Utility of Allylic Azides for the Synthesis of Fused Triazoles and Tetrazoles via Intramolecular Cycloaddition [¹]

Abstract

The synthesis of a variety of annulated triazoles and tetrazoles from differently substituted allyl azides, afforded from the Baylis-Hillman adduct of acrylates, using intramolecular cycloaddition approach is described.

Recent times have witnessed a stupendous increase in the number of applications of azide derivatives for the synthesis of a plethora of 1,2,3-triazole derivatives; this is because they are of use in several spheres including bioconjugation, [²] material, [³] and medicinal chemistry. [4] Generally, syntheses of 1,2,3-triazoles have been achieved either through Husigen [5] or click reactions. [6] Due to the importance of triazoles and their annulated analogues, investigations with newer substrates to accomplish the synthesis of diverse derivatives is an active area of research. We have been interested in the synthesis of heterocycles from intermediates offered via Baylis-Hillman­ chemistry and during the course of this program we became interested in the synthesis of annulated 1,2,3-triazoles. The literature includes several strategies for obtaining triazoles using Baylis-Hillman derivatives, which essentially employ intramolecular or intermolecular cycloaddition reactions. [7] We, thus, embarked on an intramolecular cycloaddition approach wherein we utilized the ester moiety to obtain the acetylene or the azide unit for the synthesis of [1,2,3]triazolo[5,1-c][1,4]oxazepines and [1,2,3]triazolo[1,5-a][1,4]diazepines. During the course of the study it became apparent that substrates generated in this work could be extended for the synthesis of an annulated tetrazole system through the cycloaddition reaction. We report results of our studies in this direction.

Synthesis of 7-benzylidene-4,6,7,8-tetrahydro[1,2,3]triazolo[5,1- c ][1,4]oxazepine: We initiated our study with the synthesis of allyl azides via an earlier reported procedure. [8] We selected azide 2f to optimize the reaction conditions (Scheme  [¹] ). Reduction of the ester group in 2f with diisobutylaluminum hydride smoothly produced the alcohol 3f stereoselectively as the E-isomer within 30 minutes. The alcohol 3f was reacted with propargyl bromide in the presence of sodium hydride to yield 4f, which then served as the substrate for intramolecular dipolar cycloaddition. Unfortunately, 4f was found to be unstable and, therefore, it was subjected to further reaction without purification. Refluxing compound 4f in toluene for five hours furnished a mixture of two products which were separated via a careful column chromatography. Based on the spectral analysis, we expected these compounds to be the E- and Z-isomers of the expected annulated triazole 5f. In order to confirm the assigned structure and investigate the relative stereochemistry of these two products, detailed NMR experiments were performed. Combined application of ^¹H, ^¹³C, and 2D NMR (viz. HSQC, HMBC, and NOESY) spectra revealed that the less polar compound was the E-isomer (E)-5f (Figure  [¹] ) whereas the polar analogue was the Z-isomer of (Z)-5f (Figure  [²] ).

In order to assess the general applicability of our protocol several azides 2a-e,g-i were subjected to a similar sequence of reactions (Scheme  [¹] , Table  [¹] ). Notably however we discovered that the stereoselectivity of the products obtained via cyclization was influenced by the substitution present on the phenyl ring (5g and 5h, Table  [¹] ). To provide chemical support for the existence of 5a-f,i as a mixture of E- and Z-isomers, in a representative experiment, (E/Z)-5a was subjected to catalytic hydrogenation in the presence of palladium-on-carbon to afford 6a in 92% yield. Alternatively, treatment of (E/Z)-5a with DBU was expected to furnish a single product due to isomerization of the double bond. [9] Therefore, (E/Z)-5f was treated with DBU under heating at reflux. Unexpectedly, this reaction yielded a mixture of two products, which were established to be 7f and (Z)-5f. This result implied that in the presence of DBU, the (E)-5f undergoes isomerization to afford 7f but (Z)-5f is unaffected. Further experimental support to this observation was gained via another set of experiments wherein (E)-5f and (Z)-5f were independently treated with DBU. It was observed that (E)-5f underwent smooth isomerization to produce 7f in four hours whereas (Z)-5f remained unaffected (16 h). Study with another set of isomers of 5a gave similar results to afford a mixture of 7a and (Z)-5a, which were readily separated. This finding inferred that in these compounds the isomerization is favored in the E-isomer as compared to the Z-isomer.

Synthesis of 7-Arylidene-5,6,7,8-tetrahydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine: This success prompted us to investigate a similar strategy for another allyl azide that could be generated from the allylamine of adduct of acrylate. For this sequence the optimization study was carried out using 1a. Initially, tosyl derivative 8a was obtained via reaction between 1a and 4-toluenesulfonamide. [¹0] Treatment of 8a with propargyl bromide in the presence of sodium hydride gave 9a (Scheme  [²] ). Reduction of the ester group in 9a with diisobutylaluminum hydride followed by sequential mesylation and azidation yielded the required substrate 12a. Cycloaddition reaction by heating 12a in toluene resulted in a mixture of two products. These products were separated via column chromatography in 55% and 40% yields and established to be the E- and Z-isomers, respectively, of the expected tria­zolodiazepine 13a. The scope of the protocol was studied by subjecting different substrates 8c,d,f,g to a similar series of reactions (Scheme  [²] , Table  [²] ). Interestingly here also reaction for substrate 8g with a 2,4-dichlorophenyl group was observed to be highly stereoselective to afford (E)-13g exclusively. Subsequently the effect of DBU on (E)-13g was examined. In contrast to results achieved with 5, here the isomerization reaction produced two products which were identified as 14g and 15g. Although it is known that under the influence of base detosylation occurs, [¹¹] we did not observe the formation of detosylated product during this reaction.

Application of the protocol was further investigated using allylamine 16. Treatment of 1g with 4-toluenesulfon­amide in the presence of DABCO under aqueous conditions gave the tosyl derivative 16g (Scheme  [²] ). Substituting the NH group in 16g with propargyl bromide afforded the tertiary amide 17g. Reducing the ester group in 17g with diisobutylaluminum hydride, however, resulted in formation of 10g instead of the expected alcohol.

Synthesis of 6-Arylidene-4-alkyl-4,5,5,6-tetrahydro­tetraazolo[1,5- a ]pyrimidines: Based on our previous experience with N-allylcyanamides, [¹²] it occurred to us that substrates afforded during this endeavor can be employed to achieve the synthesis of annulated tetrazoles. Tetrazoles are another important class of molecule that have found significant application as pharmacological agents. [¹³] Accordingly, an optimization study with 3f was initiated. Reacting 3f with mesyl chloride in the presence of triethylamine in dichloromethane afforded the mesyl derivative 18f (Scheme  [³] ). Substituting mesyl group with benzyl­amine produced secondary amine 19f in 77% yield. Compound 19f was readily transformed to cyanamide 21f by reaction with cyanogen bromide in the presence of sodium hydrogen carbonate in methanol. Heating 21f in N,N-di­methylformamide at 90 ˚C for two hours yielded the annulated tetrazole 23f as a mixture of E- and Z-isomers. Despite several attempts, both the isomers in this case could not be separated. The protocol was found to be general over several substrates and here too the 2,4-dichlorophenyl or 2,6-dichlorophenyl groups furnished products solely as the E-isomer (Scheme  [³] , Table  [³] ). Subsequently, in a representative reaction, treatment of 23g with DBU resulted in the formation of a mixture of 25g and 26g. In order to create the more diversity benzylamine was replaced by propylamine to synthesize 20a,e-h. A similar set of reactions produced 24a,e-h in good yields.

Though benzylamine and propylamine worked well for the strategy, the reaction of 4-toluenesulfonamide with the mesylate 18 did not proceed smoothly forcing us explore an alterative route. As a consequence the alcohol 3f was transformed into allyl bromide 27f by reaction with phosphorus tribromide in dichloromethane. Substitution reaction of 27f with 4-toluenesulfonamide proceeded smoothly to yield allyl azide 28f (Scheme  [4] ). The reaction of cyanogen bromide in the presence of sodium hydride resulted in the formation of cyanamide 29f, which on heating in N,N-dimethylformamide at 90 ˚C readily yielded (E)-30f exclusively. This protocol was also found to be of a general nature as evident from the preparation of 30a,e and 30g also. For this set of compounds, 30e and 30g were obtained as a mixture of E- and Z-isomers which could not be separated, but 30a was isolated as the E-isomer exclusively (Scheme  [4] , Table  [4] ).

In summary we have developed a synthesis of new annulated triazole and tetrazole derivatives from different allyl azides afforded from Baylis-Hillman chemistry. This further demonstrates the synthetic utility of Baylis-Hillman derivatives for heterocyclic synthesis. Moreover the work presented here shows that the diastereoselectivity of the afforded annulated triazoles was influenced by the nature of substitutions present on the aromatic ring present in the molecule. Moreover it was observed that the isomerization of the exocyclic double bond in products synthesized herein is influenced by the stereochemistry. All compounds reported in this study were evaluated for antimicrobial activity, but no significant activity was detected.

Melting points are uncorrected and were determined in capillary tubes on an apparatus containing silicon oil. IR spectra were recorded using a Perkin Elmer’s RX I FTIR spectrophotometer. ^¹H and ^¹³C NMR spectra were recorded on either a Bruker DPX-200 FT, a Bruker Avance DRX-300 or a Bruker Avance 400 spectrometer, using TMS as an internal standard. The ^¹³C NMR spectra of fluoro derivatives contain more signals due to carbon-fluoro coupling. Representative spectral data for compounds 4 are provided, as these compounds were found to have a short shelf-life. ESMS were recorded on a Micromass Quadro-II LCMS system. HRMS spectra were recorded as EI-HRMS on a Jeol system. Elemental analyses were performed on a Carlo Erba 108 or an Elementar Vario EL III microanalyzer.

( E )-2-(Azidomethyl)-3-phenylprop-2-en-1-ol (3a); Typical Procedure for 3a-i, 10a,c,d,f,g

To a stirred soln of 2a (2.10 g, 9.68 mmol) in toluene (50 mL), was added 1.0 M DIBAL-H in toluene (19.36 mL, 19.36 mmol) at 0 ˚C under N₂. The mixture was stirred at r.t. for 30 min (TLC monitoring). When the reaction was complete, it was quenched with MeOH (30 mL) and the separated precipitate was filtered through Celite. The filtrate was evaporated to afford the crude product as oil. Purification by column chromatography (silica gel, 100-200 mesh, EtOAc-hexanes, 1:4) furnished 3a (1.51 g, 83%) as reddish brown oil; R _f  = 0.30 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 3443 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.79 (s, 1 H, OH), 4.10 (s, 2 H, CH₂), 4.35 (d, J = 1.1 Hz, 2 H, CH₂), 6.83 (s, 1 H, =CH), 7.23-7.32 (m, 3 H, ArH), 7.35-7.40 (m, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 48.8, 65.9, 127.6, 128.5, 128.8, 131.2, 132.1, 135.3, 135.7.

MS (ES+): m/z = 190.0 [M⁺ + 1].

Anal. Calcd for C₁₀H₁₁N₃O: C, 63.48; H, 5.86; N, 22.21. Found: C, 63.46; H, 5.74; N, 22.18.

(E)-2-(Azidomethyl)-3-(2-chlorophenyl)prop-2-en-1-ol (3b)

Colorless oil; yield: 0.71 g (80%); R _f = 0.33 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 3487 (OH) cm^-¹.

^¹H NMR (300 MHz, CDCl₃,): δ = 3.99 (s, 2 H, CH₂), 4.38 (d, J = 1.1 Hz, 2 H, CH₂), 6.83 (s, 1 H, =CH), 7.23-7.28 (m, 3 H, ArH), 7.34-7.43 (m, 2 H, ArH).

^¹³C NMR (CDCl₃, 75 MHz): δ = 48.8, 65.2, 117.8, 126.7, 127.9, 129.1, 129.6, 130.5, 134.2, 137.2.

MS (ES+): m/z = 224.1 (M⁺ + 1).

Anal. Calcd for C₁₀H₁₀ClN₃O: C, 53.70; H, 4.51; N, 18.79. Found: C, 53.68; H, 4.62; N, 18.82.

(E)-2-(Azidomethyl)-3-(2-fluorophenyl)prop-2-en-1-ol (3c)

Brown oil; yield: 1.00 g (76%); R _f = 0.35 (EtOAc-hexanes, 1:4).

IR (neat): 2106 (N₃), 3483 (OH) cm^-¹.

^¹H NMR (200 MHz, CDCl₃): δ = 1.80 (s, 1 H, OH), 3.97 (s, 2 H, CH₂), 4.39 (s, 2 H, CH₂), 6.77 (s, 1 H, =CH), 7.17-7.29 (m, 3 H, ArH), 7.43 (m, 1 H, ArH).

^¹³C NMR (CDCl₃, 50 MHz): δ = 49.4, 65.6, 127.3, 127.6, 129.8, 129.9, 131.6, 133.1, 134.8, 135.2, 138.5.

MS (ES+): m/z = 208.1 (M⁺ + 1).

Anal. Calcd for C₁₀H₁₀FN₃O: C, 57.97; H, 4.86; N, 20.28. Found: C, 58.25; H, 4.92; N, 20.40.

( E )-2-(Azidomethyl)-3-(4-chlorophenyl)prop-2-en-1-ol (3d)

Orange oil; yield: 0.15 g (68%); R _f  = 0.25 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 3439 cm^-¹ (OH).

^¹H NMR (200 MHz, CDCl₃): δ = 1.70 (s, 1 H, OH), 4.05 (s, 2 H, CH₂), 4.34 (s, 2 H, CH₂), 6.76 (s, 1 H, =CH), 7.17 (d, J = 8.4 Hz, 2 H, ArH), 7.34 (d, J = 8.5 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 49.0, 66.1, 129.0, 129.1, 129.4, 130.2, 130.5, 134.0, 134.5, 136.5.

MS (ES+): m/z = 224.0 [M⁺ + 1].

Anal. Calcd for C₁₀H₁₀ClN₃O: C, 53.70; H, 4.51; N, 18.79. Found: C, 53.79; H, 4.42; N, 18.82.

( E )-2-(Azidomethyl)-3-(4-fluorophenyl)prop-2-en-1-ol (3e)

Brown oil; yield: 1.02 g (68%); R _f  = 0.35 (EtOAc-hexanes, 1:4).

IR (neat): 2103 (N₃), 3481 cm^-¹ (OH).

^¹H NMR (200 MHz, CDCl₃): δ = 1.84 (s, 1 H, OH), 4.07 (s, 2 H, CH₂), 4.35 (s, 2 H, CH₂), 6.78 (s, 1 H, =CH), 7.02-7.10 (m, 2 H, ArH), 7.19-7.22 (m, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 49.2, 65.5, 127.1, 127.5, 129.8, 129.9, 131.6, 133.1, 134.7, 135.0, 138.3.

MS (ES+): m/z = 208.1 [M⁺ + 1].

Anal. Calcd for C₁₀H₁₀FN₃O: C, 57.97; H, 4.86; N, 20.28. Found: C, 58.22; H, 4.73; N, 20.44.

( E )-2-(Azidomethyl)-3-(4-methylphenyl)prop-2-en-1-ol (3f)

Brown oil; yield: 0.76 g (72%); R _f  = 0.33 (EtOAc-hexanes, 1:4).

IR (neat): 2103 (N₃), 3781 cm^-¹ (OH).

^¹H NMR (200 MHz, CDCl₃): δ = 1.86 (s, 1 H, OH), 2.36 (s, 3 H, CH₃), 4.10 (s, 2 H, CH₂), 4.39 (s, 2 H, CH₂), 6.65 (s, 1 H, =CH), 7.17-7.24 (m, 4 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.6, 49.3, 66.5, 127.2, 129.1, 129.3, 129.5, 129.6, 131.8, 133.2.

MS (ES+): m/z = 204.1 [M⁺ + 1].

Anal. Calcd for C₁₁H₁₃N₃O: C, 65.01; H, 6.45; N, 20.68. Found: C, 65.30; H, 6.24; N, 20.53.

( E )-2-(Azidomethyl)-3-(2,4-dichlorophenyl)prop-2-en-1-ol (3g)

Brown oil; yield: 0.32 g (70%); R _f  = 0.38 (EtOAc-hexanes, 1:4).

