2.5- Dimethyl-l,3,4-oxadiazole

Additional nitrogen atoms facilitate such reactions, particularly if they are a or y to the alkyl group, and, if a, act across a formal double bond. Thus, the 5-methyl group in 3,5-dimethyl-l,2,4-oxadiazole is much more reactive than the 3-methyl group in this compound or the methyl groups in 2,5-dimethyl-l,3,4-oxadiazole (76AHC(20)65). 

Dipicryl-l,3,4-oxadiazole has been described as an initiating explosive, 2,5-dimethyl-l,3,4-oxadiazole has been used to extract aromatic hydrocarbons from mixtures with alkanes. The use of 4,4 -carbonyl-bis(2-phenyl-5-oxo-l,3,4-oxadiazole) as a blowing agent for foaming thermoplastic compositions (e.g., polycarbonates) has been described < 1996CHEC-II(4)268>. 

In an attempt to induce a normal electron demand cycloaddition, the electron rich 2,5-dimethyl-l,3,4-oxadiazole 436 (Scheme 16.87) has been combined with the electron-poor 1,2-ditrifluoromethylacetylene. Unfortunately, only product 439 is isolated in low yield and the expected [4+2] cycloaddition has not been observed. 

In einer Photoreaktion reagiert 2,5-Diphenyl-l,3,4-oxadiazol mit l,3-Dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin unter Ringspaltung. Das gebildete 5-(a.-Benzoylhydrazono-ben-zyl)-1,3-dimethyl-2.4-dioxo-1.2,3,4-teirahydro-pyrimidm (4 44%) kann zu anderen Folgepro-dukten wciterreagieren78". 

An interesting but not synthetically useful reaction has been reported by Mloston and co-workers <2002CEJ2184>. The treatment of 2,2,4,4-tetramethylcyclobutan-l,3-dithione with dimethoxycarbene, generated by thermolysis of 2,2-dimethoxy-5,5-dimethyl-2,5-dihydro-[l,3,4]oxadiazole, led to the formation of 4-isopropyl-idene-3,3-dimethyl-thietane-2-thione in trace amounts (2% yield), together with other products (Equation 23). 

The same carbene can also be generated by thermolysis of 2,2-diphenyl-5-diphenyl-methylene-2,5-dihydro-l,3,4-oxadiazole. When the reaction was carried out in the presence of either dimethyl ( )-but-2-enedioate or dimethyl (Z)-but-2-enedioate one cyclopropane, dimethyl 3,3-diphenylcyclopropane-tranj-l,2-dicarboxylate (1), was formed, most likely via a 4,5-dihydro-3//-pyrazole intermediate. ... 

A solution of diphenylacetyl chloride (692 mg, 3.0 mmol) in dry CHjClj (10 mL) was added dropwise to a solution of 5,5-dimethyl-Af-phenyl-2,5-dihydro-l,3,4-oxadiazole-3-imine (473 mg, 2.5 mmol) in CHjClj (20 mL) under Nj at — 20 °C. The mixture was stirred overnight, then washed with sat. aq NaHCOj and brine. The aqueous layers were rewashed twice with CH CIj, and the combined organic layers dried (MgS04) and filtered. Removal of the solvent afforded the / -lactam oxadiazole in nearly pure form as a white solid yield 90% mp 154°C. 

Dialkoxycarbenes, such as dimethoxycarbene I, constitute a very reactive class of compounds that were initially difficult to handle [2,3]. Fortunately, a convenient, efficient, and safe procedure was developed by Warkentin and coworkers [4]. The protocol generates dimethoxycarbene, together with acetone and nitrogen, by thermolysis of the corresponding 2,2-dimethoxy-5,5-dimethyl-2,5-dihydro-l,3,4-oxadiazole 1 (Scheme 5.3). 

Oxadiazoles from diacylhydra-zines. SOGI2 added at 0° to a soln. of dibenzoylhydrazide in dimethyl-formamide, and stirred 15 hrs. at room temp. 2,5-diphenyl-l,3,4-oxadiazole. Y 45%. 

Dihydro-2(l,3-dimethyluracil-5-yl)-l,3,4-oxadiazole was obtained in 53% yield by the [3+2] cycloaddition of diazomethane to the formyl group of l,3-dimethyl-5-formyluracil <1997T7045>. The reaction of l-acetyl-2-benzyl-hydrazine with methyl glyoxalate in toluene afforded an oxadiazolidine derivative <1996TL4323>. 

