Reaction with benzoic acid

Hammen equation A correlation between the structure and reactivity in the side chain derivatives of aromatic compounds. Its derivation follows from many comparisons between rate constants for various reactions and the equilibrium constants for other reactions, or other functions of molecules which can be measured (e g. the i.r. carbonyl group stretching frequency). For example the dissociation constants of a series of para substituted (O2N —, MeO —, Cl —, etc.) benzoic acids correlate with the rate constant k for the alkaline hydrolysis of para substituted benzyl chlorides. If log Kq is plotted against log k, the data fall on a straight line. Similar results are obtained for meta substituted derivatives but not for orthosubstituted derivatives. 

Mitsubishi Chemical Industries, Ltd. practiced a Henkel II technology starting with toluene to produce benzoic acid. Reaction of benzoic acid with potassium hydroxide resulted in potassium benzoate, which was subjected to a disproportionation reaction to produce dipotassium terephthalate and benzene. Dipotassium terephthalate reacted with sulfuric acid, and the resulting terephthahc acid was recovered by filtration and drying (65,66). Here, dipotassium sulfate was the by-product. 

Table 4 shows results of a few representative 3 -diethylaminofluorans (68 R1, R2 = C2H5) prepared by the reaction of 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid (66b) with phenols. 

A rather complex fused isoindoline (87) has been found to show good anorectic activity. This substance differs from other anorectic agents by not being a p-phenethylamine analogue. Preparation of this compound starts by reaction of a substituted benzoyl-benzoic acid (82) with ethylene diamine. The product (84) can be rationalized as being the aminal from the initially obtained monoamide 83. This is then subjected to reduction with lithium aluminum hydride... 

Alkylation of several substituted benzoic acid salts with n-octyl bromide was performed under solvent-free PTC with excellent yields (95 %) within a very short reaction time [93] (2-7 min). Oil bath heating (A) led to yields equivalent to those produced under the action of microwave irradiation, which thus revealed only thermal effects in the range of temperature used (145-202 °C) (Eq. 39). 

Reports have appeared claiming that triperoxo vanadates behave as nucleophilic oxidants. In particular, triperoxo vanadium complexes, A[V(02)3]3H20 (A=Na or K), are proposed as efficient oxidants of a,-unsaturated ketones to the corresponding epoxide, benzonitrile to benzamide and benzil to benzoic acid, reactions which are usually carried out with alkaline hydrogen peroxide. Subsequent studies concerning the oxidation of cyclobutanone to 4-hydroxybutanoic acid, carried out with the above-cited triperoxo vanadium compound, in alcohol/water mixtures, clearly indicated that such a complex does not act as nucleophilic oxidant, but only as a source of HOO anion. 

However, 2,4,6-trisubstituted pyrylium salts with certain active methyl and methylene compounds undergo ring fission and subsequent cyclization to benzenoid products. 2,4,6-Triphenylpyrylium ion (261 Z = O) in this way forms 2,4,6-triphenylnitrobenzene (299) with nitromethane and the substituted benzoic acid (300) with malonic acid, the latter reaction involving a decarboxylation. In reactions of this type, 1,3-oxazinium salts react with active hydrogen compounds to give pyridines (Scheme 25). 

The oriAo-benzoyl-benzoic acids readily yield anthraquinone and its derivatives (see p. 82). It may be noted that o-benzoyl-benzoic acid itself, with benzene and aluminium chloride, yields phthalophenone the same compound is made directly from phthalic anhydride by increasing the amount of the latter or by adding acetic anhydride. The same holds for p-toluoylbenzoic acid and ditoluoylphthalide. (Am. Soc., 43, 1965 J. C. S., 122, 539.) (For the use of carbomethoxylbenzoyl chlorides and of homophthalic anhydrides in these reactions, see Am. Soc., 43, 1950.)... 

Organic chemists have studied the influence of substituents on various reactions for the better part of a century. Linear free energy relationships have played an important role in this pursuit by correlating equilibrium and rate processes. One of the earliest examples is now known as the Hammett equation. It emerged from the observation that the acidities of benzoic acids correlated with the rates at which ethyl esters of benzoic acids hydrolyzed. The relationship was expressed as follows in which K represents an equilibrium constant and k is a rate constant. The proportionality constant, m, is the slope of the log-log data plot for the two processes. 

To further understand the mechanistic difference between aromatic substitution and the e reactions, reaction rate constants of disubstituted benzenes reacting with e were studied. Specifically, substituted benzoic acid was studied, and one substituent (-COOH) was kept constant. Table 12.6 lists the rate constants of substituted benzoic acid reacting with e. It also calculates r, which is defined as the following ... 