IR (neat): 2100 (N₃), 3443 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.81-1.85 (m, 1 H, OH), 3.97 (s, 2 H, CH₂), 4.39 (d, J = 4.6 Hz, 2 H, CH₂), 6.77 (s, 1 H, =CH), 7.19-7.21 (m, 1 H, ArH), 7.27-7.29 (m, 1 H, ArH), 7.44 (d, J = 2.0 Hz, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 48.7, 65.1, 126.7, 127.1, 129.5, 131.2, 132.7, 134.2, 134.6, 137.9.

MS (ES+): m/z = 258.1 [M⁺ + 1].

Anal. Calcd for C₁₀H₉Cl₂N₃O: C, 46.53; H, 3.51; N, 16.28. Found: C, 46.74; H, 3.67; N, 16.01.

( E )-2-(Azidomethyl)-3-(2,6-dichlorophenyl)prop-2-en-1-ol (3h)

Brown oil; yield: 1.35 g (75%); R _f  = 0.38 (EtOAc-hexanes, 1:4).

IR (neat): 2105 (N₃), 3450 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.96 (s, 1 H, OH), 3.81 (s, 2 H, CH₂), 4.42 (d, J = 1.1 Hz, 2 H, CH₂), 6.52 (s, 1 H, =CH), 7.20 (t, J = 8.2 Hz, 1 H, ArH), 7.35 (d, J = 7.9 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 50.0, 64.6, 124.1, 128.4, 129.7, 134.0, 135.2, 140.1.

MS (ES+): m/z = 258.0 [M⁺ + 1].

Anal. Calcd for C₁₀H₉Cl₂N₃O: C, 46.53; H, 3.51; N, 16.28. Found: C, 46.35; H, 3.58; N, 16.30.

( E )-2-(Azidomethyl)-3-(thiophen-2-yl)prop-2-en-1-ol (3i)

Colorless oil yield: 1.50 g (86%); R _f  = 0.20 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 3439 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.74 (s, 1 H, OH), 4.29 (s, 2 H, CH₂), 4.34 (d, J = 4.6 Hz, 2 H, CH₂), 6.87 (s, 1 H, =CH), 7.05-7.07 (m, 2 H, ArH), 7.34-7.36 (m, 1 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 49.1, 66.3, 123.8, 126.7, 127.5, 128.9, 133.4, 138.1.

MS (ES+): m/z = 196.0 [M⁺ + 1].

Anal. Calcd for C₈H₉N₃OS: C, 49.21; H, 4.65; N, 21.52. Found: C, 49.01; H, 4.72; N, 21.48.

( E )-3-Phenyl-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-en-1-ol (10a)

White solid; yield: 1.50 g (74%); mp 85-87 ˚C; R _f  = 0.27 (EtOAc-hexanes, 1:4).

IR (KBr): 3304 (≡CH), 3420 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.75 (t, J = 2.4 Hz, 1 H, ≡CH), 2.41 (s, 3 H, CH₃), 2.84 (s, 1 H, OH), 4.00 (d, J = 2.3 Hz, 2 H, CH₂), 4.06 (s, 2 H, CH₂), 4.33 (s, 2 H, CH₂), 6.84 (s, 1 H, =CH), 7.15 (d, J = 7.0 Hz, 2 H, ArH), 7.21-7.30 (m, 5 H, ArH), 7.69 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 36.3, 43.1, 64.7, 73.9, 76.1, 127.1, 127.7, 128.2, 128.8, 129.6, 131.9, 135.4, 135.7, 135.9, 143.9.

MS (ES+): m/z = 356.0 [M⁺ + 1].

Anal. Calcd for C₂₀H₂₁NO₃S: C, 67.58; H, 5.95; N, 3.94. Found: C, 67.65; H, 5.76; N, 4.04.

( E )-3-(2-Fluorophenyl)-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-en-1-ol (10c)

White solid; yield: 0.90 g (83%); mp 89-90 ˚C; R _f  = 0.20 (EtOAc-hexanes, 1:4).

IR (KBr): 3302 (≡CH), 3403 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.66 (t, J = 2.3 Hz, 1 H, ≡CH), 2.40 (s, 3 H, CH₃), 2.83 (t, J = 6.8 Hz, 1 H, OH), 3.99 (t, J = 2.8 Hz, 4 H, 2 CH₂), 4.36 (d, J = 5.9 Hz, 2 H, CH₂), 6.72 (s, 1 H, =CH), 6.97-7.27 (m, 6 H, ArH), 7.69 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.5, 36.1, 43.4, 64.3, 73.6, 75.9, 115.3, 115.6, 123.5, 123.7, 123.8, 124.6, 127.7, 129.1, 129.2, 129.5, 130.9, 135.4, 138.1, 143.8, 158.4, 161.7.

MS (ES+): m/z = 374.0 [M⁺ + 1].

Anal. Calcd for C₂₀H₂₀FNO₃S: C, 64.32; H, 5.40; N, 3.75. Found: C, 64.68; H, 5.66; N, 3.69.

( E )-3-(4-Chlorophenyl)-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-en-1-ol (10d)

White solid; yield: 1.31 g (70%); mp 121-122 ˚C; R _f  = 0.24 (EtOAc-hexanes, 1:4).

IR (KBr): 3305 (≡CH), 3433 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.66 (t, J = 2.3 Hz, 1 H, ≡CH), 2.42 (s, 3 H, CH₃), 4.00 (d, J = 1.9 Hz, 2 H, CH₂), 4.02 (s, 2 H, CH₂), 4.32 (s, 2 H, CH₂), 6.78 (s, 1 H, =CH), 7.09 (d, J = 8.2 Hz, 2 H, ArH), 7.24-7.28 (m, 4 H, ArH), 7.68 (d, J = 8.2 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 36.4, 43.1, 64.6, 74.0, 76.1, 127.7, 128.4, 129.6, 130.2, 130.6, 133.1, 134.4, 135.3, 136.6, 144.0.

MS (ES+): m/z = 390.1 [M⁺ + 1].

Anal. Calcd for C₂₀H₂₀ClNO₃S: C, 61.61; H, 5.17; N, 3.59. Found: C, 61.85; H, 4.87; N, 3.74.

( E )-3-(4-Methylphenyl)-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-en-1-ol (10f)

Off white solid; yield: 0.71 g (76%); mp 95-97 ˚C; R _f  = 0.23 (EtOAc-hexanes, 1:4).

IR (KBr): 3302 (≡CH), 3452 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.80 (t, J = 2.4 Hz, 1 H, ≡CH), 2.31 (s, 3 H, CH₃), 2.43 (s, 3 H, CH₃), 2.87 (t, J = 7.2 Hz, 1 H, OH), 4.01 (d, J = 2.3 Hz, 2 H, CH₂), 4.07 (s, 2 H, CH₂), 4.32 (d, J = 6.4 Hz, 2 H, CH₂), 6.79 (s, 1 H, =CH), 7.04-7.10 (m, 4 H, ArH), 7.25-7.27 (m, 2 H, ArH), 7.70 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.1, 21.5, 36.3, 43.3, 64.9, 73.9, 76.3, 127.7, 128.7, 128.9, 129.5, 129.6, 132.0, 132.8, 135.0, 135.4, 136.8, 143.8.

MS (ES+): m/z = 370.0 [M⁺ + 1].

Anal. Calcd for C₂₁H₂₃NO₃S: C, 68.27; H, 6.27; N, 3.79. Found: C, 68.15; H, 6.36; N, 3.81.

( E )-3-(2,4-Dichlorophenyl)-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-en-1-ol (10g)

White solid; yield: 1.02 g (71%); mp 109-110 ˚C; R _f  = 0.24 (EtOAc-hexanes, 1:4).

IR (KBr): 3304 (≡CH), 3406 cm^-¹ (OH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.68 (t, J = 2.4 Hz, 1 H, ≡CH), 2.41 (s, 3 H, CH₃), 2.85 (s, 1 H, OH), 3.91 (s, 2 H, CH₂), 4.00 (d, J = 2.3 Hz, 2 H, CH₂), 4.37 (s, 2 H, CH₂), 6.72 (s, 1 H, =CH), 7.05 (d, J = 8.3 Hz, 1 H, ArH), 7.16 (dd, J ₁ = 8.2 Hz , J ₂ = 2.0 Hz, 1 H, ArH), 7.26-7.28 (m, 2 H, ArH), 7.37 (d, J = 2.0 Hz, 1 H, ArH), 7.69 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 36.0, 42.8, 64.1, 73.7, 75.7, 126.7, 127.7, 128.0, 129.1, 129.6, 131.6, 133.0, 133.8, 134.6, 135.3, 137.9, 144.0.

MS (ES+): m/z = 424.1 [M⁺ + 1].

Anal. Calcd for C₂₀H₁₉Cl₂NO₃S: C, 56.61; H, 4.51; N, 3.30. Found: C, 56.95; H, 4.32; N, 3.36.

( E )-1-{3-Azido-2-[(prop-2-ynyloxy)methyl]prop-1-enyl}-4-chlorobenzene (4d); Typical Procedure for 4a-i

To a stirred soln of 3d (0.50 g, 2.24 mmol) in anhyd THF (10 mL) was added NaH (0.09 g, 3.36 mmol, 60% in oil). After 10 min, 80% propargyl bromide in toluene (0.32 mL, 2.69 mmol) was added and the mixture was stirred at r.t. for 2 h. When the reaction was complete, the solvent was removed and the residue was diluted with EtOAc (20 mL) and H₂O (20 mL). The aqueous layer was separated and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (anhyd Na₂SO₄) and concentrated to obtain the crude product, which was purified by column chromatography (silica gel, 100-200 mesh, EtOAc-hexanes, 3:97) yielded pure 4d (0.41 g, 70%) as a colorless oil; R _f  = 0.73 (EtOAc-hexanes, 1:9).

IR (neat): 1086 (-O-), 2099 (N₃), 3299 cm^-¹ (≡CH).

^¹H NMR (300 MHz, CDCl₃): δ = 2.45 (s, 1 H, ≡CH), 3.99 (s, 2 H, CH₂), 4.23 (d, J = 1.8 Hz, 4 H, CH₂), 6.76 (s, 1 H, =CH), 7.19 (d, J = 8.4 Hz, 2 H, ArH), 7.33 (d, J = 8.4 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 48.8, 55.7, 72.6, 75.5, 96.6, 128.9, 129.1, 129.4, 130.5, 130.8, 132.2, 133.9.

MS (ES+): m/z = 262.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₂ClN₃O: C, 59.66; H, 4.62; N, 16.06. Found: C, 59.72 H, 4.54; N, 16.18.

( E )-1-{3-Azido-2-[(prop-2-ynyloxy)methyl]prop-1-enyl}-2-fluorobenzene (4c)

Orange oil; yield: 0.30 g (83%); R _f  = 0.65 (EtOAc-hexanes, 1:9).

IR (neat): 1087 (-O-), 2102 (N₃), 3306 cm^-¹ (≡CH).

^¹H NMR (300 MHz, CDCl₃): δ = 2.45 (t, J = 2.3 Hz, 1 H, ≡CH), 3.98 (s, 2 H, CH₂), 4.24 (d, J = 2.3 Hz, 2 H, CH₂), 4.28 (d, J = 0.8 Hz, 2 H, CH₂), 6.77 (s, 1 H, =CH), 7.24-7.32 (m, 4 H, ArH).

^¹³C NMR: not recorded due to the unstable nature of compound.

MS (ES+): m/z = 246.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₂FN₃O: C, 63.66; H, 4.93; N, 17.13. Found: C, 63.74; H, 4.82; N, 17.25.

( E )-2-{3-Azido-2-[(prop-2-ynyloxy)methyl]prop-1-enyl}thiophene (4i)

Brown oil; yield: 0.75 g (74%); R _f  = 0.57 (EtOAc-hexanes, 1:9).

IR (neat): 1081 (-O-), 2102 (N₃), 3304 cm^-¹ (≡CH).

^¹H NMR (200 MHz, CDCl₃): δ = 2.47 (t, J = 2.3 Hz, 1 H, ≡CH), 4.21-4.23 (m, 6 H, 3 CH₂), 6.87 (s, 1 H, =CH), 7.02-7.08 (m, 2 H, ArH), 7.34 (dd, J ₁ = 4.9 Hz , J ₂ = 1.0 Hz, 1 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 49.0, 57.5, 72.8, 75.1, 77.8, 125.9, 126.9, 127.4, 129.2, 130.5, 137.9.

MS (ES+): m/z = 234.1 [M⁺ + 1].

Anal. Calcd for C₁₁H₁₁N₃OS: C, 56.63; H, 4.75; N, 18.01. Found: C, 56.74; H, 4.70; N, 18.14.

( E )-7-Benzylidene-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( E )-5a] and ( Z )-7-Benzylidene-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( Z )-5a]; Typical Procedure for 5a-i, 13a,c,d,f,g

Compound 4a (1.20 g, 5.29 mmol) was dissolved in anhyd toluene and heated at reflux for 7 h. Then the mixture was cooled to r.t. and solvent was evaporated to obtain a residue, which was purified by column chromatography (silica gel, 230-400 mesh) to furnish pure (E)-5a (EtOAc-CHCl₃, 3:97) (0.60 g, 50%) and (Z)-5a (EtOAc-CHCl₃, 3:97) (0.45 g, 38%).

( E )-5a

White solid; mp 103-104 ˚C; R _f  = 0.24 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1090 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 4.57 (s, 2 H, CH₂), 4.85 (s, 2 H, CH₂), 5.29 (s, 2 H, CH₂), 6.86 (s, 1 H, =CH), 7.20 (s, 1 H, ArH), 7.23 (d, J = 1.4 Hz, 1 H, ArH), 7.32-7.42 (m, 3 H, ArH), 7.54 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 49.5, 62.1, 78.9, 128.6, 129.0, 129.1, 130.6, 132.0, 134.8, 135.4, 136.0.

MS (ES+): m/z = 228.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₃N₃O₂: C, 68.70; H, 5.77; N, 18.49. Found: C, 68.87; H, 5.85; N, 18.37.

( Z )-5a

White solid; mp 105-106 ˚C; R _f  = 0.24 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1099 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 4.69 (s, 2 H, CH₂), 4.77 (s, 2 H, CH₂), 5.26 (s, 2 H, CH₂), 6.93 (s, 1 H, =CH), 7.17 (d, J = 7.2 Hz, 2 H, ArH), 7.31 (s, 1 H ArH), 7.37 (d, J = 7.4 Hz, 2 H, ArH), 7.47 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 55.4, 63.1, 71.7, 128.2, 128.5, 129.0, 131.1, 131.9, 134.8, 134.9, 135.1.

MS (ES+): m/z = 228.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₃N₃O: C, 68.70; H, 5.77; N, 18.49. Found: C, 68.89; H, 5.89; N, 18.41.

( E )-7-(2-Chlorobenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( E )-5b]

White solid; yield: 0.17 g (49%); mp 127-128 ˚C; R _f  = 0.24 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1046 cm^-¹ (-O-).

^¹H NMR (200 MHz, CDCl₃): δ = 4.57 (d, J = 1.1 Hz, 2 H, CH₂), 4.85 (s, 2 H, CH₂), 5.30 (s, 2 H, CH₂), 6.86 (s, 1 H, =CH), 7.20-7.24 (m, 1 H, ArH), 7.28-7.45 (m, 3 H, ArH), 7.55 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 49.3, 61.9, 78.7, 128.4, 128.8, 128.9, 130.4, 131.8, 134.6, 135.3, 135.8.

MS (ES+): m/z = 262.1 [M⁺ + 1].

DART-HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₃H₁₃ClN₃O: 262.07471; found: 262.07288.

( Z )-7-(2-Chlorobenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( Z )-5b]

White solid; yield: 0.15 g (43%); mp 98-99 ˚C; R _f  = 0.24 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1046 (-O-) cm^-¹.

^¹H NMR (200 MHz, CDCl₃): δ = 4.69 (d, 2 H, CH₂), 4.77 (s, 2 H, CH₂), 5.26 (s, 2 H, CH₂), 6.93 (s, 1 H, =CH), 7.17 (d, J = 6.5 Hz, 2 H ArH), 7.36 (d, J = 6.3 Hz, 2 H ArH), 7.48 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 55.5, 63.2, 71.8, 128.3, 128.6, 129.1, 131.2, 132.0, 134.9, 135.2.

MS (ES+): m/z = 262.1 [M⁺ + 1].

DART-HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₃H₁₃ClN₃O: 262.07471; found: 262.07288.

( E / Z )-7-(2-Fluorobenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]tria­zolo[5,1- c ][1,4]oxazepine [( E / Z )-5c]

White solid; yield: 0.20 g (80%); ratio of diastereomers 2:1; mp 137-138 ˚C; R _f  = 0.22 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1097 cm^-¹ (-O-).

