Cyclization acid chloride activation

Preparation of thiadiazoles via the Hurd-Mori cyclization has led to the synthesis of a variety of biologically active and functionally useful compounds. Discussion of reactions prior to 1998 on the preparation of thiadiazoles have been compiled in a review by Stanetty et al Recent syntheses of thiadiazoles as intermediates for useful transformations to other heterocycles have appeared. For example, the thiadiazole intermediate 36 was prepared from the hydrazone 35 and converted to benzofuran upon treatment with base. Similarly, the thiadiazole acid chloride 38 was converted to the hydrazine 39 which, upon base treatment, provided the pyrazolone, which can be sequentially alkylated in situ to provide the product 40. ... 

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

Acyl-transfer reactions are some of the most important conversions in organic chemistry and biochemistry. Recent work has shown that adjacent cationic groups can also activate amides in acyl-transfer reactions. Friedel-Crafts acylations are known to proceed well with carboxylic acids, acid chlorides (and other halides), and acid anhydrides, but there are virtually no examples of acylations with simple amides.19 During studies related to unsaturated amides, we observed a cyclization reaction that is essentially an intramolecular acyl-transfer reaction involving an amide (eq 15). The indanone product is formed by a cyclization involving the dicationic species (40). To examine this further, the related amides 41 and 42 were studied in superacid promoted conversions (eqs 16-17). It was found that amide 42 leads to the indanone product while 41... 

Optically active namral and unnamral amino acids as well as various cyclic amino alcohols have been utilized in the synthesis of a wide variety of bis(oxazo-line) ligands. As previously mentioned, the first bis(oxazoline) ligands, py-box la-d, were synthesized by Nishiyama and co-workers in 1989. The common material for their syntheses was pyridine 2,6-dicarboxylic acid 19. Conversion of 19 to the acid chloride was achieved by treatment with thionyl chloride, as illustrated in Figure 9.4. This was followed by condensation with (5)-valinol in the presence of triethylamine. Conversion of the resulting bis(amidodiol) 20 to py-box-ip lb was achieved by sequential treatment of 20 with thionyl chloride at 50 °C followed by cyclization with aqueous sodium hydroxide in methanol to afford py-box-/p lb in 60% overall yield. The same synthetic scheme can be used to obtain the other... 

The key sequence in a somewhat involved stereospecihc total synthesis of a carbacephem starts by preparation of a chiral auxiliary. It is interesting to note that nitrogen is the only atom from this molecule retained in the hnal product. Constmction of this moiety starts with the formation of the carbethoxy derivative (37-2) from L(- -)-phenylglycine (37-1). Selective reduction of the free carboxyl group with borane. THF leads to the hydroxycarbamate (37-3). In a one-pot sequence, this is first cyclized to the corresponding oxazolidinone (37-4) by means of sodium hydride and then alkylated with ethyl bromoacetate (37-5). Saponification of the side chain then affords the chiral acetic acid (37-6). The carboxyl group is then activated by conversion to its acid chloride (37-7). 

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