Cyclization base-catalyzed

Another approach uses the reaction of 6-chloro-5-nitropyrimidines with a-phenyl-substituted amidines followed by base-catalyzed cyclization to pteridine 5-oxides, which can be reduced further by sodium dithionite to the heteroaromatic analogues (equation 97) (79JOC1700). Acylation of 6-amino-5-nitropyrimidines with cyanoacetyl chloride yields 6-(2-cyanoacetamino)-5-nitropyrimidines (276), which can be cyclized by base to 5-hydroxypteridine-6,7-diones (27S) or 6-cyano-7-oxo-7,8-dihydropteridine 5-oxides (277), precursors of pteridine-6,7-diones (278 equation 98) (75CC819). 

An example of an exo-dig process would be the base-catalyzed cyclization of an -hydroxy-a,/S-ynone ... 

In agreement with these analyses, it was found that conqiound S was unreactive toward base-catalyzed cyclization to 6, even though the double bond would be expected to be reactive toward nucleophilic conjugate addition. On the other hand the acetylene 7 is readily cyclized to 8 ... 

AB-Dinorsteroids have been prepared by Dauben et al from B-nor-A" -3-ketones by reactions analogous to the sequence (4) - (7). Pyrolysis of the B-nor-2,3-seco diacid anhydride gives the AB-dinor-A -2-ketone in 5 % yield. However, refluxing the diacid with acetic anhydride containing potassium cyanide for 2 days gives the ketone in 50-60% yield, apparently by base-catalyzed cyclization of an intermediate bis-acylcyanide. 

Asymmetric induction by sulfoxide is a very attractive feature. Enantiomerically pure cyclic a-sulfonimidoyl carbanions have been prepared (98S919) through base-catalyzed cyclization of the corresponding tosyloxyalkylsulfoximine 87 to 88 followed by deprotonation with BuLi. The alkylation with Mel or BuBr affords the diastereomerically pure sulfoximine 89, showing that the attack of the electrophile at the anionic C-atom occurs, preferentially, from the side of the sulfoximine O-atom independently from the substituent at Ca-carbon. The reaction of cuprates 90 with cyclic a,p-unsaturated ketones 91 was studied but very low asymmetric induction was observed in 92. 

Smiles rearrangement was observed also in base-catalyzed cyclization of 2-hydroxy-2 -nitrodiphenylsulfones leading to low yields (about 5%) of phenoxathiine 10,10-dioxides (34JCS422, 56JA5357). However, this type of compounds can be easily prepared by other methods (05CB1411, 06CB1340). 

The alternative product from pyridine-3,4-diamine and ethyl acetoacetate, compound 12, is obtained by the base-catalyzed cyclization of the ester 11, which is formed from the diamine and ethyl acetoacetate in the presence of zinc(II) chloride.298... 

A-(Carbamoylmethyl)-o-chloroaniline (4) gave 3,4-dihydro-2(l//)-quinoxali-none (5) ( base-catalyzed cyclization >80%). " ... 

Fig. 47. Mechanism for the base-catalyzed cyclization of 44 —> 45. Adapted from Ref. (163).

Chiral 4,7-disubstituted perhydropyrazino[l,2-f]pyrimidine-l,6,8-triones 170 were synthesized from [4+2] atom fragments by reacting separately, the four diastereomers of 169 with isocyanates in a base-catalyzed cyclization (Scheme 23) <2002TL4899>. 

The [l,4]oxazino[3,4-3]quinazoline-3,6-dione 345 was formed in the base-catalyzed cyclization of 2-(l-bro-moethyl)quinazoline-3-acetic acid 344 (Scheme 54) <1998H(48)1851>. 

The tricyclic system 99 can be accessed by the base-catalyzed cyclization of the dithiodicyanopyridine 98 (Equation 23) <1998EJM887>. 

Chukhadzyan et al. made N-junction fused tricyclic systems such as 123 via a base-catalyzed cyclization onto the tetrazole 122 (Equation 29). The exothermic reaction proceeds at room temperature <1999CHE343>. 

