152, 135, 124.

3-Methyl-4-thiocyanatophenol (7i)^14h,14i

Beige solid (28 mg, 85%), mp 67–69 °C. R_f = 0.33 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 2.47 (s, 3H, CH₃), 6.08 (s, 1H, OH), 6.71 (H₆: dd, J = 8.4, 2.8 Hz, 1H), 6.79 (H₂: d, J = 2.8 Hz), 7.46 (H₅: d, J = 8.4, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 20.9 (CH₃), 111.8 (SCN), 112.6 (C₄), 114.9 (C₆), 118.5 (C₂), 136 (C₅), 143.2 (C₃), 158.4 (C₁). IR (KBr, cm^–1): 1238, 1572, 2160, 3337. MS (EI, 70 eV) m/z (%): 165 [M⁺], 146, 137, 121, 110, 94, 77, 69.

3-Methoxy-4-thiocyanatophenol (7j)^14k

Yellow solid (19 mg, 52%), mp 139–141 °C. R_f = 0.53 (AcOEt/Hex 7:3). ¹H NMR (400 MHz, DMSO-d₆): δ 3.86 (s, 3H, OCH₃), 6.49 (H₆: dd, J = 8.0, 4.0 Hz, 1H), 6.57 (H₂: d, J = 4 Hz, 1H), 7.40 (H₅: d, J = 8 Hz, 1H), 10.23 (s, 1H, OH). ¹³C NMR (101 MHz, DMSO-d₆): δ 56.2 (OCH₃), 98.6 (C₄), 100.4 (C₂), 109 (C₆), 111.9 (SCN), 135 (C₅), 159.4 (C₃), 161.8 (C₁). IR (KBr, cm^–1): 792, 852, 2155, 1201, 3361.

6-Methoxybenzo[d][1,3]oxathiol-2-one (8j′)³⁵

White solid (5.2 mg, 14%), mp 59–61 °C. R_f = 0.66 (Hex/AcOEt 3:1). IR (KBr, cm^–1): 786, 870, 1731. MS (EI, 70 eV) m/z (%): 182 [M⁺], 126, 123, 111, 95.

6-Hydroxybenzo[d][1,3]oxathiol-2-one (7k′)³⁶

Orange solid (7.5 mg, 22%), mp 138–140 °C. R_f = 0.29 (CHCl₃/MeOH 10:1). ¹H NMR (400 MHz, DMSO-d₆): δ 6.76 (H₅: dd, J = 8.0, 4.0 Hz, 1 H), 6.86 (H₇: d, J = 4 Hz, 1H), 7.49 (H₄: d, J = 8 Hz), 10.04 (s, 1H, OH). ¹³C NMR (101 MHz, DMSO-d₆): δ 99.6 (C7), 110.7 (C3a), 113.1 (C5), 123.7 (C4), 148.4 (C6), 157.6 (C7a), 169.9 (C2). IR (KBr, cm^–1): 803, 832, 1022, 1161, 1448, 1609, 1658, 3299. MS (EI, 70 eV) m/z (%): 168 [M⁺], 140, 124, 112, 95, 84.

5-Formylbenzo[d][1,3]oxathiol-2-one (7l)

White solid (5.0 mg, 14%), mp 116–118 °C. R_f = 0.39 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 7.46 (H₇: d, J = 8.0 Hz, 1H), 7.88 (H₆: dd, J = 8.0, 2.0 Hz, 1H), 8.00 (H₄: d, J = 2.0 Hz, 1H), 9.99 (s, 1H, CHO). ¹³C NMR (101 MHz, CDCl₃): δ 112.5 (C₇), 123.4 (C₄), 124.7 (C_3a), 130.2 (C₆), 133.8 (C₅), 151.9 (C_7a), 167.5 (C₂), 189.6 (CHO). IR (KBr, cm^–1): 840, 901, 1691, 1746. MS (EI, 70 eV) m/z (%): 180 [M⁺], 152, 135, 124, 107, 96, 79, 69, 51. HRMS (ESI, m/z): [M + H]⁺ calculated for C₈H₅O₃S, 180.9881; found, 180.9931.

5-Methoxybenzo[d][1,3]oxathiol-2-one (7m)³⁷

White solid (11 mg, 30%), mp 66–68 °C. R_f = 0.64 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 3.81 (s, 3H, OCH₃), 6.84 (H₆: dd, J = 8.0, 4.0 Hz, 1 H), 6.92 (H₄: d, J = 4 Hz, 1H), 7.18 (H₇: d, J = 8 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 55.9 (OCH₃), 107.3 (C₄), 112.5 (C₇), 113.5 (C₆), 123.9 (C_3a), 142.2 (C_7a), 157.1 (C₅), 168.9 (C₂). IR (KBr, cm^–1): 803, 867, 1025, 1087, 1734. MS (EI, 70 eV): m/z (%): 182 [M⁺], 154, 139, 126, 111, 97, 85, 79, 69.

