Structure of tricyclics

Figure 20.3 The basic structure of tricyclic antidepressants with some well-known examples...

The nonplanar structure of tricyclic compounds 117 has also been confirmed by photoelectron spectral studies [78JOM( 146)235 83JCS (P2) 1109]. Data on the ionization potentials and the UV-absorption spectra of these compounds [70RRC501 78JOM( 146)235 83JCS(2)1109] are given in Table VIII. 

Mori M, Saitoh F, Uesaka N, Okamura K, Date T (1994) Synthesis and X-Ray Crystal Structures of Tricyclic Ketones Containing trans-Fused Azabicyclo[3.3.0]octane Units. J Org Chem 59 4993... 

Fig. 2. Structure of tricyclic triazolines 72 and 73, based on proton NMR data.

Cyclization of benzoyl acrylates 174 to condensed fluoroquinolones 180 takes place via intermediates 179, which are not always isolated because of the fast closure of the thiadiazine ring. The structure of tricyclic fluoroquinoline 180 (R = thiomorpholin-l-yl) was established by X-ray analysis. 

Finally, the more complicated structures of tricyclic compounds that present the hydroxy ketone and hydroxy lactone moieties can be substrates for the enantioselective resolution process and some examples are presented in Scheme 52 [237,238]. 

Intramolecular cycloadditions of substrates with a cleavable tether have also been realized. Thus esters (37a-37d) provided the structurally interesting tricyclic lactones (38-43). It is interesting to note that the cyclododecenyl system (w = 7) proceeded at room temperature whereas all others required refluxing dioxane. In each case, the stereoselectivity with respect to the tether was excellent. As expected, the cyclohexenyl (n=l) and cycloheptenyl (n = 2) gave the syn adducts (38) and (39) almost exclusively. On the other hand, the cyclooctenyl (n = 3) and cyclododecenyl (n = 7) systems favored the anti adducts (41) and (42) instead. The formation of the endocyclic isomer (39, n=l) in the cyclohexenyl case can be explained by the isomerization of the initial adduct (44), which can not cyclize due to ring-strain, to the other 7t-allyl-Pd intermediate (45) which then ring-closes to (39) (Scheme 2.13) [20]. While the yields may not be spectacular, it is still remarkable that these reactions proceeded as well as they did since the substrates do contain another allylic ester moiety which is known to undergo ionization in the presence of the same palladium catalyst. 

Historically, both the tricyclic antipsychotic and antidepressant agents are derived in almost direct line from a series of tricyclic antihistaminic compounds (see 104 below). Minor changes in structure in some of the newer... 

The pharmaceutical interest in the tricyclic structure of dibenz[6,/]oxepins with various side chains in position 10(11) stimulated a search for a convenient method for the introduction of functional groups into this position. It has been shown that nucleophilic attack at the carbonyl group in the 10-position of the dibenzoxepin structure renders the system susceptible to water elimination. Formally, the hydroxy group in the enol form is replaced by nucleophiles such as amines or thiols. The Lewis acids boron trifluoride-diethyl ether complex and titanium(IV) chloride have been used as catalysts. 

Sutton, P. W. Dahl, L. F. (1967) "The molecular structure of Co3(CO)g CCH3. A tricyclic organocobalt complex containing a metal-coordinated triply bridging aliphatic carbon atom, J. Am. Chem. Soc. 89,261-268. 

Of the fundamental nonalternant hydrocarbons, only two prototypes were known about fifteen years ago azulene (XI, Fig. 5), the molecular structure of which was determined by Pfau and Plattner and fulvene (XIX) synthesized by Thiec and Wiemann. Early in the 1960 s many other interesting prototypes have come to be synthesized. Doering succeeded in synthesizing heptafulvene (XX) fulvalene (XXI) and heptafulvalene (XXIII). Prinzbach and Rosswog reported the synthesis of sesquifulvalene (XXII). Preparation of a condensed bicyclic nonalternant hydrocarbon, heptalene (VII), was reported by Dauben and Bertelli . On the other hand, its 5-membered analogue, pentalene (I), has remained, up to the present, unvanquished to many attempts made by synthetic chemists. Very recently, de Mayo and his associates have succeeded in synthesizing its closest derivative, 1-methylpentalene. It is added in this connection that dimethyl derivatives of condensed tricyclic nonaltemant hydrocarbons composed of 5- and 7-membered rings (XIV and XV), known as Hafner s hydrocarbons, were synthesized by Hafner and Schneider already in 1958. 

