N-Methylene bridges

Ethyl chloroformate/triethylamine Expansion of N,N-heterocycles via bridgehead lactams Elimination of N-methylene bridges... 

Formation of N-methylene bridges from and reductiye ring opening of N-condensed hydrazinium salts... 

Ring closure by N-methylene bridging with formaldehyde s. 18, 417... 

Finally, the selective cleavage of a N-CH2-N methylene bridge in phospho-nium chlorides [R-P-PTA]C1 (Scheme 7.5) with Na chunks in liquid ammonia at low temperature produces a mixture of 1 and 7-phospha-3-methyl-l,3,5-triazabi-cyclo[3.3.1]nonane [15, R = Me (a), Ph (b), Et (c), Bz (d), Cy (e)]. The desired products can be generally isolated as pure compounds by sublimation under reduced pressure, albeit in low yields [13]. Compounds 15a and 15b, i.e. PTN(R) (R = Me, Ph) have found application as hgands to Rh(I) precursors and the corresponding complexes were used as catalysts for olefin hydroformylation with some success (see Sect. 7.3). The synthesis of PTN(Me) has been recently rivisited and improved [20]. 

On the other hand, the mono-, bis- and trishomoaromatic (N, O, P) species are formally derived from the triborirane dianion M by successive incorporation of methylene bridges into the ring. 

Lithiacarboranes are obtained when 1,2,4-triboracyclopentanes and 1,3,5-triboracyclohexanes are reacted with elemental Li in donor solvents. In the contact ion pairs Li ions coordinate to B-B and B-C bonds depending on the number of methylene bridges in bis- and trishomoaromatic species (O, P). The 3c2e bonds in N, O are described as 7i,cr-distorted (indicated as dashed circles) and the overlapping sp3 hybrid orbitals in P practically yield a bonding (dashed triangle). Derivatives of N, O, and P fully characterized by X-ray structure analyses, are presented. 

Finally, replacement of the methylene bridge by a sulfur bridge leads to compoxmds such as 117 and 123 which are major tranquilizers. Thus, Ullmann condensation of thiosalicylic acid 112 with ortho-chloronitrobenzene affords thioether 113 the nitro group is then reduced to the aniline (114). Cycliza-tion as above leads to the lactam 115, which is then converted to the iminochloride derivative (116). Condensation with N-methylpiperazine affords clothiapine... 

If one connects the two double bonded end groups X in form RED of general structure /I (n = 1) with two methylene bridges instead of the usual a-bond, then 4(5red should result. With well adapted X-groups this cyclobutane derivative 6red may... 

The preference of 2,7-disubstituted oxepins for this tautomeric form at equilibrium may be rationalized in terms of a steric substituent effect. The eclipsing interactions of the 2,7-substituents in the arene oxide form will be diminished by isomerization to the oxepin. When the 2,7-substituents form part of an annelated ring system, e.g. (22)-(24), the tautomeric preference will be determined by the size of the methylene bridge (67AG(E)385). Thus when n = 5 the annelated oxepin (24) was present in approximately equal proportions with the arene oxide form. However with n =4. (23) tetralin 9,10-oxide was dominant. The... 

If R1 and R2 are a tri- or tetra-methylene bridge then the products (127) are heterocyclic propellanes (78CI(L)95>. Photolysis of the sulfone (128) eliminates sulfur dioxide to give a 47r-electron system which can be trapped by N- phenylmaleimide (Scheme 41) (78JOC3374). 

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