Since cumulenes and alkynes are often easily interconvertible, many syntheses discussed above have allenic counterparts, especially base-catalyzed cyclizations of allenic alcohols.77 And, of course, several of the alkyne-based syntheses may well have allenic intermediates. There are, however, a few syntheses based specifically upon allene chemistry. In an important one, due to Stirling and his collaborators,78 an allenic sulfonium salt reacts with an enolate anion. Scheme 12 sketches the main features yields as high as 86% are recorded. Methoxyallene is easily metallated by butyllithium and so converted into an allenic epoxide that can be isomerized by fe/T-butoxide into a furan (Scheme 13) or an exocyclic equivalent similar to 15 clearly this method is particularly suited to the preparation of 3-methoxyfuran... 

The related syn diol epoxide isomers were synthesized from the 1,2- and 7,8-dihydrodiols of 5-MC by reaction with N-bromoacetamide in moist DMSO followed by base-catalyzed cyclization by the usual Method I procedures (60). 

Dioxane solutions of 4(5)-aminoimidazole (64) have been treated with several reagents [92JCS(P1)2789], Imidazo[l,5-a]-l,3,5-triazines (65 R = Ph, Me SMe) were obtained by reaction with methyl N-cyanobenzimidate (57 R = Ph), ethyl N-cyanoacetimidate (58 R = Me), and dimethyl yV-cyanodithioiminocarbonate (59 R = SMe). The uncy-clized product (68 R = H) (73%), obtained by condensation with ethyl N-cyanoformimidate (58 R = H), underwent facile cyclization to give the imidazo[l,5-a]-l,3,5-triazine (65 R = H). Likewise, the condensation adduct (69 R = H) (78%) was obtained using ethoxy methyleneurethane (60 R = H) and this underwent base-catalyzed cyclization to give the imidazo[ 1,5-a]-1,3,5-triazinone (67). Imidazo[l, 5-a]pyrimidines (66 R = H, Me) were obtained from the condensation of 4(5)-aminoimidazole... 

Substituted 3-thio-l,2,4-triazoles were prepared by the base-catalyzed cyclization of acylsemicarbazides 177 to give the corresponding 1,2,4-triazoles 178a-g in excellent yields (Equation 55 and Table 37) <2004EJM535>. 

Base-catalyzed cyclization of semicarbazide 189 gave the triazolidine 3,5-dione 190, subsequent treatment of which with phosphorus oxychloride gave 3,5-dichloro-4-aryl-l,2,4-triazole 191 (Scheme 17). <2006T2677>. 

Less common synthetic methods for 1,3,4-thiadiazoles include the oxidative thermal base-catalyzed cyclization of thiosemicarbazido arylates (Equation 40) <2005HAC12> and a tetracyanoethylene (TCNE)-assisted cyclization (Equation 41) <2004ZNB910>. 

Several syntheses of l,3-dioxoperhydropyrrolo[l,2-c]imidazoles have been developed using different strategies. a-Substituted bicyclic proline hydantoins were prepared by alkylation of aldimines 135 of resin-bound amino acids with a,tu-dihaloalkanes and intramolecular displacement of the halide to generate cr-substituted prolines 136 and homologs (Scheme 18). After formation of resin-bound ureas 137 by reaction of these sterically hindered secondary amines with isocyanates, base-catalyzed cyclization/cleavage yielded the desired hydantoin products <2005TL3131>. 

Dieckmann Condensation The intramolecular equivalent of a Claisen condensation where dicarboxylic acid ester undergoes base-catalyzed cyclization to form a P-keto ester. 

The mixed hydrazones (667), prepared from diacetyl monobenzoyl hydrazone and arylhydrazines, undergo oxidative cyclization to 2-aryl-jV-benzoyl-4,5-dimethyl-l,2,3-triazol-l-ylimines (668) in 32-76% yield upon treatment with lead tetraacetate in acetonitrile (Scheme 132) <92JOC2252>. The cychzation of bishydrazones to 1,2,3-triazoles can also occur in acidic or basic media. For instance, the tetrahydrobenzo[ /]triazol-4-one (669) is prepared by the base-catalyzed cyclization of the corresponding a-hydrazono oxime (Equation (53)) <85HCA1748>. 3-Methyl-1,2-cyclohexanedione reacts... 

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