Guanidines 250 arylation

Amidines and related systems such as guanidines react with a-halogenoketones to form imidazoles. a-Hydroxyketones also take part in this reaction to form imidazoles, and a variety of substituents can be introduced into the imidazole nucleus by these procedures. Reaction of the a-halogenoketone (73) with an alkyl- or aryl-substituted carboxamidine (76) readily gave the imidazole (77) (01CB637, 48JCS1960). Variation of the reaction components that successfully take part in this reaction process is described in Chapter 4.08. 

Ultraviolet spectral comparisons indicate that structure 107 predominates over 108 when R = H or OH, but that 107 is the predominant form when R = aryl. - Similarly, 109 predominates over 110 by a large factor when R = H, OH, or Me, and by a smaller factor when R is a higher alkyl group, but 110 predominates when R is an aryl group. (For a discussion of guanidine derivatives corresponding to 110, see reference 110.)... 

A (pentamethylcyclopentadienyl)iridium chelating guanidinate complex has been conveniently prepared by treatment of [Cp IrCl2]2 with N,N, N"-th-p-tolylguanidine and base in THF at room temperature followed by recrystallization of the green product from toluene and pentane (Scheme 154). Insertion reactions of the product with heterocumulenes (diaryl carbodiimides, aryl isocyanates) have been investigated. It was found that the complex serves as highly active catalyst for the metathesis of diaryl carbodiimides with each other and for the more difficult metathesis of diaryl carbodiimides with aryl isocyanates (cf. Section V.C). ... 

In the case of 4-(./V,./V -diaryl)guanidines 64, base-induced cyclization occurs at carbon bearing the methylthio to give the corresponding 7-aryl-6-arylamino-2-methyl-777-[l,2,4]triazolo[4,3- ][l,2,4]triazol-3(2//)-thiones 65 (Equation 12) <1986H(24)3363,1987JP(1)2667>. 

The reaction may be carried out successfully by the conventional fusion-technique. In the course of the s5mthesis of numerous aryl- and alkyl-biguanides by this procedure, the substituted guanidine rather than the biguanide was occasionally formed in a side reaction. In such cases the biguanide first formed may be cleaved partially by way of an intramolecular hydrogen-bonded form (602) (cf. section VI, B3). 

Many different alkyl- and aryl-guanidines have been obtained by this procedure [85, 86, 111, 119-132], as have alkoxyguanidines [97, 133], and benzoylguanidines [134, 135]. 

An important development of the synthesis described above is derived from the observations of Scott, O Donovan and Reilly [159], which were taken up by others [109]. l-Guanyl-3,5-dimethylpyrazole nitrate reacts with alkyl- and aryl-amines in hot water, ethanol, or without solvent to give good yields of guanidines. Use of this pyrazole nitrate or other salt for obtaining guanidines now competes with older methods if yield and ease of isolation of the product are the main considerations [95, 138, 140, 143, 160-164]. 

Ishikawa and co-workers also reported a class of structurally modified guanidines for promotion of the asymmetric Michael reaction of ierf-butyl-diphenylimino-acetate to ethyl acrylate [124,125]. In addition to a polymer support design (Scheme 69), an optical resolution was developed to achieve chiral 1,2-substituted ethylene-l,2-di-amines, a new chiral framework for guanidine catalysis. The authors discovered that incorporating steric bulk and aryl substituents in the catalyst did improve stereoselec-tivitity, although the reactivity did suffer (Scheme 70, Table 4). 

Tan also found that guanidine 21, acting as a base to activate the o [3], X [3] tautomers of diaryl phosphine oxides, catalyzes the asymmetric phospha-Michael reachon of aryl nitroalkenes (Scheme 5.42) [76]. He later employed 21 to realize highly enantioselective Michael additions of dithiomalonate and 3-keto thioesters with a range of acceptors, including maleimides, cyclic enones, furanone, and acyclic 1,4-dicarbonylbutenes [77]. 

Substituted malondialdehydes form pyrimidines substituted in the 5-position with an alkyl, aryl, halo, or hetero substituent. The pyrimidine is unsubstituted in the 4- and 6-positions. /3-Dialdehyde equivalents are frequently used in these reactions, for example, 3-alkoxy- or 3-aminoacroleins. With aldehydo ketones, the pyrimidine carries a substituent in the 4- or 6-position. The formyl group in the ketone is normally masked as an alkoxymethylene ketone or as an aminomethylene ketone. A commonly used procedure involves the preparation of a dimethylaminomethyl-ene ketone 645 by reaction of a methyl ketone 644 with DMF dimethylacetal and subsequent reaction with an amidine or guanidine to form the target pyrimidine 646 <2003MI237, 2004JHC461>. 

