Pyridine compounds cycloaddition reactions

Pyridazine carboxylates and dicarboxylates undergo cycloaddition reactions with unsaturated compounds with inverse electron demand to afford substituted pyridines and benzenes respectively (Scheme 45). 

The other main source of various pyridopyridazines from pyridines are the [4 + 2] cycloaddition reactions, already mentioned (Section 2.15.8.3), between vinylpyridines and azodicarboxylic esters (79T2027, 79KGS639) or triazolidinediones e.g. 78KGS651). 2-Vinyl-pyridines gave reduced pyrido[3,2-c]pyridazines (370), 4-vinylpyridines gave [3,4-c] analogues, whilst 2-methyl-5-vinylpyridine furnishes a mixture of the [2,3-c] and [4,3-c] compounds. Yields are low, however, and these remain curiosities for practical synthetic purposes. 

Pyridine compounds 45 can also be produced by the NHC-Ni catalysed cycloaddition between nitriles 43 and diynes 44 (Scheme 5.13) [16]. The SIPr carbene was found to be the best ligand for the nickel complex in this reaction. The reaction required mild reaction conditions and low catalyst loadings, as in the case of cycloaddition of carbon dioxide. In addition to tethered aUcynes (i.e. diynes), pyridines were prepared from a 3-component coupling reaction with 43 and 3-hexyne 23 (Scheme 5.13). The reaction of diynes 44 and nitriles 43 was also catalysed by a combination of [Ni(COD)J, NHC salts and "BuLi, which generates the NHC-Ni catalyst in situ. The pyridines 45 were obtained with comparable... 

Closure of the oxadiazole ring is still achieved through cycloaddition between pyridine iV-oxides and isocyanates, affording adducts such as 142 (Scheme 38) <1995T6451>. Nonaromatic imine fV-oxides exhibited similar reactivities, since azasugar-derived fV-oxides as a mixture of 143 and 144 underwent cycloaddition reactions in the presence of phenyl isocyanate or trichloroacetonitrile. Compounds 145 and 146 (Scheme 39) were obtained from the aldoxime W-oxide 143 two other regioisomeric heterocycles arose from the ketoxime derivative 144 <1996T4467>. 

Reaction of aldoximes with dimedone derivatives under microwave irradiation leads to partially hydrated acridine derivatives . Eused heterocyclic compounds containing partially hydrogenated pyridine and quinoUne rings were prepared by intramolecular cycloaddition reaction of 5-alkynyl oxime derivatives . (Z)-l,10a-Dihydropyrrolo[l,2-i>]... 

A one-step synthesis of furo[3,2-c]- and furo[3,2-6]-pyridines has been realized using a cycloaddition reaction of an alkynic compound with 3,5-dichloropyridine 1-oxide (Scheme 15) (75JA3227). Formation of (75) probably proceeds through a 1,2-dihydropyridine (73) with a subsequent 1,5-sigmatropic shift to (74) elimination of hydrogen chloride yields... 

Cyclic nitrones with substituents a to the nitrogen atom (38) undergo 1,3-dipolar cycloaddition with methyl propiolate to form isoxazolo[2,3-a]pyridines (39) and (40) with high regio- and stereo-specificity (Scheme 14).64 The chiral cyclic nitrones (41) undergo asymmetric 3 + 2-cycloaddition reaction with a, /i-unsaturated carbonyl compounds to form cycloadducts (42) with very high diastereomeric excess (>99%) (Scheme 15).65... 

Substitution of two carbons in position 2,3 of the pentadienyl anion (see Section 6.1) creates a type 2,3 system. Such molecules are the dihydropyrazolo-pyridines (DHPP) 42.50 51 The 1,3 dipolar cycloaddition reaction, which is so effective as a method for synthesizing five-membered rings, can also be used to prepare spiroheterocyclic compounds of the 2,3 type. If a suitable bromo-substituted dibenzopentafulvene is reacted with pyridine the pyrazolo-pyridine 42 is formed in 30-90% yields (Scheme 18). 

The pyridine ring system has also been obtained via the [4 + 2] cycloaddition reaction between enamines and acyclic azadienes like a,/ -unsaturated carbodiimides165,166. In this way, compounds like 297 (obtained from the vinyliminotriphenylphosphorane 296... 

The // treatment with pyridine to 4-bromoisothiazolin-3-one 1,1-dioxide. The compounds formed by the cycloaddition reactions of 2-substituted isothiazolin-3-one 1,1-dioxides can be aromatized using ddq, manganese dioxide or nickel dioxide <89HCA1416>. 2-Acetyl-3-acetoxyl-2,3-dihydro-1,2-benzisothiazole 1,1 -dioxide (see Section 3.05.9.1.2) aromatizes with sulfuric add to 1,2-benzisothiazole 1,1-dioxide <83CC520>. 

The resulting iV-sulfinyl derivatives can often be distilled and/or crystallized but are water sensitive and thus are frequently prepared in situ for subsequent cycloaddition reactions. Symmetrically substituted sulfur diimides can usually be prepared by the reaction of SCI2 or S2CI2 with the parent NH2 compound in the presence of a base such as pyridine or triethylamine [Eq. (4)]. ... 

Several ring-fused tetrazole compounds have been reported. 2-Methyl-3-cyanopyridines were converted into their corresponding 2-azidomethyl derivatives, which underwent intramolecular cycloaddition reactions to give 3-(tetrazol-5-yl)pyridines 186 <04TL9127>. Fused tetrazole derivatives 187 were obtained via tandem cycloaddition and yV-allylation reactions <04JOC1346>. Expeditive synthesis of homochiral fused tetrazole piperazines 188 from 3-amino alcohols has been reported <04TL3725>. A novel Ugi-five-center-four-component reaction (U-5C-4CR) of aldehydes, primary amines, trimethylsilyl azide and 2-isocyanoethyl tosylate afforded tetrazolopiperazine type compounds <04TL6421>. 

The fluorescence quantum yields of pyrene-1-carboxaldehyde in water and methanol are 0.98 and 0.07/ an effect attributed to solvent effects on 7c,n and n,n states. Cycloaddition reactions of 1-naphthonitrile to 1,2-dimethyl-cyclopentene are attributed to both and Lj, states.It is pointed out that although dual fluorescence is known, this is the first example of divergent reaction from two nearly isoenergetic singlet states. An analysis of the u.v. spectra of some acyl pyridines, including a theoretical examination of the molecular geometry, and excited states of bipyrimidine compounds have also been made. Photo tautomerism and the fluorescence of the cation of 4-amino-pyrazole[3,4-iflpyrimidine, an analogue of adenine, has been published by Wierzchowski et Intramolecular heteroexcimer formation in... 

The synthesis of [2.2.3]cyclazines, aza[2.2.3]cyclazines and their derivatives has also been covered. The attention of the reviewers has been focused on the study of the developments in the synthesis of several benzocyclazines and azacyclazines by the [8 -I- 2] cycloaddition reaction of the dimethyl acetylene dicarboxylate with various types of indolizines. The synthesis of indolizines, imidazo[l, 2-a]pyridines, and related compounds, which are key intermediates for the synthesis of cyclazines, is also described <88H(27)225i>. 

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