^¹H NMR (200 MHz, CDCl₃): δ = 4.56 (s, 2 H, CH₂), 4.60 (d, J = 1.0 Hz, 2 H, CH₂), 4.77 (s, 2 H, CH₂), 4.86 (s, 2 H, CH₂), 5.25 (s, 2 H, CH₂), 5.28 (s, 2 H, CH₂), 6.86 (s, 1 H, =CH), 6.90 (s, 1 H, =CH), 7.04 (s, 1 H, ArH), 7.08 (s, 1 H, ArH), 7.13-7.20 (m, 3 H, ArH), 7.28-7.36 (m, 3 H, ArH), 7.48 (s, 1 H, =CH), 7.53 (s, 1 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 49.4, 55.3, 62.1, 63.1, 72.0, 76.8, 78.3, 127.8, 127.9, 128.0, 130.3, 130.4, 130.5, 130.6, 130.7, 131.3, 131.7, 131.8, 132.7, 135.7.

MS (ES+): m/z = 246.2 [M⁺ + 1].

HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₂FN₃O: 245.0964; found: 245.0993.

( E )-7-(4-Chlorobenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( E )-5d]

White solid; yield: 0.18 g (50%); mp 118-119 ˚C; R _f  = 0.23 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1048 cm^-¹ (-O-) .

^¹H NMR (300 MHz, CDCl₃): δ = 4.57 (s, 2 H, CH₂), 4.87 (s, 2 H, CH₂), 5.28 (s, 2 H, CH₂), 6.81 (s, 1 H, =CH), 7.17 (d, J = 8.4 Hz, 2 H ArH), 7.37-7.40 (m, 2 H, ArH), 7.56 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 49.2, 62.0, 78.6, 129.2, 130.2, 131.2, 131.9, 133.0, 133.9, 134.5, 135.8.

MS (ES+): m/z = 262.1 [M⁺ + 1].

HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₂ClN₃O: 261.0669; found: 261.0669.

( Z )-7-(4-Chlorobenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( Z )-5d]

White solid; yield: 0.16 g (46%); mp 89-90 ˚C; R _f  = 0.23 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1048 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 4.64 (s, 2 H, CH₂), 4.78 (s, 2 H, CH₂), 5.25 (s, 2 H, CH₂), 6.87 (s, 1 H, =CH), 7.11 (d, J = 7.7 Hz, 2 H, ArH), 7.35 (d, J = 8.4 Hz, 2 H, ArH), 7.48 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 55.5, 63.3, 71.7, 128.8, 130.3, 131.3, 132.8, 133.4, 133.8, 134.3, 134.8.

MS (ES+): m/z = 262.1 [M⁺ + 1].

HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₂ClN₃O: 261.0669; found: 261.0669.

( E )-7-(4-Fluorobenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( E )-5e]

White solid; yield: 0.10 g (50%); mp 98-99 ˚C; R _f  = 0.23 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1084 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 4.56 (s, 2 H, CH₂), 4.85 (d, J = 1.4 Hz, 2 H, CH₂), 5.27 (d, J = 1.5 Hz, 2 H, CH₂), 6.80 (s, 1 H, =CH), 7.06-7.12 (m, 2 H, ArH), 7.20 (d, J = 1.9 Hz, 2 H, ArH), 7.54 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 49.5, 62.2, 78.9, 116.1, 116.4, 130.8, 130.9, 131.0, 132.2, 134.3, 136.1, 161.2, 164.5.

MS (ES+): m/z = 246.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₂FN₃O: C, 63.66; H, 4.93; N, 17.13. Found: C, 63.71; H, 4.83; N, 17.07.

( Z )-7-(4-Fluorobenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( Z )-5e]

White solid; yield: 0.08 g (40%); mp 100-101 ˚C; R _f  = 0.23 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1046 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 4.65 (d, J = 1.1 Hz, 2 H, CH₂), 4.78 (s, 2 H, CH₂), 5.25 (s, 2 H, CH₂), 6.88 (s, 1 H, =CH), 7.06 (t, J = 8.7 Hz, 2 H, ArH), 7.13-7.18 (m, 2 H, ArH), 7.48 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 55.4, 63.1, 71.6, 115.4, 115.7, 130.7, 130.8, 130.89, 130.94, 131.2, 131.8, 133.9, 134.8, 160.8, 164.1.

MS (ES+): m/z = 246.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₂FN₃O: C, 63.66; H, 4.93; N, 17.13. Found: C, 63.69; H, 4.87; N, 17.10.

( E )-7-(4-Methylbenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( E )-5f]

White solid; yield: 0.13 g (52%); mp 106-107 ˚C; R _f  = 0.23 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1010 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 2.36 (s, 3 H, CH₃), 4.55 (s, 2 H, CH₂), 4.84 (s, 2 H, CH₂), 5.29 (s, 2 H, CH₂), 6.82 (s, 1 H, =CH), 7.11 (d, J = 7.6 Hz, 2 H, ArH), 7.20 (d, J = 7.4 Hz, 2 H, ArH), 7.53 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 49.7, 62.0, 79.0, 129.0, 129.85, 129.90, 132.0, 132.1, 135.6, 136.1, 138.7.

MS (ES+): m/z = 242.0 [M⁺ + 1].

DART-HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₄H₁₆N₃O: 242.1934; found: 242.12781.

( Z )-7-(4-Methylbenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( Z )-5f]

White solid; yield: 0.10 g (40%); mp 106-107 ˚C; R _f  = 0.23 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1100 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 2.36 (s, 3 H, CH₃), 4.69 (s, 2 H, CH₂), 4.76 (s, 2 H, CH₂), 5.24 (s, 2 H, CH₂), 6.89 (s, 1 H, =CH), 7.07 (s, 2 H, ArH), 7.18 (d, J = 5.3 Hz, 2 H, ArH), 7.46 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 55.8, 63.5, 72.1, 129.3, 129.6, 131.5, 132.4, 135.2, 135.5, 138.6.

MS (ES+): m/z = 242.0 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₅N₃O: C, 69.69; H, 6.27; N, 17.41. Found: C, 69.87; H, 6.38; N, 17.25.

( E )-7-(2,4-Dichlorobenzylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( E )-5g]

White solid; yield: 0.05 g (71%); mp 98-99 ˚C; R _f  = 0.24 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1010 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 4.63 (s, 2 H, CH₂), 4.89 (s, 2 H, CH₂), 5.20 (s, 2 H, CH₂), 6.86 (s, 1 H, =CH), 7.08 (d, J = 8.3 Hz, 1 H, ArH), 7.33 (d, J = 8.4 Hz, 1 H, ArH), 7.46 (s, 1 H, ArH), 7.59 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 49.2, 62.1, 78.0, 127.6, 129.6, 131.1, 131.3, 131.9, 132.7, 134.4, 135.1, 135.6.

MS (ES+): m/z = 296.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₁Cl₂N₃O: C, 52.72; H, 3.74; N, 14.19. Found: C, 52.32; H, 4.04; N, 14.49.

( E )-7-[2,6-Dichlorobenzylidene]-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( E )-5h]

White solid; yield: 0.65 g (81%); mp 110-112 ˚C; R _f  = 0.21 (EtOAc-CHCl₃, 3:97).

IR (KBr): 1095 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 4.68 (d, J = 1.0 Hz, 2 H, CH₂), 4.88 (s, 2 H, CH₂), 5.00 (s, 2 H, CH₂), 6.64 (s, 1 H, =CH), 7.22-7.25 (m, 1 H, ArH), 7.35-7.37 (m, 2 H, ArH), 7.48 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 49.3, 61.9, 77.8, 128.3, 129.4, 130.1, 131.3, 132.4, 134.7, 135.0, 135.5.

MS (ES+): m/z = 296.1 [M⁺ + 1].

DART-HRMS (ESI+): m/z [M + H]⁺ calcd for C₁₃H₁₂Cl₂N₃O: 296.0357; found: 296.0323.

( E / Z )-7-(2-Thiophenylidene)-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine [( E / Z )-5i]

Brown oil ; yield: 0.21 g (78%); ratio of diastereomers 3:2; R _f  = 0.24 (EtOAc-CHCl₃, 3:97).

IR (neat): 1102 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 4.52 (d, J = 0.8 Hz, 2 H, CH₂), 4.81 (s, 4 H, 2 CH₂), 4.86 (s, 2 H, CH₂), 5.25 (s, 2 H, CH₂), 5.46 (s, 2 H, CH₂), 6.85 (s, 1 H, =CH), 6.95 (s, 1 H, =CH), 7.00 (d, J = 3.3 Hz, 1 H, ArH), 7.04-7.07 (m, 2 H, ArH), 7.14 (d, J = 3.5 Hz, 1 H, ArH), 7.36-7.39 (m, 2 H, ArH), 7.44 (s, 1 H, ArH), 7.49 (s, 1 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 49.3, 55.0, 61.5, 64.2, 72.1, 76.5, 78.3, 125.9, 127.3, 127.6, 127.7, 129.5, 129.6, 130.7, 131.5, 134.3, 135.5, 137.0, 137.6.

MS (ES+): m/z = 234.0 [M⁺ + 1].

DART-HRMS (ESI+): m/z [M]⁺ calcd for C₁₁H₁₂N₃OS: 234.0701; found: 234.0675.

( E )-7-Benzylidene-5-tosyl-5,6,7,8-tetrahydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine [( E )-13a]

White solid; yield: 0.22 g (55%); mp 164-165 ˚C; R _f  = 0.27 (EtOAc-CHCl₃, 3:97).

^¹H NMR (300 MHz, CDCl₃): δ = 2.31 (s, 3 H, CH₃), 4.31 (s, 2 H, CH₂), 4.72 (s, 2 H, CH₂), 4.99 (s, 2 H, CH₂), 6.76 (s, 1 H, =CH), 7.02-7.04 (m, 2 H, ArH), 7.16 (d, J = 8.1 Hz, 2 H, ArH), 7.30-7.38 (m, 4 H, ArH), 7.51 (d, J = 8.3 Hz, 1 H, ArH), 7.56 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.4, 41.1, 49.5, 57.3, 126.4, 127.1, 128.5, 128.6, 128.8, 128.9, 129.8, 132.4, 133.4, 134.2, 135.7, 136.6, 144.2.

MS (ES+): m/z = 381.1 [M⁺ + 1].

Anal. Calcd for C₂₀H₂₀N₄O₂S: C, 63.14; H, 5.30; N, 14.73. Found: C, 63.21; H, 5.27; N, 14.73.

( Z )-7-Benzylidene-5-tosyl-5,6,7,8-tetrahydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine [( Z )-13a]

White solid; yield: 0.16 g (40%); mp 162-163 ˚C; R _f  = 0.23 (EtOAc-CHCl₃, 3:97).

^¹H NMR (300 MHz, CDCl₃): δ = 2.41 (s, 3 H, CH₃), 4.37 (s, 2 H, CH₂), 4.53 (s, 2 H, CH₂), 5.00 (s, 2 H, CH₂), 6.92 (s, 1 H, =CH), 7.17 (d, J = 7.4 Hz, 2 H, ArH), 7.33-7.40 (m, 4 H, ArH), 7.50 (s, 1 H, ArH), 7.55 (d, J = 7.4 Hz, 3 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 41.5, 49.9, 55.3, 127.1, 128.5, 128.6, 128.8, 128.9, 129.8, 130.0, 131.6, 132.4, 134.4, 136.8, 144.3.

MS (ES+): m/z = 381.1 [M⁺ + 1].

Anal. Calcd for C₂₀H₂₀N₄O₂S: C, 63.14; H, 5.30; N, 14.73. Found: C, 63.21; H, 5.27; N, 14.73.

( E / Z )-7-(2-Fluorobenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine [( E / Z )-13c]

White solid; yield: 0.51 g (85%); ratio of diastereomers 10:1; mp 150-152 ˚C; R _f  = 0.24 (EtOAc-CHCl₃, 3:97).

^¹H NMR (300 MHz, CDCl₃): δ = 2.34 (s, 3 H, CH₃), 2.43 (s, 3 H, CH₃), 4.27 (s, 2 H, CH₂), 4.36 (s, 2 H, CH₂), 4.57 (s, 2 H, CH₂), 4.74 (s, 2 H, CH₂), 5.01 (d, J = 8.3 Hz, 4 H, 2 CH₂), 6.88 (s, 2 H, 2 =CH), 7.07-7.20 (m, 14 H, ArH), 7.32-7.36 (m, 4 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.5, 22.7, 41.4, 50.1, 50.2, 55.0, 115.7, 116.0, 122.0, 122.2, 124.20, 124.24, 126.9, 127.1, 129.58, 129.61, 129.8, 130.0, 130.5, 130.6, 130.8, 131.6, 132.6, 135.3, 144.3, 158.0, 161.3.

MS (ES+): m/z = 399.2 [M⁺ + 1].

Anal. Calcd for C₂₀H₁₉FN₄O₂S: C, 60.29; H, 4.81; N, 14.06. Found: C, 60.34; H, 4.72; N, 14.17.

( E )-7-(4-Chlorobenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine [( E )-13d]

White solid; yield: 0.43 g (54%); mp 184-186 ˚C; R _f  = 0.25 (EtOAc-CHCl₃, 3:97).

^¹H NMR (300 MHz, CDCl₃): δ = 2.32 (s, 3 H, CH₃), 4.30 (s, 2 H, CH₂), 4.71 (s, 2 H, CH₂), 4.96 (s, 2 H, CH₂), 6.70 (s, 1 H, =CH), 6.97 (d, J = 7.7 Hz, 2 H, ArH), 7.16 (d, J = 7.0 Hz, 2 H, ArH), 7.26-7.34 (m, 2 H, ArH), 7.51 (t, J = 7.9 Hz, 2 H, ArH), 7.57 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.4, 41.2, 49.4, 57.2, 127.1, 129.0, 129.8, 130.0, 132.5, 133.3, 134.5, 135.2, 135.7, 144.2.

MS (ES+): m/z = 415.1 [M⁺ + 1].

Anal. Calcd for C₂₀H₁₉ClN₄O₂S: C, 57.90; H, 4.62; N, 13.50. Found: C, 57.86; H, 4.73; N, 13.45.

( Z )-7-(4-Chlorobenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine [( Z )-13d]

White solid; yield: 0.32 g (40%); mp 185-186 ˚C; R _f  = 0.23 (EtOAc-CHCl₃, 3:97).

^¹H NMR (300 MHz, CDCl₃): δ = 2.42 (s, 3 H, CH₃), 4.30 (s, 2 H, CH₂), 4.53 (s, 2 H, CH₂), 5.02 (s, 2 H, CH₂), 6.86 (s, 1 H, =CH), 7.11 (d, J = 8.1 Hz, 2 H, ArH), 7.26-7.36 (m, 4 H, ArH), 7.50 (s, 1 H, ArH), 7.56 (d, J = 8.0 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.5, 41.6, 49.8, 55.3, 127.0, 128.8, 129.1, 130.0, 130.2, 131.7, 132.3, 132.8, 134.4, 135.1, 135.2, 144.4.

MS (ES+): m/z = 415.1 [M⁺ + 1].

Anal. Calcd for C₂₀H₁₉ClN₄O₂S: C, 57.90; H, 4.62; N, 13.50. Found: C, 57.86; H, 4.73; N, 13.45.

( E / Z )-7-(4-Methylbenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine [( E / Z )-13f]

Colorless oil; yield: 0.66 g (83%); ratio of diastereomers 1:1; R _f  = 0.24 (EtOAc-CHCl₃, 3:97).

^¹H NMR (300 MHz, CDCl₃): δ = 2.36 (s, 6 H, 2 CH₃), 2.38 (s, 6 H, 2 CH₃), 4.31 (s, 4 H, 2 CH₂), 4.39 (s, 2 H, CH₂), 4.53 (s, 2 H, CH₂), 4.72 (s, 4 H, 2 CH₂), 6.69 (s, 1 H, =CH), 6.75 (s, 1 H, =CH), 6.90-6.96 (m, 4 H, ArH), 7.09 (d, J = 7.9 Hz, 4 H, ArH), 7.16-7.28 (m, 4 H, ArH), 7.51-7.59 (m, 6 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.8, 22.0, 30.1, 41.8, 41.9, 50.5, 50.7, 55.4, 55.5, 124.6, 127.39, 127.40, 127.6, 130.1, 130.4, 130.9, 131.0, 131.2, 132.1, 133.1, 135.6, 144.7.