The first derivatives of the 4(5/f)-oxazolone ring system 1 were prepared almost 90 years ago when Traube and Ascher described the synthesis of 2-amino-4(5H)-oxazolones (pseudohydantoins) 2 via condensation of guanidine with a-hydroxy esters (Scheme 6.1). This is quite remarkable in that it was 36 years later before Sheehan and Izzo prepared the hrst example of a simple 2-aryl analogue via... 

Aus Anilino-guanidin werden mit a -Brom-acetophenonen 4-Aryl-2-(2-phenyl-hydrazino)-imidazole und nicht die ebenfalls als Produkte denkbaren 2-Amino-l-anilino-imidazole erhalten106 (s.a. Bd.X/2, S. 739) ... 

Analogerhalt man aus (Benzylidenamino)-guanidin die entsprechenden 4-Aryl-2-(2-benzyl-iden-hydrazino)- bzw. 2-(2-Benzyliden-hydrazino)-4,5-diary 1-imidazole107,108 ... 

Bei der Thermolyse kondensieren (per)fiuorierte Aryl-guanidine in einer nukleophilen Substitution zu Benzimidazolen die nicht fluorierten Analoga ergeben Carbodiimide124 ... 

Scheme 14 shows a typical example in a series of reactions in which a supported amino acid reacted with fluorenylmethoxycarbonyl isothiocyanate to give a supported (on Rink s amide)35 thiourea.36 Removal of the protection followed by 5-alkylation gave supported isothioureas. Reaction of these with amines, then cleavage from the resin, afforded substituted guanidines. For 10 examples the purities were between 40 and 92%. An aryl group separates the resin from the guanidine, just as in the sequences shown in Schemes 11 and 12. 

Barvian, M. R. Showalter, H. D. H. Doherty, A. M. Preparation of N,N Bis(aryl)guanidines from Electron Deficient Amines Via Masked Carbodi-imides, Tetrahedron Lett. 1997, 38, 6799-6802. 

A polymer-bound guanidine base 31 has been used for the formation of aryl ethers from suitable phenols and alkyl halides. In addition to serving as a base to affect deprotonation, reagent 31 also acts as a sequestering agent for excess starting phenol (reaction 11).26... 

More decisive evidence is provided by the interconvertibility of N-aryl-JV-arylamidinothioureas (28) and Hector s bases by oxidation-reduction.63, B4,67b The former compounds are accessible (as salts) (i) by the condensation of arylthioureas (24) with arylcyanamides (23),63 (ii) by the extrusion of sulfur from the recently described40,41 s-diaryldithioformamidine hydrobromidesB4a (22), (tit) by the oxidation of arylthioureas (24) with 0.5 moles of hydrogen peroxide in the presence of mineral acids,B4a and (iv) by the mild reduction of Hector s bases by hydrogen sulfide in acid media.B4a The first of these four reactions limitB the structure of the products to the three alternatives 25, 28, and 30. Of these, 25 is excluded by the non-identity of the product with authentic67 N-phenyl-i -phenylamidinothiourea (25 R = Ph). The monosulfide structure (30) is not reconciled as readily with the observedB4a hydrolytic fission of the products into diaryl-guanidines (29) and thiocyanic acid as is structure 28. Indeed, as in the case of thioamides and nitriles (see Section II, C, 1), the present condensation may involve the primary formation of an intermediate diimido-monosulfide (30) and its isomerization to 28. 

Di(alkyl or aryl)amino-l,2,4-thiadiazoles (90 R,R = alkyl or aryl) are similarly obtainable in 60-85% yields from the appropriate disubstituted amidinothioureas (89 R,R = alkyl or aryl).56,57 The preparation of the latter from monosubstituted guanidines (87) and isothiocyanate esters (88) might conceivably yield the isomeric ami-... 

Like the inorg compds of the azido acid, and unlike the alkyl and aryl derivs, the guanidine salt is photosensitive. In the dark it may be stored below 10°, in vacuo, for days without appreciable decompn. On long standing at RT, the salt decomps quanty, yielding Na, sulfur and guanidine thiocyanate. In aq soln the azido salt reacts with AgNOs to form the insol Ag azidodithiocarbonate... 

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