1.3- Dioxane, 2- -, ring expansion

Early efforts to effect the photoinduced ring expansion of aryl azides to 3H-azepines in the presence of other nucleophiles met with only limited success. For example, irradiation of phenyl azide in hydrogen sulfide-diethyl ether, or in methanol, gave 17/-azepine-2(3//)-thione35 (5% mp 106—107 " O and 2-methoxy-3//-azepine (11 %),2 3 respectively. Later workers194 failed to reproduce this latter result, but found that in strongly basic media (3 M potassium hydroxide in methanol/dioxane) and in the presence of 18-crown-6, 17/-azepin-2(3//)-one was produced in 48% yield. In the absence of the crown ether the yield of azepinone falls to 35%. 

Azido-5-chloroisoquinoline (18) in methoxide/methanol/dioxane solution undergoes ring expansion to the 5//-pyrido[3.4-c]azepine 19 accompanied by its hydrolysis product, the py-ridoazepinone 20. 5//-Pyrido[3,4-c]azepin-9(8//)-one is the main product from the photolysis of 5-azidoisoquinoline under the same conditions.151... 

Ring expansions of 3-aryl-7-azido-2-chloroquinolines, e.g. 21, in potassium methoxide-meth-anol/dioxane yield mixtures of the expected 3-aryl-2-chloro-7-methoxy-9//-pyrido[2,3-f]pyrid-ines, e.g. 22, and the 2,7-dimethoxy derivatives, e.g. 23, formed by nucleophilic displacement of the 2-chloro group.154 ... 

An elegant extension of these ring expansions involving diazidonaphthalenes has been reported. Early results on the photolysis of 1,8-diazidonaphthalene (14) indicated the formation of benz[t d]indazole (17).176 However, it has since been found that photolysis of the diazide in sodium methoxide-methanol/dioxane solution for a short period (20 -40 min) yields, in addition to the benz[c,d]indazole (17, 40%), a mixture of 9-azido-l-methoxy-5//-2-benzazepine (15 15-20%) and l,10-dimethoxy-5,5a-dihydroazepino[3,4-c]azepine (16 10-15%).117... 

The ring expansion mechanism is of course only a special case of the well-known mechanism by which dioxolan reacts with non-cyclic formals e.g., (I) and CH2-(OMe)2 give (MeOCH2OCH2-)2 in this way. It also accounts in a simple manner for the cleanness of the monomer-polymer equilibrium and for the high yields of cyclic dimer (without any detectable linear fragments) which are obtainable from 1,3-dioxane and 1,3-dioxepan [8]. 

Ring expansion of a four- or five-membered ring is a more common route for the preparation of 1,3-dioxanes, 1,3-dithianes, and 1,3-oxathianes and various methods have been developed. 

One general method for the preparation of 6,7-dihydro-l,4-dioxepins of type (362) involves ring expansion thus, treatment of 2-(methoxymethyl)-l,3-dioxane (361) with dodecylbenzenesulfonic acid at 250°C and simultaneous distillation gave (362) with 69% conversion and 84% selectivity... 

Amino-l-methylimidazole (169) reacted with DMAD145 in dioxane to form 30% of imidazo[l,2-a]pyrimidone (170), identified by the low-field 3-proton, and 5% of the diazepine 171, which was presumably built up by cyclobutene formation across the 4,5-double bond of 169 and ring expansion.148 Both l-methyl-2-methylthioimidazoline and its... 

An interesting ring expansion of the 1,2-benzothiazepine derivative 14 was observed when it was treated with azirine 15 in dioxane to give the benz-fused 10-membered heterocyclic derivative 16 in moderate yield (Equation 2) <1996HCA1121 >. With the more sterically hindered azirine 17, no ring expansion occurred. 

