Cyclocondensation

Y = benzotriazol-1-yl, benzotriazol-2-yl, or X X = alkyl, aryl, OH, OR, NRCOR, carbazol-9-yl, etc. 

Compound 642, obtained by condensation of glyoxal with benzotriazole and morpholine undergoes interesting [2+3] cyclocondensation with 2-aminopyridine to give imidazo[l,2- ]pyridine 643 (Equation 15) 2003JOC4935 . Similar derivatives of piperidine and pyrrolidine are also described. 2-Amino- and 6-aminopyrimidines react similarly to give imidazo[l,2- ]- and imidazoll - pyrimidines, respectively. 

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In the reverse reaction, thioheteroaryl amides reacted under reflux in alcohol with haloketones or aldehydes to give the corresponding 2-heteroarylthiazole derivatives (238, 271, 482, 550, 751, 765, 776, 781). 2,2 -Bithiazoles (4,4 -disubstituted) have been obtained in 80 to 90% yield by cyclocondensation of 1 mole rubeanic acid with 2 moles of a-bromoketones in polyphosphoric acid at 95 to 135 C (780). Some multiheteroaryl substituted thiazoles have been also reported (704). 

Lactones are piepaied from formaldehyde and carbon monoxide by cyclocondensation with propylene glycol in the presence of a strong acid and a Cu(l) or Ag carbonyl catalyst (20). 

Ketopantolactone (19) is conveniently prepared by oxidation of (R,5)-pantolactone (18). Various oxidising agents have been patented for the oxidation of pantolactone, such as MnO ( 1)> DMSO—AC2O (32), and hypohahtes (33). An improved yield of ketopantolactone (19) via electrolytic oxidation of pantolactone with an aqueous solution containing an alkaH metal salt was reported (34). Ketopantolactone (19) has been prepared in good yield via cyclocondensation of the 2-keto-3-methylbutyrate (20) with formaldehyde (35). 

As shown in Scheme 2, two heteroatom-carbon bonds are constructed in such a way that one component provides both heteroatoms for the resultant heterocycle. By variation of X and Z entry is readily obtained into thiazoles, oxazoles, imidazoles, etc. and by the use of the appropriate oxidation level in the carbonyl-containing component, further oxidized derivatives of these ring systems result. These processes are analogous to those utilized in the formation of five-membered heterocycles containing one heteroatom, involving cyclocondensation utilizing enols, enamines, etc. 

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

The syntheses of ring-fused systems with both C—C and C—-N fusion points are particularly suited for cyclocondensations of this type. Treatment of the 4,5-diaminopyrazole... 

Several reactive species which may be considered bielectrophilic equivalents (Type 4, Scheme 5) have been utilized in cyclocondensations. The aryl-substituted dicyanooxirane... 

This process is not as common as the other oxidative procedures and usually involves ring closure onto an aromatic or heteroaromatic ring. The following examples illustrate the structural types required for this cyclocondensation. 

Cyclobut[/lisobenzofuran, 1,3,4,7-tetrahydro-nomenclature, 1, 20 Cyclocondensation alkynes, 1, 672... 

Amino-l,2,4-triazole undergoes a cyclocondensation with 3-etlioxyacrolein (7) to form 1,2,4-triazolo[l,5-a]pyrimidine (3) or its [4,3-u] isomer (5), according to whether it reacts as IH or 4H tautomer 2 or 4. Moreover, the pyrimidines 3 and 5 can interconvert by a Dimroth rearrangement. Since the H NMR spectrum 30a does not enable a clear distinction to be made AMX systems for... 

The original compound, maleimide (2,5-dioxo-A -pyrroline), is synthesized by the cyclo-condensation of ammonia and maleic acid. Similarly, primary amine is added to maleic anhydride, followed by cyclocondensation, to form N-substituted maleimide (Fig. 2). This reaction is applied to the preparation of bis-maleimides (BMl) [1]. At first, BMI was used as a crosslinking agent for natural rubber (NR). An o-dichlorobenzene solution of NR was crosslinked by BMI at I08-150°C in the presence of peroxides. The radicals generated from peroxides react with the double bonds of both BMI and NR [ 1 ]. 

Cyclocondensation reactions starting from two components are possible only when both of them have two reactive centers An initial electrophilic-nucleophilic interaction yielding a linear product is followed by a second electrophilic-nucleo-... 

Cyclocondensation reactions with perfluoroalkyl-subsbtuted CO and CN multiple bond systems can be divided into several subgroups, according to the charge pattern of both reactants On the basis of this simple concept, hetero-l,3-dienes should undergo two types of condensation reactions, classified by the number of skeleton atoms of the diene being incorporated into the ring system (equation 10). 

Bis(trifluoromethyl)-substituted pyrimidines are also available fromtrifluoro-acetonitrde on reaction with enamines and ynamines [d ] With dimethylami-nocrotonates, a cyclocondensation takes place to give 2-pyridones. 5-Cyano-6-trifluoromethyluracil is available via a similar route [95] (equation 18)... 

In a related cyclocondensation six-membered rings containing the NSeN functionality may be prepared by the reaction of imidoylamidines with SeCU (Eq. 2.10). 

The cyclocondensation route is also effective for the synthesis of planar C2N4S2 rings from benzamidines and sulfur dichloride in the presence of a strong base (Eq. 2.11). ... 

The cyclocondensation of trimethylsilyl azide with a bis(sulfenyl chloride) is an efficient synthesis of dithiazolium cations (Section 11.3.5) (Eq. 2.15). ... 

A more versatile synthesis of 11.1 (and the selenium analogue) involves the cyclocondensation of trisilylated amidines with sulfur dichloride or SeCl2 generated in situ (Eq. 11.3). This route can be used to prepare the prototypal systems [HCNEEN]" (E = S, Se). It is also readily extended to the synthesis of multi-dichalcogenadiazolium cations such as 1,3- or 1,4-C6H4(CNEEN)2] (H-2, E = S, Se), °... 

The primary route to 1,3,2-dithiazolium salts involves the cyclocondensation of l,2-bis(sulfenyl chlorides) with trimethylsilyl azide, which is illustrated for benzo-fused derivatives in Eq. 11.11. ° This method can be extended to the synthesis of bis( 1,3,2-dithiazolylium) salts. 

Dithiatetrazocines, 12.20 (R = Ph) and 12.21, were first prepared by the cyclocondensation of benzamidine or dimethylguanidine, respectively, with SCI2 in the presence of a base. The yields are low. 

The 1,5-isomers 13.3 (E = S) are colourless, air-stable solids. They are prepared by the cyclocondensation reaction of R2PN2(SiMe3)3 with sulfur dichloride or thionyl chloride. A similar cyclocondensation process, using a mixture of SeCU and Sc2Cl2 as a source of selenium, produces a mixture of the isomers 13.2 and 13.3 (E = Se, R = Ph). The structures of 13.3 (E = S, R = alkyl, aryl) are folded eight-membered rings with a cross-ring S S distance of ca. 2.50 This structural... 

Tellurium chemistry is often significantly different in comparison with selenium chemistry owing to the larger size and metallic character of tellurium (Section 1.1). As an illustration, the cyclocondensation of... 

Attempted dehydrocyclization of the 6-acylhydrazinopyrimidine 65 by heating with polyphosphoric acid led, instead, to pyrimidine ring rupture, yielding the l,l-diamino-2-nitro-2-(3-phenyl-l,2,4-triazol-5-yl)ethene 66. Cyclocondensation of the latter with triethyl orthoformate gave the fully aromatic triazolopyrimidine 67 (94JHC1171) (Scheme 23). 

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