Monocyclic systems

Afl referencos ar (3) unless otherwise Indicated by boldfaced number to lower left. Where shift data are not provided, the Information Is currently unavailable In the literature. 

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It is interesting to compare the dimensions of the monocyclic systems with those recorded for their dibenzo counterparts where the aromatic nature of the heterocyclic ring is expected to be much diminished. Comparison of the data in Table 4 with that in Table 2 shows that... 

The reactivity sequence furan > tellurophene > selenophene > thiophene is thus the same for all three reactions and is in the reverse order of the aromaticities of the ring systems assessed by a number of different criteria. The relative rate for the trifluoroacetylation of pyrrole is 5.3 x lo . It is interesting to note that AT-methylpyrrole is approximately twice as reactive to trifluoroacetylation as pyrrole itself. The enhanced reactivity of pyrrole compared with the other monocyclic systems is also demonstrated by the relative rates of bromination of the 2-methoxycarbonyl derivatives, which gave the reactivity sequence pyrrole>furan > selenophene > thiophene, and by the rate data on the reaction of the iron tricarbonyl-complexed carbocation [C6H7Fe(CO)3] (35) with a further selection of heteroaromatic substrates (Scheme 5). The comparative rates of reaction from this substitution were 2-methylindole == AT-methylindole>indole > pyrrole > furan > thiophene (73CC540). 

The various combinations of XYZ and ABD in the monocyclic system in Scheme 15 which illustrate the scope of the rearrangement are shown in Table 5. 

While HiickeTs 4n + 2 rule applies only to monocyclic systems, HMO flieory is applicable to many other systems. HMO calculations of fused-ring systems are carried out in much the same way as for monocyclic species and provide energy levels and atomic coefficients for the systems. The incorporation of heteroatoms is also possible. Because of the underlying assumption of orthogonality of the a and n systems of electrons, HMO dieory is restricted to planar molecules. 

It is of interest to be able predict the stability of such fiised-ring compounds. Because Huckel s rule applies only to monocyclic systems, it cannot be applied to the fiised-ring compounds, and there have been many efforts to develop relationships which would predict their stabihty. The underlying concepts are the same as for monocyclic systems stabilization should result from a particularly stable arrangement of MOs whereas instability would be associated with unpaired electrons or electrons in high-energy orbitals. 

When submitted to oxidation by a 2 per cent, solution of permanganate, pinononic acid, CgHj Og, melting at 128° to 129° C., the semi-carbazone of which melts at 204° C. Lastly the constitution of verbenone, as expressed by the above formula, is further confirmed by the fact that the bicyclic system is convertible into a monocyclic system by boiling with 25 per cent, sulphuric acid, with the formation of acetone and 3-methylcyclohexene-(2)-one-(l). This cyclohexenone has been characterised by its semi-carbazone (melting-point 198° C.) and by its conversion into y-acetobutyric acid (melting-point 36° C). The oily liquid, which did not react with sulphite, was submitted to benzoylation after dilution with pyridine. It thus gave rise to a benzoate from which was... 

Dehydrogenation is a rarely used method for the production of fully unsaturated azepines, and there are no examples of its use for the formation of simple monocyclic systems, although 3-hydroxy- and 3-methoxy-2//-azepin-2-ones can be obtained by dehydrogenation of the corresponding l,5-dihydro-2//-azepin-2-ones with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in benzene in a sealed tube at 100 48-51-52-67... 

When the cnolate of an enone is brought into reaction with an enone, usually a carbocyclic system is prepared by two consecutive Michael additions (M1MIRC reactions). Due to the lower temperatures employed and the absence of diene polymerization these reactions are useful alternatives for Diels-Alder reactions and proceed in general with high diastereoselectivities. When neither enolate nor enone is cyclic a monocyclic system is formed 338 which can be converted into a bicyclic system when the Michael addition is followed by an aldol reaction339. When, however, the enolate is cyclic a bicyclic or a tricyclic system is formed340 341. 

