Heterocyclics 1.3- dioxolanes

Relatively few such heterocyclic systems have been studied by microwave spectroscopy some data are Included in Table 2. In 1,3-dioxolane the bent form is more stable than the... 

Calculation of group increments for oxygen, sulfur and nitrogen compounds has allowed the estimation of conventional ring-strain energies (CRSE) for saturated heterocycles from enthalpies of formation. For 1,3-dioxolane, CRSE is about 20 kJ mol . In 2,4-dialkyl-l,3-dioxolanes the cis form is always thermodynamically the more stable by approximately 1 kJ mol" . 

Saturated five-membered heterocyclic compounds are non-planar, existing in half-chair or envelope conformations. The far-IR spectra of THE and 1,3-dioxolane (127) show both to have barriers of ca. 0.42 kJ moP ... 

Considering the formation of saturated five-membered heterocycles with two heteroatoms, it is worth to note the possibility to prepare 1,3-dioxolanes, dithiane, oxathianes 148 [93] and dioxolanones 149 [94] by condensation of the corresponding carbonyl compounds under microwave irradiation in acid medium (Scheme 52). The reaction, which is very useful for the protection of carbonyl compounds or for the preparation of useful synthetic intermediates, has also been carried out under batch conditions over Montmorillonite KIO clay in more than 150 g scale, using a 1 L quartz reactor [95]. 

A new heterocyclic system, 3 ,4-dihydro-3//-benzo[4,5]imidazo[l,2-f]oxazol-l-one 462, was synthesized by reaction of 4,4-dimethyl-5-methylene-l,3-dioxolan-2-one with o-phenylenediamine in the presence of copper bromide as catalyst in carbone dioxide at 60-80 °C under high pressure (Equation 217) <1999CHC216>. 

As part of an investigation into new synthetic routes to the important acyclic nucleoside class of antiviral drugs, the cross metathesis of 9-allyl-6-chloropurine with 2,2-dimethyl-4-vinyl-l,3-dioxolane was attempted <2003TL9177>. The reaction was confounded by the coordination of the ruthenium metathesis catalyst with the purine heterocyclic nitrogens. This was overcome to some extent by using the /i-toluenesulfonic acid or hydrogen chloride salts of the... 

Five-membered non-aromatic heterocycles containing more than one heteroatom 1-Pyrazolines, 1,3-dioxolanes, 2-pyrazolines Five-membered aromatic heterocycles containing one heteroatom Pyrrole, furan, thiophene... 

The enolates of l,3-dioxolan-4-ones 1 and l,3-oxathiolan-4-ones2, which are y-lactones substituted with a heteroatom, can be prepared using normal conditions (LDA, THF) and subsequently alkylated. If one takes, e.g.. a nonracemic a-hydroxy acid such as lactic acid 3, then on formation of the heterocycles 1 (R1 = CH3 R2 = alkyl) chirality is transferred from the a-po-sition (C-5) in the starting acid to C-2 in 1, forming (2R,5R)-4 and (2S,5R)-5. If 4 and 5 are easily separable or, even better, if one of them is formed diastereoselectively from 3 then 4 and/or 5 can be transformed to the respective enolates 6 and 7 and alkylated with R X. 

The insertions of PTC-generated dichlorocarbene into CH bonds of 1,3-dioxane and 1,3-dioxolane rings represent examples of C-alkylation of heterocyclic nucleophiles.119,120 The mechanism is different from those just considered because a carbanion on the heterocyclic ring probably is not formed during insertion. 

Relatively few such heterocyclic systems have been studied by microwave spectroscopy some data are included in Table 5. In 1,3-dioxolane the bent form is more stable than the twisted, and pseudorotation occurs. In 1,2,4-trioxocyclopentane the equilibrium conformation is twisted, and there is a barrier of 6.3 kJ mol 1 opposing pseudorotation (74PMH(6)53). 

Data on l70 NMR spectra of five-membered oxygen-containing heterocycles are scarce. 170 chemical shifts, 80 (with respect to H2nO), near 350 ppm have been observed for isoxazoles and 280 and 303 ppm for 1,2-dioxolane (124) and its bridged analogue (125) (85JOC4484). 

In recent years there has been a growing interest in the use of carbonyl ylides as 1,3-dipoles for total synthesis.127-130 Their dipolar cycloaddition to alkenic, alkynic and hetero multiple bonded dipolaro-philes has been well documented.6 Methods for the generation of carbonyl ylides include the thermal and photochemical opening of oxiranes,131 the thermal fragmentation of certain heterocyclic structures such as A3-l,3,4-oxadiazolines (141) or l,3-dioxolan-4-ones132-134 (142) and the reaction of carbenes or car-benoids with carbonyl derivatives.133-138 Formation of a carbonyl ylide by attack of a rhodium carbenoid... 