5-Methylbenzo[d][1,3]oxathiol-2-one (7n)³⁷

White solid (7.5 mg, 23%), mp 80–82 °C. R_f = 0.68 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 2.38 (s, 3H, CH₃), 7.10–7.12 (H₆: m, 1H), 7.16 (H₇: d, J = 8 Hz, 1H), 7.19–7.20 (H₄: m, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 21.1 (CH₃), 111.6 (C₇), 122.4 (C₄), 122.8 (C_3a), 128.1 (C₆), 135.2 (C₅), 146.2 (C_7a), 169 (C₂). IR (KBr, cm^–1): 811, 883, 1015, 1087, 1235, 1479, 1742, 2853, 2917. MS (EI, 70 eV) m/z (%): 166 [M⁺], 138, 121, 110, 84, 66.

5,7-Dimethylbenzo[d][1,3]oxathiol-2-one (7o)³⁷

Yellow solid (6.5 mg, 18%), mp 64–65 °C. R_f = 0.70 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 2.32 (s, 3H, CH₃ (7)), 2.34 (s, 3H, CH₃ (5)), 6.92 (H₆: s, 1H), 7.00 (H₄: s, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 15.7 (CH₃ (7)), 21 (CH₃ (5)), 119.7 (C₄), 122.1 (C₇), 122.3 (C₅), 129.7 (C₆), 134.8 (C_3a), 144.8 (C_7a), 169.2 (C₂). IR (neat, cm^–1): 1728, 1756. MS (EI, 70 eV) m/z (%): 180 [M⁺], 152, 135, 124, 109, 97, 91, 77, 65.

N,N-Dimethyl-4-thiocyanatoaniline (10)^14j,14l

White solid (16 mg, 45%), mp 66–68 °C. R_f = 0.58 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 3.00 (s, 6H, CH₃), 6.69 (H_2,6: d, J = 8 Hz, 2H), 7.42 (H_3,5: d, J = 8 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃): δ 40.2 (CH₃), 106.8 (C₄), 112.5 (SCN), 113.3 (C_2,6), 134.4 (C_3,5), 151.5 (C₁). IR (neat, cm^–1): 805, 945, 990, 2145, 1370. MS (EI, 70 eV) m/z (%): 178 [M]⁺, 152, 145, 136, 118, 104, 88, 104, 88.

1-Methoxy-4-thiocyanatobenzene (12a)^14i,38

Colorless oil (16 mg, 48%), R_f = 0.77 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 3.83 (s, 3H, OCH₃), 6.95 (H_2,6: d, J = 8 Hz, 2H), 7.51 (H_3,5: d, J = 8 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃): δ 55.5 (OCH₃), 111.6 (SCN), 113.8 (C4), 115.8 (C_2,6), 133.8 (C_3,5), 161.3 (C₁). IR (KBr, cm^–1): 824, 1025, 1173, 1249, 1494, 1590, 2154, 2840, 2926. MS (EI, 70 eV) m/z (%): 165 [M⁺], 150, 134, 122, 104, 95, 90, 78.

1,2,3-Trimethoxy-5-thiocyanatobenzene (12b)

Colorless liquid (40 mg, 89%), R_f = 0.47 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 3.88 (s, 3H, OCH₃(2)), 3.89 (s, 3H, OCH₃(1)), 4.00 (s, 3H, OCH₃(3)), 6.73 (H₆: d, J = 8 Hz, 1H), 7.25 (H₅: d, J = 8 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 56.2 (OCH₃ (2)), 61 (OCH₃ (1)), 61.3 (OCH₃ (3)), 108.4 (C₆), 109.5 (C₄), 111.1 (SCN), 125.4 (C₅), 142.8 (C₂), 151.7 (C₃), 155.4 (C₁). IR (KBr, cm^–1): 766, 783, 862, 1092, 1228, 1298, 1579, 2156, 2837, 2946. MS (EI, 70 eV) m/z (%): 225 [M⁺], 211, 195, 182, 167, 153, 139, 127, 110. [M + H]⁺ calculated for C₁₀H₁₂NO₃S, 226,0460; found, 226,0541.

1,3,5-Trimethoxy-2-thiocyanatobenzene (12c)¹⁴ⁱ

White solid (26 mg, 58%), mp 150–152 °C. R_f = 0.38 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 3.84 (s, 3H, OCH₃ (5)), 3.92 (s, 6H, OCH₃ (1,3)), 6.16 (H_4,6: s, 2H). ¹³C NMR (101 MHz, CDCl₃): δ 55.6 (OCH₃ (5)), 56.3 (OCH₃ (1,3)), 89.8 (C₂), 91.3 (C_4,6), 111.8 (SCN), 161.4 (C_1,3), 164.2 (C₅). IR (KBr, cm^–1): 822, 1344, 1417, 1457, 1475, 1585, 2149, 2846, 2944, 3106. MS (EI, 70 eV) m/z (%): 225 [M⁺], 210, 192, 179, 162, 150, 141, 125, 111.

