Cyclodehydration phosphorus oxychloride

Reduction of the imine with sodium borohydride leads to an intermediate amino-ester that cyclizes spontaneously to the <5-lactam function. Solvolysis of the acetyl group with methoxide followed by acylation of the hydroxyl group thus liberated with trimethoxybenzoyl chloride leads to 38. Bischler-Napieralski cyclodehydration (phosphorus oxychloride) effects closure of the remaining ring. Reduction of the imine thus formed with sodium borohydride gives 39. This, it should be noted, leads to the... 

Derivatives of oxazolofS -eNl ltriazines 620 were prepared (87AJC977) by cyclodehydration of the respective 6-acylaminotriazin-5-ones 619, obtained by acylating 618, with phosphorus oxychloride or phosphorus pentoxide. 6-Phenyloxazolotriazines 620 (R1 = Ph) were also obtained directly when aminotriazinones 618 were heated with benzoic acid anhydride. By a different route, 6-aminotriazin-5-one 618 was con-... 

Treatment of the product with phosphorus oxychloride leads to a cyclodehydration reaction possibly via the imino chloride. There is thus obtained the antipsychotic compound loxapine (38-7) [39]. 

AHC(18)337>. The 3-alkylbenzo[6 ]furans result from cyclodehydration of aryloxyacetones the most common dehydrating agents are sulfuric acid, phosphorus oxychloride and poly-phosphoric acid. The allyl ethers of phenols can be converted to 2-alkyl-2,3-dihydro-benzo[6]furan by heating with polyphosphoric acid, pyridine hydrochloride or magnesium chloride at 180 °C the intermediate o-allylphenol is not isolated. 

The indolyl oxazoles are regarded as masked tryptamines, and the published syntheses inevitably employ tryptamine derivatives as starting materials. For the first preparation of pimprinine (70) (Scheme 6), 3-aminoacetylindole hydrobromide 73 was acetylated, and the diacetyl derivative 74 thus formed quantitatively was cyclodehydrated with phosphorus oxychloride to N-acetylpimprinine (75), acid hydrolysis of which yielded 70 (30). 

Cyclization of the alcohols (142) with phosphorus oxychloride gives the derivatives (143) (Equation (10)) <72AHC(l4)i>. The meso-ionic derivatives (145) are produced by cyclodehydration of the acids (144) using acetic anhydride (Equation (11)) <83IJC243>. Reacting amine (146) with ethyl... 

Cyclodehydration of a /J-hydroxyethylamine group to a neighbouring ring-nitrogen is induced by PPA (p. S37), but phosphorus oxychloride may be a more efficient reagent and was recently used in the synthesis of the first member of a tetracyclic ring system. 

Cyclodehydration of a side-chain ketone and lactam thiocarbonyl requires heating with phosphorus oxychloride, PPA or sulphuric acid. 

Thiazoles can also be derived from 1,4-dicarbonyl compounds, which are available through N-H insertion reactions of rhodium carbenoids <04T3967>. For example, the dirhodium(II) carboxylate-catalyzed reaction of diazocarbonyl compound 7 in the presence of primary amide 8 results in the formation of a-acylaminoketone 9, which is converted into thiazole 10 by treatment with Lawesson s reagent. The cyclodehydration of P-keto thioamide 11 to thiazole 12 is carried out with pyridine-buffered phosphorus oxychloride <04JA12897>. 

As described previously, thiazolines are versatile intermediates to thiazoles. In addition, thiazoline rings are structural motifs found in numerous natural products. Among a variety of methods for the construction of thiazolines, the cyclodehydration protocol is perhaps most popular. Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) is used as the cyclo-dehydrating agent for the conversion of 3-hydroxy thioamide 60 to the bis(thiazoline) 15 <04H(63)773>. A more recent protocol for the cyclodehydration of P-hydroxy thioamides to thiazolines involves pyridine-buffered phosphorus oxychloride as exemplified by the formation of 62 from 61 <04JA12897>. 

The chemistry of 1,3,4-thiadiazole has been recently reviewed <04MI405>. The 2-substituted 1,3,4-thiadiazoles 258 are formed by the reactions of thiohydrazides 257 with DMF and diethyl chlorophosphate. This cyclodehydrating agent is superior to several commonly used ones such as ethyl orthoformate, ethyl formate or even phosphorus oxychloride for this type of cyclization <04817>. Reaction of/ -tolualdehyde hydrazone 259 with disulfur dichloride in the presence of DBU gives 2,5-di(p-tolyl)-1,3,4-thiadiazole 260 <04S1929>. 

Cyclodehydration of 3-carboxymethylthio-1,2,4-triazoles (215) with acetic anhydride or phosphorus oxychloride yields 5,6-dihydrothiazolo[3,2-( ][l,2,4]triazol-2-ones (216) (Equation (55)) <83JPR869, 88MI 805-01,91IJC(B)38>. 

The key to this approach was the formation of the oxazole ring in the presence of the thiazoline rings. Cyclization of 1298 with Burgess reagent" gave the expected intermediate oxazoline (not shown), but this could not be oxidized to 1299 using Ni02, NBS/benzoyl peroxide, or CuBr/tert-butyl perbenzoate. Thionyl chloride, phosphorus oxychloride, titanium tetrachloride, or triphenylphosphine/iodine did not effect cyclodehydration of the p-ketoamide produced from the Dess-Martin periodinane oxidation. 

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