INTRODUCTION

An enamide fragment is present in molecules of many biologically active natural products [1]. These include fungal and cytotoxic antibiotics crocacins [2], macrocyclic lactones salicylihalamides A and B [3], apicularen A [4], cruentaren [5], zampanolides [6], and lactam macrolides such as cryptophycin [7], apratoxin A [8], poecillastrins [9, 10], and herbimycin A [11]. Pepper alkaloids containing an enamide fragment showed high anticancer, gastroprotective, and anxio­lytic activities [12–14]. Synthetic cinnamic acid amides exhibited high fungicidal and insecticidal effects [15], and their N-aryl-substituted analogs efficiently acted as antibiotics against staphylococci and tuberculosis bac­teria [16]. Acrylamides were used to create a number of known antitumor drugs such as afatinib, canertinib, panobinostat, ibrutinib, anthramycin, and belinostat, antitubercular drug rifampicin, and anticonvulsant medication entacapone [17].

α,β-Unsaturated amides can be involved in Michael reaction with aromatic amines to protect the amino group and obtain benzothiazepine and benzodiazepine lactames [18], Morita–Baylis–Hillman reactions with the formation of both linear olefinic alcohols [19] and cyclic ones (intramolecular cyclization products) [20], arylation with aryl iodides at the β-position of the double bond in the presence of Pd(OAc)2 or AgOAc [21], trifluoromethylation using Umemoto’s reagent [22], C2-alkylation of benzimidazoles in the presence of a rhodium(I) complexes [23], annulation of al­kynoates leading to biologically important 6-oxo-1,6-dihydropyridine-3-carboxylic acid esters [24], aerobic rhodium(III)-catalyzed oxidative cross-coupling with alkenes to produce dienamides [25], and reaction with 2-thiocyanato-2,3-dihydro-1H-benzimidazole accom­panied by cyclization of the amide fragment to 1,2-thia­zole derivative [26]. (Z)-3-Azidoprop-2-enamides gen­erated in situ from 3-(trimethylsilyl)propynamides and ammonium azide underwent cyclization to 5-amino-1,2-oxazoles on heating under solvent-free conditions [27]. Acrylamides are widely used in the synthesis of polymers [28] and copolymers [29], including those widely used in petroleum industry to increase oil recovery [30, 31], and for the preparation of functional polyacrylamide nanoparticles as potential vehicles for targeted drug delivery to macrophages [32].

α,β-Unsaturated amides can be synthesized by acylation of amines with acryloyl chlorides [15, 16], as well as by multicomponent Ugi reaction of isocyanide, amine, aldehyde, and substituted cinnamic or benzoic acid, which produced α-(acylamino)acrylamides [33]. β-Functionalized prop-2-enamides were synthesized by nucleophilic addition of amines [34], sodium selenide [35], or benzeneselenolate [36] to terminal prop-2-ynamides generated in situ from 3-(trimethylsilyl)prop-2-ynamides. Base-catalyzed hydration of 3-(trimethyl­silyl)prop-2-ynamides in the presence of DABCO (10 mol %) afforded symmetrical (E,E)-β,β′-oxybis­acrylamides in good yields [37, 38].

Herein we describe a new synthetic approach to previously unknown difficultly accessible polyfunc­tional 3-chloro-3-(trimethylsilyl)prop-2-enoic acid amides and hydrazides starting from 3-(trimethylsilyl)­propynoic acid.

RESULTS AND DISCUSSION

Examples of geminally substituted (Si, Cl) alkenes containing an electron-withdrawing group are 2-chloro-2-(trialkylsilyl)vinyl ketones [39] and 3-chloro-3-(tri­methylsilyl)prop-2-enal [40] which were synthesized by reaction of the corresponding trimethylsilyl-substi­tuted acetylenic carbonyl compounds with gaseous hy­drogen chloride. We have found that, unlike 3-(tri­methylsilyl)prop-2-ynal and structurally related ketones, 3-(trimethylsilyl)prop-2-ynamides 1a and 1b failed to react with gaseous HCl under similar condi­tions (CHCl3, 25°C, 6 h). On the other hand, terminal propynamides 2a and 2b were thus converted to (E,Z)-3-chloroprop-2-enamides 4a and 4b in 3 h and were isolated in 63–90% yield (Scheme 1).

Scheme
scheme 1

1.

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A probable reason for the inertness of the triple bond of 3-(trimethylsilyl)prop-2-ynamides with respect to electrophiles is its low polarizability in comparison to trimethylsilylpropynal and ketones, which can be rationalized by comparability of the electron-withdraw­ing effects of the trimethylsilyl and amide groups.