The crystal of 2 OPr recrystallized from EtOH/H20 solution, and the mixed crystal of the same ethyl and propyl cinnamate derivatives (2 OEt and 2 OPr), on photoirradiation for 2h at room temperature with a 500 W super-high-pressure Hg lamp, afforded the highly strained tricyclic [2.2] paracyclophane (2 OEt-2 OPr-cyclo) crystal quantitatively (Maekawa et ai, 1991b). A crystal structure analysis was carried out of a single crystal of the complex of 2 OEt-2 OPr-cyclo with HFIP (recrystallization solvent) in a 1 2 molar ratio. Fig. 13 shows the molecular structure of 2 OEt-2 OPr-cyclo viewed along the phenylene planes. The short non-bonded distances and deformation of the benzene rings, as seen in Fig. 13, are common to those of [2.2] paracyclophanes, as previously reported (Hope et ai, 1972a,b). 

Another example of an efficient domino RCM is the synthesis of the highly functionalized tricyclic ring system 6/3-72 by Hanna and coworkers [252], which is the core structure of the diterpene guanacastepene A (6/3-73) (Scheme 6/3.21) [253]. Reaction of 6/3-71 in the presence of 10 mol% of Grubbs II catalyst 6/3-15 led to 6/3-372 in 93 % yield. Interestingly, the first-generation Ru-catalyst 6/3-13 did not allow any transformation. 

Although 1,3,2-diazaphospholenium cations are usually prepared from neutral NHPs or 1,3,2-diazaphospholes via Lewis-acid induced substituent abstraction or A-alkylation, respectively (cf. Sect. 3.1.2), the group of Cowley was the first to describe a direct conversion of a-diimines into cationic heterocycles by means of a reaction that can be described as capture of a P(I) cation by diazabutadiene via [4+1] cycloaddition [31] (Scheme 4). The P(I) moiety is either generated by reduction of phosphorus trihalides with tin dichloride in the presence of the diimine [31] or, even more simply, by spontaneous disproportionation of phosphorus triiodide in the presence of the diimine [32], The reaction is of particular value as it provides a straightforward access to annulated heterocyclic ring systems. Thus, the tricyclic structure of 11 is readily assembled by addition of a P(I) moiety to an acenaphthene-diimine [31], and the pyrido-annulated cationic NHP 12 is generated by action of appropriate... 

An intramolecular azomethine ylide-mediated cyclization has been used to access the core 5 6 5 angular tricyclic structure of martinellic acid by Snider (Equation 113) <20010L4217>. Reaction of IV-benzylglycine 420 with the aldehyde 419 led to intramolecular cyclization, giving 421 in good yield. 

Proton and 13C NMR spectroscopy have been widely used to elucidate the structures of compounds discussed in this chapter. 1SN NMR investigations have been reported for some hetero tricyclic derivatives <2003JA10288>. Several more specialized studies are mentioned below. 

Lindsay and Pyne utilized microwave heating for a base-catalyzed cleavage of the oxazolodinone group during the total synthesis of the tricyclic core structure of the cromine alkaloids (Scheme 6.160 b) [263]. 

This class of rigid tricyclic fused oxazolidinones was synthesized in order to gain an understanding of the importance of the spatial relationship and torsional angle between the aryl and oxazolidinone rings with regard to antibacterial activity [51,65]. Considering the structure of an early lead compound,... 

Dup-721 (please see Fig. 2 for the structure), these tricyclic fused oxazolidinones have their aryl and oxazolidinone rings joined together by either one or two carbon linkers, resulting in the formation of the [6,5,5] and the... 

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