1,3,5-Oxadiazine-4,6-diones

UV-curable dental cement composites consisting of 20% asymmetrical 1,3,5-oxadiazine-2,4-dione trimethacrylate derivatives have been prepared that have lower shear viscosities than their symmetric triazole counterpart. This property is particularly needed for preparing flowable pre-cured cement paste. 

Oxadiazine-3,5-diones are acidic the parent compound has pKa 7.6.5 These compounds arc included in this section because of formal tautomerism with unsaturatcd dihydroxy forms such as 5. However, there is no evidence for the existence of such tautomers. The oxadiazinediones exhibit two NH absorptions in the region 3200 3100 and two carbonyl bands, one at ca. 1750 and the other at 1710-1670 cm 1. The, 3C NMR spectra of oxadiazine-dione and its 2-substituted derivatives are informative C3 resonates at ca. 5 = 150, C5 at ca. 5 = 169 and C6 at ca. <5 = 70 ppm. An X-ray analysis of the parent compound confirmed its dione structure the structure shown gives bond lengths (pm) and angles of 2//-l,2,4-oxadi-azine-3,5(4/7,6//)-dione.6... 

Selective reduction of the 7-oxo group in pyrido[23-synthetic approach to 5,10-dideazatetrahydrofolic acid <00H(53)1207>. Cycloaddition of pyrimido[4,5-c][l,2,5]oxadiazine 96 with 2,3-dihydrofuran affords a new synthesis of dimethyllumazine derivative 97 which undergoes a ring-opening reaction to give pyrazine derivative 98 <00JHC419>. 

A review on the synthesis of 1,3,4-thiadiazines and 1,3,4-oxadiazines shows the formation of the diones 105 and 106 (Equation 57) <1998H(49)557>. TPHA3 was preparedby treatment of 107 with DBU in air (Scheme 10) <1998JA2989,... 

Preparation of 3,5-bis(6-(6-Hexyl Carbamate-Methacrylate)-6-[(6-Hexyl Carbamate-Methacrylate)Imino]-l,3,5-Oxadiazine-2,4-Dione... 

In DMF containing lithium perchlorate, reduction of o -bromopropiophenone at mercury gives l,4-diphenyl-2,3-dimethylbutan-l,4-dione in 65% yield [236]. However, electrolysis of a-bromopropiophenone in the presence of benzoyl chloride affords only l,3-diphenyl-2-methylpropan-l,3-dione. Other studies involving reduction of phenacyl bromides include the electrosynthesis of 4-aryl-2-methylfurans [237] and the regioselective synthesis of enol carbonates [238] semicarbazones of phenacyl bromide can be converted into 3,7-diaryl-2/7-imidazo[2,l-Z>][l,3,4]oxadiazines [239]. Reduction of 1,2-dibenzoyl-chloroethane at mercury in DMF containing lithium perchlorate affords mixtures of phenyl tribenzoyl cyclopentanols and diphenyl dibenzoyl butanediones [240]. 

Reaction of DBD with 1-A-morpholino- or 1-iV-piperidinocyclohexene gives the 1,3,4-oxadiazine (170), hydrolysis of which gives the monosubstitution product (171) or cyclohexane-1,2-dione (172) (Scheme 179). The analogous adduct to 170 from the pyrrolidine enamine could only be isolated by working with an excess of the enamine. Otherwise, further reaction occurred to give the products of 2,6-disubstitution (173 and 174) on hydrolysis however, the main product was the oxadiazine (175) derived by 2,2-disubstitution and isolated in 50-80% yield Such is the reactivity of DBD that simply heating with cyclohexanone gives 171 . With 2-methylcyclohexanone enamines the normal product 176 of 2,6-disubstitution is, however, formed (Scheme 180). 