We previously showed that 3-chloro-3-(trimethyl­silyl)prop-2-enoyl chloride can be obtained in 20% yield [in a mixture with 3-(trimethylsilyl)prop-2-ynoyl chloride] by the solvent-free reaction of 3-(trimethyl­silyl)prop-2-ynoic acid with thionyl chloride [41]. (E,Z)-3-Chloroalk-2-enoic acids were previously syn­thesized in good yields by reaction of propynoic acid and alkyl(phenyl)propynoic acids with thionyl chloride in DMF at room temperature [42].

We isolated 3-chloroacrylates instead of aryl pro­pynoates while attempting to perform esterification of propynoic acids using thionyl chloride as chlorinating and dehydrating agent, followed by treatment with ethanol in the presence of 4-(dimethylamino)pyridine [43]. Urdaneta et al. [44] synthesized (E,Z)-3-chloro­prop-2-enamides in 70–82% yield by reacting 3-phe­nyl­propynoic and but-2-ynoic acids with oxalyl chloride in DMF at 0°C and subsequent amination in methylene chloride at –50°C. However, we failed to obtain 3-chloro-N-phenyl-3-(trimethylsilyl)prop-2-en­amide (3a) from trimethylsilylpropynoic acid 5 in the system oxalyl chloride–DMF according to the proce­dure described in [44] at –25 or 0°C. The C≡C triple bond of 5 turned out to be inert toward addition of HCl, and the only product was N-phenyl-3-(trimethylsilyl)­prop-2-ynamide (1a) which was isolated in 86 and 81% yield, respectively (Table 1; entry nos. 1, 2). When oxalyl chloride was added to acid 5 at a higher tem­pera­ture, 10 or 25°C, the reaction was accompanied by appreciable decomposition (the mixture turned dark brown). Presumably, the reaction involved oligomeriza­tion and heterolytic dissociation of the Si–Csp2 bond in 3-chloro-3-(trimethylsilyl)prop-2-enoyl chloride (7). According to the 1H NMR data, the yield of target amide 3a at 10°C was very low (5%), whereas the major product was compound 1a (52%); at 25°C, the yield of 3a increased to 25%, and 13% of 3-chloroprop-2-enamide (4a) was also formed (Table 1; run nos. 3, 4; the yields were based on the initial acid 5).

Table 1. Synthesis of 3-chloro-3-(trimethylsilyl)prop-2-enamide (3a) from 3-(trimethylsilyl)prop-2-ynoic acid (5) using the system oxalyl chloride–DMF
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We previously showed that silicon-containing pro­pyn­amide 1a can be obtained with a high yield from acid 5 by a one-pot procedure including chlorination of 5 with oxalyl chloride in the presence of a catalytic amount of DMF and subsequent amination [45] (Table 1, entry no. 5).

Our failure to obtain 3-chloro-3-(trimethylsilyl)­prop-2-enamide (3a) under the above conditions prompted us to examine the possibility of synthesizing target compounds from 3-(trimethylsilyl)propynoic acid in several preparative steps. We synthesized 3-chloro-3-(trimethylsilyl)prop-2-enoic acid (6) in 63% yield according to the procedure described in [42] by hydrochlorination of acid 5 with thionyl chloride in DMF (Scheme 2). 3-Chloro-3-(trimethylsilyl)prop-2-enoyl chloride 7 was obtained by treatment of acid 6 with oxalyl chloride in the presence of DMF (4 mol %) without a solvent (Scheme 3). The yield of 7 was 40% based on the initial acid 5.

Scheme
scheme 2

2.

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Scheme
scheme 3

3.

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Previously unknown (Z/E)-3-chloro-3-(trimethyl­silyl)prop-2-enamides 3a–3e were synthesized in 63–78% yield by adding acid chloride 7 to a solution of 2 equiv of amine 8a–8d in diethyl ether at room tem­perature (Table 2, entry nos. 1–5). The reaction was chemoselective. For example, no substitution of chlorine at the double bond was observed even when compound 7 was treated with 4 equiv of morpholine (8b). Presumably, the reactivity of the β-chlorine atom toward nucleophilic substitution is reduced due to steric effect of the neighboring trimethylsilyl group.

Table 2. Synthesis of 3-chloro-3-(trimethylsilyl)prop-2-enamides 3a–3f and hydrazides 3g–3i
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The reaction of 7 with an equimolar amount of N,O-bis-trimethylsilyl leucine derivative 8f in diethyl ether at 25°C, followed by hydrolysis, gave 2-[(E,Z)-3-chloro-3-(trimethylsilyl)prop-2-enoylamino]-4-methyl­pentanoic acid (3f) in 91% yield (Table. 2, entry no. 6). Bis-silyl derivative 8f was prepared by treatment of leucine (8e) with hexamethyldisilazane in the presence of a catalytic amount of sulfuric acid on heating under reflux (Scheme 4).

Scheme
scheme 4

4.

