Chlorobutyric acid

The 4 -chloro-4-fluorobutirophenone (6.3.4) needed for this is synthesized by the acylation of fluorobenzene using 4-chlorobutyric acid chloride. 

As illustrated by the chlorobutyric acids discussed above, in saturated molecules inductive effects usually fall off quite rapidly with distance. 

By analogy with ethyl 4-bromobutyrate thermolysis, the kinetics of the pyrolysis and the product formed from ethyl 4-chlorobutyrate were examined172. At the same time, the pyrolysis of the expected stable product 4-chlorobutyric acid product (equation 78), which results in butyrolactone formation, was also carried out. 

The reaction proceeds via the normal six-membered transition state mechanism of ester elimination. The intermediate chlorobutyric acid yielded butyrolactone through participation of the COOH group under the reaction conditions. The pure chlorobutyric acid was pyrolyzed and gave butyrolactone in quantitative yield. The mechanism is similar to that of bromobutyric acid pyrolysis (equation 76). The data are shown in Table 23. 

The first influence, known for a considerable time, appears from the variation of the acid strength in the series i-chloro-butyric acid 1.45 io 3 2-chlorobutyric acid 8.8 io 5 3-chlorobutyric acid 3 io 5 butyric acid 1.5 io 5. 

Reaction of 272 with acrylic acid, /9-chlorobutyric acid, /9-diketones, or a,/9-unsaturated ketones gave the expected diazepines, while acetoacetic ester and diketene reacted only at the primary amino group.323 Similarly, 273 was obtained from acetylacetone and 2,3-dimethyl - 7- aminoindole.32 4... 

The same method of preparation may be used for a-chloropropi-onic acid, a-chlorobutyric acid, and a-chlorocaproic acid. 

The Second polymeric substrate with a longer chain length was prepared by the Friedel-Crafts alkylation of Bio-Bead SXl and AICI3 with 4-chlorobutyric acid in nitrobenzene for 5 hours at 80 C. The resin was washed with AcOH, 61 HCl-dioxane (1 1), HaOrdioxane (1 1), dioxane and CH2CI2. Titration was effected as stated earlier 0.9 mequiv of carboxyl per gram of polymer was determined. 

Amino-2-methoxymethyl pyrrolidine (SAMP) was prepared from L-proline according to a literature procedure. The synthesis began with the reaction of SAMP and the commercially available 4-chlorobutyric acid chloride (66) (Scheme 19). Treatment of the lo-chlorobutyro-hydrazide (67) with AgBp4 resulted in butyrolactone-SAMP hydrazone... 

Preparation of 2-chlorobutyric acid by chlorination of the acid chloride at the b.p. in the presence of iodine has long been known.536... 

It is very easy to halogenate malonic acid and its esters and alkyl or arylalkyl derivatives. Chloromalonic acid is obtained by hydrolysis of diethyl chloro-malonate, which is formed when chlorine is passed into the malonic ester at 70°.575 Cloves576 describes the preparation of 2-chlorobutyric acid by way of diethyl ethylmalonate. 

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