Various methylene derivatives of spiroorthocarbonates and spiroorthocstcrs have been reported to give double ring-opening polymerization e.g. Scheme 4.36). Like the parent monocyclic systems, these monomers can be sluggish to polymerize and reactivity ratios are such that they do not undergo ready copolymerization with acrylic and styrenic monomers. Copolymerizations with VAc have been reported.170 These monomers, like other acetals, show marked acid sensitivity. 

Degradation of bicyclic p-lactams has been used as a route to the monocyclic system. Highly functionalised P-lactams have been obtained in good yield by ozonolysis of A -cephems <96T10205> and enantiomerically pure 4-hydroxymethylazetidin-2-ones have been produced by degradation of a bicyclic oxazolidine, though in poor to moderate yield <96JCS(P1)227>. 

The sulphur-bridged pentaoxyphosphorane (41) has been prepared by the route shown and its ground state structure studied by a combination of 1H, l9F, 31P and 15C n.m.r. spectroscopy35. The 19F n.m.r. data indicate that at -65°C (wnere three 19F triplets are observed) the phosphorane exists as structure (42) whereas at 26°C the spectrum (two 19F triplets, ratio 2 1) is consistent with conventional pseudorotation in a monocyclic system at 110°C the three trifluoroethoxy groups become equivalent. 

Relatively little systematic work has been carried out on the thermal behaviour of the bicyclic peroxides compared to monocyclic systems 63). From the few results obtained to date, oxygen diradicals appear to be reasonable intermediates to account for the observed products (Eq. 51). 

For bicyclic and polycychc systems, fewer conformations and interconversion pathways need to be considered than is the usual case for monocyclic systems. For example, placing a CHj bridge on a... 

Tris(dimethylamino)borane similarly fails to 3deld a trivalent boron heterocycle, but gives the spiro-compound (CLXV). A monocyclic system of type (CLXVI) does arise from diethylaminodiphenylborane, and of type (CLXVII) from phenylboronic acid and its analogues 436). 

The stabilization through heterosubstitution is not confined to monocyclic systems it can be achieved for bicyclic and polycyclic antiaromatic... 

The same type of ring cleavage occurs in the benz[d]isoxazole series. Thus, benz[d]isoxazole is cleaved by aqueous alkali to give the anion of 2-hydroxybenzonitrile (27) (73JOC2294). As for the monocyclic systems, the reaction can be represented as a concerted E2 elimination since there is a substantial kinetic isotope effect. Salts of benz[d]isoxazole-3-carboxylic adds are also cleaved, with loss of carbon dioxide, in a concerted manner (72JOC2498 75JA7305). 

Diazepines (106) have received rather less attention than their 1,2-isomers, but there are several preparative routes available to the partially and fully saturated systems and recently the first routes to the fully unsaturated monocyclic system (61) and to 1H- 1,3-benzodiazepines (135) have been reported. 

These are the most widely used routes to 1,3-diazepines and provide easy access to the monocyclic system, 1,3- and 2,4-benzodiazepines, and dibenzodiazepines by the reactions of (113)-(116) (and their derivatives) respectively with 1,1-bis-electrophilic reagents. The use of aldehydes produces the rather unstable fully saturated —NHCH2NH— linkage and has been rarely applied to the synthesis of monocyclic systems. (67AHC(8)2l, p. 40) but provides useful syntheses of 1,3-benzodiazepines, e.g. (117) (67AHC(S)2l, p. 43), and 2,4-benzodiazepines, e.g. (118) (68CRV747, p.783). A 5,7-dihydroxy-6fT-dibenzo[[Pg.605]

Reactions of this type provide major routes to both the monocyclic system and to 1,5-benzothiazepines. In some cases the reactions are single-stage processes but in many cases the intermediate produced by the primary formation of the S—C bond can be isolated. Thus 2-aminoethanethiol reacts with a,/3-unsaturated or j3-halogeno ketones to give (408). Similarly reaction with a,/3-unsaturated acids, esters or acid chlorides and with 3-halogenopropionyl halides gives the 5-oxo derivative (409). 2-Aminoethanethiol also reacts with activated 2-chlorobenzophenones to give 1,4-benzothiazepines. 

The monocyclic system (606) has been prepared by the reaction of the Af-chlorosulfonyl /3-lactam (605) with 1,2-dimethylhydrazine (75CB2137). 

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