Acetals ring closure with

Moreover, compounds of type 7-127, which were obtained from 7-125 by reaction with Pb(OAc)4, can undergo a further domino process when treated with potassium carbonate in a mixture of water and methanol [57]. This includes saponification of the acetate moieties in 7-127 to provide 7-129 via the unstable cyclic hemiacetal 7-128 (Scheme 7.35). Retro-Claisen reaction and ring closure with the proposed intermediates 7-130 and 7-131 led to the bridged ring-system 7-132 as a mixture of di-astereomers with preference of the (3-isomer. 

The formal total synthesis of the novel /3-lactam antibiotic thienamycin has been accomplished from an isoxazoline derivative generated by [3 + 2] dipolar cycloaddition <79H(l2)l 183). Reaction of the nitrile oxide derived from 3-nitropropanal dimethyl acetal with methyl crotonate gave the isoxazoline (477) regio- and stereo-selectively. The isoxazoline was converted to amino ester (478) by hydrogenation and then to /3-lactam (479) by ester saponification and ring closure with DCC. Treatment of (479) with p-nitrobenzyl chloroformate and reaction of the derived acetal (480) with excess N-p-nitrobenzyloxycar-bonylcysteamine gave thioacetal (481), a compound which has previously been converted into ( )-(8S )-thienamycin (Scheme 106). 

An alternative approach to synthesis of this ring system involves insertion of CO into the brominated secondary base (43), by treatment with carbon monoxide, lead tetra-acetate, and triphenylphosphine in tributylamine, the product being the amide (44), reduction of which affords the amine.81 Govadine (42 R1 = R4 = OMe, R2 = R5 = OH, R3 = H) has been synthesized by the conventional ring-closure, with formaldehyde, of the diphenolic base (45), or of its dibenzyl ether, in acid solution.82 Tetrahydroberberines, together with N-benzyltetrahydroisoquinolines, have also been obtained by the electrolytic reduction of 3,4-dihydroisoquinolines of structure (46).83... 

Brief reference has already been made to the work of Cragoe and his colleagues on the preparation of amino-A-amidinopyrazinecarbox-amides which has led to the development of clinically useful diuretics (see Section V, B 254-260). Aminocarboxamides of type 120 give 4-pteridones (121) on ring closure with triethyl orthoformate in boiling acetic anhydride.330... 

Another strategy is the conversion of isoxazolo[3,4-d]pyridazin-7(6//)-ones (63) via pyrazole derivatives (64) into the new pyrazolo[l, 5 l,6]pyrimido[4,5-c/]pyridazin-7(8//)-ones (65) by final ring closure with acetic anhydride (Scheme 12) <86H(24)3143>. 

Dihydro- and 2,3,5,6-tetrahydro-imidazo[2,l -6 ]thiazoles have been prepared in large numbers by condensation of phenacyl bromides with thiazolines followed by acetylation, sodium borohydride reduction, and ring closure with thionyl chloride and acetic anhydride (Scheme 2) <77JMC563, 66JMC545). 

Also the 18-trimethoxybenzoate (XLV) can undergo the same series of reactions as given for the acetate XLII. Ring closure with phosphorus oxychloride to an analogous quaternary compound (XLVII) can also be carried out with the racemic or optically active lactone XLVI (192). 

Several examples have been reported of similar ring closures with the formation of heterocyclic Y-oxides, Y-hydroxy compounds, or hydroxamic acids [55-58]. For the ring closure of 2-(2-nitrophenylthio)-acetic acid to 4-hydroxy-2Y-l,4-benzothiazine-3(4Y)-one the reduction in an ammonical buffer is preferable [59]. 

In 1892, Michels reported the synthesis of 2-methylselenazoline (68) through the reaction of bis(2-aminoethyl)diselenide (67) with acetic anhydride followed by ring closure with phosphorus pentachloride. The same selenazoline was also prepared from 2-bromoethylamine(hydrochloride) (69) and selenoacetamide [Eq. (17)]. 

In the presence of ammonium acetate, one of the Michael-acceptor systems in 4,5-bis(aryl-methylene)-4,5-dihydropyridazine-3,6-(l//,2//)-diones undergoes addition to ethyl cyanoac-etate at 160-170°C26 or malononitrile in refluxing ethanol.25 This is followed by ring closure with the appropriately situated oxo group and ammonia yielding the pyrido-fused moiety in... 

Sodium acetate Uracil ring closure with change of configuration s. 3, 404 CH3COONa... 

Thehydroxybenzofuranderivative,5-hydroxy-2-oxo-3-phenyl-2,3-dihydrobenzo-furan underwent 2-alkylation and ring closure with 4-(2-n-butoxyethoxy)mandelic acid in acetic acid at 110°C containing sulphuric acid during 9 hours, followed by oxidation by the addition of ammonium persulphate with further reaction at 110°Cfor 1 hour (ref.72). 

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