MS (ES+): m/z = 395.3 [M⁺ + 1].

Anal. Calcd for C₂₁H₂₂N₄O₂S: C, 63.94; H, 5.62; N, 14.20. Found: C, 64.12, H, 5.53; N, 14.31.

( E )-7-(2,4-Dichlorobenzylidene)-5-tosyl-5,6,7,8-tetrahydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine [( E )-13g]

White solid; yield: 0.25 g (83%); mp 150-152 ˚C; R _f  = 0.30 (EtOAc-CHCl₃, 3:97).

^¹H NMR (300 MHz, CDCl₃): δ = 2.42 (s, 3 H, CH₃), 4.15 (s, 2 H, CH₂), 4.55 (s, 2 H, CH₂), 5.03 (s, 2 H, CH₂), 6.90 (s, 1 H, =CH), 7.15 (d, J = 8.3 Hz, 1 H, ArH), 7.25-7.30 (m, 4 H, ArH), 7.43 (d, J = 2.0 Hz, 1 H, ArH), 7.52-7.54 (m, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 41.4, 49.9, 55.0, 127.0, 127.2, 129.6, 130.1, 130.7, 131.3, 132.0, 132.4, 132.8, 134.3, 134.9, 135.2, 144.5.

MS (ES+): m/z = 449.2 [M⁺ + 1].

Anal. Calcd for C₂₀H₁₈Cl₂N₄O₂S: C, 53.46; H, 4.04; N, 12.47. Found: C, 53.15; H, 4.32; N, 12.55.

7-Benzyl-7,8-dihydro-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine (6a)

To a soln of diastereomeric mixture of 5a (0.10 g, 0.44 mmol) in MeOH was added 10% Pd/C (0.01 g) under N₂. Thereafter, the atmosphere of the vessel was replaced by H₂ gas and reaction was carried out on the Parr assembly at 24 mbar at r.t. for 2 h. The catalyst was then filtered through Celite and the filtrate was evaporated on a rotavapor under reduced pressure to yield a residue that was purified by recrystallization or column chromatography (silica gel, EtOAc-hexanes, 1:1), to give pure 6a (0.09 g, 89%) as white solid; mp 113-115 ˚C; R _f  = 0.31 (EtOAc-hexanes, 1:1).

IR (KBr): 1090 cm^-¹ (-O-).

^¹H NMR (300 MHz, CDCl₃): δ = 2.22-2.26 (m, 1 H, CH), 2.45-2.60 (m, 2 H, CH₂), 3.93 (dd, J ₁ = 12.7 Hz, J ₂ = 5.9 Hz, 1 H, CH₂), 4.03 (dd, J ₁ = 12.7 Hz, J ₂ = 2.4 Hz, 1 H, CH₂), 4.56 (dd, J ₁ = 14.3 Hz, J ₂ = 6.6 Hz, 1 H, CH₂), 4.63 (d, J = 1.8 Hz, 1 H, CH₂), 4.68 (s, 1 H, CH₂), 4.80 (d, J = 14.7 Hz, 1 H, CH₂), 7.14-7.17 (m, 2 H, ArH), 7.21-7.27 (m, 1 H, ArH), 7.29-7.34 (m, 2 H, ArH), 7.58 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 35.1, 40.3, 53.7, 63.0, 77.8, 127.0, 129.0, 129.4, 133.0, 136.6, 138.5.

MS (ES+): m/z = 230.2 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₅N₃O: C, 68.10; H, 6.59; N, 18.33. Found: C, 68.33; H, 6.41; N, 18.53.

7-(4-Methylbenzyl)-4 H ,6 H -[1,2,3]triazolo[5,1- c ][1,4]oxazepine (7f); Typical Procedure for 7a,f, 14g, 15g, 25g, 26g

To a stirred soln of (E/Z)-5f (0.10 g, 0.41 mmol) in anhyd THF (5 mL) was added DBU (0.09 mL, 0.62 mmol) and the mixture was heated at 80 ˚C in an oil bath. (E)-5f was consumed to give product within 2 h, (Z)-5f was unreacted. The reaction was continued for 24 h (TLC monitoring). THF was evaporated under vacuum and the residue was extracted with EtOAc (3 × 20 mL). The combined organic layers were washed with brine (30 mL), dried (anhyd Na₂SO₄), and concentrated to give crude product. Purification by column chromatography (silica gel, 100-200 mesh, EtOAc-hexanes, 2:3) afforded 7f (0.049 g, 49%) as a white solid and also (Z)-5f (0.047 g, 48%) as a white solid; mp 95-98 ˚C; R _f  = 0.26 (EtOAc-hexanes, 2:3).

IR (KBr): 1031 cm^-¹ (-O-).

^¹H NMR (200 MHz, CDCl₃): δ = 2.34 (s, 3 H, CH₃), 3.37 (s, 2 H, CH₂), 4.43 (s, 2 H, CH₂), 4.79 (s, 2 H, CH₂), 7.13 (s, 4 H, =CH, ArH), 7.34 (s, 1 H, ArH), 7.48 (s, 1 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.5, 39.4, 63.7, 74.8, 117.9, 121.8, 129.0, 130.0, 130.9, 131.6, 134.4, 136.6, 137.2, 156.7.

MS (ES+): m/z = 242.0 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₅N₃O: C, 69.69; H, 6.27; N, 17.41. Found: C, 69.35; H, 6.43; N, 17.15.

7-Benzyl-4H,6H-[1,2,3]triazolo[5,1-c][1,4]oxazepine (7a)

White solid; yield: 0.047 g (47%); mp 90-92 ^oC; R _f = 0.23 (EtOAc-hexanes, 2:3).

IR (KBr): 1083 cm^-¹ (-O-).

^¹H NMR (200 MHz, CDCl₃): δ = 3.39 (s, 2 H, CH₂), 4.46 (s, 2 H, CH₂), 4.81 (s, 2 H, CH₂), 7.16-7.18 (m, 5 H, CH and ArH), 7.35 (s, 1 H, ArH), 7.50 (s, 1 H, =CH).

^¹³C NMR (CDCl₃, 50 MHz): δ = 39.9, 63.5, 73.9, 120.5, 129.0, 130.0, 130.9, 131.6, 133.4, 136.4, 137.3.

MS (ES+): m/z = 228.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₃N₃O: C, 68.70; H, 5.77; N, 18.49. Found: C, 68.88; H, 5.89; N, 18.40.

( Z )-7-(2,4-Dichlorobenzylidene)-5-tosyl-5,8-dihydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine (14g)

White solid; yield: 0.048 g (48%); mp 153-154 ˚C; R _f  = 0.30 (EtOAc-hexanes, 1:1).

^¹H NMR (300 MHz, CDCl₃): δ = 2.36 (s, 3 H, CH₃), 3.46 (s, 2 H, CH₂), 4.25 (s, 2 H, CH₂), 4.72 (s, 2 H, CH₂), 6.87 (s, 1 H, =CH), 7.07-7.15 (m, 3 H, ArH), 7.22-7.28 (m, 3 H, ArH), 7.44 (d, J = 2.0 Hz, 1 H, ArH), 7.49 (s, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.5, 37.3, 42.3, 51.9, 122.8, 124.9, 126.7, 127.7, 129.6, 130.0, 131.9, 132.0.

MS (ES+): m/z = 449.2 [M⁺ + 1].

Anal. Calcd for C₂₀H₁₈Cl₂N₄O₂S: C, 53.46; H, 4.04; N, 12.47. Found: C, 53.15; H, 4.32; N, 12.55.

( Z )-7-(2,4-Dichlorobenzylidene)-5-tosyl-5,6-dihydro-4 H -[1,2,3]triazolo[1,5- a ][1,4]diazepine (15g)

White solid; yield: 0.046 g (46%); mp 150-152 ˚C; R _f  = 0.29 (EtOAc-hexanes, 1:1).

^¹H NMR (300 MHz, CDCl₃): δ = 2.40 (s, 3 H, CH₃), 3.54 (s, 2 H, CH₂), 4.86 (s, 2 H, CH₂), 4.97 (s, 2 H, CH₂), 6.64 (s, 1 H, =CH), 7.09 (d, J = 8.3 Hz, 1 H, ArH), 7.21-7.25 (m, 4 H, ArH), 7.31 (s, 1 H, ArH), 7.43 (d, J = 2.1 Hz, 1 H, ArH), 7.50 (d, J = 8.3 Hz, 1 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 29.7, 39.0, 48.9, 126.7, 126.8, 127.6, 129.88, 129.90, 131.1, 131.2, 132.0, 132.2, 135.1.

MS (ES+): m/z = 449.2 [M⁺ + 1].

Anal. Calcd for C₂₀H₁₈Cl₂N₄O₂S: C, 53.46; H, 4.04; N, 12.47. Found: C, 53.15; H, 4.32; N, 12.55.

4-Benzyl-6-(2,4-dichlorobenzyl)-4,5-dihydrotetrazolo[1,5- a ]pyrimidine (25g) and 4-Benzyl-6-(2,4-dichlorobenzyl)-4,7-dihydrotetrazolo[1,5- a ]pyrimidine (26g)

White solid; yield: 0.087 g (87%); ratio 25g/26g 1:1; mp 142-143 ˚C; R _f  = 0.23 (EtOAc-hexanes, 1:1).

IR (KBr): 1614 cm^-¹ (C=N).

^¹H NMR (200 MHz, CDCl₃): δ = 3.39 (s, 2 H, CH₂), 3.44 (s, 2 H, CH₂), 3.95 (s, 2 H, CH₂), 4.64 (s, 2 H, CH₂), 4.85 (s, 4 H, 2 CH₂), 5.96 (s, 1 H, =CH), 6.75-6.76 (s, 1 H, =CH), 7.11 (dd, J ₁ = 8.2 Hz, J ₂ = 1.9 Hz, 2 H, ArH), 7.19-7.24 (m, 4 H, ArH), 7.32-7.35 (m, 8 H, ArH), 7.39-7.42 (m, J = 2.0 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 45.5, 50.5, 54.2, 126.7, 127.5, 128.2, 128.6, 128.9, 129.2, 130.0, 131.1, 132.0, 134.8, 135.2, 135.7, 155.7.

MS (ES+): m/z = 372.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₅Cl₂N₅: C, 58.08; H, 4.06; N, 18.81. Found: C, 58.26; H, 4.17; N, 18.64.

Methyl ( E )-3-Phenyl-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-enoate (9a); Typical Procedure for 9a,c,d,f,g and 17g

To a stirred soln of 8a (2.23 g, 6.46 mmol) in anhyd DMF (10 mL) was added K₂CO₃ (1.34 g, 9.69 mmol) and the mixture was stirred for 10 min. Then 80% propargyl bromide in toluene (1.16 mL, 7.75 mmol) was added and mixture was stirred at r.t. for 2 h. When the reaction was complete, the mixture was diluted with H₂O (40 mL) and extracted with EtOAc (3 × 30 mL). The combined organic layers were dried (anhyd Na₂SO₄) and concentrated to obtain the crude product, which was purified by column chromatography (silica gel, 100-200 mesh, EtOAc-hexanes, 1:9) to yield pure 9a (1.97 g, 80%) as a yellow solid; mp 90-91 ˚C; R _f  = 0.25 (EtOAc-hexanes, 3:17).

IR (KBr): 1712 (CO₂CH₃), 3308 cm^-¹ (≡CH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.78 (t, J = 2.3 Hz, 1 H, ≡CH), 2.39 (s, 3 H, CH₃), 3.79 (s, 3 H, OCH₃), 4.07 (d, J = 2.4 Hz, 2 H, CH₂), 4.27 (s, 2 H, CH₂), 7.19 (d, J = 8.1 Hz, 2 H, ArH), 7.39 (s, 5 H, ArH), 7.50 (d, J = 8.3 Hz, 2 H, ArH), 7.89 (s, 1 H, =CH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.5, 37.6, 42.9, 52.2, 73.5, 128.1, 128.5, 128.9, 129.3, 129.6, 134.5, 135.3, 143.5, 143.7, 167.8.

MS (ES+): m/z = 383.9 [M⁺ + 1].

Anal. Calcd for C₂₁H₂₁NO₄S: C, 65.78; H, 5.52; N, 3.65. Found: C, 65.89; H, 5.73; N, 3.60.

Methyl ( E )-3-(2-Fluorophenyl)-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-enoate (9c)

White solid; yield: 1.30 g (69%); mp 92-93 ˚C; R _f  = 0.25 (EtOAc-hexanes, 3:17).

IR (KBr): 1716 (CO₂CH₃), 3310 cm^-¹ (≡CH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.75 (t, J = 2.3 Hz, 1 H, ≡CH), 2.39 (s, 3 H, CH₃), 3.80 (s, 3 H, OCH₃), 4.06 (d, J = 2.3 Hz, 2 H, CH₂), 4.19 (s, 2 H, CH₂), 7.07-7.20 (m, 4 H, ArH), 7.34-7.41 (m, 2 H, ArH), 7.50 (d, J = 8.3 Hz, 2 H, ArH), 7.82 (s, 1 H, =CH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.5, 37.5, 43.14, 43.17, 52.2, 73.4, 115.5, 115.8, 122.4, 122.6, 124.0, 124.1, 128.0, 129.3, 130.4, 130.7, 130.8, 130.96, 131.01, 135.3, 136.4, 136.5, 143.5, 158.4, 161.7, 167.1.

MS (ES+): m/z = 402.2 [M⁺ + 1].

Anal. Calcd for C₂₁H₂₀FNO₄S: C, 62.83; H, 5.02; N, 3.49. Found: C, 62.66; H, 5.10; N, 3.42.

Methyl ( E )-3-(4-Chlorophenyl)-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-enoate (9d)

Yellow solid; yield: 2.20 g (88%); mp 110-110 ˚C; R _f  = 0.23 (EtOAc-hexanes, 3:17).

IR (KBr): 1714 (CO₂CH₃), 3307 cm^-¹ (≡CH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.82 (t, J = 2.4 Hz, 1 H, ≡CH), 2.41 (s, 3 H, CH₃), 3.79 (s, 3 H, OCH₃), 4.06 (d, J = 2.4 Hz, 2 H, CH₂), 4.23 (s, 2 H, CH₂), 7.22 (d, J = 8.2 Hz, 2 H, ArH), 7.32-7.40 (m, 4 H, ArH), 7.51 (d, J = 8.3 Hz, 2 H, ArH), 7.82 (s, 1 H, =CH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.5, 37.6, 42.8, 52.3, 73.7, 128.0, 128.5, 128.7, 129.3, 131.0, 132.9, 135.0, 135.1, 142.3, 143.7, 167.5.

MS (ES+): m/z = 417.9 [M⁺ + 1].

Anal. Calcd for C₂₁H₂₀ClNO₄S: C, 60.35; H, 4.82; N, 3.35. Found: C, 60.54; H, 4.93; N, 3.23.

Methyl ( E )-3-(4-Methylphenyl)-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-enoate (9f)

Orange-white solid; yield: 2.00 g (91%); mp 104-105 ˚C; R _f  = 0.26 (EtOAc-hexanes, 3:17).

IR (KBr): 1712 (CO₂CH₃), 3306 cm^-¹ (≡CH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.82 (t, J = 2.3 Hz, 1 H, ≡CH), 2.39 (s, 3 H, CH₃), 2.40 (s, 3 H, CH₃), 3.77 (s, 3 H, OCH₃), 4.05 (d, J = 2.3 Hz, 2 H, CH₂), 4.30 (s, 2 H, CH₂), 7.20-7.22 (m, 4 H, ArH), 7.32 (d, J = 7.9 Hz, 2 H, ArH), 7.55 (d, J = 8.2 Hz, 2 H, ArH), 7.85 (s, 1 H, =CH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.4, 21.5, 37.4, 43.0, 52.1, 73.4, 126.7, 128.1, 129.2, 129.8, 131.5, 135.3, 139.3, 143.4, 144.0, 168.0.

MS (ES+): m/z = 397.8 [M⁺ + 1].

Anal. Calcd for C₂₂H₂₃NO₄S: C, 66.48; H, 5.83; N, 3.52. Found: C, 66.35; H, 5.88; N, 3.34.

Methyl ( E )-3-(2,4-Dichlorophenyl)-2-{[(prop-2-ynyl)tosylamino]methyl}prop-2-enoate (9g)

White solid; yield: 1.40 g (80%); mp 131-132 ˚C; R _f  = 0.25 (EtOAc-hexanes, 3:17).

