Synthesis and Structure of N -(1-(Bromomethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-yl)benzenesulfonamide

: A new bicyclic sulfonamide derivative, N -(1-(bromomethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-yl)benzenesulfonamide, was synthesized in the reaction of benzenesulfonamide and camphene in the presenceof N -bromosuccinimideinacetonitrile. Theproposedmechanismofinvestigatedreactioninvolves the Wagner–Meerwein rearrangement stage. 3-(Bromomethylene)-2,2-dimethylbicyclo[2.2.1]heptane was isolated as a minor product. The products were characterized by IR, NMR spectroscopy, X-ray diffraction analysis, HRMS and elemental analysis data.


Introduction
The relevance of expanding the library of modified monoterpene compounds is associated with their diverse biological activity. For example, camphene derivatives alleviate oxidative stress, reduce skeletal muscle atrophy [1], and exhibit antibacterial [2], antiinflammatory [3], antioxidant [4] and antiviral activity [5]. Camphene derivatives show insecticidal properties [6]. Thiosemicarbazide derivatives of camphene significantly increase antifungal activity compared to unsubstituted thiosemicarbazide ( Figure 1) [7]. Microorganisms' and viruses' resistance to drugs is a growing concern that poses a challenge for chemists to search for synthesis methods of new biocompatible substances, so the modification of terpenes is an urgent task.

Introduction
The relevance of expanding the library of modified monoterpene compo sociated with their diverse biological activity. For example, camphene derivat ate oxidative stress, reduce skeletal muscle atrophy [1], and exhibit antibacteri inflammatory [3], antioxidant [4] and antiviral activity [5]. Camphene deriva insecticidal properties [6]. Thiosemicarbazide derivatives of camphene signi crease antifungal activity compared to unsubstituted thiosemicarbazide (Figur croorganisms' and viruses' resistance to drugs is a growing concern that poses for chemists to search for synthesis methods of new biocompatible substan modification of terpenes is an urgent task.

Results and Discussion
The reaction of benzenesulfonamide 1 and camphene 2 was carried out in in the presence of N-bromosuccinimide at room temperature. The reaction led mation of two products: N- (

Results and Discussion
The reaction of benzenesulfonamide 1 and camphene 2 was carried out in acetonitrile in the presence of N-bromosuccinimide at room temperature. The reaction led to the formation of two products: N-(1-(bromomethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-yl)benzenesulfonamide 3 with good yield and 3-(bromomethylene)-2,2-dimethylbicyclo[2.2.1]heptane 4 as a minor product (Scheme 1). The first step of the reaction was the attack of the bromine cation by NBS at the ter minal carbon atom of the camphene 1 C=C bond. The next step was accompanied by Wag ner-Meerwein rearrangement, followed by the attack of sulfonamide 1 to form the fina structure 3 (Scheme 2): The reactions of camphene 2 and similar substrates are sometimes accompanied by Wagner-Meerwein rearrangement processes [8,9].
The structure and composition of the resulting products were established with NMR IR spectroscopy, high resolution mass spectrometry (HRMS) and elemental analysis data The 1 H NMR spectrum of compound 3 displayed the doublet of the NH group, and CH2Br doublets at 3.47 and 3.34 ppm with J = 10.5 Hz ( Figure S3). The 13 С NMR spectrum con tained signals of the carbon atom CHN: CH2Br and CH3 groups at 59, 38 and 20 ppm respectively ( Figure S4). The IR spectrum of compound 3 showed bands at νNH = 3289 cm − and νSO2 = 1322 cm −1 . Structure 3 was proved by X-ray analysis ( Figure 2, Tables S1 and S2). Compound 4 had the following structure of 3-(bromomethylene)-2,2-dimethylbicy clo[2.2.1]heptane according to the presence in the 1 H NMR spectrum of a signal at 5.62 ppm, which had 1 H-13 C satellites with 1 JCH = 196.12 Hz, which proved the presence of the =CHBr group ( Figures S5 and S6). In reference [6], the preparation of compound 4 under similar conditions in the absence of benzenesulfonamide was described.

