Benzene with 1,2-dicarbonyl compounds

Prakash, Olah, and co-workers256 have prepared Mosher s acid analogs by the hydroxyalkylation of substituted benzenes with ethyl trifluoropyruvate [Eq. (5.95)]. Deactivated aromatics (fluorobenzene, chlorobenzene) required the use of excess triflic acid indicative of superelectrophilic activation.3 5 In contrast to these observations, Shudo and co-workers257 reported the formation gem-diphenyl-substituted ketones in the alkylation of benzene with 1,2-dicarbonyl compounds [Eq. (5.96)]. In weak acidic medium (6% trifluoroacetic acid-94% triflic acid), practically no reaction takes place. With increasing acidity the reaction accelerates and complete conversion is achieved in pure triflic acid, indicating the involvement of diprotonated intermediates. 

A large proportion of the condensation products of sugars with dicarbonyl compounds have been obtained in the crystalline state however, some have not yet been crystallized. All are more soluble in hot than in cold water. Those resulting from the condensations with heptoses, hexoses, and pentoses are almost insoluble in benzene. Generally speaking, all are soluble in ethyl acetate. 

Bacteriochlorins, 851 Barbituric acid metal complexes, 798 Barium alkoxides synthesis, 336 Barium complexes phthalocyanines, 863 porphyrins, 820 Becium homblei copper accumulation, 964 Benzaldehyde, 2-amino-self-condensation aza macrocycles from, 900 Benzamide, o-mercapto-metal complexes, 655 Benzamide oximes metal complexes, 274 Benzamidine, /V, V -diphenyl-metal complexes. 275 Benzene, 1,2-diamino-reactions with dicarbonyl compounds aza macrocycles from, 902 Benzene, 4 methylthionitroso-metal complexes, 804 Benzenedithiolates metal complexes, 605... 

Scheme 3b). It is instructive at this point to reiterate that the furan nucleus can be used in synthesis as a progenitor for a 1,4-dicarbonyl. Whereas the action of aqueous acid on a furan is known to provide direct access to a 1,4-dicarbonyl compound, exposure of a furan to an alcohol and an acid catalyst should result in the formation of a 1,4-diketal. Indeed, when a solution of intermediate 15 in benzene is treated with excess ethylene glycol, a catalytic amount of / ara-toluenesulfonic acid, and a trace of hydroquinone at reflux, bisethylene ketal 14 is formed in a yield of 71 %. The azeotropic removal of water provides a driving force for the ketalization reaction, and the presence of a trace of hydroquinone suppresses the formation of polymeric material. Through a Finkelstein reaction,14 the action of sodium iodide on primary bromide 14 results in the formation of primary iodide 23, a substance which is then treated, in crude form, with triphenylphosphine to give crystalline phosphonium iodide 24 in a yield of 93 % from 14.

The standard method for the preparation of 3//-1.5-benzodiazepines 2 is the condensation of benzene-1,2-diamine with 1,3-dicarbonyl compounds. Selected examples are given.255... 

In some cases the reaction of a 1,3-dicarbonyl compound with benzene-1,2-diamine yields 3//-1,5-benzodiazepines which are sufficiently stable to be isolated as the free bases. 

Benzodiazepines are also formed by the reaction of benzene-1,2-diamine with synthetic equivalents of 1,3-dicarbonyl compounds. l-Ethoxy-l,3,3-trimethoxypropane, for instance, gives the parent benzodiazepine, which is isolated as the perchlorate 9.257... 

On a commercial scale, furan is obtained from 2-formylfuran (furfural, furan-2-carbaldehyde) (see Section 6.2.7) by gas-phase decarbonylation, but in the laboratory, furans can be formed by the cyclodehydration of 1,4-dicarbonyl compounds. Heating in boiling benzene with a trace of /7-toluenesulfonic acid as a catalyst in a Dean-Stark apparatus is often effective (Scheme 6.30a). 

The reaction between 1,3-dicarbonyl compounds 1 and hydrazines is the most general method for preparing l//-pyrazoles 2 (Scheme 2).2-4,5 If a 2,2-disubstituted 1,3-diketone is employed (1 R3, R4 H), reaction with hydrazine hydrate gives instead a 4//-pyrazole 3, as was first reported by Knorr.Sa Generally, the reactants are heated under reflux in a solvent such as methanol, ethanol, benzene, or carbon tetrachloride yields range from 50% to quantitative. 

V-Aminopyrroles, easily prepared from the reaction of azoalkenes with enamines and /3-dicarbonyl compounds, have been shown to react with electron deficient alkynes to afford substituted benzenes (79TL2969). While the N-methoxycarbonylaminopyrrole (208) reacted with DM AD under rather vigorous conditions to afford (211) in only 13% yield, the N-unsubstituted aminopyrrole (209) prepared from (208) by NaCN treatment reacted with DMAD in CHC13 solution at room temperature to give (211) in 50% isolated yield. The formation of the aromatic system probably occurs by extrusion of the heteroatom bridge from (210) to afford a relatively stable nitrene (212 Scheme 45). 

