Diazoles, addition

In addition to intermolecular interactions in the solid state, the relative importance of the two resonance structures A and B is an important issue in the structural determinations of selena- and tellura-diazoles. ° The Se-N bond lengths fall within the range 1.78-1.81 A and the Te-N bond lengths are 2.00-2.05 A compared to single bond values of 1.86 and 2.05 A, respectively. It can be concluded that resonance structure A is more important than B for the Se and, especially, the Te... 

In a related example, reaction of N-hydroxy-N-methylthiophene-2-carboximidamide 56 with DMAD gave a double Michael addition product 57, which when heated at reflux in xylenes, afforded hydroxypyrimidinone 60 in 57% overall yield (Scheme 6.21) [9f]. The mechanism invoked was opening of the oxa-diazole 57 to 58, followed by a [3,3]-Claisen-type rearrangement to 59, which, after tautomerization and cyclization, afforded 60. 

Cyclic amidines (213) react with chlorocarbonylsulfenyl chloride to give bicyclic 1,2,4-thia-diazoles. The product isolated from this reaction depends on the mode of addition. When (213) is added to chlorocarbonylsulfenyl chloride, 3-oxo derivatives (214) are isolated via the postulated intermediate (215). Addition of chlorocarbonylsulfenyl chloride to (213) leads to 5-oxo derivatives (216), via the proposed bis(intermediate) (217) (Scheme 47) <84CHEC-I(6)463). Cyclic amidines (213) have also been treated with 1-chloro-l-phenyliminomethanesulfenyl chloride (210) to afford 2>H-1,2,4-thiadiazoles (218). The other possible product from this reaction, the 2/7-isomer (219) has been shown to be unstable, rearranging to a benzothiazole. Heterocycles (213) which have been used in this transformation include 2-aminopyridine, 3-aminopyridazine, 2-aminobenzothiazole, 2-aminopyrimidine and 2-aminothiazole (Equation (33)) <86S1027>. 

Addition of nucleophiles to the cyano group of cyanothiadiazole under basic conditions takes place with unusual ease <88AG(E)434,94ACS372). Hydrolysis to the amide, for example, can be effected at 0°C in the presence of a catalytic amount of sodium hydroxide or basic ion-exchange resin. At reflux temperature, hydrazine and monosubstituted hydrazines convert 3,4-dicyano-l,2,5-thia-diazole into the l,2,5-thiadiazole[3,4-. The base-catalyzed addition of acetone to cyanothiadiazole forms an enamino ketone, used as a key intermediate for the synthesis of a number of heterocyclic ring systems, e.g. isothiazole, isoxazole, pyrazole, pyrimidine, and thiazole <77H(6)1985>. 

Aliphatic nitrile oxides are too unstable to be isolated. They immediately dimerize unless a 1,3 dipolar addition of the nitrile oxide immediately occurs on the active double bond of a suitable reagent (C=C, C=0, C=N). The following paragraphs describe the preparation of oxa-diazoles from those starting materials. 

Thieno[2,3-r 1-l,2,3-thiadiazoles 40a-f heated with CS2 in a double compartment autoclave produced thieno[2,3-rfl-l,3-dithiol-2-thiones 41a-f <2001MOL145>. In addition to the thermolysis product 41e, thieno[2,3- / -l,2,3-thia-diazoles 40e also produced bisthieno[2,3-/ 2, 3 -< ][l,4]dithiine 42 in 36% yield (Equation 3). 

Das durch Addition von 2-Isocyanat-tetrahydropyran an N-Hydroxy-carbamidsaure-ethyl-ester leicht zugangliche N-Ethoxycarbonyl-0-(2-tetrahydropyranylaminocarbonyl)-hydroxyl-amin cyclisiert im alkalischen Medium unter Ethanol-Austritt zu 3,5-Dihydroxy-1,2,4-oxa-diazol ... 