Monocyclic 1,2,4-oxadiazines with maximum unsaturation, which fall within the scope of this section, are 5-aroyl-3.6-diaryl-4/7-l,2,4-oxadiazines 1 and their 4-methyl derivatives, 5-amino-2/7-1,2.4-oxadiazin-3(6/7)-one 2, 4/7-1,2,4-oxadiazi n-5(6/7)-ones 3, 477-1,2,4-oxadiazin-6(5/7)-ones 4 and 277-1,2,4-oxadiazine-3,5(4/7,677)-diones 5. 

Oxadiazine-3,5-diones are readily alkylated at N2 by alkyl halides to give 3 in an alkaline medium16,17 and they undergo addition to 2,3-dihydrofuran and 2,3-dihydropyran (DHP) in the presence of bis(4-nitrophenyl) phosphate to give analogous products.16... 

Oxadiazine-3,5-dione and its 2-alkyl derivatives react with phosphorus pentasulfide in boiling dioxane to yield 5-thioxo-5,6-dihydro-2//-l, 2,4-oxadiazin-3(4//)-ones 2, whose structures follow from their l3C NMR spectra, which show that the chemical shift of C5 changes from <5 = 169 to 6 = 203 while those of C3 and C6 are virtually unaltered.5... 

Af,Af -disubstituted 2/f-l,2,4-oxadiazin-3,5(4//,6//)-diones (e.g. (199)) can be synthesized by condensing sodium bromoacetate with an A -hydroxyurea (e.g. (197)), followed by cyclization of the resulting oxyacetic acid (198) with thionyl chloride in THF (Scheme 34) <89JAP(K)oi 186882>. Likewise, AT-aryl-AT -alkyl-Ar -hydroxyureas (200), prepared by the addition of an alkylhydroxylamine (RNHOH) to an aryl isocyanate (ArNCO), are precursors of 2-alkyl-4-aryl-5,6-dihydro-2 -1,2,4-oxadiazin-3(4//)-ones (201), the two carbon fragment in this instance being provided by 1,2-dichloroethane (Equation (15)) <91FRP2660158). 

There are no general methods for the preparation of 1,2,6-oxadiazines, and 2,1,3-benzoxadiazines appear to be unknown. A solitary example of the 1,2,6-oxadiazine system has been prepared by the action of hydroxylamine on (diphenylmethylene)-malonaldehyde (Section 6.16.9.1.3), and 1,2,6-oxadiazine A-oxides are reported to be formed by oxidation of the dioximes of butane-1,3-dione with lead tetraacetate (Section 6.16.9.1.3). 

Likewise, hydrolysis, alcoholysis, and aminolysis of 6-substituted 1,3,5-oxadiazine-2,4(3/7)-diones (76) proceed readily to yield 77,77 -disubstituted ureas (77 = H, CO2 alkyl, CONR R ) <86CB669>. 

Carbonyl diisocyanate (119) adds to iV-substituted amides to yield the unstable but isolable 1,3,5-oxadiazine-2,4(3//)-diones (120). However, with primary amides the resulting 1,3,5-oxa-diazinediones (120 = H) undergo a Dimroth rearrangement to the isomeric l,3,5-triazine-2,4,6-... 

However, with 1 equivalent of benzoic acid at room temperature, a slow cyclization to the 1,3,5-oxadiazine-2,4(3//)-dione (125 R = Ph) takes place via a Chapman rearrangement (123)(124) of the 6-benzoyloxy-l,3,5-oxadiazine-2,4(3//)-dione (123 R = Ph) as outlined in Scheme 13 <86CB669>. Other aryl carboxylic acids yield only complex mixtures, whereas with alkyl carboxylic acids and with trichloroacetic acid, l,3,5-oxadiazine-2,4(3//)-diones (125 R = alkyl and H, respectively) are... 

Treatment of carbonyl diisocyanate with A-substituted amides or with alkyl carboxylic acids produces l,3,5-oxadiazine-2,4-diones (see Section 6.18.10.1.1), which are also prepared by base-catalyzed cyclocondensation of aroyl isocyanates with aryl isocyanates (see Section 6.18.10.2.2.i). 