Methyl(4-thiocyanatophenyl)sulfane (14)¹³

Colorless oil (12 mg, 33%), R_f = 0.63 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 2.43 (s, 3H, SCH₃), 7.20 (H_2,6: d, J = 8 Hz, 2H), 7.38 (H_3,5: d, J = 8 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃): δ 15.3 (SCH₃), 110.7 (SCN), 119.4 (C₄), 127.4 (C_2,6), 131.2 (C_3,5), 142.1 (C₁). IR (neat, cm^–1): 545, 743, 807, 960, 1009, 1075, 1097, 1186, 1391, 1431, 1474, 1574, 1722, 2155, 2923. MS (EI, 70 eV) m/z (%): 181 [M⁺], 166, 155, 135, 122.

8-Thiocyanatonaphthalen-1-ol (16)³⁹

Dark red solid (31 mg, 77%), mp 93–95 °C. R_f = 0.39 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, DMSO-d₆): δ 6.98 (H₂: d, J = 8 Hz, 1H), 7.63 (H₇: t, J = 8 Hz, 1H), 7.78 (H₆: t, J = 8 Hz, 1H), 7.88 (H₃: d, J = 8 Hz, 1H), 8.22 (H₅: d, J = 8 Hz, 1H), 8.29 (H₈: d, J = 8 Hz, 1H), 11.13 (s, 1H, OH). ¹³C NMR (101 MHz, DMSO-d₆): δ 107.9 (C₄), 109.1 (C₂), 112.8 (SCN), 123.7 (C₈), 124.7 (C₅), 126.2 (C_8a), 126.3 (C₇), 129.2 (C₆), 134.2 (C_4a), 137 (C₃), 157.7 (C₁). IR (neat, cm^–1): 2160, 3390.

3-Thiocyanato-1H-indole (18)^14j

Brown oil (14 mg, 40%). R_f = 0.33 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 7.21–7.25 (H_5,6: m, 2H), 7.32–7.37 (H₇: m, 1H), 7.40 (H₂: d, J = 4 Hz, 1H), 7.70–7.74 (H₄: m, 1H), 8.68 (s, 1H, NH). ¹³C NMR (101 MHz, CDCl₃): δ 92.2 (C₃), 111.9 (C₇), 112.1 (SCN), 118.7 (C₅), 121.9 (C₆), 123.8 (C₄), 127.6 (C_3a), 130.9 (C₂), 136 (C_7a). IR (KBr, cm^–1): 743, 1239, 1456, 2156, 3119, 3395. MS (EI, 70 eV) m/z (%): 174 [M⁺], 142, 120, 89, 77.

(Z)-1,2-bis(4-Thiocyanatophenyl)diazene Oxide (20)

Orange solid (3.0 mg, 5.0%). R_f = 0.35 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 7.62 (H_2′,6′: d, J = 8 Hz, 1H), 7.66 (H_2,6: d, J = 8 Hz, 1H), 8.25 (H_3′,5′: d, J = 8 Hz, 1H), 8.40 (H_3,5: d, J = 8 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ 122.4 (SCN (4′)), 124.1 (C_3,5), 124.6 (SCN (4)), 125.9 (C_1′), 127.2 (C_3′,5′), 129.1 (C_2,6), 129.5 (C_2′,6′), 129.8 (C₁), 144.1 (C_4′), 148.5 (C₄). [M + H]⁺ calculated for C₁₄H₉N₄OS₂, 313,0140; found, 313,0253.

4,6-Dichloro-N-(2′-nitrophenyl)-1,3,5-triazin-2-amine (3b″)⁴⁰

Yellow solid (28 mg, 49%), mp 191–193 °C. R_f = 0.5 (Hex/AcOEt 3:1). ¹H NMR (400 MHz, CDCl₃): δ 7.25–7.27 (H_4′: t, J = 8 Hz, 1H), 7.67–7.71 (H_5′: t, J = 8 Hz, 1H), 8.20 (H_6′: d, J = 8 Hz, 1H), 8.60 (H_3′: d, J = 8 Hz, 1H), 10.47 (s, 1H, NH). ¹³C NMR (75 MHz, CDCl₃): δ 123.1 (C_6′), 124.7 (C_4′), 126.2 (C_3′), 132.7 (C_5′), 135.6 (C_2′), 137.9 (C_1′), 156.5 (C₄), 164.3 (C₆), 161.2 (C₂). IR (neat, cm^–1): 1139–1293, 1491, 1598, 3278, 3430.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c05131.

• Experimental procedures, characterization data, and NMR spectra of all compounds (PDF)

• Determination of the green parameters (XLS)

• Mathematical expression for reaction yield (ε), AE, SF, and MRP and their relationships (ZIP)

Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

The authors declare no competing financial interest.