Enaminones as building blocks in organic syntheses: on the reaction of 3-dimethylamino-2-propenones with malononitrile

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Introduction
Enaminones are versatile building blocks in organic synthesis and their chemistry has received considerable interest. 12][13][14][15] Sometime ago we reported that enaminones 1 react with malononitrile in refluxing ethanolic sodium ethoxide solution to yield alkoxypyridines 2. 16 However, it was subsequently noted that in ethanolic piperidine solution compound 3 was produced. 17Recently Kappe et al. 18 reported a 1,4-addition of malononitrile to enaminones using microwave heating.This led us to reconsider the structure assigned for 3, as if it were correct it would be the only example of 1,2addition of an active methylene to an enaminone.Recently we 19 concluded that 3 actually has structure 4 based on spectral data (cf.Scheme 1).It seemed to us of value to further confirm this conclusion and to explore the chemistry of this newly formed diene.In addition, examining the behavior of other active methylenes towards 1b under similar conditions seemed of value.

Results and Discussion
Both 1a,b were reacted with malononitrile in ethanolic piperidine to yield products whose analytical and spectral data agree well with both the old structures 3a,b and revised ones 4a,b.Firstly we obtained an X-ray crystal structure for the product of reacting 1a with malononitrile in ethanolic piperidine.We assume that malononitrile initially undergoes 1,4 addition to the double bond in 1a,b yielding the adduct A that cyclizes into aminopyran B before undergoing a rearrangement to 4a,b via a 1,3-nitrogen shift.The X-ray data 20 established the structure of 2cyano-5-(dimethylamino)-5-(furan-2-yl)-penta-2,4-dienamide 4b, clearly confirming previous recent conclusion. 19It also shows that the molecule adapts the (E,E) form indicated (cf. Figure 1 and Table 1).Compound 4a could be converted into pyridone 5 upon treatment with acetic anhydride in the presence of hydrochloric acid whereas in AcOH/HCl compound 6 was produced.It is logical to assume the hydrolysis of the initially formed 5 under this condition.Unexpectedly, reacting 4a with malononitrile in ethanolic piperidine resulted in the formation of the dienodinitrile 7 in an excellent yield (95 %).We assume that malononitrile initially added to 4a forming the Michael adduct 8 that then looses cyanoacetamide to yield 2-(3-(dimethylamino)-3-phenylallylidene)malononitrile 7. Structure 7 was confirmed by an X-ray crystal structure 16 determination (cf. Figure 2).The data clearly indicate that, the molecule adapts an E configuration.In Table 2 selected bond lengths and bond angles are reported.In the light of the established behavior of 1 toward malononitrile we inspected its behavior toward other active methylene reagents.Reaction of 1a with cyanoacetic acid in Ac 2 O afforded the pyranone 10 while reaction with ethyl cyanoacetate in ethanolic piperidine gave a product that could be assigned structure 11 or its isomer 12, based on the analytical and the spectral data. 1 H NMR data indicated the presence of two doublet protons at δ = 5.81 and δ = 7.71 ppm with J = 12 Hz, typical for adjacent cis protons.Thus structure 12 is preferred over 11.It is assumed that the initially formed Michael adduct 13 cyclized to 14 and that the latter then undergoes a 1,2-dimethylamino group shift accompanying the elimination of the cyano group to yield the final isolable 12.The latter was readily converted into compound 9 when reacted with hydrazine hydrate.Coupling 3-(dimethylamino)-6-phenyl-2H-pyran-2-one 12 with benzenediazonium chloride afforded the known phenylhydrazone 17.It is believed that initially 15 is formed then undergoes ring opening to 16 and then is hydrolyzed under coupling reaction conditions to yield phenylhydrazone 17 (cf.Scheme 3).At the moment we are looking into the behavior of 1b with a variety of other enaminones.

Experimental Section
General Procedures.All melting points are uncorrected and were determined on a Sanyo (Gallaenkamp) instrument.Infrared spectra were recorded in KBr on a Perkin-Elmer 2000 FT-IR system. 1 H-NMR and 13 C-NMR spectra were determined on a Bruker DPX spectrometer operating at 400 MHz for 1 H-NMR and 100 MHz for 13 C-NMR using in CDCl  (15), 115 (10), 77 (10).

Synthesis of 3-oxo-3-phenyl-2-(2-phenylhydrazono)-propanal (17).
A solution of compound 12 (2.15g, 0.01 mol) in ethanol (50 mL) was treated with sodium acetate (5 g).Aniline diazonium chloride (prepared according to the standard literature procedures from aniline (0.93 g, 0.01 mol), which was added gradually with stirring to a cooled mixture of concentrated hydrochloric acid, and sodium nitrite).After complete addition of the diazonium salt, the reaction mixture was kept at room temperature for one hour.The solid, so formed, was collected by filtration and crystallized from benzene to give orange dark crystals; yield 90%; mp 96-97 ºC (literature mp 96 ºC).

Table 1 .
Selected bond lengths and bond angles for compound 4b
3or DMSO-d6 as solvents and TMS as internal standard; chemical shifts are reported in δ (ppm).Mass spectra were measured on VG Autospec Q MS 30 and MS 9 (AEI) spectrometers, with EI 70 EV.Elemental analyses were measured by means of LEOCHNS-932 Elemental Analyzer.General purpose silica gel on polyester 20 x 20 cm TLC plates with UV indicator were used in TLC experiments.