IR (KBr): 1722 (CO₂CH₃), 3304 cm^-¹ (≡CH).

^¹H NMR (300 MHz, CDCl₃): δ = 1.75 (t, J = 2.4 Hz, 1 H, ≡CH), 2.40 (s, 3 H, CH₃), 3.81 (s, 3 H, OCH₃), 4.03 (d, J = 2.4 Hz, 2 H, CH₂), 4.14 (s, 2 H, CH₂), 7.22 (d, J = 8.1 Hz, 2 H, ArH), 7.28 (d, J = 1.0 Hz, 2 H, ArH), 7.45 (s, 1 H, ArH), 7.53 (d, J = 8.3 Hz, 2 H, ArH), 7.83 (s, 1 H, =CH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 37.3, 42.7, 52.4, 73.5, 127.0, 128.0, 129.37, 129.41, 130.3, 131.66, 131.67, 134.8, 135.2, 135.4, 139.7, 143.7, 166.9.

MS (ES+): m/z = 451.8 [M⁺ + 1].

Anal. Calcd for C₂₁H₁₉Cl₂NO₄S: C, 55.76; H, 4.23; N, 3.10. Found: C, 55.68; H, 4.38; N, 3.19.

Methyl 2-{(2,4-Dichlorophenyl)[(prop-2-ynyl)tosylami­no]meth­yl}acrylate (17g)

White solid; yield: 1.40 g (80%); mp 131-132 ˚C; R _f  = 0.32 (EtOAc-hexanes, 3:17).

IR (KBr): 1722 cm^-¹ (CO₂CH₃).

^¹H NMR (300 MHz, CDCl₃): δ = 2.06 (t, J = 2.4 Hz, 1 H, ≡CH), 2.44 (s, 3 H, CH₃), 3.60 (s, 3 H, OCH₃), 4.05-4.29 (m, 2 H, CH₂), 5.87 (d, J = 1.3 Hz, 1 H, CH), 6.32 (s, 1 H, =CH₂), 6.62 (s, 1 H, =CH₂), 7.22-7.30 (m, 4 H, ArH), 7.37 (d, J = 8.4 Hz, 1 H, ArH), 7.70 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.8, 36.6, 52.4, 59.4, 73.1, 127.4, 128.1, 129.4, 129.9, 130.7, 131.1, 134.2, 134.9, 137.4, 138.0, 143.8, 165.8.

MS (ES+): m/z = 451.8 [M⁺ + 1].

Anal. Calcd for C₂₁H₁₉Cl₂NO₄S: C, 55.76; H, 4.23; N, 3.10. Found: C, 55.68; H, 4.38; N, 3.19.

3-(Methylsulfonyloxy)-1-phenyl-2-{[(prop-2-ynyl)tosylamino]methyl}prop-1-ene (11a); Typical Procedure for 11a,c,d,f,g and 18a,e-h

To a stirred soln of 10a (0.80 g, 2.25 mmol) in anhyd CH₂Cl₂ (40 mL) was added Et₃N (0.48 mL, 3.38 mmol) and then MsCl (0.22 mL, 2.93 mmol) in CH₂Cl₂ (15 mL) was added dropwise at 0 ˚C. The mixture was stirred at r.t. for 30 min. When the reaction was complete it was quenched with H₂O (30 mL) and partitioned in a separating funnel. The organic layer was collected and the aqueous layer was extracted with CHCl₃ (2 × 20 mL). The combined organic layers were washed with brine (50 mL), dried (anhyd Na₂SO₄), and concentrated to give crude 11a which was used in next step without purification.

3-Azido-1-phenyl-2-{[(prop-2-ynyl)tosylamino]methyl}prop-1-ene (12a); Typical Procedure for 12a,c,d,f,g

To a stirred soln of 11a (0.65 g, 1.50 mmol) in DMF (5 mL) was added NaN₃ (0.20 g, 3.00 mmol) in H₂O (1.0 mL) and mixture was allowed to react at r.t. for 1 h. When the reaction was complete, the mixture was diluted with H₂O (20 mL) and extracted with EtOAc (20 mL). The aqueous layer was separated and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (anhyd Na₂SO₄) and concentrated to crude 12a which was used in next step without purification.

( E , Z )-2-(Azidomethyl)- N -benzyl-3-phenylprop-2-en-1-amine [( E / Z )-19a]; Typical Procedure for 19a,e-h and 20a,e-h

To a stirred soln of 18a (1.50 g, 5.62 mmol) in anhyd THF (15 mL) was added BnNH₂ (1.8 mL, 16.85 mmol) and KI (cat.) and the mixture was heated at 80 ˚C in an oil bath for 2 h. When the reaction was complete (TLC monitoring), THF was evaporated under vacuum and the residue was extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with brine (50 mL), dried (anhyd Na₂SO₄), and concentrated to yield the crude product. Purification by column chromatography (silica gel, 100-200 mesh, EtOAc-hexanes, 1:4) afforded the diastereomeric mixture of (E/Z)-19a (1.25 g, 80%) as brown oil; R _f  = 0.26 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 3451 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 3.49 (s, 4 H, 2 CH₂), 3.73 (s, 2 H, CH₂), 3.85 (s, 2 H, CH₂), 4.07 (s, 2 H, CH₂), 4.08 (s, 2 H, CH₂), 6.67 (s, 1 H, =CH), 6.77 (s, 1 H, =CH), 7.22-7.44 (m, 20 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 49.6, 53.4, 54.0, 56.6, 56.8, 126.6, 127.1, 127.2, 127.4, 127.5, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6, 128.8, 128.9, 129.0, 129.2, 129.5, 130.9, 131.6, 131.7, 135.2, 135.4, 136.4, 140.2.

MS (ES+): m/z = 279.1 [M⁺ + 1].

Anal. Calcd for C₁₇H₁₈N₄: C, 73.35; H, 6.52; N, 20.13. Found: C, 73.62; H, 6.50; N, 20.41.

( E / Z )-2-(Azidomethyl)- N -benzyl-3-(4-fluorophenyl)prop-2-en-1-amine [( E / Z )-19e]

Brown oil; yield: 1.47 g (75%); ratio of diastereomers 1:1; R _f  = 0.27 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 3421 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 3.43 (d, J = 0.6 Hz, 2 H, CH₂), 3.47 (d, J = 1.3 Hz, 2 H, CH₂), 3.73 (s, 2 H, CH₂), 3.84 (s, 2 H, CH₂), 4.04 (s, 4 H, 2 CH₂), 6.61 (s, 1 H, =CH), 6.71 (s, 1 H, =CH), 6.94-7.09 (m, 4 H, ArH), 7.17-7.37 (m, 14 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 47.3, 49.7, 53.0, 53.2, 53.5, 55.8, 115.3, 115.4, 115.7, 123.8, 124.0, 124.2, 127.1, 127.2, 128.0, 128.2, 128.3, 128.4, 128.5, 128.6, 129.2, 129.3, 129.4, 130.7, 137.0, 139.7.

MS (ES+): m/z = 297.1 [M⁺ + 1].

Anal. Calcd for C₁₇H₁₇FN₄: C, 68.90; H, 5.78; N, 18.91. Found: C, 69.05; H, 6.03; N, 18.67.

( E / Z )-2-(Azidomethyl)- N -benzyl-3-(4-methylphenyl)prop-2-en-1-amine [( E / Z )-19f]

Brown oil; yield: 1.60 g (77%); ratio of diastereomers 5:4; R _f  = 0.29 (EtOAc-hexanes, 1:4).

IR (neat): 2098 (N₃), 3372 cm^-¹ (NH).

^¹H NMR (300 MHz, CDCl₃): δ = 2.36 (s, 6 H, 2 CH₃), 3.48 (s, 2 H, CH₂), 3.74 (s, 2 H, CH₂), 3.78-3.83 (m, 4 H, 2 CH₂), 4.05 (s, 2 H, CH₂), 4.09 (s, 2 H, CH₂), 4.84 (br s, 2 H, 2 NH), 6.64 (s, 1 H, =CH), 6.73 (s, 1 H, =CH), 7.10-7.44 (m, 16 H, ArH), 7.79 (s, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.5, 21.6, 49.9, 53.3, 53.5, 53.6, 54.4, 127.3, 127.4, 128.4, 128.6, 128.88, 128.93, 129.0, 129.1, 129.2, 129.4, 129.5, 130.18, 130.20, 132.0, 134.9, 136.6, 139.7, 140.7.

MS (ES+): m/z = 293.1 [M⁺ + 1].

Anal. Calcd for C₁₈H₂₀N₄: C, 73.94; H, 6.89; N, 19.16. Found: C, 73.76; H, 6.95; N, 19.20.

( E / Z )-2-(Azidomethyl)- N -benzyl-3-(2,4-dichlorophenyl)prop-2-en-1-amine [( E / Z )-19g]

Brown oil; yield: 0.80 g (78%); ratio of diastereomers 4:1; R _f  = 0.30 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 3433 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 3.34 (d, J = 0.7 Hz, 2 H, CH₂), 3.50 (s, 2 H, CH₂), 3.69 (s, 2 H, CH₂), 3.85 (s, 2 H, CH₂), 3.95 (s, 2 H, CH₂), 4.12 (d, J = 1.0 Hz, 2 H, CH₂), 4.84 (d, J = 1.3 Hz, 2 H, 2 NH), 6.63 (s, 1 H, =CH), 6.76 (s, 1 H, =CH), 7.14-7.44 (m, 16 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 46.9, 49.4, 53.0, 53.3, 55.7, 126.8, 127.0, 127.2, 127.5, 127.6, 128.0, 128.2, 128.3, 128.4, 128.5, 128.6, 129.3, 129.4, 129.8, 130.8, 131.3, 131.4, 133.1, 133.3, 133.9, 134.0, 134.3, 134.5, 137.4, 139.6, 139.9.

MS (ES+): m/z = 347.1 [M⁺ + 1].

Anal. Calcd for C₁₇H₁₆Cl₂N₄: C, 58.80; H, 4.64; N, 16.13. Found: C, 59.10; H, 4.45; N, 16.32.

( E )-2-(Azidomethyl)- N -benzyl-3-(2,6-dichlorophenyl)prop-2-en-1-amine [( E )-19h]

Brown oil; yield: 0.83 g (80%); R _f  = 0.31 (EtOAc-hexanes, 1:4).

IR (neat): 2109 (N₃), 3448 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 3.55 (s, 2 H, CH₂), 3.80 (s, 2 H, CH₂), 3.88 (s, 2 H, CH₂), 6.47 (s, 1 H, =CH), 7.15-7.23 (m, 2 H, ArH), 7.26-7.37 (m, 6 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 50.6, 52.4, 53.2, 125.1, 127.5, 128.4, 128.7, 128.9, 129.5, 134.5, 135.3, 139.5, 140.6.

MS (ES+): m/z = 347.1 [M⁺ + 1].

Anal. Calcd for C₁₇H₁₆Cl₂N₄: C, 58.80; H, 4.64; N, 16.13. Found: C, 59.02; H, 4.93; N, 15.87.

( E / Z )-2-(Azidomethyl)-3-phenyl- N -propylprop-2-en-1-amine [( E / Z )-20a]

Brown oil; yield: 1.00 g (89%); ratio of diastereomers 1:1; R _f  = 0.24 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 3295 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 0.95 (t, J = 7.5 Hz, 6 H, 2 CH₃), 1.50-1.65 (m, 4 H, 2 CH₂), 2.47-2.55 (m, 2 H, CH₂), 2.63 (t, J = 6.5 Hz, 2 H, CH₂), 3.08-3.12 (m, 4 H, 2 CH₂), 3.46 (s, 2 H, CH₂), 4.03-4.06 (m, 2 H, CH₂), 4.66 (br s, 2 H, 2 NH), 6.67 (s, 1 H, =CH), 6.76 (s, 1 H, =CH), 7.27-7.35 (m, 10 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 11.5, 12.1, 23.3, 23.8, 40.6, 35.4, 51.5, 51.8, 127.69, 127.75, 128.7, 128.8, 129.15, 129.20, 132.0, 135.0, 135.2, 136.6.

MS (ES+): m/z = 231.0 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₈N₄: C, 67.80; H, 7.88; N, 24.33. Found: C, 67.92; H, 7.56; N, 24.52.

( E / Z )-2-(Azidomethyl)-3-(4-fluorophenyl)- N -propylprop-2-en-1-amine [( E / Z )-20e]

Brown oil; yield: 1.00 g (88%); ratio of diastereomers 1:1; R _f  = 0.23 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 3296 cm^-¹ (NH).

^¹H NMR (300 MHz, CDCl₃): δ = 0.97 (t, J = 7.3 Hz, 6 H, 2 CH₃), 1.54-1.64 (m, 4 H, 2 CH₂), 2.51 (t, J = 7.2 Hz, 2 H, CH₂), 2.61 (t, J = 7.2 Hz, 2 H, CH₂), 3.10-3.14 (m, 4 H, 2 CH₂), 3.42-3.44 (m, 2 H, CH₂), 4.01 (s, 2 H, CH₂), 4.25 (br s, 2 H, 2 NH), 6.60 (s, 1 H, =CH), 6.70 (s, 1 H, =CH), 7.01-7.07 (m, 4 H, ArH), 7.18-7.25 (m, 4 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.5, 12.1, 23.6, 23.8, 40.7, 45.4, 51.7, 52.0, 115.4, 115.5, 115.8, 116.0, 130.3, 130.6, 130.7, 130.9, 131.0, 132.6, 135.8, 136.0.

IR (ES+): m/z = 249.0 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₇FN₄: C, 62.88; H, 6.90; N, 22.56. Found: C, 62.98; H, 7.07; N, 22.63.

( E / Z )-2-(Azidomethyl)-3-(4-methylphenyl)- N -propylprop-2-en-1-amine [( E / Z )-20f]

Red oil; yield: 0.90 g (69%); ratio of diastereomers 4:1; R _f  = 0.20 (EtOAc-hexanes, 3:1).

IR (neat): 2101 (N₃), 3292 cm^-¹ (NH).

^¹H NMR (300 MHz, CDCl₃): δ = 0.97 (t, J = 7.4 Hz, 6 H, 2 CH₃), 1.57-1.67 (m, 4 H, 2 CH₂), 2.32 (s, 3 H, CH₃), 2.35 (s, 3 H, CH₃), 2.52 (t, J = 7.1 Hz, 1 H, CH₂), 2.61 (t, J = 7.1 Hz, 1 H, CH₂), 3.07-3.14 (m, 4 H, 2 CH₂), 3.45 (d, J = 7.3 Hz, 2 H, CH₂), 4.01 (s, 2 H, CH₂), 4.05 (s, 2 H, CH₂), 4.42 (br s, 2 H, 2 NH), 6.61 (s, 1 H, =CH), 6.71 (s, 1 H, =CH), 7.09-7.16 (m, 8 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.5, 23.8, 40.6, 45.4, 111.4, 127.8, 129.1, 129.4, 129.5, 132.5.

MS (ES+): m/z = 245.1 [M⁺ + 1].

Anal. Calcd for C₁₄H₂₀N₄: C, 68.82; H, 8.25; N, 22.93. Found: C, 68.72; H, 8.35; N, 22.91.

( E / Z )-2-(Azidomethyl)-3-(2,4-dichlorophenyl)- N -propylprop-2-en-1-amine [( E / Z )-20g]

Brown oil; yield: 0.70 g (78%); ratio of diastereomers 1:1; R _f  = 0.34 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 3451 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 0.85-0.99 (m, 6 H, 2 CH₃), 1.34-1.59 (m, 4 H, 2 CH₂), 2.47 (t, J = 7.1 Hz, 2 H, CH₂), 2.64 (t, J = 7.5 Hz, 2 H, CH₂), 3.33 (s, 2 H, CH₂), 3.49 (s, 2 H, CH₂), 3.93 (s, 2 H, CH₂), 4.08 (s, 2 H, CH₂), 6.61 (s, 1 H, =CH), 6.69 (s, 1 H, =CH), 7.17-7.26 (m, 4 H, ArH), 7.43 (s, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.7, 11.8, 22.9, 23.0, 47.6, 49.4, 51.0, 51.3, 53.6, 55.5, 126.8, 127.0, 127.2, 128.0, 129.3, 129.4, 131.3, 131.5, 133.3.

MS (ES+): m/z = 299.1 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₆Cl₂N₄ C, 52.19; H, 5.39; N, 18.73. Found: C, 52.32; H, 5.57; N, 18.72.

