Novel Convenient Approach to 6-, 7-, and 8-Numbered Nitrogen Heterocycles Incorporating Endocyclic Sulfonamide Fragment

A new effective method for the construction of nitrogen heterocycles incorporating endocyclic pharmacophore sulfonamide fragment, based on the use of easy accessible N-(chlorosulfonyl)imidoyl chloride, CCl3C(Cl)=NSO2Cl (1), has been developed. Thus, a reaction of 1 as bielectrophilic 1,3-C–N–S reagent with benzylamines that act as 1,4-N–C–C-C binucleophiles, affords respective 1,2,4-benzothiadiazepine-1,1-dioxides. On the other hand, 1 reacts with alkenyl amines with the formation of respective N-alkenyl amidines undergoing Lewis acids initiated intramolecular cyclization to afford derivatives of 1,2,4-thiadiazines and 1,2,4-thiadiazocines bearing a halomethyl group able for further functionalization. The first examples of electrophilic heterocyclization of the chlorosulfonyl group onto an alkenyl or alkynyl group have been revealed.

(Z)-4,6-Dichloro-N-(4-chlorophenyl)quinoline-3-carbimidoyl chloride

The title imidoyl chloride, C16H8Cl4N2, has formed accidentally as a side product during the synthesis of a quinolin-3-one derivative. The molecule is not flat [the dihedral angle between the 4,6-dichloroquinoline and the imidoyl chloride planes is 53.43 (5)°], preventing π-conjugation over the complete entity. In the crystal, C—H...N hydrogen bonding between a chlorophenyl C—H group and the quinoline N atom, as well as π–π stacking between neighbouring quinoline rings, consolidate the packing.

Organic Functional Group Protection

Masato Kitamura of Nagoya University investigated (Chemistry Lett. 2009, 38, 188) the Ru-mediated deprotection of allyl ethers such as 1. The same catalyst was effective for the preparation of allyl ethers from the alcohol 2 and allyl alcohol. István E. Markó of the Université Catholique de Louvain showed (Organic Lett. 2009, 11, 2752) that SmI2 effected the reductive cleavage of an aryl ester 3, liberating the alcohol 4. Osamu Onomura of Nagasaki University found (Tetrahedron Lett. 2009, 50, 1466) that catalytic CuCl2 mediated the selective monoallylation of symmetrical diols such as 5. Péter Fügedi of the Hungarian Academy of Sciences, Budapest, observed (Tetrahedron Lett. 2009, 50, 2914) that TMSOTf catalyzed the selective reduction of 7 to the benzyl ether. BH3. NMe2 delivered the opposite regioisomer. Direct amination of an ester has been a long-sought transformation. Vladimir B. Birman of Washington University found (Organic Lett. 2009, 11, 1499) that 1,2,4-triazole 11 in combination with DBU was an effective catalyst for this reaction. Unactivated esters required higher reaction temperatures. Deprotection of amides often requires vigorous conditions, and the product free amines can be challenging to handle. Stefan G. Koenig of Sepracor Chemical Process devised (Organic Lett. 2009, 11, 433) a simple protocol for in situ formation and hydrolysis of the imidoyl chloride from 12 that delivered the amine hydrochloride 13 directly. Remarkably, benzamides are stable under these conditions. Hongmei Li of Merck Process devised (Tetrahedron Lett. 2009, 50, 1010) a related procedure: heating the more reactive trifluoroacetamide 14 with stoichiometric p-toluenesulfonic acid, and isolating the product as the p-toluenesulfonate salt 15. There has been a reluctance to use sulfonamide protecting groups, as they have been thought to be difficult to remove. Göran Hilmersson of the University of Gothenburg established (Organic Lett. 2009, 11, 503) that SmI2 instantaneously deprotected 16. Daniel E. Falvey of the University of Maryland designed (J. Org. Chem. 2009, 74, 3894) the benzyl ester 17, which was readily released under photolysis. Stanislaw Krompiec of the University of Silesia described (Tetrahedron Lett. 2009, 50, 1193) what appears to be a general strategy for the preparation of ortho esters such as 21.