Munetaka Kunishima

4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride: an efficient condensing agent leading to the formation of amides and esters

Abstract 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was quantitatively synthesized by the coupling of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) in THF, and characterized. Condensation of carboxylic acids and amines by DMTMM proceeded effectively in THF to give the corresponding amides in good yields. The corresponding esters can be obtained by esterification of caiboxylic acids with DMTMM in methanol, ethanol, isopropy1 alcohol, or t-butyl alcohol in the presence of NMM. The amount of alcohols can be reduced to a stoichiometric amount by conducting the reaction in THF. Since the reactions proceed under atmospheric conditions without drying of the solvent, and the co-product (4,6-dimethoxy-1, 3,5-triazin-2(1H)-one) arising from DMTMM after condensation can be readily removed by extraction, this method is a very practical one.

Formation of carboxamides by direct condensation of carboxylic acids and amines in alcohols using a new alcohol- and water-soluble condensing agent: DMT-MM

Abstract Selective formation of carboxamides in an alcohol or water by an exceptionally convenient one-step procedure in which a condensing agent is simply added to a mixture of acids and amines has been achieved successfully by using a new condensing agent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). Activation of carboxylic acids by DMT-MM in the presence of amines and subsequent aminolysis of the resulting acyloxytriazine in alcoholic solvents occurred selectively and led to the formation of carboxamides in excellent yields. The rate of aminolysis of the acyloxytriazine intermediate can be estimated to be about 2×10 4 times greater than that of methanolysis. The amide/ester selectivity observed using DMT-MM was much larger than that obtained with DCC or EDC. Condensation of polar substrates, such as amino acid esters and their hydrochlorides, glucosamine hydrochloride, sodium acetate and dicarboxylic acids, proceeded successfully in MeOH, water or aqueous MeOH in good yields. The present reaction is technically quite simple and easy to achieve. It proceeds by simple mixing of acids, amines and DMT-MM without any additives, and the MeOH is readily removable by a rotary evaporator after completion of the reaction.

Synthesis and characterization of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride

Abstract 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was quantitatively synthesized by the coupling of 2-chloro-4,6-dimethoxy-1,3,5-triazine and N-methylmorpholine in THF, and fully characterized. Condensation of car☐ylic acids and amines by DMTMM proceeded effectively in THF to give the corresponding amides in good yield.

GENERATION OF BETA -(PHENYLSULFONYL)ALKYLIDIENECARBENES FROM HYPERVALENT ALKENYL- AND ALKYNYLIODONIUM TETRAFLUOROBORATES AND SYNTHESIS OF 1-(PHENYLSUL FONYL)CYCLOPENTENES

Michael-type addition of benzenesulfinic acid to alkynyl(phenyl) iodonium tetrafluoroborates in methanol gives stereoselectively (Z)-(β-(phenylsulfonyl) alkenyl) iodonium tetrafluoroborates in high yields. [β-(Phenylsulfonyl) alkylidene] carbenes derived from the (Z)-(β-(phenylsulfonyl) alkenyl) iodonium tetrafluoroborates by base treatment predominantly undergo intramolecular 1,5-carbon-hydrogen insertions to give 1-(phenylsulfonyl) cyclopentenes along with a small amount of rearranged alkynes, which is in a marked contrast with the facile 1,2-migration of β-(phenylsulfenyl) and β-(phenylsulfinyl) groups of alkylidenecarbones. Reaction of alkynyl(phenyl) iodonium tetrafluoroborates with benzenesulfinates directly affords 1-(phenylsulfonyl) cyclopentenes via tandem Michael-carbene insertion reactions. The mechanism of 1,2-migration of [β-(phenylsulfonyl) alkylidene] carbenes is also discussed

A Novel Acid-Catalyzed O-Benzylating Reagent with the Smallest Unit of Imidate Structure

Formal trimerization of the smallest unit of benzyl imidate leads to 2,4,6-tris(benzyloxy)-1,3,5-triazine (TriBOT), which can be used as an acid-catalyzed O-benzylating reagent. The reaction of various functionalized alcohols with 0.4 equiv of TriBOT in the presence of trifluoromethanesulfonic acid afforded the benzyl ethers in good yields. TriBOT is an inexpensive stable crystalline solid with high atom economy.

Approach to green chemistry of DMT-MM: recovery and recycle of coproduct to chloromethane-free DMT-MM

Abstract A simple procedure for the isolation of 2-hydroxy-4,6-dimethoxy-1,3,5-triazine (HO-DMT), a coproduct arising from dehydrating condensation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) has been established. HO-DMT can be recycled by treatment with POCl 3 to give 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT), which is further converted to DMT-MM. Alternatively, reaction with triflic anhydride followed by addition of N -methylmorpholine gives DMT-MM triflate.

Alkylidenecarbenes from 1,1-dihalogenoalkenes with samarium diiodide: Mild and efficient method for the synthesis of cyclopentenes

A new mild method for construction of cyclopentenes via 1,5-CH insertion of alkylidenecarbenes by the reaction of 2,2-dialkyl-1,1-dihalogenoalkenes with SmI2 in benzene—hexamethylphosphoric triamide (HMPA) was developed.

Substrate-Selective Dehydrocondensation at the Interface of Micelles and Emulsions of Common Surfactants†

The utilization of micelles for controlling organic reactions has been attracting considerable attention. The micellar interface is well known as an excellent reaction field for hydrolysis. In spite of this fact, the reverse reaction, that is, the dehydrocondensation of a carboxylic acid and an amine, can also be accelerated at the micellar interface. In fact, we successfully showed that a remarkable rate acceleration for the reaction of aliphatic carboxylic acids (A) and amines (B) by 1,3,5-triazine-based amphiphilic dehydrocondensing agents (C), which are available in water similar to 4-(4,6dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), 7] occurred up to 2000 times faster in micelles than in a normal homogeneous molecular dispersion phase (Figure 1). Because both carboxylic acids and amines

Convenient modular method for affinity labeling (MoAL method) based on a catalytic amidation

A modular methodology for affinity labeling, in which three essential elements generally constituting affinity probes are prepared separately as individual molecules, has been developed based on a catalytic amidation.

Generation and Reactions of Alkynylsamariums

Abstract Three methods have been developed for generating alkynylsamariums: (1) reduction of iodoalkynes with SmI 2 in the presence of HMPA, (2) deprotonation at the terminal position of 1-alkynes either by tetrahydrofurylsamarium generated by PhI and SmI 2 in THF, or, (3) deprotonation by butyllithium followed by metal–metal exchange with SmI 3 . Alkynylsamariums arising from iodoalkynes with SmI 2 undergo coupling with carbonyl compounds under both Barbier and Grignard conditions in benzene-HMPA or THF-HMPA as a solvent system. Tetrahydrofurylsamarium generated from iodobenzene and SmI 2 in THF can deprotonate from terminal alkynes to yield alkynylsamariums whereas other alkylsamariums, such as ethyl-, isopropyl-, cyclohexyl-, and cyclopentylsamarium do not work well. Metal–metal exchange between an alkynyllithium and SmI 3 is also effective; the reactive species in this case would be alkynylsamariums rather than alkynyllithiums. To reveal the properties of alkynylsamariums, we examined the stability and reactivity of alkynylsamariums toward various electrophiles.