Pyridazines from furans

Several methods for the preparation of pyridazines from furan derivatives were already known. However, a new method has been developed by using furan vinamidinium salts 60 as starting material. They react with hydrazine at position 5, thereafter they add to the enamine system with subsequent ring opening and ring closure to give 61 (88CCC1297). 

There are several examples of the formation of pyridazines from other heterocycles, such as azirines, furans, pyrroles, isoxazoles, pyrazoles or pyrans and by ring contraction of 1,2-diazepines. Their formation is mentioned in Section 2.12.6.3.2. 

The most important derivatives of 2,5-dihydrofuran are the 2,5-dialkoxy and 2,5-diacetoxy compounds which are easily prepared from furans (Section 3.11.2.3). Their vast utility is as synthetic equivalents of malealdehyde and its derivatives (60MI31100). Suitable intermediates for Robinson-Schopf synthesis have been obtained in this way. Pyridazines are readily obtained (Scheme 121), and 3-pyridinols are available from 2-furylmethanamines (Scheme 122). This approach has been used in a synthesis of pyridoxine. The 2,5-diacetoxy... 

Other syntheses involve the preparation from the monoacetate of the enolic form of nitrosuccindialdehyde/ or the dibenzoyldioxime of maleic aldehyde/ or by dehydrogenation of l-tosyl-l,4-dihydro-pyridazine. From 2,5-diacetoxy- or 2,5-dimethoxy-2,5-dihydro-furan pyridazine can be obtained in high yield. Maleic aldehyde has been obtained also when decomposing the adduct obtained in the Diels-Alder reaction between furan and diethyl azodicarboxylate and straightforward condensation with hydrazine afforded pyridazine in 55% yield.Another direct reaction involving maleic aldehyde... 

Pyridazines have been prepared from furans and their reduced analogs. One of the most investigated reactions was introduced by Clauson-Kaas. Furans are treated with bromine in methanolic solution to give derivatives of 2,5-dihydrofuran (39). These are then submitted to acid hydrolysis and the intermediate en-dione (40) (or the aldehydic analog) reacts with hydrazine to form the corresponding pyridazine (41). - The intermediate 40 should... 

Recently, many transformations of various heterocycles into pyridazines have been reported. From the synthetic point of view it appears that furan derivatives are the most valuable. 

Phthalides — see Benzo[c]furan-l (3H)-one Phthalimide, 2-amino-pyridazine synthesis from, 3, 53 Phthalimide, N-cyclohexylthio-as vulcanization accelerator, 1, 404 Phthalimide. methylidine-polymerization, 1, 273 Phthalimide, N-(trichloromethylthio)-biocide, 1, 399 Phthalimide, 1-vinyl-polymerization, 1, 273 Phthalimide, N-vinyl-copolymer... 

JOC6503>, and new pyridazino-psoralens 15 were prepared via a furan ring expansion reaction <05T4805>. The reaction of 3-acetylcoumarins with alloxan followed by NH2NH2 easily produced 3-(2-oxo-2//-chromen-3-yl)-6//,8//-pyrimido[4,5-c]pyridazine-5,7-diones <05JHC1223>. Furano- and pyrano[2,3-c]pyridazines 17 and 18a,b as well as substituted quinolines were conveniently prepared from pyridazinone 16 and vinyl- and allyltriphenyl-phosphonium salts <05HAC56>. 

Starting from 3-acetonyltropolone 99, tropones fused to furan (100), pyrrole (101), and (after dehydrogenation) pyridazine (102) are accessible (65BCJ301 68BRP1114916 69MI1). 

Apart from a very unconventional synthesis of 274 via fragmentation of the tetrazine 273 in the presence of furan (Equation 97) <2003AJC811>, interest in the furo[3,4-r/ pyridazines has waned since the coverage in CHEC-II(1996) <1996CHEC-II(7)229>. 

Tsuchiya, T., Arai, H. and Igeta, H. (1973) Photochemistry - IX. Formation of cyclopropenyl ketones and furans from pyridazine N-oxides by irradiation. Tetrahedron, 29 (18), 2747-2751. 

An appropriately substituted furan derivative (206 X,Y = Br, Cl), prepared from the corresponding ketone and a hydrazine, can undergo cyclization by displacing a halogen to give a furo[3,2-c]pyridazine (207) (Equation (72)) <86MI 707-05). 

Since many furans are not particularly sensitive to light they often form as products of photochemical reactions. A high pressure mercury arc can be used to eject nitrogen from pyridazine Ai-oxides and form cyclopropenyl ketones and their furan isomers.29 High yields of 2-acetylfuran can be achieved by irradiating the pyrilium ion in Scheme 5 (i.e., the requisite pyrone dissolved in sulfuric acid) although the conditions, mainly the acidity, have to be carefully controlled.30 Surprisingly, the intermediate cyclopen-tenone diol can be isolated with 50% sulfuric acid it is converted to the furan in a separate step. 

The simple unsubstituted heterocyclic systems show a wide range of electronic absorption, from the simple 200 nm band of furan, for example, to the 340 nm maximum shown by pyridazine. As is true for benzenoid compounds, the presence of substituents that can conjugate causes profound changes in electronic absorption, but the many variations possible are outside the scope of this section. 

Diethyl azodicarboxylate also reacts with furans to give an adduct which is transformed into a pyridazine by acid.165 In a photochemical synthesis, l,2-diarylhexahydropyridazine-3,5-diones (44) are formed from azobenzenes and diketene.166... 

Saturated 1,4-diketones can suffer in this approach from the disadvantage that they can react with hydrazine in two ways, giving mixtures of the desired dihydropyridazine and an A -aminopyrrole this complication does not arise when unsaturated 1,4-diketones are employed.Synthons for unsaturated 1,4-diketones are available as cyclic acetals from the oxidation of furans (section 15.1.4), and react with hydrazines to give the fully aromatic pyridazines directly. ... 

Oxidative ring opening of the acetyl or benzyl derivatives of the furan 86 by metachloroperbenzoic acid gave the respective hexene dione 87 cis-trans isomerization did not take place because of the acidic conditions (Fig. 15). Reaction of 87 with hydrazine furnished the pyridazine 88 [36]. The gluco-syl derivative 90 was prepared from the respective furan 86 by the action of bromine water to give 89 which cyclized upon reaction with hydrazine to... 

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