( E )-2-(Azidomethyl)-3-(2,6-dichlorophenyl)- N -propylprop-2-en-1-amine [( E )-20h]

Green oil; yield: 1.00 g (75%); R _f  = 0.29 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 3445 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 0.95 (t, J = 7.4 Hz, 3 H, CH₃), 1.50-1.58 (m, 2 H, CH₂), 2.66 (t, J = 6.9 Hz, 2 H, CH₂), 3.53 (s, 2 H, CH₂), 3.76 (s, 2 H, CH₂), 6.43 (s, 1 H, =CH), 7.14-7.22 (m, 1 H, ArH), 7.32-7.36 (m, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 12.2, 23.6, 50.6, 51.3, 53.1, 124.6, 128.3, 129.5, 134.6, 135.3, 139.7.

MS (ES+): m/z = 299.0 [M⁺ + 1].

Anal. Calcd for C₁₃H₁₆Cl₂N₄: C, 52.19; H, 5.39; N, 18.73. Found: C, 52.10; H, 5.42; N, 18.44.

( E / Z )- N -[2-(Azidomethyl)-3-phenylprop-2-enyl)- N -benzylcyanamide [( E / Z )-21a]; Typical Procedure for 21a,e-h and 22a,e-h

To a stirred soln of mixture of (E/Z)-19a (0.90 g, 3.24 mmol) in MeOH (15 mL) was added CNBr (0.41 g, 3.89 mmol) and NaHCO₃ (0.27 g, 3.24 mmol) and the mixture was stirred at r.t. for 15 min. When the reaction was complete, MeOH was removed and the residue was diluted with EtOAc (40 mL) and H₂O (40 mL). The aqueous layer was separated and extracted with EtOAc (4 × 20 mL). The combined organic layers were dried (anhyd Na₂SO₄) and evaporated under vacuum to obtain a residue, that was purified by column chromatography (silica gel, EtOAc-hexanes, 3:17) to yield (E/Z)-21a (0.76 g, 78%) as a brown oil; ratio of diastereomers 1:1; R _f  = 0.32 (EtOAc-hexanes, 1:4).

IR (neat): 2100 (N₃), 2211 cm^-¹ (CN).

^¹H NMR (200 MHz, CDCl₃): δ = 3.77 (t, J = 1.0 Hz, 4 H, 2 CH₂), 4.06-4.10 (m, 6 H, 3 CH₂), 4.27 (s, 2 H, CH₂), 6.76 (s, 1 H, =CH), 6.93 (s, 1 H, =CH), 7.14-7.42 (m, 20 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 47.7, 48.7, 55.1, 55.4, 55.6, 117.7, 128.0, 128.2, 128.59, 128.62, 128.7, 128.76, 128.80, 128.85, 128.93, 129.0, 129.1, 129.7, 129.8, 134.1, 134.4, 134.9, 135.8, 136.2.

MS (ES+): m/z = 304.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₇N₅: C, 71.27; H, 5.65; N, 23.09. Found: C, 71.16; H, 5.74; N, 23.20.

( E / Z )- N -[2-(Azidomethyl)-3-(4-fluorophenyl)prop-2-enyl]- N -benzylcyanamide [( E / Z )-21e]

Brown oil; yield: 0.49 g (74%); ratio of diastereomers 1:1; R _f  = 0.32 (EtOAc-hexanes, 1:4).

IR (neat): 2103 (N₃), 2214 cm^-¹ (CN).

^¹H NMR (300 MHz, CDCl₃): δ = 3.73 (s, 2 H, CH₂), 3.80 (s, 2 H, CH₂), 4.03 (s, 2 H, CH₂), 4.08 (s, 4 H, 2 CH₂), 4.26 (s, 2 H, CH₂), 6.67 (s, 1 H, =CH), 6.82 (s, 1 H, =CH), 7.08-7.18 (m, 8 H, ArH), 7.28-7.30 (m, 4 H, ArH), 7.36-7.40 (m, 6 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 48.7, 48.8, 49.4, 55.0, 55.1, 55.6, 116.0, 116.4, 122.9, 124.5, 124.6, 128.6, 128.9, 129.0, 129.1, 129.3, 129.5, 130.4, 130.5, 130.6, 130.7, 130.9, 131.0, 132.6, 134.4, 134.7, 162.8.

MS (ES+): m/z = 322.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₆FN₅: C, 67.28; H, 5.02; N, 21.79. Found: C, 67.42; H, 5.13; N, 21.52.

( E / Z )- N -[2-(Azidomethyl)-3-(4-methylphenyl)prop-2-enyl]- N -benzylcyanamide [( E / Z )-21f]

Brown oil; yield: 0.42 g (78%); ratio of diastereomers 1:1; R _f  = 0.34 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 2213 cm^-¹ (CN).

^¹H NMR (300 MHz, CDCl₃): δ = 2.32 (s, 3 H, CH₃), 2.36 (s, 3 H, CH₃), 3.75 (d, J = 2.3 Hz, 2 H, CH₂), 3.78 (s, 2 H, CH₂), 4.07-4.11 (m, 6 H, 3 CH₂), 4.25 (d, J = 3.0 Hz, 2 H, CH₂), 6.71 (s, 1 H, =CH), 6.88 (s, 1 H, =CH), 7.06-7.19 (m, 8 H, ArH), 7.29-7.37 (m, 10 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.6, 21.7, 48.2, 48.4, 54.5, 54.6, 55.7, 55.8, 127.0, 129.0, 129.1, 129.2, 129.3, 129.5, 129.65, 129.71, 130.0, 131.7, 134.89, 138.93.

MS (ES+): m/z = 318.2 [M⁺ + 1].

Anal. Calcd for C₁₉H₁₉N₅: C, 71.90; H, 6.03; N, 22.07. Found: C, 72.12; H, 6.32; N, 21.94.

( E / Z )- N -[2-(Azidomethyl)-3-(2,4-dichlorophenyl)prop-2-enyl]- N -benzylcyanamide [( E / Z )-21g]

Brown oil; yield: 0.75 g (87%); ratio of diastereomers 2:1; R _f  = 0.29 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 2211 cm^-¹ (CN).

^¹H NMR (200 MHz, CDCl₃): δ = 3.51 (d, J = 8.1 Hz, 2 H, CH₂), 3.64 (s, 2 H, CH₂), 3.79 (s, 2 H, CH₂), 3.96 (s, 2 H, CH₂), 4.09 (s, 2 H, CH₂), 4.28 (s, 2 H, CH₂), 6.69 (s, 1 H, =CH), 6.83 (s, 1 H, =CH), 7.05-7.17 (m, 4 H, ArH), 7.31-7.51 (m, 12 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 48.2, 49.1, 54.7, 54.9, 55.5, 55.7, 127.5, 127.6, 128.9, 129.1, 129.2, 129.3, 129.4, 129.5, 129.9, 130.0, 131.6, 131.9, 132.3, 132.4, 132.7, 132.8, 134.6, 134.9.

MS (ES+): m/z = 372.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₅Cl₂N₅: C, 58.08; H, 4.06; N, 18.81. Found: C, 58.23; H, 3.87; N, 18.69.

( Z )- N -[2-(Azidomethyl)-3-(2,6-dichlorophenyl)prop-2-enyl]- N -benzylcyanamide [( Z )-21h]

Brown solid; yield: 0.69 g (88%); mp 142-143 ˚C; R _f  = 0.29 (EtOAc-hexanes, 1:4).

IR (KBr): 2113 (N₃), 2211 cm^-¹ (CN).

^¹H NMR (200 MHz, CDCl₃): δ = 3.85 (s, 4 H, 2 CH₂), 4.30 (s, 2 H, CH₂), 6.45 (s, 1 H, =CH), 7.20-7.28 (m, 1 H, ArH), 7.36-7.41 (m, 7 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 49.9, 53.8, 55.1, 128.6, 128.8, 129.2, 129.3, 129.5, 130.2, 133.1, 134.6, 134.7, 135.1.

MS (ES+): m/z = 372.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₅Cl₂N₅: C, 58.08; H, 4.06; N, 18.81. Found: C, 58.14; H, 3.93; N, 18.76.

( E / Z )- N -[2-(Azidomethyl)-3-phenylprop-2-enyl]- N -propyl­cyanamide [( E / Z )-22a]

Brown oil; yield: 0.84 g (80%); mixture of diastereomers 2:1; R _f  = 0.30 (EtOAc-hexanes, 1:4).

IR (neat): 2100 (N₃), 2210 cm^-¹ (CN).

^¹H NMR (300 MHz, CDCl₃): δ = 0.94 (t, J = 3.8 Hz, 3 H, CH₃), 1.02 (t, J = 7.4 Hz, 3 H, CH₃), 1.57-1.64 (m, 2 H, CH₂), 1.72-1.79 (m, 2 H, CH₂), 2.90 (t, J = 7.4 Hz, 2 H, CH₂), 3.04 (t, J = 7.4 Hz, 2 H, CH₂), 3.83 (s, 4 H, 2 CH₂), 4.08 (s, 2 H, CH₂), 4.12 (s, 2 H, CH₂), 6.82 (s, 1 H, =CH), 6.94 (s, 1 H, =CH), 7.23-7.26 (m, 5 H, ArH), 7.30-7.41 (m, 5 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 11.4, 11.5, 21.2, 21.4, 49.1, 49.3, 53.5, 53.7, 55.4, 56.7, 128.4, 128.5, 129.0, 129.1, 129.2, 130.5, 135.3, 135.7, 136.3.

MS (ES+): m/z = 256.2 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₇N₅: C, 65.86; H, 6.71; N, 27.43. Found: C, 66.04; H, 6.92; N, 27.30.

( E / Z )- N -[2-(Azidomethyl)-3-(4-fluorophenyl)prop-2-enyl]- N -propylcyanamide [( E / Z )-22e]

Colorless oil; yield: 0.90 g (84%); mixture of diastereomers 10:7; R _f  = 0.25 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 2210 cm^-¹ (CN).

^¹H NMR (300 MHz, CDCl₃): δ = 0.96 (t, J = 7.4 Hz, 3 H, CH₃), 1.03 (t, J = 7.4 Hz, 3 H, CH₃), 1.68-1.71 (m, 2 H, CH₂), 1.73-1.83 (m, 2 H, CH₂), 2.94 (t, J = 7.4 Hz, 2 H, CH₂), 3.06 (t, J = 7.4 Hz, 2 H, CH₂), 3.80-3.83 (m, 4 H, 2 CH₂), 4.09 (d, J = 5.1 Hz, 4 H, 2 CH₂), 6.79 (s, 1 H, =CH), 6.90 (s, 1 H, =CH), 7.06-7.12 (m, 4 H, ArH), 7.21-7.28 (m, 4 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 11.4, 11.5, 21.2, 21.4, 49.0, 49.2, 53.7, 53.9, 55.4, 56.6, 115.8, 116.3, 130.7, 130.8, 130.9, 131.0, 131.1, 131.4, 134.5, 135.2, 165.2.

MS (ES+): m/z = 274.2 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₆FN₅: C, 61.52; H, 5.90; N, 25.62. Found: C, 61.35; H, 6.10; N, 25.69.

( E / Z )- N -[2-(Azidomethyl)-3-(4-methylphenyl)prop-2-enyl]- N -propylcyanamide [( E / Z )-22f]

Red oil; yield: 0.80 g (86%); mixture of diastereomers 10:6; R _f  = 0.27 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 2210 cm^-¹ (CN).

^¹H NMR (200 MHz, CDCl₃): δ = 0.93-1.05 (m, 6 H, 2 CH₃), 1.56-1.80 (m, 4 H, 2 CH₂), 2.37 (s, 6 H, 2 CH₃), 2.90 (t, J = 7.1 Hz, 2 H, CH₂), 3.03 (t, J = 7.5 Hz, 2 H, CH₂), 3.82 (s, 4 H, 2 CH₂), 4.06 (s, 2 H, CH₂), 4.12 (s, 2 H, CH₂), 6.78 (s, 1 H, =CH), 6.89 (s, 1 H, =CH), 7.17-7.26 (m, 8 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 11.4, 11.5, 21.2, 21.4, 21.7, 49.2, 49.3, 53.4, 53.7, 55.6, 56.8, 129.1, 129.2, 129.7, 129.8, 132.4, 135.7, 136.4, 138.5.

MS (ES+): m/z = 270.2 [M⁺ + 1].

Anal. Calcd for C₁₅H₁₉N₅: C, 66.89; H, 7.11; N, 26.00. Found: C, 67.07; H, 6.96; N, 26.15.

( E / Z )- N -[2-(Azidomethyl)-3-(2,4-dichlorophenyl)prop-2-enyl]- N -propylcyanamide (22g)

Brown oil; yield: 0.66 g (87%); mixture of diastereomers 10:8; R _f  = 0.29 (EtOAc-hexanes, 1:4).

IR (neat): 2103 (N₃), 2212 cm^-¹ (CN).

^¹H NMR (200 MHz, CDCl₃): δ = 0.89-1.05 (m, 6 H, 2 CH₃), 1.54-1.65 (m, 2 H, CH₂), 1.70-1.81 (m, 2 H, CH₂), 2.88 (t, J = 7.3 Hz, 2 H, CH₂), 3.05 (t, J = 7.4 Hz, 2 H, CH₂), 3.69 (s, 2 H, CH₂), 3.86 (s, 2 H, CH₂), 3.97 (s, 2 H, CH₂), 4.10 (s, 2 H, CH₂), 6.73 (s, 1 H, =CH), 6.81 (s, 1 H, =CH), 7.15-7.31 (m, 4 H, ArH), 7.45 (s, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.3, 11.5, 21.2, 21.4, 49.2, 49.5, 53.4, 53.7, 54.8, 56.0, 117.4, 117.6, 127.6, 128.8, 129.0, 129.6, 130.0, 131.3, 131.6, 131.9, 132.45, 132.54, 133.1, 133.2, 134.8, 134.9, 135.19, 135.24.

MS (ES+): m/z = 324.2 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₅Cl₂N₅: C, 51.86; H, 4.66; N, 21.60. Found: C, 51.97; H, 4.82; N, 21.43.

( Z )- N -[2-(Azidomethyl)-3-(2,6-dichlorophenyl)prop-2-enyl]- N -propylcyanamide [( Z )-22h]

Colorless oil; yield: 0.86 g (80%); R _f  = 0.27 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 2212 cm^-¹ (CN).

^¹H NMR (200 MHz, CDCl₃): δ = 1.01 (t, J = 7.4 Hz, 3 H, CH₃), 1.71-1.81 (m, 2 H, CH₂), 3.07 (t, J = 7.3 Hz, 2 H, CH₂), 3.81 (s, 2 H, CH₂), 3.93 (s, 2 H, CH₂), 6.48 (s, 1 H, =CH), 7.21 (d, J = 8.8 Hz, 1 H, ArH), 7.37 (d, J = 7.4 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.5, 21.3, 49.9, 53.0, 55.3, 117.9, 128.2, 128.4, 128.5, 129.7, 130.2, 133.1, 135.0, 135.1.

MS (ES+): m/z = 324.1 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₅Cl₂N₅: C, 51.86; H, 4.66; N, 21.60. Found: C, 51.82; H, 4.74; N, 21.54.

( E / Z )-4-Benzyl-6-benzylidene-4,5,6,7-tetrahydrotetrazolo[1,5- a ]pyrimidine [( E / Z )-23a]; Typical Procedure for 23a,e-h, 24a,e-h, and 30a,e-g

Compound (E/Z)-21a (0.50 g, 1.65 mmol) was dissolved in anhyd DMF and heated at 90 ˚C for 2 h. Then the mixture was cooled to r.t., diluted with H₂O (30 mL), and extracted with EtOAc (30 mL). The aqueous layer was separated and extracted with EtOAc (3 × 20 mL). The combined organic layers were dried (anhyd Na₂SO₄) and evaporated to furnish a residue, which was purified by column chromatography (silica gel, 230-400 mesh, EtOAc-hexanes, 3:7) to furnish (E/Z)-23a (0.38 g, 76%) as a brown oil; ratio of diastereomers 2:1; R _f  = 0.23 (EtOAc-hexanes, 1:1).

