Starting materials 1,4-dicarbonyl

The Feist-Benary furan synthesis occurs when an a-halocarbonyl (1) reacts with a P-dicarbonyl (2) in the presence of a base. The resulting product (3) is a 3-furoate that incorporates substituents present in the two starting materials. ... 

In the case of NH2OH with a sharp difference in the nucleophilicity of the two functions, the primary amino group reacts with the carbocation C-1 center. For example, the reaction of l-alkylaminoalk-l-en-3-ynes with hydroxylamine leads to selective synthesis of alkylisoxazoles (69ZOR1179). A preparative value of this method is evident because the use of dicarbonyl compounds as starting materials for the synthesis of alkylisoxazoles results in a mixture of isomers. 

The obvious Vfittig disconnection gives stabilised ylid (5fi) and keto-aldehyde (57). We have used many such long-chain dicarbonyl compounds in this Chapter and they are mostly produced from available alkenes by oxidative cleavage (e.g. ozonolysis). In this case, cyclic alkene (58) is the right starting material, and this can be made from alcohol (59) by elimination,... 

Dicarbonyl disconnection of symmetrical (38) again reveals a suitable 1,6-dicarbonyl starting material (39) but reconnection gives an impossibly strained alkene (40). 

The cis stereochemistry of (7) is irrelevant to (10 or (11), as cyclisation can give only ais fusion of two five-membered rings, but it might be a problem for (9). In any case, no disconnection, other than removing single carbon atoms, can easily be made on (9). Much the same is true of (12), but reconnection of the 1,6-dicarbonyl in (13) provides a good starting material (14). 

The starting material is aspirin. The acetyl group in (35) is an activating group, present to allow the synthesis of (35) and removed by 1,3-dicarbonyl cleavage. The strategy is therefore a 1,5-dlcarbonyl disconnection to (37) and a 1,3-dicarbonyl disconnection to (38). 

Diaminofurazans 156 are useful starting materials for the synthesis of fused heterocyclic compounds. For example, 3,4-diaminofurazans 156 reacted with dicarbonyl compounds (e.g., with ct-keto acids) to produce a series of 5-hydroxy[l,2,5]oxadiazolo[3,4-A pyrazines 163 (Equation 26) <2003BML3133>. 

In addition to the abovementioned results consisting only the increasing yields (Scheme 6) [38], another example of effective microwave-assisted synthesis of azolopyrimidine carboxamides should be described. Tu et al. [47] reported eco-friendly three-component reaction of 2-aminobenzimidazole, aromatic aldehydes, and some p-dicarbonyl compounds under microwave irradiation (Scheme 8). It was shown that the treatment of the starting materials can be most efficiently carried out at 90°C (200 W MW power) in water medium instead of traditional organic solvents like ethanol, acetic acid, or DMF. 

In classical Hantzsch procedure, an enaminocarbonyl is formed in sim by condensation of ammonia source onto the 1,3-dicarbonyl substrate. But many groups have used a three-component modified-Hantzsch protocol in which the preformed enamine is introduced as a partner. Thus, utilization of cyclic or acyclic 1,3-dicarbonyl compounds, aldehydes, and acyclic or cyclic enamines has been reported, leading regioselectively to diversely substituted 1,4-DHP derivatives (Scheme 7). The sequence involving such starting materials was performed in numerous efficient systems, and more particularly in the following (1) microwave-assisted reaction in acetic acid [50], DMF [51], or an acetic acid/DMF system [52] (2) sonification in ethylene glycol [53] and (3) use of ionic liquids such as [bmim]BF4 [54]. 

Next, you need to determine how to produce the ester in Figure 17-3. (This is a (3-dicarbonyl compound like the starting material. This relationship may be important.) One way to produce this ester is shown in Figure 17-4. This step requires you to start with a carbanion, which can form through the reaction of a strong base with a (3-dicarbonyl compound. This step is in Figure 17-5. We use the t-butoxide ion as the base, but other bases are acceptable. 

In the second study, diketones were used as electrophiles and reacted with N-benzoylglycine to give a (Z/E) mixture of oxazolones 366 and 367 derived from condensation at the less hindered carbonyl group of the 1,2-dicarbonyl compound (Scheme 7.116). The ( )-isomers 367 were used as starting materials to prepare (Z) -5 - alky lidene- 3 - (benzoy lamino) -2(5//)-furanones 368... 

Methylthiopyrimidine-4,5-dicarbonyl chloride 242, obtained by hydrolysis of the diester followed by reaction with oxalyl chloride, serves as a suitable starting material for the formation of 243 (Equation 87). The corresponding aniline and benzylamine were employed in the synthesis of 243a and 243b <2000MI19>. 

