5.6- Dihydro-l,4-oxathiins

Intramolecular nucleophilic attacks of nitrogen [106a] and sulfur [126] at 0-0 bond have been recently proposed to explain the formation of unexpected products in the oxygenation of 2(o-aminophenyl)-4,5-dihydro-furans 148 (Sch. 81) and 5,6-dihydro-l,4-oxathiins 149 (Sch. 82). 

Dihydro-l,4-oxathiins 481 (Z = 0) and 5,6-dihydro-l,4-dithiins 481 (Z = S) are easily obtained from 1,3-oxathio-lanes 480 (Z = O) and 1,3-dithiolanes 480 (Z = S), respectively (Scheme 223), by treatment with bromine <1991S223>, TV-bromosuccinimide <1994T7265>, or chlorine <1987JOC5374, 1991S223>. 

Figure 8.25 The non-nucleoside reverse transcriptase inhibitor NSC 615985 and percent remaining after incubation at 10 Xg/ml for 24 h at 37°C in plasma and blood of the species listed (data from Nomeir, A.A., et al. Liquid chromatographic analysis in mouse, dog and human plasma stability, absorption, metabolism, and pharmacokinetics of the anti-HIV agent 2-chloro-5-(2-methyl-5,6-dihydro-l,4-oxathiin-3-yl carboxamido)isopropylbenzoate (NSC 615985, UC84). J. Pharm. Biomed. Anal 1998, 17, 27-38.)...

Langa et al. [67] described the microwave-induced Diels-Alder reaction of o-quino-dimethane, generated in situ from 4,5-benzo-3,6-dihydro-l,2-oxathiin-2-oxide (74) (sultine), [68, 69] leading to cycloadduct 75 (Scheme 9.21). This reaction was the first application of microwave irradiation to the preparation of a functionalized C60 [67]. 

SYNS 5-CARBOXANILIDO-2,3-DIHYDRO-6-METHYD 1,4-OXATHIIN aCARBOXIN (USDA) D 735 DCMO 2,3-DIHYDRO-5-CARBOXANILIDO-6-METHYL-l, 4-OXATHIIN 5.6-DIHYDRO-2-METHYL-3-CARBOX-ANILIDO-l,4-OXATHIIN (GERMAN) 2.3-DIHYDRO-6-... 

DIHYDRO-5-CARBOXANILlDO-6-METHYL-l,4-OXATHIIN see CCC500 DIHYDROCAR EOL see DKV150... 

A significant application of this procedure has been described for [GOjfiillerene cycloaddition under microwave conditions by Langa et al. [17]. More recently, Chi et al. have applied the concept to the Diels-Alder reaction of [60]fiillerene with o-quinodimethane derivatives, generated in situ from 4,5-benzo-3,6-dihydro-l,2-oxathiine-2-oxide derivatives (thienosultines) under reflux in 1,2-dichlorobenzene solution the reaction was highly accelerated by microwave irradiation giving comparable yields of the mono and bis cycloadducts [18]. 

Synonyms 5-Carboxanilido-2,3-dihydro-6-methyl-l,4-oxathiin Carboxine D 735 DCMO 2,3-Dihydro-5-carboxanilido-6-methyl-l,4-oxatiin 2,3-Dihydro-6-methyl-l,4-oxathiin-5-carboxanilide 5,6-Dihydro-2-methyl-1,4-oxathiin-3-carboxanilide 5,6-Dihy-dro-2-methyl-A -phenyl-l,4-oxathiin-3-carboxamide F 735 Flo pro V seed protectant Vitavax. 

Carboxanilido-2,3-dihydro-6-methyl-l,4-oxathiin, see Carboxin Carboxin... 

Various dihydro-1,4-oxathiins and dihydro-1,4-dithiins are reported to be useful in areas other than agriculture. Thus, 2,3-dihydro-l,4-dithiin-5,6-dicarboximides display a wide spectrum of biological activity (77SST(4)332) while derivatives of the basic structure (243) have been patented as tranquilizers, anticonvulsants and hypnotics (76GEP2550163). Sedative, myorelaxant and cataleptic properties are associated with certain 2,1-benzoxathiane 2,2-dioxides (75BRP1383459). 

METHYL-1,4-OXATHIIN-5-CARBOXANILIDE 5,6-DIHYDRO-2-METHYL-l,4-OXATHIIN-3-CARBOX-ANILIDE 5,6-DIHYDRO-2-METHYL-N-PHENYL-l,4-OXATHIIN-3-CARBOXAMIDE F 735 FLO PRO V SEED PROTECTANT VITAVAX... 

DIHYDRO-2-METHYX-N-PHENYL-l,4-OXATHIIN-3-C.YRBOX.M nDE see CCC500... 

The most widely used fungicide of the carboxamide group, carboxin (9), contains an oxathiin ring. Its composition is 5,6-dihydro-2-methyl-l,4-oxathiin-3-carboxanilide (Von Schmeling and Kulka, 1966). Its synthesis starts with acetoacetanilide (7), which with sulfuryl chloride gives 2-chloro-3-oxobutyranilide... 

Dihydro-2-methyl-l,4-oxathiin-3-carboxanilide (92), known as Carboxin (a fungicide), rearranges to the enamine (93) when refluxed in toluene with / -toluenesulfonic acid. The structural assignment of (93) are made on the basis of crystal x-ray diffraction analysis <84MI 609-02>. 

The dechlorination of 2,3,5,6-tetrachloro-2,3-difluoro-2,3-dihydro-l,4-dioxin with zinc in dimethylformamide afforded 2,3-dichloro-5,6-difluoro-1,4-dioxin as a distillate contamination with dimethylformamide <91J0C3915>. In the oxathiin series, sulfur dichloride added to vinylic ethers gave 2,6-dichloro-l,4-oxathianes (197). Dehydrohalogenation of these products by potassium t-butoxide gives the fully unsaturated compounds 1,4-oxathiin and 3,5-dimethyl-l,4-oxathiin (198) in moderate to reasonable yields <80RTC12>. 

Condensation of benzoin (461) with ethylene glycol or 2-mercaptoethanol 462 in the presence of PTSA as a catalyst imder MWI for 1 min gave 5,6-dihydro-2,3-diphenyl-l,4-dioxene 463 and 5,6-dihydro-2,3-diphenyl-l,4-oxathiin 464 in 95% and 65% yields, respectively (Scheme 91) (01MI4). 

N-[(trichloromethy1)thio)-4-cyclohexene-l,2-dicarboximide) 5,6-Dihydro-2-methy1-1,4 oxathiin-3-carboxani1ide... 

Carboxin (5,6-dihYdro-2-methyI-l,4-oxathiin-3-carbox-anilide) 5.7%... 

Whereas 1,4-dioxin is planar, 1,4-dithiin 173 and 1,4-oxathiin are significantly distorted from planarity [98JST11]. For 173 a planar nonequilibrium structure was computed to be destabilized by about 2.5 kcal/mol with respect to the boat con-former. The half-chair and boat conformations of 3,4-dihydro-l,2-dithiin, 3,6-dihydro-1,2-dithiin, 4//-l,3-dithiin, and 2,3-dihydro-1,4-dithiin 174 were investigated at the MP2/6-31G level [98JCC1064] (see the structures of the corresponding dioxines in Scheme 114). The half-chair conformers are stabilized with respect to the corresponding boat conformers, and the most stable structure was found to be the half-chair conformer of 174. 

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