IR (neat): 1662 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 3.91 (d, J = 1.0 Hz, 2 H, CH₂), 4.01 (d, J = 0.8 Hz, 2 H, CH₂), 4.70 (s, 2 H, CH₂), 4.79 (s, 2 H, CH₂), 5.00 (d, J = 1.3 Hz, 2 H, CH₂), 5.16 (d, J = 1.7 Hz, 2 H, CH₂), 6.79 (s, 1 H, =CH), 6.89 (s, 1 H, =CH), 7.01-7.03 (m, 1 H, ArH), 7.19 (d, J = 6.8 Hz, 2 H, ArH), 7.28-7.45 (m, 17 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 45.3, 45.5, 50.4, 51.9, 54.0, 54.1, 123.7, 124.0, 128.17, 128.22, 128.3, 128.5, 128.6, 128.7, 128.8, 128.9, 129.0, 131.7, 131.9, 134.85, 134.90, 135.6, 155.6.

MS (ES+): m/z = 304.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₇N₅: C, 71.27; H, 5.65; N, 23.09. Found: C, 71.14; H, 5.34; N, 23.14.

( E / Z )-4-Benzyl-6-(4-fluorobenzylidene)-4,5,5,6-tetrahydrotetrazolo[1,5- a ]pyrimidine [( E / Z )-23e]

Brown oil; yield: 0.53 g (88%); ratio of diastereomers 5:4; R _f  = 0.19 (EtOAc-hexanes, 1:1).

IR (neat): 1620 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 3.88 (s, 2 H, CH₂), 3.92 (d, J = 0.9 Hz, 2 H, CH₂), 4.69 (s, 2 H, CH₂), 4.78 (s, 2 H, CH₂), 5.00 (s, 2 H, CH₂), 5.02 (d, J = 1.3 Hz, 2 H, ArH), 6.72 (s, 1 H, =CH), 6.80 (s, 1 H, =CH), 6.88 (t, J = 7.4 Hz, 1 H, ArH), 6.98-7.18 (m, 5 H, ArH), 7.29-7.40 (m, 12 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 45.8, 46.0, 50.4, 51.9, 54.2. 54.3, 116.2, 116.3, 122.6, 122.8, 124.5, 124.7, 124.8, 125.0, 126.4, 126.5, 128.4, 128.5, 128.7, 129.0, 129.2, 130.5, 130.8, 130.9, 135.7, 155.5, 155.7, 158.8, 158.9, 161.3, 161.4.

MS (ES+): m/z = 322.3 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₆FN₅: C, 67.28; H, 5.02; N, 21.79. Found: C, 67.60; H, 4.79; N, 21.82.

( E / Z )-4-Benzyl-6-(4-methylbenzylidene)-4,5,6,7-tetrahydrotetrazolo[1,5- a ]pyrimidine [( E / Z )-23f]

Brown oil; yield: 0.30 g (86%); ratio of diastereomers 5:2; R _f  = 0.23 (EtOAc-hexanes, 1:1).

IR (neat): 1610 cm^-¹ (C=N).

^¹H NMR (200 MHz, CDCl₃): δ = 2.35-2.37 (m, 6 H, 2 CH₃), 3.88 (s, 2 H, CH₂), 4.00 (s, 2 H, CH₂), 4.69 (s, 2 H, CH₂), 4.77 (s, 2 H, CH₂), 4.96 (s, 2 H, CH₂), 5.14 (s, 2 H, CH₂), 6.73 (s, 1 H, =CH), 6.83-6.92 (m, 2 H, =CH, ArH), 7.05-7.08 (m, 4 H, ArH), 7.18-7.38 (m, 13 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.7, 45.7, 45.9, 52.2, 54.4, 123.1, 126.0, 128.6, 128.9, 129.0, 129.2, 129.3, 129.7, 129.9, 130.1, 131.9, 132.1, 132.3, 135.9, 138.9.

MS (ES+): m/z = 318.2 [M⁺ + 1].

HRMS (EI): m/z [M]⁺ calcd for C₁₉H₁₉N₅: 317.1640; found: 317.1691.

( E )-4-Benzyl-6-(2,4-dichlorobenzylidene)-4,5,6,7-tetrahydro­tetrazolo[1,5- a ]pyrimidine [( E )-23g]

White solid; yield: 0.53 g (88%); mp 156-157 ˚C; R _f  = 0.21 (EtOAc-hexanes, 1:1).

IR (KBr): 1614 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 3.81 (s, 2 H, CH₂), 4.68 (s, 2 H, CH₂), 5.03 (d, J = 1.2 Hz, 2 H, CH₂), 6.72 (d, J = 8.3 Hz, 1 H, ArH), 6.80 (s, 1 H, =CH), 7.03 (dd, J ₁ = 8.2 Hz, J ₂ = 2.0 Hz, 1 H, ArH), 7.26-7.29 (m, 2 H, ArH), 7.32-7.34 (m, 3 H, ArH), 7.40 (d, J = 2.0 Hz, 1 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 45.5, 50.5, 54.2, 126.7, 127.5, 128.2, 128.6, 128.9, 129.2, 130.0, 131.1, 132.0, 134.8, 135.2, 135.7, 155.7.

MS (ES+): m/z = 372.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₅Cl₂N₅: C, 58.08; H, 4.06; N, 18.81. Found: C, 58.23; H, 4.19; N, 18.69.

( E )-4-Benzyl-6-(2,6-dichlorobenzylidene)-4,5,6,7-tetrahydro­tetrazolo[1,5- a ]pyrimidine [( E )-23h]

White solid; yield: 0.65 g (93%); mp 150-151 ˚C; R _f  = 0.35 (EtOAc-hexanes, 1:1).

IR (KBr): 1621 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 3.96 (s, 2 H, CH₂), 4.72 (d, J = 1.5 Hz, 2 H, CH₂), 4.82 (s, 2 H, CH₂), 6.58 (s, 1 H, =CH), 7.22-7.30 (m, 1 H, ArH), 7.34-7.38 (m, 7 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 46.1, 51.2, 54.3, 126.4, 128.5, 128.6, 128.7, 128.8, 129.3, 130.6, 132.5, 135.0, 135.8, 155.7.

MS (ES+): m/z = 372.2 [M⁺ + 1].

DART-HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₈H₁₆Cl₂N₅: 372.07828; found: 372.07608.

( E / Z )-6-Benzylidene-4-propyl-4,5,6,7-tetrahydrotetrazolo[1,5- a ]pyrimidine [( E / Z )-24a]

Brown oil; yield: 0.65 g (86%); ratio of diastereomers 2:1; R _f  = 0.23 (EtOAc-hexanes, 1:1).

IR (neat): 1665 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 0.88 (t, J = 7.4 Hz, 3 H, CH₃), 0.99 (t, J = 7.4 Hz, 3 H, CH₃), 1.61-1.79 (m, 4 H, 2 CH₂), 3.43 (t, J = 7.5 Hz, 2 H, CH₂), 3.52 (t, J = 7.5 Hz, 2 H, CH₂), 4.03 (d, J = 0.7 Hz, 2 H, CH₂), 4.13 (s, 2 H, CH₂), 4.99 (d, J = 1.3 Hz, 2 H, CH₂), 5.13 (d, J = 1.6 Hz, 2 H, CH₂), 6.87 (s, 1 H, =CH), 6.91 (s, 1 H, =CH), 7.21 (d, J = 7.1 Hz, 4 H, ArH), 7.34-7.44 (m, 6 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.0, 11.2, 20.1, 20.2, 45.3, 46.0, 50.0, 52.0, 52.1, 52.6, 123.7, 128.2, 128.4, 128.6, 128.7, 128.8, 131.3, 131.6, 134.7, 135.0.

MS (ES+): m/z = 256.2 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₇N₅: C, 65.86; H, 6.71; N, 27.43. Found: C, 65.99; H, 6.81; N, 27.24.

( E / Z )-6-(4-Fluorobenzylidene)-4-propyl-4,5,6,7-tetrahydrotetrazolo[1,5- a ]pyrimidine [( E / Z )-24e]

Brown oil; yield: 0.73 g (86%); ratio of diastereomers 2:1; R _f  = 0.30 (EtOAc-hexanes, 1:1).

IR (neat): 1664 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 0.88 (t, J = 7.4 Hz, 3 H, CH₃), 0.98 (t, J = 7.4 Hz, 3 H, CH₃), 1.61-1.77 (m, 4 H, 2 CH₂), 3.43 (t, J = 7.6 Hz, 2 H, CH₂), 3.51 (t, J = 7.5 Hz, 2 H, CH₂), 4.02 (d, J = 0.6 Hz, 2 H, CH₂), 4.09 (d, J = 0.7 Hz, 2 H, CH₂), 4.98 (d, J = 1.2 Hz, 2 H, CH₂), 5.10 (d, J = 1.5 Hz, 2 H, CH₂), 6.83 (s, 1 H, =CH), 6.87 (s, 1 H, =CH), 7.07-7.21 (m, 8 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.0, 11.1, 11.2, 20.1, 20.2, 20.9, 45.2, 45.9, 52.0, 52.1, 52.5, 115.5, 115.7, 115.8, 115.9, 116.0, 116.2, 117.9, 123.8, 127.6, 127.7, 130.2, 130.4, 130.46, 130.51, 130.6, 130.8, 131.0, 164.1.

MS (ES+): m/z = 274.2 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₆FN₅: C, 61.52; H, 5.90; N, 25.62. Found: C, 61.43; H, 5.94; N, 25.46.

( E / Z )-6-(4-Methylbenzylidene)-4-propyl-4,5,6,7-tetrahydrotetrazolo[1,5- a ]pyrimidine [( E / Z )-24f]

Brown oil; yield: 0.64 g (84%); ratio of diastereomers 10:7; R _f  = 0.32 (EtOAc-hexanes, 1:1).

IR (neat): 1619 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 0.89 (t, J = 7.4 Hz, 3 H, CH₃), 0.99 (t, J = 7.4 Hz, 3 H, CH₃), 1.55-1.78 (m, 4 H, 2 CH₂), 2.38 (s, 3 H, CH₃), 2.39 (s, 3 H, CH₃), 3.44 (t, J = 7.6 Hz, 2 H, CH₂), 3.49-3.54 (m, 2 H, CH₂), 4.02 (s, 2 H, CH₂), 4.13 (s, 2 H, CH₂), 4.97 (d, J = 1.3 Hz, 2 H, CH₂), 5.14 (d, J = 1.6 Hz, 2 H, CH₂), 6.83 (s, 1 H, =CH), 6.87 (s, 1 H, =CH), 7.10 (d, J = 8.0 Hz, 4 H, ArH), 7.16-7.23 (m, 4 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.0, 11.2, 20.1, 20.2, 29.1, 29.3, 45.3, 46.1, 50.0, 52.0, 52.1, 52.6, 123.0, 123.4, 128.6, 128.7, 129.39, 129.44, 131.1, 131.4, 131.9, 132.1, 138.2, 138.4.

MS (ES+): m/z = 270.2 [M⁺ + 1].

DART-HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₅H₂₀N₅: 270.17187; found: 270.17281.

( E / Z )-6-(2,4-Dichlorobenzylidene)-4-propyl-4,5,6,7-tetrahydro­tetrazolo[1,5- a ]pyrimidine [( E / Z )-24g]

Brown oil; yield: 0.50 g (83%); ratio of diastereomers 5:3; R _f  = 0.23 (EtOAc-hexanes, 1:1).

IR (neat): 1617 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 0.90 (t, J = 7.4 Hz, 3 H, CH₃), 0.99 (t, J = 7.4 Hz, 3 H, CH₃), 1.58-1.66 (m, 2 H, CH₂), 1.72-1.79 (m, 2 H, CH₂), 3.44 (t, J = 7.6 Hz, 2 H, CH₂), 3.55 (t, J = 7.5 Hz, 2 H, CH₂), 3.95 (d, J = 0.6 Hz, 2 H, CH₂), 4.07 (d, J = 0.8 Hz, 2 H, CH₂), 4.97 (d, J = 1.6 Hz, 2 H, CH₂), 5.04 (d, J = 1.3 Hz, 2 H, CH₂), 6.87 (s, 2 H, 2 =CH), 7.11 (d, J = 8.3 Hz, 2 H, ArH), 7.31 (dd, J ₁ = 8.3 Hz, J ₂ = 1.9 Hz, 2 H, ArH), 7.49 (t, J = 2.2 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 11.3, 11.4, 20.4, 20.5, 45.5, 46.6, 50.0, 52.3, 52.4, 52.5, 126.8, 127.0, 127.6, 127.9, 130.1, 130.2, 130.9, 131.3, 131.9, 132.2, 134.9, 135.3, 135.5, 155.2, 155.4.

MS (ES+): m/z = 324.2 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₅Cl₂N₅: C, 51.86; H, 4.66; N, 21.60. Found: C, 51.92; H, 4.43; N, 21.73.

( E )-6-(2,6-Dichlorobenzylidene)-4-propyl-4,5,6,7-tetrahydro­tetrazolo[1,5- a ]pyrimidine [( E )-24h]

Brown oil; yield: 0.64 g (85%); R _f  = 0.30 (EtOAc-hexanes, 1:4).

IR (neat): 1624 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 1.00 (t, J = 7.4 Hz, 3 H, CH₃), 1.73-1.80 (m, 2 H, CH₂), 3.57 (t, J = 7.7 Hz, 2 H, CH₂), 4.10 (s, 2 H, CH₂), 4.72 (s, 2 H, CH₂), 6.67 (s, 1 H, =CH), 7.29 (s, 1 H, ArH), 7.38 (d, J = 8.4 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 11.1, 20.2, 45.6, 51.7, 52.0, 125.6, 128.3, 130.1, 130.2, 132.1, 134.7, 155.1.

MS (ES+): m/z = 324.2 [M⁺ + 1].

Anal. Calcd for C₁₄H₁₅Cl₂N₅: C, 51.86; H, 4.66; N, 21.60. Found: C, 51.90; H, 4.50; N, 21.48.

( E )-6-Benzylidene-4-tosyl-4,5,6,7-tetrahydrotetrazolo[1,5- a ]pyrimidine [( E )-30a]

White solid; yield: 0.49 g (82%); mp 156-157 ˚C; R _f  = 0.24 (EtOAc-hexanes, 3:7).

IR (KBr): 1665 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 2.43 (s, 3 H, CH₃), 4.61 (s, 2 H, CH₂), 5.16 (d, J = 1.5 Hz, 2 H, CH₂), 7.03 (s, 1 H, =CH), 7.18 (d, J = 6.4 Hz, 2 H, ArH), 7.30-7.43 (m, 5 H, ArH), 8.04 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.8, 46.4, 52.0, 121.1, 126.6, 128.7, 128.8, 129.07, 129.10, 129.8, 130.1, 134.5, 145.8.

MS (ES+): m/z = 368.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₇N₅O₂S: C, 58.84; H, 4.66; N, 19.06. Found: C, 58.95; H, 4.74; N, 18.84.

( E / Z )-6-(4-Fluorobenzylidene)-4-tosyl-4,5,6,7-tetrahydrotet­razolo[1,5- a ]pyrimidine [( E / Z )-30e]

Brown oil; yield: 0.19 g (76%); ratio of diastereomers 10:7; R _f  = 0.21 (EtOAc-hexanes, 3:7).

IR (neat): 1664 cm^-¹ (C=N).

^¹H NMR (300 MHz, CDCl₃): δ = 2.43 (s, 3 H, CH₃), 2.44 (s, 3 H, CH₃), 4.60 (s, 2 H, CH₂), 4.76 (s, 2 H, CH₂), 5.14 (d, J = 1.3 Hz, 2 H, CH₂), 5.30 (s, 2 H, CH₂), 7.00 (s, 2 H, 2 =CH), 7.09-7.20 (m, 6 H, ArH), 7.26-7.36 (m, 6 H, ArH), 7.82 (d, J = 8.3 Hz, 2 H, ArH), 8.04 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 30.1, 46.6, 52.2, 116.3, 116.8, 128.4, 129.0, 130.4, 130.8, 131.0, 133.7.

MS (ES+): m/z = 386.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₆FN₅O₂S: C, 56.09; H, 4.18; N, 18.17. Found: C, 55.89; H, 4.27; N, 18.25.

( E )-6-(4-Methylbenzylidene)-4-tosyl-4,5,6,7-tetrahydrotetrazolo[1,5- a ]pyrimidine [( E )-30f]

Brown oil; yield: 0.39 g (78%); R _f  = 0.23 (EtOAc-hexanes, 3:7).

IR (neat): 1666 cm^-¹ (C=N).

