Cyclic iminoethers

WASSERMANN BORMANN Maciocydiclactamsynttwsis Ring expansion sequence of lactams by reaction with cyclic Iminoethers followed by reductive ring opening to a macrocyclic lactam. 

While screening for p-lactam antibiotics stable to p-lactamases, a strain of Streptomyces lactamdurans was found to contain several such agents which have a 6-a-methoxy group whose electronic and steric properties protect the antibiotic from enzymatic attack. Cephamycin C (29a), one of these substances, is not of commercial value, but side chain exchange has led to much more potent materials. Of the various ways of effecting this transformation, one of the more direct is to react cephamycin C with nitrous acid so that the aliphatic diazo product (29b) decomposes by secondary amide participation giving cyclic iminoether 30. The imino ether moiety solvolyzes more readily than the p-lactam to produce 7-aminocephamycinic... 

Other examples of syntheses where a hydrazide is the probable intermediate appear in Section I,C,l,b. The hydrazide cyclization can be used to prepare tetrahydrotriazolopyridines (60), starting from cyclic iminoethers.84-87... 

LPEI is obtained by cationic polymerization of cyclic iminoethers as oxazoline and oxazine derivatives producing a linear low-molecular compound with a high crystallinity [6-20]. 

The following monomers have been classified as donors styrene [78, 79], vinyl ethers and vinyl sulphides [78], vinyl acetate [80] vinylcarbazole [81, aziridine [82], 2-oxazoline [83], 2-benzyliminotetrahydrofuran [84], five-and six-membered cyclic iminoethers, cyclic amines, cyclic phospholanes and Schifif bases [85]. Trialkoxyethylenes [86]... 

Thus, we first discuss thermodynamics, paying attention to features that are important for polymer synthesis (e.g., dependence of equilibrium monomer concentration on polymerization variables) then we describe kinetics and thermodynamics of macrocyclization, trying to combine these two related problems, usually discussed separately. In particular we present the new theory of kinetic enhancement and kinetic reduction in macrocyclics. Thereafter, we describe the polymerization of several groups of monomers, namely cyclic ethers (oxiranes, oxetanes, oxolanes, acetals, and bicyclic compounds) lactones, cyclic sulfides, cyclic amines, lactams, cyclic iminoethers, siloxanes, and cyclic phosphorus-containing compounds, in this order. We attempted to treat the chapters uniformly we discuss practical methods of synthesis of the corresponding polymers (monomer syntheses and polymer properties are added), and conditions of reaching systems state and reasons of deviations. However, for various groups of monomers the quality of the available information differ so much, that this attempt of uniformity can not be fulfilled. 

Saegusa et al. invented a new method of preparing linear polyEI67). This method involves the izomerization polymerization of cyclic iminoethers (cf. Chap. 12), followed by alkaline hydrolysis, leading to perfectly linear crystalline polymers. Using oxazoline (x = 2) and oxazine (x = 3), polyEI and poly(trimethyleneamine) were prepared ... 

The Thermal Insolubilization Step. Nishikubo et al have used the ring-opening modification of oxazolines and other similar cyclic iminoethers to perform crosslinking reactions in solution. In particular, they observed that crosslinking occurred when polymers containing cyclic iminoethers were heated in solution with bifimctional nucleophilic compounds such as diacids or bisthiols (5). Subsequent work has also shown that monofunctional nucleophiles may be used to modify oxazoline rings in solution (9). 

Dihydropyrano[2,3-b]pyridine diester 11 was our key intermediate for the synthesis of imidazolinyldihydropyrano[2,3-b] pyridines. Our initial strategy to synthesize this diester was focused on the Vilsmeier route by way of a cyclic iminoether such as 9. 

Cyclic enamines with an isomeric position of the double bond have been obtained by the addition of Grignard reagents to five- (78-81), six- (82-86), seven- (87-90), and thirteen- (89-91) membered lactams, whereas other medium-sized (92,93) lactams furnished amino ketones. The reaction has been extended to substituted lactams (94-98), and iminoethers (99,100). 

The schemes for preparing imidazolines take advantage of the fact that this heterocyclic system in effect consists simply of a cyclic amidine of ethylenediamine. Thus, treatment of the iminoether (81-1) from phenylacetonitrile with ethylenediamine can be envisaged to result in the initial displacement of ethoxide to give a transient intermediate such as (81-2) internal addition-elimination by the remaining side chain... 

Some cyclic amines, iminoethers, sulfides, ethers, esten, and acetals were indeed demonstrated to polymerize without appreciable transfer and/or termination. It cannot be excluded that for monomers belonging to other compound classes, e.g. lactams or cyclic esters of phosphoric acid, the conditions for the transfer- and terminationless processes will be found in the near future. 

Table 12. Rate constants of propagation and activation parameters in the cationic polymerization of cyclic sulfides, amines and iminoethers at 0 °C... 

Reactions between substituted allylic Grignard reagents and cyclic iminothioethers or iminoethers have been tried with 2-methylthio-2-thiazolines or 2-oxazolines. Interestingly, only one addition-elimination reaction is observed [77 Eq. (38)] ... 

This led to the idea that a similar cyclic interchange of bonds might occur in chemical reactions and a number of such mechanisms were suggested from time to time. One example was the rearrangement of iminoethers to amides,... 

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