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We previously demonstrated the efficiency of using silylated amino acids and amino alcohols generated in in situ in the synthesis of N-[3-(trimethylsilyl)prop-2-ynoyl] amino acids [46] and N-(hydroxyalkyl) 3-(tri­methylsilyl)prop-2-ynamides [47]. Acid chloride 7 reacted with N-phenylhydrazinecarbothioamide (8g), N′-phenylacetohydrazide (8h), and benzohydrazide (8i) in THF in the presence of pyridine at room temperature to afford 33–76% of the corresponding (E)-3-chloro-3-(trimethylsilyl)prop-2-enehydrazides 3g–3i (Table 2, entry nos. 7–9).

The structure of compounds 3a–3i was proved by IR and 1H, 13C, and 29Si NMR spectra. Their con­figuration was determined on the basis of the vicinal 1H–29Si spin–spin coupling constant (3JSiH). It is known that the trans coupling constant is higher than cis coupling constant [48]. The 3JSiH values for the E (trans) isomers ranged from 6 to 8 Hz against 3–5 Hz for the Z (cis) isomers. It should also be noted that the olefinic proton of the E isomers resonated at a lower field (δ 6.64–6.89 ppm) than that of the Z isomer (δ 6.34–6.54 ppm, Table 2).

As follows from the data in Table 2, compounds 3b, 3c, 3g, and 3h were isolated as E isomers (entry nos. 2, 3, 7, 8). Compounds 3a, 3f, and 3i were mixtures of the Z and E isomers, the latter prevailing (entry nos. 1, 6, 9). Pure (E)- and (Z)-3-chloro-N-(3-hydroxy-2-methylpropan-2-yl)-3-(trimethylsilyl)prop-2-enamides 3d and 3e were isolated by column chromatography (entry nos. 4, 5).

EXPERIMENTAL

The 1H, 13C, and 29Si NMR spectra were recorded on a Bruker DPX-400 spectrometer at 400.13, 101.62, and 79.49 MHz, respectively. The 1H and 13C chemical shifts were measured relative to the residual proton and carbon signals of the deuterated solvents (CHCl3, δ 7.27 ppm; CDCl3, δC 77.1 ppm; DMSO-d5, δ 2.50 ppm; DMSO-d6, δC 39.6 ppm); the 29Si chemical shifts were measured relative to hexamethyldisiloxane as internal standard (δSi 7.5 ppm). The IR spectra were recorded on a Bruker Vertex-70 spectrometer. The melting points were measured with a PolyTherm A micro hot stage. Silica gel (0.060–0.2 mm, 70– 230 mesh; Alfa Aesar) was used for column chromatog­raphy. Elemental analyses were obtained using a Flash EA 1112 CHNS-O analyzer.

3-(Trimethylsilyl)prop-2-ynoic acid (5) [49] and 3-(trimethylsilyl)prop-2-ynamides 1a and 1b [45] were synthesized according to reported procedures. (E)-3-Chloroacrylamides 4a and 4b were described previously [50, 51], and only their 1H NMR spectra were recorded.

3-Chloro-3-(trimethylsilyl)prop-2-enamides 3a–3e (general procedure). A solution of 3 mmol of 3-chloro-3-(trimethylsilyl)prop-2-enoyl chloride (7) in 5 mL of diethyl ether was added dropwise with stirring at room temperature to a solution of 6 mmol of amine 8a–8d in 20 mL of diethyl ether. The mixture was stirred for 1 h, washed with 5 mL of 5% aqueous HCl, and extracted with diethyl ether, the organic phase was dried over MgSO4 and evaporated under reduced pres­sure, and the product was isolated by recrystallization or column chromatography.