One of the most general pyrrole syntheses is the cyclizative condensation of 1,4-dicarbonyl compounds with ammonia, a primary amine or related compound. The mechanistic pattern involves formation of carbinolamine and imine intermediates followed by aromatization. This method is sometimes referred to as the Paal-Knorr pyrrole synthesis (equation 65) (B-77MI30601). Once the dicarbonyl compound is available, the cyclization normally proceeds in good yield, so ease of access to the diketone is of major importance in determining the applicability of this method to specific pyrroles. Pyrrole formation usually takes place on heating the diketone in a solvent such as benzene or toluene with a catalytic amount of acid. An alternative method involves heating the dicarbonyl compound and an amine salt... 

Sequential addition of hydrogen sulfide to an a,/3 -unsaturated ketone, followed by condensation with an a -dicarbonyl compound, leads directly to thiophenes. Thus addition of hydrogen sulfide to a benzene solution of cyclohexenone, followed by an a -dicarbonyl compound and reflux, gave the respective 6,7-dihydro-5//-benzo[6]thiophene-4-ones (274). Compounds were obtained by this method where R1 and R2 = H, R1 = Ph or Me and R2 = H, and where R1 = R2 = Me (71lJS(A)(i)62). This is closely related to a patented process previously described (cf. Section 3.15.3.4). 

The use of triflic acid in the alkylation with other dicarbonyl compounds, such as isatins,258 parabanic acid,259 and ninhydrin,260 has also been explored. A significant acidity dependence was found in the reaction of isatin with benzene.258 Alkylation does not take place in the presence of trifluoroacetic acid (Ho = —2.7) at 25°C in 12 h. Adding 22% of triflic acid (//0 10.6) brings about a 90% yield of the 3,3-... 

In the intermolecular mode, this reaction has been utilized for the preparation of products 28 from various nucleophiles, including C-nucleophiles (e. g. (3-dicarbonyl compounds). A similar reaction in the intramolecular mode provides a powerful synthetic tool for the preparation of various polycyclic compounds via oxidative biaryl coupling [21,27 - 30]. Several examples of these C-C bond forming reactions are shown in Schemes 13-15. Specifically, various dibenzoheterocyclic compounds 30 have been prepared by the oxidation of phenol ether derivatives 29 with [bis(trifluoroacetoxy)iodo]benzene in the presence of BF3-etherate in dichloromethane (Scheme 13) [27-29]. 

Diphenyl diselenide is an especially useful co-reagent with [bis(acetoxy)-iodo]benzene. For example, the BAIB/PhSeSePh (2 1) combination has been employed for trans, Markovnikov additions of PhSeOAc and PhSeOH to alkenes [35]. Such formal additions appear to be regulated by seleniranium intermediates, and were extended to intramolecular cyclizations of olefinic alcohols, carboxylic acids, and / -dicarbonyl compounds (Scheme 12). 

Similar oxygen stabilized ethylene dications were proposed in several types of superacid-catalyzed condensation reactions involving 1,2-dicarbonyl compounds. For example, 2,3-butanedione condenses in high yield with benzene and the superelectrophile (35) is considered to be the key intermediate, because the monoprotonated species (78) is not sufficiently electrophilic to react with benzene (eq 17).35 Several biologically important a-ketoacids were also found to generate superelectrophiles... 

An important modification is reaction of p-dicarbonyl compounds with [hydrox y(tosyloxy)iodo]benzene and selenourea as a one-pot synthesis [177], Similarly, a-tosyloxylation of acetophenones, cyclohexanone, or pentan-3-one with the same reagent, followed by treatment with arylselenobenzamides, gives 2,4-disubstituted and 2,4,5-trisubstituted 1,3-selenazoles [178],... 

The starting compound 251 was reduced to 252 with sodium borohydride. The latter was heated under reflux in 6% sulfuric acid in methanol to afford compound 253. Treatment of the latter with maleic anhydride at 170° for 3 hr afforded compound 254. Bisdecarboxylation of 254 with dicarbonyl bistriphenylphosphinenickel in anhydrous diglyme under nitrogen at reflux temperature for 6 hr afforded the olefin 255 in 69% yield (171). The latter was reduced with lithium aluminium hydride to the primary alcohol 256, which was oxidized to the aldehyde 257 with Ar,A -dicyclohexylcarbodiimide, dimethyl sulfoxide and pyridine in dry benzene. Treatment of the aldehyde 257 with an excess of the Grignard reagent prepared from l-bromo-3-benzyloxybutane afforded a mixture of diastereoisomers represented by the structure 258. 

Reaction of 2-(4-nitrophenylsulfonyloxy)-l, .3-dicarbonyl compounds 31 with a base (e.g., tri-ethylamine or l,8-diazabicyclo[5.4.0]undec-7-ene) gives 1,2,3-tricarbonyl compounds32 in high yield. The tricarbonyl compound can be further reacted, without isolation, with benzene-1,2-di-aminc to give quinoxalines 33 in excellent yields. ... 

---