Contrary to the 1-vinylcyclopropanol derivatives which easily underwent an acid catalyzed or thermally induced C3 -> C4 ring expansion as discussed in Sect. 5.1.1, the acetylenic cyclopropanols 9 were surprisingly unreactive towards acids. Thus, on heating for two hours to 55 °C in acidic (0.75N HC1) 50 % aqueous dioxane containing a catalytic amount of mercuric chloride or upon treatment with m-chloroper-benzoic acid (MCPBA) for 12 hours at room temperature, the alcohol 9 (R = H) was recovered unchanged. However, treatment of 9 with an alcohol free solution of t-butylhypochlorite (t-BuOCl) in chloroform resulted in an exothermic reaction which yielded 2-chloromethylenecyclobutanone 39 as the only isolable product, Eq. (13)10). 

The mechanism for the gas-phase reaction of trans-2,3-dideuterioethene oxide with HBr and HCl has been shown to involve anti ring-opening, with the formation of e fhro-R(CHD)2 0H (R = Cl or Br). The reaction of ethene oxide with HF followed a somewhat different course, affording only 5% of fluorohydrin together with (126) (37%) and oligomers and polymers. A possible mechanism for this reaction is shown (see Scheme 8) in which two moles of oxiran react with HF to give intermediate (125), which is open to polymerization with other oxiran molecules or to ring-expansion, with the subsequent formation of dioxane (126). 

Dimethyl 1,4-cyclohexadiene-1,2-dicarboxylate has been traditionally prepared by three methods (i) dimethyl 3-vinyl-1,2-dichlorocyclobutane-1,2-dicarboxylate undergoes a ring expansion, with concomitant loss of the chlorine atoms to give the cyclohexadiene in 52% yield, upon treatment with Ni(CO)4 in refluxing benzene-dimethylformamide [68], (ii) butadiene sulfone and dimethyl acetylenedicarboxylate have been allowed to reflux in xylene for 150 min, and (iii) butadiene and dimethyl acetylendicarboxylate have been mixed in dioxane in a sealed tube, and allowed to stand at room temperature for 5 days [69]. 

Besides the fully unsaturated 5 f-l,4-dioxepin (45), the unsaturated 1,4-dioxepins, 6,7-dihydro-5Ef-l,4-dioxepin (46), and 2,3-dihydro-5 f-l,4-dioxepin (47), incorporate either the structural feature of an enediol ether or an enol ether. One general method for the preparation of seven-membered rings of type (46) involves ring expansion thus, treatment of 2-(methoxymethyl)-l,3-dioxane with dodecylbenzenesulfonic acid in vacuum gas oil at 250 °C and simultaneous distillation gave (46) with 69% conversion and 84% selectivity. Several 6,6-disubstituted derivatives (49), which have found interest as intermediates for agrochemicals, drugs, and plastics, have analogously been... 

Dioxane from 2-a-hydroxy-2-spiro-l,3-dioxolane ring with benzocyclobutene ring expansion... 

Rearomatization is much more common in bi- and tricyclic azides than ring expansion although ring expansion may be achieved employing sodium methoxide in methanol-dioxan as solvent. This dichotomy again may be resolved by invoking an aziridine intermediate vide supra). The formation of aminoketals from 2-azidoanthracene and 48 is of particular interest as similar products are commonly formed from aliphatic azirines on treatment with mildly basic methanol. At the moment, the intermediacy of benzazirine in phenyl azide photolysis at room temperature cannot be ruled out. In the case of bi- and tricyclic aromatic azides and azidouracil decompositions the nature of the products strongly supports azirine involvement. Only further experimental work will resolve this mechanistic dilemma. With this in mind, benzazirine intermediacy will be assumed for the purposes of this discussion. 

The yields of azepine and o-diamine may be optimized by varying the ratio of nucleophile to cosolvent used for photolysis. Photolysis of a- and P azidoarenes in methoxide-methanol-dioxan can either lead to ring expansion or... 

In contrast to 2-phenyl-l,3-dioxan-5-one, where nucleophiles add, regardless of their size, from the axial side of the carbonyl group, the same nucleophiles add to 2-phenyl-l,3-dithian-5-one exclusively from the equatorial side, to yield (165). A ring-expansion reaction has been observed when 2-methy 1-2-ethyl-1,3-dithiolan was brominated, giving the dithiin (166). ... 

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