(E,Z)-3-Chloro-N-phenyl-3-(trimethylsilyl)prop-2-enamide (3a) was synthesized from 0.60 g (5.0 mmol) of 7. Yield 0.60 g (78%), white crystalline solid, mp 66–67°C (from hexane). IR spectrum (KBr), ν, cm–1: 3237 br (NH), 1664 m (C=O), 1643 s (C=O), 1596 s (C=Carom), 1583 m (C=Carom), 1542 s (δNH), 1252 s (Si–C), 847 s (Si–C), 757 s (Si–C). 1H NMR spectrum (CDCl3), δ, ppm: 0.31 s (9H, CH3Si, Z), 0.34 s (9H, CH3Si, E), 6.48 s (1H, =CH, 3JSiH = 4.6 Hz, Z), 6.83 s (1H, =CH, 3JSiH = 7.7 Hz, E), 7.06 t (1H, p-H, J = 7.6 Hz, Z), 7.12 t (1H, p-H, J = 7.8 Hz, E), 7.26 t (2H, m-H, J = 7.6 Hz, Z), 7.31 t (2H, m-H, J = 7.8 Hz, E), 7.51 d (2H, o-H, J = 7.6 Hz, Z), 7.56 d (2H, o-H, J = 7.8 Hz, E), 8.06 br.s (1H, NH, E), 8.46 br.s (1H, NH, Z); E/Z = ~5:1. 13C NMR spectrum (CDCl3), δC, ppm: –2.4 (CH3Si, Z), –0.2 (CH3Si, E), 120.2 (Co, E), 120.6 (Co, Z), 124.5 (Cp, E), 125.1 (Cp, Z), 129.0 (Cm, E), 129.2 (Cm, Z), 131.8 (=CH, Z), 136.1 (=CH, E), 137.3 (Ci, Z), 138.0 (Ci, E), 146.6 (SiC=, Z), 157.4 (SiC=, E), 161.9 (C=O, Z), 162.4 (C=O, E). 29Si NMR spectrum (CDCl3), δSi, ppm: 1.9 (E), 3.1 (Z). Found, %: C 56.61; H 6.55; Cl 13.71; N 5.83; Si 11.20. C12H16ClNOSi. Calculated, %: C 56.79; H 6.35; Cl 13.97; N 5.52; Si 11.07.

(E)-3-Chloro-1-(morpholin-4-yl)-3-(trimethyl­silyl)prop-2-en-1-one (3b) was synthesized from 0.60 g (3.0 mmol) of 7. Yield 0.52 g (70%), yellow oil which crystallized after storage for a month, mp 30–32°C. IR spectrum (KBr), ν, cm–1: 1630 s (C=O), 1570 m (C=C), 1240 s (Si–C), 840 s (Si–C), 760 s (Si–C). 1H NMR spectrum (CDCl3), δ, ppm: 0.20 s (9H, CH3Si), 3.45 t and 3.56 t (4H, NCH2, 3JHH = 4.9 Hz), 3.52–3.65 m (4H, OCH2), 6.89 s (1H, =CH, 3JSiH = 8.2 Hz). 13C NMR spectrum (CDCl3), δC, ppm: –1.2 (CH3Si), 41.7, 46.6 (CH2N), 66.5 (CH2O), 134.3 (=CH), 151.2 (SiC=), 164.4 (C=O). 29Si NMR spec­trum (CDCl3): δSi 1.0 ppm. Found, %: C 48.61; H 7.51; Cl 14.49; N 5.94; Si 11.53. C10H18ClNO2Si. Calculat­ed, %: C 48.47; H 7.32; Cl 14.31; N 5.65; Si 11.33.

(E)-3-Chloro-N-(3-hydroxypropyl)-3-(trimethyl­silyl)prop-2-enamide (3c) was synthesized from 1.00 g (5.1 mmol) of 7. Yield 0.90 g (76%), white crys­talline solid, mp 104–105°C (from hexane). IR spec­trum (KBr), ν, cm–1: 3275 br (NH, OH), 1630 s (C=O), 1575 s (C=C), 1540 m (δNH), 1235 s (Si–C), 865 s (Si–C). 1H NMR spectrum (CDCl3), δ, ppm: 0.31 s (9H, CH3Si), 1.66–1.75 m (2H, CH2CH2O), 3.02 br.s (1H, OH), 3.42–3.51 m (2H, CH2N), 3.64 t (2H, CH2O, J = 5.5 Hz), 5.89 br.s (1H, NH), 6.66 s (1H, =CH, 3JSiH = 8.1 Hz). 13C NMR spectrum (CDCl3), δC, ppm: –0.1 (CH3Si), 32.4 (CCH2N), 36.7 (CH2N), 59.4 (CH2O), 134.7 (=CH), 157.7 (SiC=), 165.3 (C=O). 29Si NMR spectrum (CDCl3): δSi 1.9 ppm. Found, %: C 46.09; H 7.89; Cl 14.96; N 5.89; Si 11.67. C9H18ClNO2Si. Calculated, %: C 45.85; H 7.69; Cl 15.04; N 5.94; Si 11.91.

(E)-3-Chloro-N-(3-hydroxy-2-methylpropan-2-yl)-3-(trimethylsilyl)prop-2-enamide (3d) was syn­thesized from 1.17 g (5.9 mmol) of 7; the product was isolated by silica gel column chromatography using diethyl ether as eluent. Yield 0.95 g (63%), white crystalline solid, mp 89–90°C. IR spectrum (KBr), ν, cm–1: 3270 br (NH, OH), 1639 s (C=O), 1585 s (C=C), 1549 s (δNH), 1242 s, 846 s (Si–C), 750 m (Si–C). 1H NMR spectrum (CDCl3), δ, ppm: 0.30 s (9H, CH3Si), 1.31 s (6H, CH3C), 3.60 s (2H, CH2), 4.75 br.s (1H, OH), 5.64 br.s (1H, NH), 6.70 s (1H, =CH, 3JSiH = 7.8 Hz). 13C NMR spectrum (CDCl3), δC, ppm: –0.4 (CH3Si), 24.8 (CH3C), 56.6 (CH3S), 70.7 (CH2), 135.6 (=CH), 156.8 (SiC=), 165.3 (C=O). 29Si NMR spec­trum (CDCl3): δSi 1.6 ppm. Found, %: C 48.26; H 8.06; Cl 13.91; N 5.89; Si 11.36. C10H20ClNO2Si. Calculat­ed, %: C 48.08; H 8.07; Cl 14.19; N 5.61; Si 11.24.