Two pyridopyrazine-fused heterocycles can be presented here, having either a [2,3- ] or a [3,4- ] junction more work has been published on the first type than on the second one. o-Diaminopyridine derivatives are the main starting materials used for constructing such fused ring systems by condensation with a-dicarbonyl compounds. 

Treatment of a readily enolizable 1,3-dicarbonyl derivative with a mixture of diethylzinc and diiodomethane generates a 1,4-dicarbonyl by a chain extension process through the corresponding cyclopropanol derivative (equation 23) . Several enolizable starting materials such as / -ketophosphonates °, / -keto amides and amino acid skeletons have been subjected to these chain extension conditions. 

Pyrrole synthesis from at-dicarbonyl compounds.15 A new approach to N-benzyl-pyrroles is formulated for biacetyl as starting material (equation I). The method is also suitable for annelation of a pyrrole group to an a-methylene carbonyl compound. 

Dicarbonyl compounds with a double bond in the 2,3-position condense with hydrazine to give pyridazines (e.g. 91 — 92). If one of the carbonyl groups in the starting material is part of a carboxyl group or a potential carboxyl group, then reactions with hydrazines or hydroxylamine lead to pyridazinones or 1,2-oxazinones (e.g. 93 — 94 Z = NH, NPh, O). Similarly a cyano group leads to an amino or imino product. 

Quite unusual processes were observed in the reactions of dimethy-laminomethylenedicarbonyl compounds 180 with the diethyl acetal of N,N-dimethylacetamide. In these cases, the latter compound reacts as an 0,N-acetal and the reaction results in the formation of new dienediamino dicarbonyl compounds 181, which in turn serve as the starting materials for the synthesis of pyridine derivatives (86KGS127 87KGS423,87KGS1470). 

These methods [which are known as the Paal-Knorr (pyrrole and furan) or Paal (thiophene) syntheses] are applicable to other 1,4-dicarbonyl compounds, the limitation being the accessibility of the dicarbonyl starting material. 

Substituted imidazole 1-oxides 228 can be prepared by N-oxidation of imidazoles 248, by N-alkylation of 1-hydroxyimidazoles 249, or by cycliza-tion using suitable starting materials derived from a 1,2-dicarbonyl compound, an aldehyde, an amine, and hydroxyamine. The substituents at the three first starting materials are transferred to the product and make control over the substituents in the imidazole 1-oxide 228 possible depending on the protocol used by the synthesis. The synthesis of 3-hydroxyimidazole 1-oxides is presented in Section 3.1.6. 

It is however possible to make such compounds in good yield from 1,3-dicarbonyl starting materials. Another isomer of 13 and 19 is the branched ketone 28. Disconnecting by a method from chapter 13, we can use the acid derivative 29 which could be made from malonate 31 by two alkylations via 30. 

This is a 1,6-dicarbonyl compound so reconnection to the cyclohexene 16 is needed. Top tip write the numbers 1-6 both on the target molecule 15 and on the starting material 16 to make sure you put the substituents on the right atoms. Now FGI and removal of the methyl group reveals a simple cyclohexanone 18. 

It might be better to start on the carbonyl disconnections immediately. The most obvious come from the 1,3-dicarbonyl relationship 50b, c and suggest two keto-ester starting materials 54- and 55. 

Other starting materials for adipic acid include butadiene and 1,4-disubsti-tuted-2-butene, which involves dicarbonylation with palladium chloride. Polar, aprotic, and nonbasic solvents are preferred for this reaction to avoid unwanted side products from hydrogenolysis or isomerization. 

Oxidative cyclization of unsaturated /3-dicarbonyl compounds with two a-hydro-gen atoms will give products that still have one a-hydrogen and can be oxidized further. If the product is oxidized at a rate competitive with that of the starting material, mixtures of products will be obtained. For instance, oxidative cyclization of 26 affords 36 % of 27 and 10 % of dienone 28 formed by further oxidation of 27, as shown in Scheme 6 [7]. The product is occasionally oxidized much more readily than the starting material so that none of the initial product is isolated. These reactions may still be synthetically useful if the products of further oxidation are monomeric. For example, oxidative cyclization of methyl 3-oxo-6-heptenoate provides 78% of methyl salicylate [29]. The overall reaction consumes 4equiv. Mn(OAc)3. Competitive oxidation of the product is not usually a problem in inter-molecular addition reactions, because a vast excess of the oxidizable substrate, for example acetone or acetic acid, is usually used as solvent. Use of excess substrate is not possible in oxidative cyclizations. 

There are two important features of this overall approach. One is the convenient use of readily available, inexpensive starting materials, i.e., cyclic 1,3-dicarbonyl derivatives and amino acids. The other is the opportunity to introduce oxygen functionality into the (3-position on a pyrrole ring without having to resort to direct oxidation methods.100 By a simple conversion of the 3-acetoxy pyrrole functionality into pyrrole-3-triflate derivatives the door is opened for a wide variety of palladium-... 

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