New Schiff bases from 2,5-bis-(butylsulfanyl)-2,3-dihydro-4 H -pyran-2- carbaldehyde

Novel densely functionalized Schiff bases have been synthesized by the reaction of 2,5-bis-(butylsulfanyl)-2,3-dihydro-4 H -pyran-2-carbaldehyde with primary amines and amino acids. Structure of the obtained compounds is confirmed using the data of elemental analysis, IR and NMR techniques, and chromatomass-spectrometry


Results and Discussion
It is found (Scheme 1) that pyran 1 reacts with an equimolar amount of butylamine 2a in THF at 24 °C for 1 h (Table 1, entry 1) to afford azomethine 3a in almost quantitative yield ( 1 H NMR), the conversion of aldehyde 1 being complete.Condensation of aldehydes with primary amines is an easily reversible reaction.The reaction mixture contains enough moisture to allow hydrolysis of compound 3. To prevent this process, drying agents (molecular sieves 4A, MgSO4) are employed.Benzylamine (2b) reacts similarly under these conditions (Table 1, entry 2).Filtration of the reaction mixture and evaporation of the solvent in vacuo leads to imines that do not require additional purification.
Schiff bases 3a and 3b were obtained as single E isomer.The NOESY spectra show cross peaks of the CHN group proton with the CH2 protons in the substituent at nitrogen.In the 1 H NMR spectra, there is one signal belonging to the CH = N proton.Scheme 1. Reaction of 2,5-bis-(butylsulfanyl)-2,3-dihydro-4H-pyran-2-carbaldehyde with primary amines.Aniline 2c and 2-aminopyridine 2d do not interact with pyran 1 under comparable conditions (24 ° C, 2 h) owing to significant decrease of their nitrogen atoms basicity (Table 1, entry 3, 5).A longer reaction time and other solvent also does not give the desired result (Table 1, entry 6, 7).Even upon refluxing in MeOH, the starting substrate 2d does not react (Table 1, entry 8).In the case of aniline 2c, changing the solvent made it possible to obtain the desired product in 85% yield (Table 1, entry 4).The imine derivatives of L-arginine have been obtained according to the method published previously. 39he reaction with arginine 2e occurs upon boiling in methanol for 1 h to deliver the iminium derivative 3e in 91% yield (Scheme 2).Scheme 2. The reaction of 2,5-bis-(butylsulfanyl)-2,3-dihydro-4H-pyran-2-carbaldehyde (1) with amino acids and their esters 2e-g.
The 1 H NMR spectrum of Schiff bases 3e,f shows a mixture of diastereomers (relative to chiral centers in the parent aldehyde and amino acid (L-arginine and phenylalanine)), existing in the form of an E-configuration (according to NOESY), as indicated by the value of the spin-spin coupling constant ( 1 JCH = 166-167 Hz,) of the carbon fragment HC=N. 41

Conclusions
In conclusion, we have reported the facile and valuable synthesis of functionalized imine derivatives of original 2,5-bis-(butylsulfanyl)-2,3-dihydro-4H-pyran-2-carbaldehyde with primary amines and amino acids.Using this protocol, we were able to assemble a range of functionalized Schiff bases that represent a promising and interesting application in construction of metallocomplexes.

Experimental Section
General.The 1 Н, 13 С and 15 N NMR spectra were recorded in CDCl3 solutions at room temperature on Bruker DPX-400 and AV-400 spectrometers (400.13,100.61 and 40.56 MHz, respectively). 1 Н, 13 С and 15 N Chemical shifts (δ in ppm) were measured with accuracy of 0.01, 0.02 and 0.1 ppm, respectively, and referred to TMS ( 1 Н, 13 С) and nitromethane ( 15 N).Chromato-mass spectrometry analysis was performed on a Shimadzu GCMS-QP5050A mass spectrometer (EI ionization, 70 eV).The IR spectra of the compounds were recorded on a Varian 3100 FT-IR spectrometer with the sample in thin film.Elemental analysis was performed on a Thermo Finnigan Flash series 1112 Elemental analyzer.