Crystal Structure
The single crystals of compound 3 were obtained through re-crystallization from a chloroform solution. Molecules of compound 3 crystallized in monoclinic space group C2/c in the crystal molecules of 3 connected by intermolecular hydrogen bonds NH···O=S by lengths 2.252 Å (Figure 3). The first step of the reaction was the attack of the bromine cation by NBS at the terminal carbon atom of the camphene 1 C=C bond. The next step was accompanied by Wagner-Meerwein rearrangement, followed by the attack of sulfonamide 1 to form the final structure 3 (Scheme 2): The first step of the reaction was the attack of the bromine cation by NBS at the ter minal carbon atom of the camphene 1 C=C bond. The next step was accompanied by Wag ner-Meerwein rearrangement, followed by the attack of sulfonamide 1 to form the fina structure 3 (Scheme 2): The reactions of camphene 2 and similar substrates are sometimes accompanied by Wagner-Meerwein rearrangement processes [8,9].
The structure and composition of the resulting products were established with NMR IR spectroscopy, high resolution mass spectrometry (HRMS) and elemental analysis data The 1 H NMR spectrum of compound 3 displayed the doublet of the NH group, and CH2B doublets at 3.47 and 3.34 ppm with J = 10.5 Hz ( Figure S3). The 13 С NMR spectrum con tained signals of the carbon atom CHN: CH2Br and CH3 groups at 59, 38 and 20 ppm respectively ( Figure S4). The IR spectrum of compound 3 showed bands at νNH = 3289 cm − and νSO2 = 1322 cm −1 . Structure 3 was proved by X-ray analysis (Figure 2, Tables S1 and S2). Compound 4 had the following structure of 3-(bromomethylene)-2,2-dimethylbicy clo[2.2.1]heptane according to the presence in the 1 H NMR spectrum of a signal at 5.62 ppm, which had 1 H-13 C satellites with 1 JCH = 196.12 Hz, which proved the presence of the =CHBr group ( Figures S5 and S6). In reference [6], the preparation of compound 4 unde similar conditions in the absence of benzenesulfonamide was described.

Crystal Structure
The single crystals of compound 3 were obtained through re-crystallization from a chloroform solution. Molecules of compound 3 crystallized in monoclinic space group C2/c in the crystal molecules of 3 connected by intermolecular hydrogen bonds NH···O=S by lengths 2.252 Å (Figure 3). The reactions of camphene 2 and similar substrates are sometimes accompanied by Wagner-Meerwein rearrangement processes [8,9].
The structure and composition of the resulting products were established with NMR, IR spectroscopy, high resolution mass spectrometry (HRMS) and elemental analysis data. The 1 H NMR spectrum of compound 3 displayed the doublet of the NH group, and CH 2 Br doublets at 3.47 and 3.34 ppm with J = 10.5 Hz ( Figure S3). The 13 C NMR spectrum contained signals of the carbon atom CHN: CH 2 Br and CH 3 groups at 59, 38 and 20 ppm, respectively ( Figure S4). The IR spectrum of compound 3 showed bands at ν NH = 3289 cm −1 and ν SO2 = 1322 cm −1 . Structure 3 was proved by X-ray analysis (Figure 2, Tables S1 and S2). Compound 4 had the following structure of 3-(bromomethylene)-2,2-dimethylbicyclo[2.2.1]heptane according to the presence in the 1 H NMR spectrum of a signal at 5.62 ppm, which had 1 H-13 C satellites with 1 J CH = 196.12 Hz, which proved the presence of the =CHBr group ( Figures S5 and S6). In reference [6], the preparation of compound 4 under similar conditions in the absence of benzenesulfonamide was described. The first step of the reaction was the attack of the bromine cation by NBS at the terminal carbon atom of the camphene 1 C=C bond. The next step was accompanied by Wagner-Meerwein rearrangement, followed by the attack of sulfonamide 1 to form the final structure 3 (Scheme 2): The reactions of camphene 2 and similar substrates are sometimes accompanied by Wagner-Meerwein rearrangement processes [8,9].
The structure and composition of the resulting products were established with NMR, IR spectroscopy, high resolution mass spectrometry (HRMS) and elemental analysis data. The 1 H NMR spectrum of compound 3 displayed the doublet of the NH group, and CH2Br doublets at 3.47 and 3.34 ppm with J = 10.5 Hz ( Figure S3). The 13 С NMR spectrum contained signals of the carbon atom CHN: CH2Br and CH3 groups at 59, 38 and 20 ppm, respectively ( Figure S4). The IR spectrum of compound 3 showed bands at νNH = 3289 cm −1 and νSO2 = 1322 cm −1 . Structure 3 was proved by X-ray analysis (Figure 2, Tables S1 and S2). Compound 4 had the following structure of 3-(bromomethylene)-2,2-dimethylbicyclo[2.2.1]heptane according to the presence in the 1 H NMR spectrum of a signal at 5.62 ppm, which had 1 H-13 C satellites with 1 JCH = 196.12 Hz, which proved the presence of the =CHBr group ( Figures S5 and S6). In reference [6], the preparation of compound 4 under similar conditions in the absence of benzenesulfonamide was described.