^¹H NMR (200 MHz, CDCl₃): δ = 2.38 (s, 3 H, CH₃), 2.42 (s, 3 H, CH₃), 4.59 (s, 2 H, CH₂), 5.16 (s, 2 H, CH₂), 6.99 (s, 1 H, =CH), 7.05-7.09 (m, 2 H, ArH), 7.21-7.36 (m, 2 H, ArH), 7.45-7.52 (m, 2 H ArH), 8.02-8.13 (m, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 21.7, 29.7, 47.0, 51.9, 62.0, 123.0, 128.5, 128.6, 129.6, 130.0, 130.1, 139.2.

MS (ES+): m/z = 382.2 [M⁺ + 1].

Anal. Calcd for C₁₉H₁₉N₅O₂S: C, 59.82; H, 5.02; N, 18.36. Found: C, 59.89; H, 5.13; N, 18.30.

( E / Z )-6-(2,4-Dichlorobenzylidene)-4-tosyl-4,5,6,7-tetrahydro­tetrazolo[1,5- a ]pyrimidine [( E / Z )-30g]

White solid; yield: 0.46 g (84%); ratio of diastereomers 5:2; mp 158-159 ˚C; R _f  = 0.22 (EtOAc-hexanes, 3:7).

IR (KBr): 1663 cm^-¹ (C=N).

^¹H NMR (200 MHz, CDCl₃): δ = 2.42 (s, 6 H, 2 CH₃), 4.57 (s, 2 H, CH₂), 4.67 (s, 2 H, CH₂), 4.99 (s, 2 H, CH₂), 5.07 (s, 2 H, CH₂), 6.95 (s, 1 H, =CH), 7.04 (s, 2 H, =CH, ArH), 7.27-7.36 (m, 7 H, ArH), 7.50 (s, 2 H, ArH), 7.91 (d, J = 6.6 Hz, 2 H, ArH), 8.03 (d, J = 7.3 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 22.1, 46.2, 46.6, 51.9, 124.3, 127.9, 128.2, 128.8, 128.9, 130.4, 130.5, 130.7, 130.8, 131.2, 131.6, 134.2, 135.0, 136.2, 146.3.

MS (ES+): m/z = 436.0 [M⁺ + 1].

HRMS (EI): m/z [M]⁺ for C₁₈H₁₆Cl₂N₅O₂S: 435.0324; found: 435.0329.

( E / Z )-2-(Azidomethyl)-3-bromo-1-phenylprop-2-ene [( E / Z )-27a]; Typical Procedure for 27a,e-g

To a stirred soln of 3a (1.00 g, 5.29 mmol) in anhyd CH₂Cl₂ (20 mL) was added dropwise a soln of PBr₃ (1.71 mL, 6.35 mmol) in CH₂Cl₂ (15 mL) at 0 ˚C and the mixture was stirred at r.t. for 30 min. When the reaction was complete, it was quenched with ice water (30 mL) and partitioned in a separating funnel. The organic layer was collected and the aqueous layer was extracted with CHCl₃ (2 × 20 mL). The organic layers were combined, washed with brine (50 mL), dried (anhyd Na₂SO₄), and concentrated to afford the crude product, which was purified by column chromatography (silica gel, 100-200 mesh, EtOAc-hexanes, 1:19) to yield pure 27a (1.06 g, 80%) as a brown oil.

( E / Z )-2-(Azidomethyl)-3-phenyl- N -tosylprop-2-en-1-amine [( E / Z )-28a]; Typical Procedure for 28a,e-g

To a stirred soln of 27a (1.50 g, 5.95 mmol) in anhyd DMF (10 mL) was added NaH (0.24 g, 5.95 mmol, 60% in oil). After 5 min, TsNH₂ (1.12 g, 6.55 mmol) was added and mixture stirred at r.t. for 2 h. When the reaction was complete, the mixture was diluted with H₂O (30 mL) and extracted with EtOAc (30 mL). The aqueous layer was separated and extracted with EtOAc (3 × 20 mL). The combined organic layers were dried (anhyd Na₂SO₄) and concentrated to obtain the crude product, which was purified by column chromatography (silica gel, 100-200 mesh, EtOAc-hexanes, 1:4) to furnish (E/Z)-28a (1.00 g, 49%) as a colorless oil; ratio of diastereomers 10:7; R _f  = 0.23 (EtOAc-hexanes, 1:4).

IR (neat): 2100 (N₃), 3424 cm^-¹ (NH).

^¹H NMR (300 MHz, CDCl₃): δ = 2.45 (s, 6 H, 2 CH₃), 3.78-3.82 (m, 4 H, 2 CH₂), 3.98 (s, 4 H, 2 CH₂), 4.66 (t, J = 6.0 Hz, 1 H, NH), 4.77 (t, J = 6.1 Hz, 1 H, NH), 6.68 (s, 1 H, =CH), 6.70 (s, 1 H, =CH), 7.09-7.16 (m, 4 H, ArH), 7.28-7.38 (m, 10 H, ArH), 7.68 (d, J = 8.3 Hz, 2 H, ArH), 7.81 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.6, 21.9, 42.3, 47.5, 48.5, 56.4, 127.6, 128.3, 129.0, 129.6, 129.8, 130.2, 133.6, 134.0,,144.1.

MS (ES+): m/z = 343.1 [M⁺ + 1].

Anal. Calcd for C₁₇H₁₈N₄O₂S: C, 59.63; H, 5.30; N, 16.36. Found: C, 59.69; H, 5.41; N, 16.27.

( E / Z )-2-(Azidomethyl)-3-(4-fluorophenyl)- N -tosylprop-2-en-1-amine [( E / Z )-28e]

Colorless oil; yield: 0.40 g (60%); ratio of diastereomers 1:1; R _f  = 0.25 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 3415 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 2.45 (s, 6 H, 2 CH₃), 3.74 (d, J = 6.0 Hz, 2 H, CH₂), 3.79 (d, J = 6.4 Hz, 2 H, CH₂), 3.96 (d, J = 5.0 Hz, 4 H, 2 CH₂), 4.73 (t, J = 5.8 Hz, 1 H, NH), 4.82 (t, J = 6.2 Hz, 1 H, NH), 6.63 (s, 1 H, =CH), 6.65 (s, 1 H, =CH), 6.96-7.16 (m, 9 H, ArH), 7.28-7.35 (m, 3 H, ArH), 7.68 (d, J = 8.3 Hz, 2 H, ArH), 7.80 (d, J = 8.3 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.9, 42.1, 48.3, 49.3, 56.3, 115.7, 116.1, 127.6, 130.2, 130.7, 130.9, 131.7, 132.4, 132.8, 137.4, 144.3.

MS (ES+): m/z = 361.1 [M⁺ + 1].

Anal. Calcd for C₁₇H₁₇FN₄O₂S: C, 56.65; H, 4.75; N, 15.55. Found: C, 56.95; H, 4.59; N, 15.57.

( E / Z )-2-(Azidomethyl)-3-(4-methylphenyl)- N -tosylprop-2-en-1-amine [( E / Z )-28f]

Colorless oil; yield: 1.00 g (50%); ratio of diastereomers 2:1; R _f  = 0.21 (EtOAc-hexanes, 1:4).

IR (neat): 2102 (N₃), 3458 cm^-¹ (NH).

^¹H NMR (300 MHz, CDCl₃): δ = 2.31 (s, 3 H, CH₃), 2.34 (s, 3 H, CH₃), 2.43 (s, 3 H, CH₃), 2.44 (s, 3 H, CH₃), 3.77 (d, J = 6.2 Hz, 2 H, CH₂), 3.92-3.96 (m, 2 H, CH₂), 4.08 (d, J = 6.1 Hz, 4 H, 2 CH₂), 4.63 (t, J = 5.8 Hz, 1 H, NH), 4.74 (t, J = 6.2 Hz, 1 H, NH), 6.62 (s, 1 H, =CH), 6.64 (s, 1 H, =CH), 6.97-7.03 (m, 3 H, ArH), 7.08-7.16 (m, 4 H, ArH), 7.26-7.33 (m, 4 H, ArH), 7.67 (d, J = 8.1 Hz, 2 H, ArH), 7.75-7.80 (m, 3 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.6, 21.9, 42.3, 47.5, 48.5, 56.4, 127.6, 128.3, 129.0, 129.58, 129.61, 129.8, 130.15, 130.21, 133.6, 134.0, 144.1.

MS (ES+): m/z = 357.1 [M⁺ + 1].

Anal. Calcd for C₁₈H₂₀N₄O₂S: C, 60.65; H, 5.66; N, 15.72. Found: C, 60.52; H, 5.84; N, 15.81.

( E )-2-(Azidomethyl)-3-(2,4-dichlorophenyl)- N -tosylprop-2-en-1-amine [( E )-28g]

Colorless viscous oil; yield: 0.75 g (45%); R _f  = 0.23 (EtOAc-hexanes­, 1:4).

IR (neat): 2102 (N₃), 3292 cm^-¹ (NH).

^¹H NMR (200 MHz, CDCl₃): δ = 2.43 (s, 3 H, CH₃), 2.88 (s, 2 H, CH₂), 2.95 (s, 2 H, CH₂), 4.97 (t, J = 6.3 Hz, 1 H, NH), 6.60 (s, 1 H, =CH), 7.02 (d, J = 8.1 Hz, 1 H, ArH), 7.21-7.40 (m, 4 H, ArH), 7.79 (d, J = 7.7 Hz, 1 H, ArH), 8.01 (s, 1 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.9, 50.2, 53.1, 126.9, 127.7, 129.0, 129.5, 129.7, 130.0, 130.7, 132.9, 133.1, 138.3, 138.6, 145.6.

MS (ES+): m/z = 411.1 [M⁺ + 1].

Anal. Calcd for C₁₇H₁₆Cl₂N₄O₂S: C, 49.64; H, 3.92; N, 13.62. Found: C, 49.75; H, 3.83; N, 13.80.

( E / Z )- N -[2-(Azidomethyl)-3-phenylprop-2-enyl]- N -tosylcyan­amide [( E / Z )-29a]; Typical Procedure for 29a,e-g

To a stirred soln of (E/Z)-28a (0.70 g, 2.05 mmol) in anhyd CH₂Cl₂ (20 mL) was added NaH (0.16 g, 4.09 mmol, 60% in oil). After 5 min, CNBr (0.28 g, 2.67 mmol) was added and mixture was stirred at r.t. for 2 h. When the reaction was complete, CH₂Cl₂ was removed from the mixture and the residue was diluted with EtOAc (30 mL) and H₂O (30 mL). The aqueous layer was separated and extracted with EtOAc (3 × 20 mL). The combined organic layers were dried (Na₂SO₄) and then concentrated to obtain the crude product, which was purified by column chromatography (silica gel, 100-200 mesh, EtOAc-hexanes, 3:7) to yield (E/Z)-29a (0.56 g, 75%) as a colorless oil; ratio of diastereomers 10:7; R _f  = 0.24 (EtOAc-hexanes­, 1:4).

IR (neat): 2103 (N₃), 2230 cm^-¹ (CN).

^¹H NMR (300 MHz, CDCl₃): δ = 2.49 (s, 6 H, 2 CH₃), 3.93 (s, 2 H, CH₂), 3.98 (s, 2 H, CH₂), 4.19 (s, 4 H, 2 CH₂), 6.81 (s, 1 H, =CH), 6.98 (s, 1 H, =CH), 7.16-7.19 (m, 4 H, ArH), 7.27-7.45 (m, 10 H, ArH), 7.78 (dd, J ₁ = 8.5 Hz, J ₂ = 2.1 Hz, 2 H, ArH), 7.90 (dd, J ₁ = 8.2 Hz, J ₂ = 2.0 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.9, 47.9, 38.2, 54.4, 54.5, 108.4, 127.6, 127.9, 128.08, 128.13, 128.4, 128.6, 128.7, 128.8, 128.9, 130.6, 130.7, 133.7, 134.5, 138.0, 138.1, 146.9.

MS (ES+): m/z = 368.2 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₇N₅O₂S: C, 58.84; H, 4.66; N, 19.06. Found: C, 59.06; H, 4.93; N, 18.73.

( E / Z )- N -[2-(Azidomethyl)-3-(4-fluorophenyl)prop-2-enyl]- N -tosylcyanamide [( E / Z )-29e]

Colorless oil; yield: 0.30 g (77%); ratio of diastereomers 1:1; R _f  = 0.27 (EtOAc-hexanes, 1:4).

IR (neat): 2103 (N₃), 2229 cm^-¹ (CN).

^¹H NMR (200 MHz, CDCl₃): δ = 2.50 (s, 6 H, 2 CH₃), 3.94 (d, J = 6.6 Hz, 4 H, 2 CH₂), 4.15 (d, J = 6.3 Hz, 4 H, 2 CH₂), 6.76 (s, 1 H, =CH), 6.94 (s, 1 H, =CH), 7.00-7.20 (m, 8 H, ArH), 7.42 (t, J = 7.3 Hz, 4 H, ArH), 7.79 (d, J = 7.9 Hz, 2 H, ArH), 7.89 (d, J = 8.0 Hz, 2 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 22.2, 48.0, 48.4, 54.7, 54.8, 115.9, 116.4, 128.2, 128.37, 128.41, 130.7, 130.9, 131.0, 131.1, 133.4, 134.0, 137.2, 137.3, 147.2, 147.3, 165.4.

MS (ES+): m/z = 386.0 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₆FN₅O₂S: C, 56.09; H, 4.18; N, 18.17. Found: C, 56.15; H, 4.25; N, 18.02.

( E / Z )- N -[2-(Azidomethyl)-3-(4-methylphenyl)prop-2-enyl]- N -tosylcyanamide [( E / Z )-29f]

Colorless oil; yield: 0.56 g (80%); ratio of diastereomers 1:1; R _f  = 0.28 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 2228 cm^-¹ (CN).

^¹H NMR (200 MHz, CDCl₃): δ = 2.34 (s, 6 H, 2 CH₃), 2.48 (s, 6 H, 2 CH₃), 3.90 (s, 2 H, CH₂), 3.98 (s, 2 H, CH₂), 4.20 (s, 2 H, CH₂), 4.49 (s, 2 H, CH₂), 6.77 (s, 1 H, =CH), 6.94 (s, 1 H, =CH), 7.02-7.45 (m, 12 H, ArH), 7.77-7.91 (m, 4 H, ArH).

^¹³C NMR (50 MHz, CDCl₃): δ = 21.2, 21.78, 21.82, 47.8, 48.1, 54.0, 54.5, 54.6, 126.9, 127.9, 128.0, 128.6, 128.8, 128.9, 129.0, 129.3, 129.4, 129.7, 130.4, 130.5, 133.6, 133.9, 138.1, 138.2, 138.6, 139.4.

MS (ES+): m/z = 382.0 [M⁺ + 1].

Anal. Calcd for C₁₉H₁₉N₅O₂S: C, 59.82; H, 5.02; N, 18.36. Found: C, 59.73; H, 5.06; N, 18.30.

( E )- N -[2-(Azidomethyl)-3-(2,4-dichlorophenyl)prop-2-enyl]- N -tosylcyanamide [( E )-29g]

Colorless oil; yield: 0.60 g (90%); R _f  = 0.30 (EtOAc-hexanes, 1:4).

IR (neat): 2101 (N₃), 2228 cm^-¹ (CN).

^¹H NMR (300 MHz, CDCl₃): δ = 2.49 (s, 3 H, CH₃), 3.89 (s, 2 H, CH₂), 4.21 (s, 2 H, CH₂), 6.74 (s, 1 H, =CH), 7.10 (d, J = 8.3 Hz, 1 H, ArH), 7.25-7.26 (m, 1 H, ArH), 7.43-7.46 (m, 3 H, ArH), 7.90 (d, J = 8.4 Hz, 2 H, ArH).

^¹³C NMR (75 MHz, CDCl₃): δ = 22.2, 48.6, 54.2, 108.5, 127.6, 128.4, 130.1, 130.9, 131.0, 131.6, 131.9, 133.9, 135.0, 135.7, 147.2.

MS (ES+): m/z = 436.0 [M⁺ + 1].

Anal. Calcd for C₁₈H₁₅Cl₂N₅O₂S: C, 49.55; H, 3.47; N, 16.05. Found: C, 49.43; H, 3.65; N, 16.12.

Supporting Information for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synthesis.

Acknowledgment

Four of the authors (A.M., S.H., S.B., and N.R.) gratefully acknowledge the financial support from CSIR, New Delhi. Authors gratefully acknowledge SAIF Division of CDRI for providing the spectroscopic data. This work was funded by a grant from DST, New Delhi.

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This is CDRI communication No. 7938.

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  Search in Google Scholar

This is CDRI communication No. 7938.