Triton-B Mediated One-Pot Multicomponent Synthesis of 3 , 5 Substituted Tetrahydro-2 H-1 , 3 , 5-Thidiazine-2-Thiones

A new-fangled, proficient, one-pot multi component, intramolecular C-S bond formation reaction, mediated by phase transfer catalyst, Triton-B, is described in this paper. The reaction of alkyl/phenyl amines, CS2 and formaldehyde catalyzed via Triton-B resulted in formation of 3-(Alkyl or aryl methyl), 5-(Alkyl or aryl methyl) substituted tetrahydro-2H-1,3,5-thiadiazine-2-thiones compounds(1a-15a). These compounds (1a-15a) were characterized with the help of elemental analysis, IR, NMR and mass spectroscopic methods. The PTC mediated reactions require mild reaction condition and reduced time period for completion. The reaction is achieved at normal temperature under solvent free conditions with good yields and great selectivity. This methodology discourages the traditional synthesis method of inorganic base for such coupling reaction.


INTROdUCTION
3,5 substituted tetrahydro-2H-1,3,5thiadiazine-2-thiones (THTT), an important scaffold have found utility as chemicals for crop protection 1 , against soil nematodes 2 , antitumor drugs 3 , precursors in organic synthesis 4 and as antimicrobial agent. 57][8][9] Also they are potential pharmaceutical drugs against microbial infection 10 , protozoa 11 , leprosy 12 , tubercular 13 , fungal, 14 Leishmaniasis 15 , Alzheimer's disease. 16wing to ample of application, there is growth of well-planned methods for preparing 3-(Alkyl or aryl methyl), 5-(Alkyl or aryl methyl) substituted tetrahydro-2H-1,3,5-thiadiazine-2-thiones.New strategies for the synthesis of 3-(Alkyl or aryl methyl), 5-(Alkyl or aryl methyl) substituted tetrahydro-2H-1,3,5-thiadiazine-2-thiones by using Triton-B, a phase transfer catalyst (PTC) delightfully supplement the conventional approach of cyclization by multicomponent reaction, [17][18] based on inorganic base reactions.The inorganic base such as NaOH, KOH, Na 2 CO 3 , H 2 O/EtOH, uniform H 2 O catalyzed intra-molecular cyclization of amines, CS 2 and formaldehyde that were produce in situ or resynthesized are the traditional recur methods 19- 20 (Previous work) "Scheme 1".On the one hand, current effort is PTC-mediated prolific methodology to prepare THTT (Current work) "Scheme 1".The adeptness of this method is (i) excess amounts of toxic reagents are avoided in this scheme that adversely affects the health.(ii) cost of PTC is low (iii) high yield (iv) reduced reaction time.(v) Triton-B is recovered from the reaction mixture by filtration 21 .These factors discourage the use of inorganic base for such coupling reactions.This simple procedure with mild reaction conditions are safer and more sustainable practices for effective coupling reaction mediated by Trimethylbenzyl ammonium hydroxide (Triton-B) without using any inorganic base 22 , "Scheme 1"

Previous Work
Current Work

MATERIALS ANd METHOdS
All the chemicals were of AR grade.Reactions were done under an envelope of Ar gas.Bomem MB-104-FTIR spectrophotometer was used for recording Infra Red Spectra in the range 4000-200 cm -1 .The AC-400F-NMR spectrometer, with Me4Si as internal standard was used for recording 1 HNMR spectra at 400 MHz.The investigation of elements were conveyed with the help of a Carlo-Erba EA 1110-CNNO-S analyzer.There is good covenant between observed and calculated values.

General Method for the synthesis of compounds (1a-15a) using Triton-B:
At room temperature 1.0 mmol of primary amine (1) and 10.0 mmol CS 2 (2) and 2.5 mmol formaldehyde (3) was stirred for 0.25 hours.Then to this solution, 1.5 mmol Triton-B was added and stirred for 0.25 hours.Afterward 1.0 mmol amine (4) was added at room temperature for 2 h, the stirring of reaction mixture was continued.The advancement of reaction was observed through Thin Layer Chromatography.After accomplishment of reaction, 50 mL water was added and thrice treated with CH 3 COOC 2 H 5 (20 mL each).The crude raw product was obtained by concentrating ether layer under low pressure which was further refined by silica gel (100-200 mesh) column chromatography by using eluent 50% (EtOAc : Hexane) to afford pure product.

RESULTS ANd dISCUSSION
In the present work, series of substituted THTT (1a-15a) are synthesized by Triton B mediated one-pot multicomponent reaction, a novel protocol (Scheme 2).Earlier THTT was produced from amines, CS 2 , formaldehyde using inorganic base [23][24][25] .A number of PTC is frequently used for the synthesis of THTT 26 .On comparing the reaction condition it was comprehended that by using Triton-B, % yields of preferred product is improved than other types of PTC.17 Triton-B give 95% yield of THTT A range of 1o amines (aliphatic, alicyclic, heterocyclic, aromatic) and formaldehyde using Triton-B/CS 2 method at r.t led to formation of product THTT in excellent yields, "Table 1".It has been observed that electron donating group in R 1 NH 2 or R 2 NH 2 gives corresponding products in good amount.These compounds were characterized by spectroscopic techniques (Fig 1-3).Proposed reaction and Mechanisms shown in "Scheme-2".

CONCLUSION
We have developed highly efficient solventfree one-pot multicomponent coupling of various amines with formaldehyde via CS 2 / Benzyl tri-methyl ammonium hydroxide system.This procedure gives corresponding products in good and excellent yield.Also, this procedure has mild reaction conditions, requires shorten time period and has environmental acceptability.This synthetic route thereby offers a more convenient approach for formation of C-S bonds.