(Z)-3-Chloro-N-(3-hydroxy-2-methylpropan-2-yl)-3-(trimethylsilyl)prop-2-enamide (3e) was syn­thesized from 1.17 g (5.9 mmol) of 7; the product was isolated by silica gel column chromatography using diethyl ether as eluent. Yield 22 mg (2%), white crys­talline solid, mp 98–99°C. IR spectrum (KBr), ν, cm–1: 3270 br (NH, OH), 1630 s (C=O), 1590 s (C=C), 1530 m (δNH), 1230 s (Si–C), 830 s (Si–C), 750 m (Si–C). 1H NMR spectrum (CDCl3), δ, ppm: 0.24 s (9H, CH3Si), 1.37 s (6H, CH3C), 3.65 s (2H, CH2), 4.46 br.s (1H, OH), 6.34 s (1H, =CH), 6.54 br.s (1H, NH). 13C NMR spectrum (CDCl3), δC, ppm: –2.8 (CH3Si), 25.0 (CH3C), 57.2 (CH3C), 70.7 (CH2), 132.2 (=CH), 145.7 (SiC=), 164.7 (C=O). 29Si NMR spec­trum (CDCl3): δSi 2.7 ppm. Found, %: C 47.92; H 8.06; Cl 14.40; N 5.79; Si 11.36. C10H20ClNO2Si. Calculat­ed, %: C 48.08; H 8.07; Cl 14.19; N 5.61; Si 11.24.

2-{[(E,Z)-3-Chloro-3-(trimethylsilyl)prop-2-enoyl]amino}-4-methylpentanoic acid (3f). A mixture of 0.73 g (5.6 mmol) of dl-leucine 8e, 2.30 g (14.0 mmol) of hexamethyldisilazane, and a catalytic amount of concentrated sulfuric acid was refluxed for 30 min. Excess hexamethyldisilazane was removed under reduced pressure, the residue was dissolved in 30 mL of anhydrous diethyl ether, and a solution of 1.10 g (5.6 mmol) of acid chloride 7 in 10 mL of diethyl ether was added dropwise with stirring. The mixture was stirred at room temperature for 1 h, washed with 10 mL of 5% aqueous HCl, and extracted with diethyl ether, the organic phase was dried over MgSO4, the solvent was removed, and the residue was purified by recrystallization. Yield 1.47 g (91%), white crystalline solid, mp 113–114°C (from heptane). IR spec­trum (KBr), ν, cm–1: 3400–2500 br (NH, OH), 1720 s (C=O, acid), 1640 s (C=O, amide), 1580 s (C=C), 1530 (δNH), 1260 s (Si–C), 850 s (Si–C), 760 m (Si–C). 1H NMR spectrum (DMSO-d6), δ, ppm: 0.23 s (9H, CH3Si), 0.89–0.94 m (6H, CH3), 1.52– 1.55 m (2H, CH2), 1.60–1.74 m [1H, CH(CH3)2], 4.25–4.31 m (1H, CHCO), 6.54 s (1H, =CH, 3JSiH = 4.2 Hz, Z), 6.89 s (1H, =CH, 3JSiH = 7.9 Hz, E), 8.10 d (1H, NH, J = 7.9 Hz, Z), 8.28 d (1H, NH, J = 8.2 Hz, E), 12.38 br.s (1H, COOH), E/Z = ~5:1. 13C NMR spectrum (DMSO-d6), δC, ppm: –2.3 (CH3Si, Z), 0.0 (CH3Si, E), 21.57 (CH3C, E), 21.61 (CH3C, Z), 23.2 (CH3C), 24.7 (CHCH2, Z), 24.8 (CHCH2, E), 50.5 (CHCO, Z), 50.6 (CHCO, E), 131.1 (=CH, Z), 136.9 (=CH, E) 146.0 (SiC=, Z), 153.7, (SiC=, E), 163.0 (NC=O, Z), 163.9 (NC=O, E), 174.1 (OC=O, E), 174.3 (OC=O, Z). 29Si NMR spectrum (DMSO-d6), δSi, ppm: 1.3 (Z), 2.3 (E). Found, %: C 49.63; H 7.89; Cl 12.35; N 4.99; Si 9.47. C12H22ClNO3Si. Calculated, %: C 49.39; H 7.60; Cl 12.15; N 4.80; Si 9.62.