Alkyl- and aryl-l,3,4-oxadiazoles are neutral compounds and 2-amino derivatives are weak bases. Protonation is believed to occur at ring nitrogen in position 3 which facilitates ring cleavage in aqueous acid. The pKa (water) value of 2-amino-5-methyl-l,3,4-oxadiazole is 2.37 and values in the range 2.3-2.7 have been recorded for 2-amino-5-phenyl- and 2-7V-methyIamino-5-phenyI-l,3,4-oxadiazoIe in 50% aqueous ethanol. In the same solvent pK values of the more basic imines, 4-methyl-2-phenyl- and 4,AT-dimethyl-2-phenyl-A2-... 

Alkyl halides give alkylthio derivatives, e.g., in the imidazoline-2-thione, thiazoline-2-thione, and l-arylpyrazoline-5-thione series. Often base is used to increase reactivity (Scheme 142) <1999JME1161, 2004RJ0447>, sometimes even Et3N is sufficient (e.g., l,3,4-oxadiazole-2-thiones <2003CHE1364>). Dimethyl sulfate -methylates 5-aryl-l,3,4-oxadiazole-2-thiones without base <1997CHE1109>. 

The reaction of 3,5-dimethyl-l-thia-3,5-diazacyclohexane 41c with 1 or 2equiv of BHa-THF initially gives the monoadduct 63, which further disproportionates to the bis-adduct 45 as shown by their NMR spectra. In both adducts, the N-BH3 groups are in the equatorial positions, as indicated by the NMR chemical shifts of the N-CH3 groups <1999EJ12069>. The nitroimino[l,3,5]oxadiazinane 119 reacts with 2-chloromethyl-5-aryl-l,3,4-oxadiazoles 120 in DMSO in the presence of NaH to give oxadiazine derivatives 121 in 26-43% yield (Equation 21) <2002HC0601>. 

AMI semi-empirical and B3LYP/6-31G(d)/AMl density functional theory (DFT) computational studies were performed with the purpose of determining which variously substituted 1,3,4-oxadiazoles would participate in Diels-Alder reactions as dienes and under what conditions. Also, bond orders for 1,3,4-oxadiazole and its 2,5-diacetyl, 2,5-dimethyl, 2,5-di(trifluoromethyl), and 2,5-di(methoxycarbonyl) derivatives were calculated <1998JMT153>. The AMI method was also used to evaluate the electronic properties of 2,5-bis[5-(4,5,6,7-tetrahydrobenzo[A thien-2-yl)thien-2-yl]-l,3,4-oxadiazole 8. The experimentally determined redox potentials were compared with the calculated highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO) energies. The performance of the available parameters from AMI was verified with other semi-empirical calculations (PM3, MNDO) as well as by ab initio methods <1998CEJ2211>. 

Acylation with the chloroacetyl chloride in o-xylene. 5-Aryl- and 5-heteryltetrazoles react with chloroacetyl chloride in o-xylene (30—10 ( ) to form 5-aryl-2-chloromethyl-l,3,4-oxadiazoles, 2-chloromethyl-5-(l,5-dimethyl-2-pyrrolyl)-1,3,4-oxadiazole, and 2-chloromethyl-5-(5-methyl-2-furyl)-l,3,4-oxadiazole in 80-93% yields (cf. Section 6.07.5.2.2, Equation 16) <2005RJA773>. 

The reaction of 3-(2-nitroaryl)-2,3-dihydro[l,2,4]oxadiazol-2-ones (385) with phosphorus pentasulfide in refluxing xylene transforms the oxadiazole ring into the thiadiazole ring concomitant reduction of the nitro group and closure of the imidazole ring affords [l,3,4]thia-diazolo[3,2-a]benzimidazoles (386). The reaction of l,3-dinitro-4,6-bis[(5-(l,l-dimethylethyl)-2-oxo-2,3-dihydro[l,3,4]oxadiazol-3-yl)benzene (387) is only partially successful and gives some 2-( 1,1 -dimethyl-ethyl)-5-[5-( 1,1 -dimethylethyl)-2-thioxo-2,3-dihydro-[l,3,4]oxadiazol-3-yl]-6-nitro-5-[l,3>4]thiadiazolo[3,2-a]benzimidazole (388) (Equation (132)) <88PS(36)139>. 

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