The photoreactions of saturated five-membered heterocycles are generally characterized by initial carbon-heteroatom bond homolysis. Tetrahydro-furans150 and 1,3-dioxolans151 behave in this way, and the major photoproducts of 2,2-dimethyl-1,3-dioxolan, for example, are acetone, propyl acetate, ethylene, acetaldehyde, methyl acetate, and oxiran. The vinyltetrahy-drofuran (180) is converted on irradiation in methanol to the ketal (181) and the ketone (182) by way of a Wagner-Meerwein shift in the carbocation... 

Selective and efficient Michael additions of heterocyclic enamines (e.g. indoles, pyrroles, and pyrazoles) to enones can be catalysed by ZrCU (2 mol%).150 Michael addition of a - cy an o k e t e n e -. V,. S - ac et al s (RS)2C=CHCN to enones R CH=CHCOR2 can be promoted by TiCl4.151 Addition of the lithium enolate, generated from (2S,5S)- (g) c -l,3-dioxolan-4-one, which in turn was prepared from (S)-mandelic acid and pival-aldehyde, to several 2-arylidene-1,3-diketones, gives the Michael adducts in good yields and diastereoselectivities.152... 

Heterocycles with two oxygen or sulfur atoms in one of the rings, i.e., dioxane and dioxolanes as well as their thia analogues have not been considered in this chapter many such ring systems are in the carbohydrate series in the form of acetals. 

Methylene- 1,3-dioxolane (15) is polymerized by peroxide initiator to produce a polyester 16 which is regarded as the product of the hypothetical ring-opening polymerization of the non-polymerizable heterocycle of y-butyrolactone (Eq. (14)).13). The opening of the cyclic species bearing a free radical 17 is the key step. 

Some heterocyclic monomers may undergo random copolymerization with vinyl monomers. This is a case of cyclic acetals (e.g., 1,3-dioxolane) which forms the random copolymers with styrene [308,309] or isoprene [310], Apparently, the oxycarbenium ions, being in equilibrium with tertiary oxonium ions (cf., Section II.B.6.b), are reactive enough to add styrene ... 

By contrast, quinoline gives a mixture of C2 and C4 addition products (Scheme 16), while the use of 1,3-dioxolane as a formyl equivalent leads to mixtures derived from hydrogen atom abstraction at C2 and C4 of the saturated heterocycle (Scheme 17). Interestingly, these reactions only work well when iron(ll) is used catalytically. At higher concentrations, the iron(IIl) salts produced oxidise trioxanyl radical 33 to the corresponding cation, thereby killing the reaction. 

The transformation of oxiranes into other oxygen-containing heterocyclic systems (e.g., cyclic ethers, dioxolanes, orthoesters, lactones, and cyclic carbonates), via a variety of heterolytic, homolytic, enzymatic, and single-electron transfer processes, has been reviewed <2004RJ01227>. 

This explanation is in a grod eement with differences observed when cationic polymerization of vinyl and heterocyclic monomers is initiated with triflic acid. In the former case some acid is bound to anions (e.g. 3 molecules of acid per anion ) wdieteas in the latter (e.g. 1,3-dioxolane) every molecule of acid used gives one macTomolecule. 

Reductive cleavage of a C—O bond of 1,3-dioxolanes may be achieved by a variety of methods commonly chemical reductants are employed and, although LAH alone is ineffective, the mixed reductants LAH/AlCb or LAH/AlBrs cleave 2-substituted dioxolanes (241) to hydroxy ethers (242), sometimes with a high degree of diastereotopic selectivity. This is usually explained in terms of the selective complexation of the reagent with one of the oxygen atoms of the ring, which then allows the delivery of hydride ion to one face of the heterocycle, rather than to the other. 

A new efficient procedure has been proposed for the synthesis of 3-aryl-5-amino-l//-pyrazoles by reaction of a-chloro-/ -arylacrylonitriles with hydrazine hydrate <2004RJ01518>. Reaction of 2-(3,3-dicyano-2-propenylidene)-4,4,5,5-tetra-methyl-l,3-dioxolane 641 with hydrazine afforded 3-(2-hydroxy-l,l,2-trimethylpropoxy)pyrazole 642 (Equation 134) <2003RJ01016>. Treatment of ethyl 3,3-dicyano-2-methoxyacrylate with alkyl, aryl, heterocyclic, and sulfonyl hydrazines led to the synthesis of N-l-substituted 3-acyM-cyano-5-aminopyrazoles, which are versatile intermediates for the synthesis of many biologically active scaffolds <2006TL5797>. 2-Hydrazinothiazol-4(5//)-one reacted with a variety of cinnamonitrile derivatives and activated acrylonitriles to yield annelated pyrazolopyrano[2,3-rf thiazole <1998JCM730>. 

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