3-Chloro-3-(trimethylsilyl)prop-2-enehydrazides 3g–3i (general procedure). A solution of 3.0 mmol of 7 in anhydrous diethyl ether (20 mL) was added dropwise with stirring at room temperature to a mixture of 3.0 mmol of hydrazine 8g–8i and 3.0 mmol of pyridine in 15 mL of THF. The mixture was stirred for 8 h, washed with 10 mL of water, and extracted with diethyl ether (3g, 3h) or chloroform (3i). The extract was dried over MgSO4, the solvent was removed under reduced pressure, and the residue was subjected to further purification.

2-[(E)-3-Chloro-3-(trimethylsilyl)prop-2-enoyl]-N-phenylhydrazine-1-carbothioamide (3g) was synthesized from 0.60 g (3.0 mmol) of 7; the product was isolated by silica gel column chromatography using chloroform–diethyl ether (1:1) as eluent. Yield 0.73 g (73%), white crystalline solid, mp 134–135°C. IR spectrum (KBr), ν, cm–1: 3450 br (NH), 1660 s (C=O), 1590 s (C=C), 1525 m (δNH), 1240 s (Si–C), 835 s (Si–C). 1H NMR spectrum (DMSO-d6), δ, ppm: 0.24 s (9H, CH3Si), 6.64 s (1H, =CH, 3JSiH = 6.6 Hz), 7.16 t (1H, p-H, J = 7.2 Hz), 7.33 t (2H, m-H, J = 7.2 Hz), 7.45 d (2H, o-H, J = 7.2 Hz), 9.67 br.s and 9.70 br.s (2H, NH–NH), 10.16 br.s (1H, NHPh). 13C NMR spectrum (DMSO-d6), δC, ppm: –2.7 (SiMe3), 125.0 (Cp), 125.2–126.2 (Co), 128.0 (Cm), 129.3 (Ci), 139.1 (=CH), 147.4 (SiC=), 162.0 (C=O), 180.8 (C=S). 29Si NMR spectrum (DMSO-d6): δSi 1.3 ppm. Found, %: C 47.90; H 5.69; Cl 11.10; N 13.14; S 10.04; Si 8.28. C13H18ClN3OSSi. Calcu­lated, %: C 47.62; H 5.53; Cl 10.81; N 12.81; S 9.78; Si 8.57.

(E)-N′-Acetyl-3-chloro-N-phenyl-3-(trimethyl­sylyl)­prop-2-enehydrazide (3h) was synthesized from 50 mg (0.25 mmol) of 7; the product was isolated by silica gel column chromatography using chloroform–diethyl ether (1:1) as eluent. Yield 21 mg (33%), white crystalline solid, mp 101–102°C. IR spectrum (KBr), ν, cm–1: 3430 br (NH), 1660 br (C=O), 1590 s (C=C), 1525 m (δNH), 1240 m (Si–C), 840 s (Si–C). 1H NMR spectrum (DMSO-d6), δ, ppm: 0.24 s (9H, CH3Si), 1.95 s (3H, CH3), 6.65 s (1H, =CH), 7.41 br.m (5H, Ph), 10.86 br.s (1H, NH). Found, %: C 54.30; H 6.43; Cl 11.25; N 9.19; Si 8.79. C14H19ClN2O2Si. Calculat­ed, %: C 54.09; H 6.16; Cl 11.41; N 9.01; Si 9.04.

(E,Z)-N′-Benzoyl-3-chloro-3-(trimethylsilyl)­prop-2-enehydrazide (3i) was synthesized from 0.46 g (2.34 mmol) of 7. Yield 0.52 g (76%), white crystalline solid, mp 211–212°C (from Et2O). IR spec­trum (KBr), ν, cm–1: 3225 (NH), 1678 m (PhC=O), 1637 s (NC=O), 1604 w (C=C), 1528 m (δNH), 1252 m (Si–C), 843 s (Si–C), 710 m (Si–C). 1H NMR spectrum (DMSO-d6), δ, ppm: 0.11 s (9H, CH3Si, Z), 0.27 s (9H, CH3Si, E), 6.44 s (1H, =CH, Z), 6.64 s (1H, =CH, 3JSiH = 6.6 Hz, E), 7.46 t (2H, m-H, J = 7.3 Hz, E), 7.54 t (1H, p-H, J = 7.3 Hz, E), 7.82 d (2H, o-H, J = 8.5 Hz, Z), 7.92 d (2H, o-H, J = 7.3 Hz, E), 10.06 d (1H, HNCOPh, J = 1.9 Hz), 10.41 d (1H, HNCOC=, J = 1.9 Hz). E/Z = ~20:1. 13C NMR spectrum (DMSO-d6), δ, ppm: –2.7 (CH3Si), 127.5, 128.0 (Co, Cm), 128.7 (Cp), 131.3 (=CH), 132.4 (Ci), 147.5 (SiC=), 161.2 (PhC=O), 164.9 (NC=O). 29Si NMR spectrum (DMSO-d6), δ, ppm: 1.5. Found, %: C 52.87; H 5.51; Cl 12.03; N 9.43; Si 9.38. C13H17ClN2O2Si. Calculat­ed, %: C 52.60; H 5.77; Cl 11.94; N 9.44; Si 9.46.

