Diethyl 1,1-cyclobutanedicarboxylate

DIETHYL 1,1-CYCLOBUTANEDICARBOXYLATE (1,1-Cyclobutanedicarboxylic acid, diethyl ester)... 

Diethyl 1,1-cyclobutanedicarboxylate has been prepared by the alkylation of diethyl sodiomalonate with trimethylene dibromide 8i4>6 7 or with trimethylene chlorobromide 6-8 and by the peroxide-catalyzed addition of hydrogen bromide to diethyl allylmalonate followed by intramolecular alkylation.9 The procedure described here is that of Mariella and Raube.6... 

Diethyl 1,1-cyclobutanedicarboxylate is prepared by the method of Mariella and Raube.2 The diester is isolated in 55% yield, b.p. 111-114° (16 mm.). The diester can be saponified by the method of Heisig and Stodola,3 but omitting the barium chloride step, to give the diacid. This material upon recrystallization from ethyl acetate gives the diacid in high purity. The diacid may also be purchased from Aldrich Chemical Company, Inc. 

Some examples of alkylation reactions involving relatively acidic carbon acids are shown in Scheme 1.3. Entries 1 to 4 are typical examples using sodium ethoxide as the base. Entry 5 is similar, but employs sodium hydride as the base. The synthesis of diethyl cyclobutanedicarboxylate in Entry 6 illustrates ring formation by intramolecular alkylation reactions. Additional examples of intramolecular alkylation are considered in Section 1.2.5. Note also the stereoselectivity in Entry 7, where the existing branched substituent leads to a trans orientation of the methyl group. 

Methylene groups can be dialkylated if sufficient base and alkylating agent are used. Dialkylation can be an undesirable side reaction if the monoalkyl derivative is the desired product. Use of dihaloalkanes as the alkylating reagent leads to ring formation, as illustrated by the diethyl cyclobutanedicarboxylate synthesis (entry 7) shown in Scheme... 

In the case of enamines derived from aldehydes a cycloaddition to give a cyclobutane occurs (48-50). Thus the enamine (16) reacted with methyl acrylate in acetonitrile to give a 91 % yield of methyl 2-dimethylamino-3,3-dimethylcyclobutane carboxylate (56). Similarly, treatment of (16) with diethylmaleate at 170° gave a 70% yield of diethyl 4-dimethylamino-3,3-dimethyl-l,2-cyclobutanedicarboxylate (57), and 16 and acrylonitrile gave a 65% yield of 2-dimethylamino-3,3-dimethylcyclobutanecarbonitrile (58). 

Dlathyl 3-methyl-2-cyano-1,2-cyclobutanedicarboxylate (2).2 Diethyl a,a dibromo-5-methyladipate 1 (20.0g. 55 mmol) and powdered NaCN (8.0 g. 160 mmol) in abs. EtOH (15... 

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