Whereas there appear to be no general synthetic routes to 2//-l,3,5-thiadiazines, the 2-thiones and the 2,4-dione derivatives are accessible by Dimroth rearrangement of l,3,5-oxadiazine-2-thiones (see Section 6.18.11.2) and by base-catalyzed cyclization of A -acyl-A -thioacylureas (see Section... 

The treatment of pyrazino[l,2-a][l,3,5]triazine-4,9-dione (26) with alkali (2N NaOH) (Equation (6)) resulted in its degradation to imidazoline (48) <75T533>. Pyridazino[6,l-c][l,2,4]oxadiazine (49), when heated in acetic anhydride, resulted in ring contracted (50) (Equation (7)) <83CPB3811>. 

Carbonyl diisocyanate (46) was shown to undergo a Diels-Alder type of cycloaddition with azomethines to give 2,3,6,7-tetrahydro-4/7,8/7-[l,3,5]triazino[2,l-Z>][l,3,5]oxadiazin-4,8-diones (16) (Scheme 5). A large variety of the triazino[2,l-ft][l,3,5]oxadiazines were realized by the suitable selection of dienophiles. Thus, l,3,5-triazino[2,l-Z>][l,3,5]oxadiazines (17), (18 R = NMe), and (19) and were synthesized by the reaction of carbonyl diisocyanate with alkyl or aryl isocyanates, dimethyl cyanamide, or aliphatic carbodiimides, respectively <86CB1133>. Due to the high reactivity of the cumulated double bonds, carbonyl diisocyanate (46) was also found to undergo [4 + 2] cycloadditions with cyclohexanone to yield cyclohexan-l-spiro-9 -[l,3,5]-oxadiazino-[3,4-e][l,3,5j-dioxazin-5 -spiro-l"-cyclohexane-2, 7 -dione (47) (Scheme 6) <76LA1634>. 

Hydroxamic acids 35, derived from +-(l-benzotriazolylcarbonyl)-amino acids, were found to cyclize under basic conditions to give the corresponding l,2,5-oxadiazine-3,6-dione derivatives 36 in modest yield (Equation 8) <2003MI175>. 

In the case of 9, the approach involved reaction of a trifluoroalkane-2,3-dione-3-oxime with cyclohexanone, while synthesis of 41 was achieved via ring expansion of A -methyloxadiazolium salts. The scope and limitations of the 2,3-dione-3-oxime route to 9 is difficult to evaluate since only a single example was reported, though a trifluoromethyl group may be required for activation of this system and thus would limit possible substitution patterns on the resulting oxadiazine ring. However, the reaction would presumably tolerate a number of different ketone partners, thereby increasing its scope. 

Heating of oxadiazine-2,6-diones 87 with polymer-bound isothiourea in anhydrous DMF in the presence of diiso-propylethylamine affords 3-amino-l,2,4-triazin-5(47/)-ones 88 (Equation 13) <2001TL4433>. 

The reaction of l,3,4-oxadiazin-2-one 91 with sodium hydride in tetrahydrofuran (THF) leads to an unprecedented Favorski-like ring contraction to form the 4,5-diphenylpyrazol-3-one 92, which then dimerizes with loss of one molecule of nitrogen to give 3,4,6,7-tetraphenyl-l,5-diazabicyclo[3.3.0]octa-3,6-dien-2,8-dione 93 (Scheme 11) <1996TL5039>. 

The treatment of 2,5-dichloro-3,6-dihydroxycyclohexa-2,5-diene-l,4-dione 269 with 2-substituted-l,8-naphthyr-idine-3-carboxylic acid hydrazides 270 in ethanol under reflux resulted in the formation of 3,8-di(2-substituted-l,8-naphthyridin-3-yl)benzo(l,2-r 4,5- )bis[l,3,4]oxadiazine-5,10[l//,6//]diones 271 <2000IJH311> (Equation 42). 

Substituted 4-(nitroimino)perhydro-l,3,5-oxadiazine derivatives 394 have been used as pesticides <1997WO9806710> and substituted iminooxadiazine dione derivatives have been utilized for the manufacture of... 

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