General procedure for hydrochlorination of prop-2-ynamides. Gaseous hydrogen chloride was passed through a solution of 1 mmol of prop-2-yn­amide 2a or 2b in 15 mL of chloroform at room tem­perature over a period of 3 h. The solvent was removed, and the residue was purified by recrystallization from benzene (4a) or column chromatography on silica gel (4b; CHCl3–MeOH, 10:1).

(Z,E)-3-Chloro-N-phenylprop-2-enamide (4a) was synthesized from 0.15 g (1 mmol) of N-phenyl­prop-2-ynamide (2a). Yield 0.17 g (90%), yellowish powder, mp 120–121°C (from benzene); published data [42]: mp 152–153°C, E isomer. IR spectrum (KBr), ν, cm–1: 3298 br (NH), 1657 s (C=O), 1597 m (C=Carom), 1546 m (δNH). 1H NMR spectrum (CDCl3), δ, ppm: 6.32 d (1H, =CHCO, J = 8.4 Hz, Z), 6.34 d (1H, =CHCO, J = 12.9 Hz, E), 6.61 d (1H, ClCH=, J = 8.4 Hz, Z), 7.06–7.18 m (1H, p-H), 7.24–7.36 m (2H, m-H), 7.39 d (1H, ClCH=, J = 12.9 Hz, E), 7.42 br.s (1H, NH, E), 7.53 d (2H, o-H, J = 6.0 Hz, E), 7.57 d (2H, o-H, J = 8.0 Hz, Z), 8.00 br.s (1H, NH, Z), E/Z = ~1:1; published data [50]: 1H NMR spectrum (CDCl3), δ, ppm: 6.45 d (1H, =CHSO, J = 14 Hz, E), 7.52 d (1H, ClCH=, J = 14.0 Hz, E), 7.52 m (5H, Ph). 13C NMR spectrum (CDCl3), δC, ppm: 120.4 (Co), 124.9 (Cp, Z), 125.1 (Cp, E), 125.9, 126.2 (=CCO), 127.4 (ClC=, Z), 129.1 (Cm, E), 129.2 (Cm, Z), 135.2 (ClC=, E), 137.2, 137.5 (Ci, E), 161.4 (C=O). Found, %: C 59.81; H 4.42, Cl 19.29; N 7.60. C9H8ClNO. Calculated, %: C 59.52; H 4.44; Cl 19.52; N 7.71.

(Z,E)-3-Chloro-1-(morpholin-4-yl)prop-2-en-1-one (4b) was synthesized from 0.30 g (1.4 mmol) of 1-(morpholin-4-yl)prop-2-yn-1-one (2b). Yield 0.24 g (63%), orange oil. IR spectrum (film), ν, cm–1: 1630 s (C=O), 1580 m (C=C). 1H NMR spectrum (CDCl3), δ, ppm: 3.37–3.50 m (2H, NCH2), 3.51–3.78 m (6H, NCH2, OCH2), 6.22 d (1H, =CHCO, J = 8.1 Hz, Z), 6.33 d (1H, ClCH=, J = 8.1 Hz, Z), 6.59 d (1H, =CHCO, J = 12.8 Hz, E), 7.19 d (1H, ClCH=, J = 12.8 Hz, E); E/Z = ~1:1; published data [51]: 1H NMR spectrum (CDCl3), δ, ppm: 3.66 br.s (8H, NCH2CH2O), 6.65 d (1H, =CHCO, J = 12.9 Hz, E), 7.31 d (1H, ClCH=, J = 12.9 Hz, E). 13C NMR spectrum (CDCl3), δC, ppm: 42.4, 42.9, 46.8, 47.3 (CH2N), 67.3, 67.6 (CH2O), 123.9, 124.5, 125.3 (=CCO, ClC=), 136.2 (ClC=, E), 163.4, 164.2 (C=O). Found, %: C 47.71; H 5.99; Cl 20.42; N 8.19. C7H10ClNO2. Calculated, %: C 47.88; H 5.74; Cl 20.19; N 7.98.

