A. F. Pozharskii

Low barrier hydrogen bond in protonated proton sponge. X-ray diffraction, infrared, and theoretical ab initio and density functional theory studies

A new proton sponge, 2,7-dibromo-1,8-bis(dimethylamino)naphthalene (Br2DMAN), and its protonated (HBr) or deuterated (DBr) forms were studied by using x-ray diffraction and infrared spectroscopy, as well as ab initio and density functional theory calculations. In the crystalline lattice of the Br2DMAN.HBr salt, symmetrical (NHN)+ hydrogen bonding of length 2.547(3) A is observed. No deuterium geometrical isotope effect was detected. The structure refinement suggests disordering of protons between two equivalent positions at the nitrogen atoms. These findings are in agreement with infrared spectra, which are characterized by an intense band centered at ∼560 cm−1 assigned to the ν(NHN) protonic transition. Deuteration leads to a shift of this band to ∼340 cm−1, so that the isotopic ratio νH/νD (ISR) of 1.65 is characteristic of an unusual potential for the proton motion. The results of MP2 calculations are in fairly good agreement with the experimental data. The theoretical N…N hydrogen bond length is 2.575...

Heterocyclic superbases: retrospective and current trends

The structural principles known to date serving as the basis for the design of heterocyclic compounds with anomalously high basicity (superbasicity) are reviewed. A general classification is given for such superbases as proton sponges, compounds that are similar to proton sponges but are not sponges (proton-sponge-like), and proton traps.

Trends and challenges in heterocyclic chemistry (review)

This review was given as a plenary report to the Fourth All-Union Conference on the Chemistry of Nitrogen Heterocycles held in Novosibirsk in 1987, and treats the major trends and challenges in modern heterocyclic chemistry.

Nucleophilic Aromatic Substitution of Hydrogen as a Tool for Heterocyclic Ring Annulation

Publisher Summary S N H methodology finds significant use in organic synthesis. A major advantage of this methodology is that it eliminates the necessity of first introducing a good leaving group into an aromatic substrate. Moreover, in classical S N ipso reactions an acid, such as HHal, H 2 SO 4 or HNO 2 is normally liberated that has to be scavenged. However, in S N H processes, a water molecule is typically formed that can contribute to “green chemistry.” This chapter deals with S N H cyclizations. S N H based heterocyclizations allow the synthesis of a great variety of heterocyclic structures differing in ring size, number of heteroatoms and their type, and degree of unsaturation. Various arenes and hetarenes with appropriate electron deficiency can be used as substrates. In context to future prospects, it is observed that a large number of known S N H cyclizations deals with the pyrrole ring closure, therefore search for new substrates, reagents, and cyclization schemes for the annulation of other heterocyclic rings is desirable. It is also important to optimize reaction conditions as many existing transformations do not provide high enough yields.

6,8-Dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione: a novel method of pyrrole-ring annulation to an azine nucleus based on a tandem SNH–SNH process

Abstract 6,8-Dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione has been shown to react with some secondary amines in the presence of an oxidant to produce 6,8-dimethylpyrrolo[2′,3′;3,4]pyridazino[6,5-d]pyrimidine-7,9(6H,8H)-dione derivatives. The reaction represents a new method of pyrrole-ring annulation to an azine nucleus via a tandem SNH–SNH process.

H-Bond-Assisted Intramolecular Nucleophilic Displacement of the 1-NMe2 Group in 1,8-Bis(dimethylamino)naphthalenes as a Route to Multinuclear Heterocyclic Compounds and Strained Naphthalene Derivatives

It has been shown that azomethines, hydrazones, and oximes derived from 2(7)-carbonyl derivatives of 1,8-bis(dimethylamino)naphthalene can undergo acid-catalyzed heterocyclization leading to a nucleophilic displacement of the 1-NMe(2) group. The process is believed to be directly connected with the proton sponge nature of the substrates, in which 1-NMe(2), being a poor leaving group, is preliminary activated via the formation of a chelated protonated form. A number of difficult to access derivatives of benzo[g]indazole, benzo[g]quinazoline, naphtho[2,1-d]isoxazole, and 8-dimethylamino-1-naphthol have been prepared in moderate to high yields.

A 1H, 13C and 15N NMR investigation of three substituted DMAN derivatives and their monoprotonated salts

We report a 1H, 13C and 15N NMR investigation of one symmetrically substituted 2,7-dichloro and two unsymmetrically substituted 2-chloro and 4-bromo DMAN [1,8-bis(dimethylamino)naphthalene] proton sponges and their protonated salts. From a consideration of the NMR data reported we conclude, that the most sensitive parameters for investigating compounds of this kind are 1J (15N–1H) and 15N and 1H chemical shifts for the nuclei in the [N8–H–N1]+ bridge. A further significant NMR parameter is 3J (1H–1H) for the bridging proton and the N(CH3)2 protons. An analysis of the values of 1J (15N–1H) for the studied compounds is consistent with the view that in the investigated system equilibrium between two tautomeric forms occurs. A study at temperatures between 27 and −40 °C, and a change of solvent, show that the values of the 15N chemical shifts and couplings 1J (15N–1H) and 3J (1H–1H) for the [N8–H–N1]+ bridge are essentially unchanged. This shows that the bonding arrangements of the bridge atoms are stable under these experimental conditions. Copyright

Purines, pyrimidines, and fused systems based on them

Abstract6,8-Dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione reacts with ammonia or primary amines in the presence of an oxidant to give the corresponding 4-amino derivatives. Reactions with secondary amines (dimethylamine, piperidine, or morpholine) proceed with difficulty, resulting in 3-amino derivatives.

1,8,1′,8′-Tetrakis(dimethylamino)-2,2′-dinaphthylmethanols: Double In/Out Proton Sponges with Low-Barrier Hydrogen-Bond Switching

Previously unknown bis[1,8-bis(dimethylamino)naphth-2-yl]phenylmethanol (5) and bis[1,8-bis(dimethylamino)naphth-2-yl]methanol (6) have been obtained and studied by combination of X-ray, NMR, and IR techniques at variable temperature. It has been established that both proton sponge units in the solid tertiary alcohol 5 exist in nonconventional in/out form, one of which is fixed by intramolecular O-H...N hydrogen bonding. In solution, a fast interconversion of two isoenergetic hydrogen chelates occurs which can be frozen below 183 K. Unlike this, the secondary alcohol 6 in the solid at 100 K adopts the in/out-in/in conformation and at 293 K demonstrates a kind of dynamic behavior which can be described as temperature-driven dimer-induced rechelation. In solution under ambient conditions 6 exists as an equilibrating mixture of chelated and unchelated monomeric forms in a approximately 1:1.8 molar ratio.

Heterocyclization of enediynes promoted by sodium azide: a case of ambiguity of X-ray data and structure revision.

It has been shown that contrary to the literature data the tandem cyclization of (Z)-1-aryl-3-hexen-1,5-diynes promoted by sodium azide results in the formation of the corresponding [1,2,3]triazolo[1,5-a]pyridines, not 1H-benzotriazole derivatives. Apparently, incorrect structure elucidation made by previous investigators originates from misinterpretation of X-ray data. A number of new transformations of this type as well as X-ray and NMR experiments are discussed.