F Azetidine

Azatricyclo[2.2.1.02 6]hept-7-yl perchlorate, 2368 f Azetidine, 1255 Benzvalene, 2289 Bicyclo[2.1.0]pent-2-ene, 1856 2-/ert-Butyl-3-phenyloxaziridine, 3406 3 -Chloro-1,3 -diphenyleyclopropene, 3679 l-Chloro-2,3-di(2-thienyl)cyclopropenium perchlorate, 3388 Cyanocyclopropane, 1463 f Cyclopropane, 1197 f Cyclopropyl methyl ether, 1608 2,3 5,6-Dibenzobicyclo[3.3.0]hexane, 3633 3,5 -Dibromo-7-bromomethy lene-7,7a-dihy dro-1,1 -dimethyl-1H-azirino[l,2-a]indole, 3474 2.2 -Di-tert-butyl-3.3 -bioxaziridinc, 3359 Dicyclopropyldiazomethane, 2824 l,4-Dihydrodicyclopropa[ >, g]naphthalene, 3452 iV-Dimethylethyl-3,3-dinitroazetidine, 2848 Dinitrogen pentaoxide, Strained ring heterocycles, 4748 f 1,2-Epoxybutane, 1609 f Ethyl cyclopropanecarboxylate, 2437 2,2 -(l,2-Ethylenebis)3-phenyloxaziridine, 3707 f Methylcyclopropane, 1581 f Methyl cyclopropanecarboxylate, 1917 f Oxetane, 1222... 

Ascaridole, see l,4-Epidioxy-2-p-menthene, 3341 2-Azatricyclo[2.2.1.02,6]hept-7-yl perchlorate, 2361 AZDN, see Azoisobutyronitrile, 3006 Azelaic acid, 3181 f Azetidine, 1251... 

A number of 2-acylazetidines have been prepared by reaction of 1,3-dihaloacyl compounds with amino derivatives (Section 5.09.2.3.l(m)). This is illustrated for azetidine 2-carboxylic acid (56), the only known naturally occurring azetidine. Ring expansion of activated aziridines (43) and contraction of 4-oxazolines (55) has also found limited use (Section 5.09.2.3.2(f) and Hi)). 

Ring expansion of haloalkyloxiranes provides a simple two-step procedure for the preparation of azetidin-3-ols (Section 5.09.2.3.2(f)) which can be extended to include 3-substituted ethers and O-esters (79CRV331 p. 341). The availability of 3-hydroxyazetidines provides access to a variety of 3-substituted azetidines, including halogeno, amino and alkylthio derivatives, by further substitution reactions (Section 5.09.2.2.4). Photolysis of phenylacylamines has also found application in the formation of azetidin-3-ols (33). Not surprisingly, few 2-0-substituted azetidines are known. The 2-methoxyazetidine (57) has been produced by an internal displacement, where the internal amide ion is generated by nucleophilic addition to an imine. 

Unter Riihren wird zu einer Losung von 0,19 g (5 mMol) Lithiumalanat in 30 ml abs. Diathylather unter Stick-stoff eine Losung von 1,2 g(5 mMol) 2-Oxo-3-phenyl-l-benzyl-azetidin in 50 ml abs. Diathylather getropft. Man kocht die Mischung 24 Stdn. unter RiickfluB, kiihlt ab, versetzt mit 0,5 ml Wasser, riihrt 4 Stdn., filtriert, trocknet das Filtrat mit Magnesiumsulfat und engt ein. Der Riickstand wird aus Diathylathcr/Pctrolathcr kristallisiert Ausbcutc 0,9 g (75"/ d.Th.) F 52-54°. 

In their search for new hgands with a very high binding affinity for the nicotinic acetylchohne receptor (nAChR), potentially useful in positron emission tomography (PET) when radiolabeled with [ F], Horti et al. described the synthesis of BOC-protected 5-(azetidin-2-ylmethoxy)-2-chloro-6 -fluoro-3,3 -bipyridine via a sequential classical heating and microwave irradiation of (2-fluoro-5-pyridinyl)(trimethyl)stannane with f-butyl 2- [(6-chloro-5-... 

From this and < 6(lq), A//f(6, lq) is predicted to be 114 kJmol-1 compared to the experimental value of 122 kJmol-1. The comparatively large discrepancy is suggestive that azetidines, like cyclobutanes, enjoy unusual substituent effects. 

ABT-594 is reported to be in clinical trials for the treatment of neuropathic pain (Thatte, 2000 Sorbero et al. 2001). Its precursor (f )-N-Boc-azetidin-2-yl-methanol is accessible in a short sequence starting from commercially available D-aspartic acid dibenzyl ester. The synthesis is concluded by Mitsunobu coupling with 6-chloropyridin-3-ol and subsequent acidic deprotection. On a larger scale the primary alcohol is activated as a mesylate prior to coupling with 6-chloropyridin-3-ol in the presence of potassium hydroxide, so that Mitsunobu conditions can be avoided (Meyer et al., 2000). 

W. F. Vaughn, R. S. Klonowski, R. 8. McElhinney, and B. B. Millward, J. Org. Chem., 26, 138 (1961). Many investigators have had difficulty in repeating this procedure. Apparently the azetidine tends to be swept out of the reaction mixture with the hydrogen. 

Frau J, Donoso J, Munoz F, Garcia Blanco F. Theoretical calculations of P-lactam antibiotics. III. AMI, MNDO, and MINDO/3 calculations of hydrolysis of P-lactam compound (azetidin-2-one ring). J Comput Chem 1992 13 681-692. 

Cyclization of the furanose derivative 340 was mediated by the action of sodium hydride to afford 341 (R = Ts) in 90% yield. The amine 340 had been obtained from the azide 342 and it was later found that thermolysis of this 1,3-azido alcohol under Staudinger reaction conditions (triphenylphosphine in f-xylene) gave the azetidine 341 (R = H) directly in 99% yield <2003TL5267>. 

The diastereospecific synthesis of novel [3.6.6.4.7]-fused pentacyclic /3-lactams via a novel 6-exo-trig,7-endo- %-tandem radical cyclization has been reported. The use of this method for the construction of a polycyclic system fused to an azetidin-2-one template has been very little exploited. The mixture of /3-lactams 509 and 510 (R = -f 4 I—Cl C. -Cl I—Cl ICH3) in their racemic forms on treatment with tributyltin hydride gave diastereomeric mixtures of tetracyclic 511 and 512 in the same ratio as in the starting materials (Equation 84) <2003TL1827>. 

The names aziridine and azetidine are derived from a reasonably logical system of nomenclature, which assigns three-part heterocycle names according to (a) the heteroatom ( az- = nitrogen, ox- = oxygen, thi- = sulfur) (b) the ring size f-ir- = 3, from trl -et- = 4, from tetra ... 

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