Reaction of 3-(trimethylsilyl)prop-2-ynoic acid (5) with oxalyl chloride in DMF, followed by amina­tion. Oxalyl chloride, 0.28 g (2.20 mmol), was added dropwise with stirring over a period of 1 h at room temperature to a solution of 0.15 g (1.05 mmol) of acid 5 in anhydrous DMF (1.0 mL). The mixture turned dark brown due to strong tarring, excess oxalyl chloride was removed under reduced pressure, and the black viscous residue was extracted with diethyl ether (4×5.0 mL). The combined extracts were added drop­wise to a solution of 0.20 g (2.10 mmol) of aniline (8a) in 10 mL of diethyl ether. The mixture was stirred for 1 h and washed with 10 mL of 5% aqueous HCl, the aqueous phase was extracted with diethyl ether, the extract was dried over MgSO4, and the solvent was removed under reduced pressure to obtain 0.78 g of a mixture containing compounds 3a and 4a. The 1H NMR spectrum of the reaction mixture showed two singlets at δ 6.48 (3JSiH = 4.6 Hz) and 6.84 ppm (3JSiH = 7.7 Hz) due to vinylic protons of the Z and E isomers of 3a and two doublets at δ 6.35 (J = 12.9 Hz) and 7.39 ppm (J = 12.9 Hz) due to vinylic protons of E-4a. According to the 1H NMR data, the ratio 3a:4a is 67:33, which corresponds to 25 and 13% yields of 3a and 4a, respectively, based on the initial acid 5.

(E,Z)-3-Chloro-3-(trimethylsilyl)prop-2-enoyl chloride (7). Thionyl chloride, 1.35 g (11.39 mmol), was added dropwise with stirring at 15–17°C over a period of 2 h to a solution of 1.34 g (9.42 mmol) of acid 5 in anhydrous DMF (8.5 mL). Excess thionyl chloride was removed under reduced pressure, and the residue was poured onto ice. The aqueous phase was separated and extracted with diethyl ether, the extract was dried over Na2SO4, and the solvent was removed under reduced pressure to obtain 3-chloro-3-(trimethyl­silyl)prop-2-enoic acid (6) as an amorphous substance. Yield 1.06 g (63%). IR spectrum (KBr), ν, cm–1: 2500–3400 br (OH), 1670 s (C=O), 1600 s (C=O), 1220 m (Si–C), 840 s (Si–C). 1H NMR spectrum (CDCl3), δ, ppm: 0.28 s (9H, CH3Si, Z), 0.32 s (9H, CH3Si, E), 6.39 s (1H, =CH, Z), 6.75 s (1H, =CH, E), 10.76 br.s (1H, COOH); E/Z = ~1.5:1. 13C NMR spectrum (CDCl3), δC, ppm: –2.3 (CH3Si), 126.3 (=CH), 157.5 (SiC=), 168.4 (C=O). A mixture of 1.06 g (5.9 mmol) of acid 6, 0.86 g (6.8 mmol) of oxalyl chloride, and a catalytic amount of DMF (4 mol %) was stirred for 1 h. Compound 7 was isolated by fractional distilla­tion. Yield 0.74 g (40%, based on 5), bp 84–85°C (17 mm Hg). IR spectrum (film), ν, cm–1: 1778 s (C=O), 1744 m (C=O), 1660 m (C=C), 1640 s (C=C), 1253 s (Si–C), 845 s (Si–C). 1H NMR spectrum (CDCl3), δ, ppm: 0.29 s (9H, CH3Si, Z), 0.31 s (9H, CH3Si, E), 6.65 s (1H, =CH, Z), 7.00 s (1H, =CH, E), E/Z = ~4:1. 13C NMR spectrum (CDCl3), δC, ppm: –2.6, –1.4 (CH3Si), 131.1, 138.0 (=CH), 159.3, 160.0 (SiC=), 163.8, 168.0 (C=O). 29Si NMR spectrum (CDCl3), δSi, ppm: 4.6, 3.4. Found, %: C 36.40; H 5.23; Cl 35.70; Si 14.03. C6H10Cl2OSi. Calculated, %: C 36.56; H 5.11; Cl 35.97; Si 14.25.

CONCLUSIONS

Previously unknown difficultly accessible polyfunc­tional β-chloro-β-(trimethylsilyl)propenoic acid amides and hydrazides were synthesized from 3-(trimethyl­silyl)propynoic acid using available reagents, mainly at room temperature, without purification of intermediate 3-chloro-3-(trimethylsilyl)prop-2-enoic acid. The ob­tained amides and hydrazides attract interest as poly­functional reagents containing four interrelated reac­tion centers, ligands, potential biologically active com­pounds, and substrates for the design of new bioactive molecules.