Crystal Structure
The single crystals of compound 3 were obtained through re-crystallization from a chloroform solution. Molecules of compound 3 crystallized in monoclinic space group C2/c in the crystal molecules of 3 connected by intermolecular hydrogen bonds NH···O=S by lengths 2.252 Å (Figure 3).

Crystal Structure
The single crystals of compound 3 were obtained through re-crystallization from a chloroform solution. Molecules of compound 3 crystallized in monoclinic space group C2/c in the crystal molecules of 3 connected by intermolecular hydrogen bonds NH···O=S by lengths 2.252 Å (Figure 3).

General Information
All starting materials have been described in the literature. All products were identified using IR, 1 H and 13 C NMR spectroscopy. IR spectra were taken on a Bruker Vertex 70 spectrophotometer in KBr. 1 H and 13 C NMR spectra were recorded in CDCl3 on Bruker DPX 400 spectrometer at working frequencies of 400 ( 1 H) and 100 ( 13 C) MHz. All shifts are reported in parts per million (ppm) relative to residual CHCl3 peak (7.27 and 77.1 ppm, 1 H and 13 C). All coupling constants (J) are reported in hertz (Hz). Abbreviations are s, singlet; d, doublet; t, triplet; m, multiplet. High-resolution mass spectra (HRMS) were measured on an Agilent 1200 HPLC chromatograph with Agilent 6210 mass spectrometer (HR-TOF-MS, ESI + ionization in acetonitrile with 0.1% HFBA). Elemental compositions were determined by accurate mass measurement with standard deviation. H3PO4 was used as reference compound. Elemental analysis of C, H and N was carried out on an elemental analyzer from Thermo-Finnigan (Milan, Italy) model Flash EA, bromine was determined by Shoniger titration method and sulfur was determined by titration with Ba(OAc)2. Melting points were measured on a Boetius apparatus. Flash chromatography was performed using silica gel, 60 Å, 300 mesh. TLC analysis was carried out on aluminum plates coated with silica gel 60 F254, 0.2 mm thickness. The plates were visualized using a 254 nm UV lamp.

General Information
All starting materials have been described in the literature. All products were identified using IR, 1 H and 13 C NMR spectroscopy. IR spectra were taken on a Bruker Vertex 70 spectrophotometer in KBr. 1 H and 13 C NMR spectra were recorded in CDCl 3 on Bruker DPX 400 spectrometer at working frequencies of 400 ( 1 H) and 100 ( 13 C) MHz. All shifts are reported in parts per million (ppm) relative to residual CHCl 3 peak (7.27 and 77.1 ppm, 1 H and 13 C). All coupling constants (J) are reported in hertz (Hz). Abbreviations are s, singlet; d, doublet; t, triplet; m, multiplet. High-resolution mass spectra (HRMS) were measured on an Agilent 1200 HPLC chromatograph with Agilent 6210 mass spectrometer (HR-TOF-MS, ESI + ionization in acetonitrile with 0.1% HFBA). Elemental compositions were determined by accurate mass measurement with standard deviation. H 3 PO 4 was used as reference compound. Elemental analysis of C, H and N was carried out on an elemental analyzer from Thermo-Finnigan (Milan, Italy) model Flash EA, bromine was determined by Shoniger titration method and sulfur was determined by titration with Ba(OAc) 2 . Melting points were measured on a Boetius apparatus. Flash chromatography was performed using silica gel, 60 Å, 300 mesh. TLC analysis was carried out on aluminum plates coated with silica gel 60 F 254 , 0.2 mm thickness. The plates were visualized using a 254 nm UV lamp.