4 - 2,4,6-trimethylphenyl-4,5-dihydro

Thieno[2,3-d]isoxazoline, 4,4-dioxo-3-(2,4,6-trimethylphenyl)-3 a,6a-dihydro-synthesis, 6, 998... 

From 3,4-dibromotetrahydrothiophene 1,1-dioxide in the presence of pyridine and mesitonitrile oxide is obtained 4,4-dioxo-3-(2,4,6-trimethylphenyl)-3a,6a-dihydro-thieno[2,3-d]isoxazoline (172). A second equivalent of nitrile oxide leads to the formation of the 2 1 adduct (173). NMR analysis and crystallographic studies show the formation of the adduct where the regioselectivity corresponds to the oxygen atom of the dipoles bonded to the carbon atom /3 to the sulfone group, the endo nature of the addition, and the anti situation of the two rings in the diadduct (173) (81JOC3502). 

Compounds of type 135 and 141 have been synthesised as inhibitors of PFT, an enzyme that catalyses the transfer of the farnesyl group from farne-syl pyrophosphate to the cysteine SH in the protozoan parasite Trypanosoma brucei, the causative agent of African sleeping sickness. The parent compound 140 (Ar = (2,4,6-trimethylphenyl) is the most active (ED50 10 xM) [44, 45]. This class of compounds has been tested also on mammalian PFTase and some of them showed inhibitory activity. In particular, none of the dihydro derivatives affects the enzyme in a concentration-dependent manner. 

Heating pyrimido[6,l-a]isoquinolin-4-one (132) in methanol gave the tetracyclic compound 133 (86CB2553). The reaction of l-amino-2-[(2,3,4-trimethylphenyl)amino]-6,7-dihydro-4H-pyrimido[6,l-a]isoquinolin-4-one hydrochloride (134) with HNO2 or with triethyl orthoesters gave the tetracyclic compounds 135 and 136, respectively [89H(29)1929]. 

Acylation of 2-[(2,4,6-trimethylphenyl)amino]-9,10-dimethoxy-6,7-dihydro-4//-pyrimido[6,l-a]isoquinolin-4-one with acetyl chloride gave a 2-acetamido derivative (84JMC1470). (Earlier the starting compound was described as a 4-amino-2-oxo-2// derivative, which afforded a mixture of 3-acetyl-4-[substituted imino]-2,3,6,7-tetrahydro-2-oxo-2// and 4-acetamido-... 

Some carotenoid metabolites apparently arise during the processing of plant material [e.g., (3S, 5R, 6S)-3-hydroxy-5,6-epoxy-5,6-dihydro-P"ionol (30), 3-oxoactinidiol (31), and l-(2,3,6-trimethylphenyl)-but-2-ene-l-one (32)] are formed during curing of tobacco (Fig. 26.15). These compounds are related to p-damascenone (33) and the aromatic carotenoids. 

A soln. of chlorocarbonyl isocyanate in chloroform added dropwise with stirring over 20 min to a soln. of 2,4,6-trimethylbenzonitrile oxide in the same solvent at 0-5, and stirred at this temp, for 2 h then at room temp, for 10 h - 4-chlorocarbonyl-3-(2,4,6-trimethylphenyl)-5-oxo-4,5-dihydro-l,2,4-oxadiazole. Y 75%. F.e.s. K.R. Rao et al.. Synthesis 1988, 994-5. 

Ni(Gl)Gp(carbene) complexes with the carbenes l,3-bis(2,4,6-trimethylphenyl)-4,5-dihydro imidazol-2-ylidene, l,3-bis(2,6-diisopropylphenyl)-4,5-dihydorimidazol-2-ylidene, and l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene have also been prepared, structurally characterized, and shown to have catalytic activities in the aryl amination and aryl halide dehalogenation reactions. Structurally similar carbene complexes have also been reported with the novel carbene formed by aryl cyclohexadienyl-ylidene rearrangement, as shown in Equation (11) the solid-state structure of this complex has shown an Ni-Gcarben bond of ca. 189 pm. 

The amidation of esters and amino alcohols is a less widely investigated area with relatively few literature examples. In 2005, nitrogen-heterocyclic carbenes (NHCs) were reported to be catalytic in this transformation." l,3-Bis(2,4,6-trimethylphenyl)-l,3-dihydro-2i -imidazol-2-ylidene (IMes) was chosen as the most suitable carbene, being readily available, reactive and easy to store. It is required in low catalytic loadings of 5 mol% in THF at 23 °C. These mild conditions are highly desirable so that the reaction is compatible with other functional groups and can potentially be used for enantioselective reactions. Reaction times varied from 1.5-24 hours depending on steric bulk and electrophilicity of the ester. 

---