Keine Metallierung an der Methyl-Gruppe tritt beim isomeren 3-Methyl-5-phenyl-l,2,4-oxa-diazol ein. Untcr analogen Bedingungen beobachtet man hier eine Addition an die C,N-Dop-pelbindung zum 4,5-Dihydro-l,2,4-oxadiazol267 (s. S. 518). 

Several reagents for derivatization of carbonyl groups are also available. Dansylhydrazine reacts with carbonyl groups in the presence of trichloroacetic acid, yielding highly fluorescent dansylhydrazones that exhibit, however, limited stability. In addition, fluorescent hydrazones can be produced from carbonyl-containing compounds after their reaction with 4-hydrazino-2-oxa-l,3-diazole or... 

In addition, the following have been described as diazo components 2,5-dichloro-4-nitroaniline (red) [49], 2-chloro-5-trifluoromethylaniline (yellow) [50], 4-nitro-2-trifluoromethylaniline (red) [51], 2-amino-5-trifluoromethyl-l,3,4-thia-diazole (red) [52], 3-methylmercapto-5-amino-l,2,4-thiadiazole (red) [53], 3-methyl-4-nitro-5-aminoisothiazole (blue-violet) [54], 2-amino-6-chlorobenzothia-zole (red) [55], and 3-amino-5-nitro-7-bromobenzisothiazole (blue with a red cast) [56],... 

The ability of the 1,2-diazole ring unit of pyrazolate to bridge two metal ions is well documented.99 Meyer reported some pyrazolyl-based ligands possessing additional chelating substituents in the 3- and 5-positions.100 101... 

Reaction of thio- and alkylthio derivatives of A -aminoazoles with aryl isothiocyanates leads to annelation of a 1,3,4-thiadiazole or a 1,2,4-triazole ring. Thus, 4-amino-3-methyl-l,2,4-triazoline-5-thione, on reaction with aryl isothiocyanates under mild conditions, gives products of addition (388), which on heating are transformed to 2-arylaminotriazolo[3,4-/>]thia-diazoles (389) (83S411 87JHC1173). 

The addition of a piperidine molecule at the C5—N4 bond of 1,2,4-oxa-diazole ring favored the progress of the reaction. This type of addition is similar to the hypothesis of Harsanyi for the rearrangement of other 1,2,4-oxadiazole derivatives.39... 

I = TS with cyclopentadiene II = TS with furan III = TS with 1,2-diazole IV = TS with 1,2-oxazole V = 1,2-thioazole a = for addition of acetylene b = for addition of ethylene c = for exo addition of cyclopropane d = for cnrfo addition of cyclopropane BOCx-Y = bond order change for bonds between atoms X and Y in the heterocycle ring required to achieve transition state structures SBOC = sum of the heterocycle bond order changes. 

Table 31. The AMI and the B3LYP/6-31G(d) computed activation barriers for the acetylene, ethylene, and cyclopropene additions to 1,2- diazole, oxadiazole and thiazole...

The other method to determine reactivity for reactions with synchronous concerted cyclic transition state structures is evaluation of the transition state ring aromaticity through bond order deviation. The results of the exo cyclopropene addition to the heterocycles and to cyclopentadiene are presented in Table 33. The higher the sum of bond order deviation from average bond order (x) is, the lower aromatic character the transition state structure has. The most reactive dienophile was cyclopentadiene, followed by furan, and then heterocycles. The most reactive heterocycle with heteroatoms in 1,3-position was 1,3-oxazole as was predicted on the basis of the FMO energy changes (Table 32). The least reactive was 1,3-diazole, as one would expect on the basis of experimental observations. It is very difficult to rely on the transition state structure bond order deviation to determine the experimental feasibility of a reaction but, because SBOD for furan and 1,3-oxadiazole were very similar, one can conclude that the cycloaddition with 1,3-oxadiazole is also experimentally feasible. 

Table 46. Bond order uniformity for six-membered transition state structure of an exo and endo cyclopropene addition to 4,4-dimethyl-[4H]-1,2-diazole computed with the AMI method.

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