In benzene derivatives, electron-donating substituents direct into the ortho-and para-positions, while in the case of the electron-withdrawing substituents considerable meta-addition is observed (Table 3.1) otherwise a more equal distribution is established [reactions (6)-(9) and Table 3.1]. In agreement with the pronounced regioselectivity, ipso-addition at a bulky substituent such as the chlorine substituent in chlorobenzene is disfavored. Evidence for this is the low HC1 yield in the case of chlorobenzene, the low yield of para adduct in 4-methyl-phenol (Table 3.1), or the decarboxylation in the case of benzoic acid [reactions (6) and (10)]. 

The intramolecular reaction of alkenes with various O and N functional groups offers useful synthetic routes to heterocycles [69-71]. The isocoumarin 83 is prepared by the intramolecular reaction of 2-(2-propenyl)benzoic acid (81) with one equivalent ofPdCl2(MeCN)2. However, the (Z)-phthalide 82 is obtained from the same acid with a catalytic amount of Pd(OAc)2 under 1 atm of 02 in DMSO. 02 alone is remarkably efficient in reoxidizing Pd(0) in DMSO. The isocoumarin 83 is obtained by the reaction of 2-(l-propenyl)benzoic acid (84) under the same conditions [2]. 2-Vinylbenzoic acid was converted to the isocoumarin, but not to the five-membered lactone [72,73]. 

The reactions are catalyzed by acyl-CoA amino acid A-acyltransferase, of which two distinct A-acyltransferases exist in mammalian mitochondria. The predominant transferase conjugates medium-chained fatty acyl CoA and substituted benzoic acid derivatives with glycine and is termed an aralkyl-CoA glycine A-acyltransferase, while the other enzyme conjugates arylacetic acid derivatives with glycine, glutamine, or arginine and is an arylacetyl-CoA amino acid A-transferase. 

Benzoic acids substituted with alkyl, halo, hydroxyl, alkoxyl, cyano, or nitro groups react to give the corresponding substituted anilines in 41-80% yields. The carboxyl group in an a-amino acid does not react with hydrazoic acid the reaction proceeds, however, if the amino group is further removed. This difference in reactivity is shown by the conversion of a-aminoadipic acid to i(-ornithlne (75%). ... 

Ethyl 4,5-Dlbenzamldopent 4-enoate (2) Ethyl 3-imidazol-4(5)-ylpropanoate 1 (9.2 g, 54 rnnwl) in ElOAc (140 ml) was treated with benzoyl chloride (IS 7 g, 112 mmol) in ElOAc (40 mL) and 1M NaHCOs (380 ml) added simultaneously In 1 h under ice-cooling. The reaction mixture was stirred for 1 h, then a further portion olbenzoyichionde (15 7 g, 112 mmol) in EtOAc) and 1M NaHCOs (280 mL) was added in the same manner, followed by an additional portion of 1M NaHCOs (200 mL) The reaction mixture was stirred for 24 h, then the organic layer was separated, concentrated, and the residue dissolved in THF (300 mL) The THF solution was stirred with 10% NaHCOa (600 mL) for 24 h to decompose any N-lormyl intermediate and to remove benzoic acid Extraction with EtOAc, drying (Na2S04), solvent evaporation and recrystallization of the residue from EtOAc hexane afforded 16 24 g of 2 (84%), mp 128-129 C... 

The chemical information available through LFER is primarily the reaction constant p, but this value depends upon the substituent constants selected for the construction of the LFER. The u values available are ct, ct", ct" or and Ui, these quantities are listed, for many substituents, in Tables 7-1, 7-3, 7-4, 7-6, and 7-7. A reasonable approach is to plot log k against the substituent constant defined by a standard reaction that is expected to be most like the reaction under study. It is also reasonable to plot log k against several of the ct quantities, seeking the best correlation. [In choosing between two types of substituent constants, it is necessary to make use of substituents for which the two scales (say ct and rr, for example) are not themselves correlated, for otherwise both LFERs will be acceptable. ] The ct or o constants should be applicable to reactions that do not combine reaction sites and para substituents of the + and — type (push-pull systems capable of through resonance) for example, one would not expect ct" or o to provide good correlations for reactions of phenols or anilines substituted with nitro or cyano or for reactions of benzoic acids substituted with amino or methoxy. 

The reaction of benzoic acid hydrazide with carbon disulfide in basic medium was first described by Busch and Starke (63) who identified the reaction product as benzoyldithiocarbazic acid (LXXXII). Hog-garth (767) found, that, in the absence of alkali, 5-phenyl-Z]4-l,3.4-oxadiazoline-2-thione (LXXXIII) and 1,2-dibenzoylhydrazine were formed in the reaction of benzoic acid hydrazide with carbon disulfide. If this same reaction is carried out in pyridine, there is formed, beside 5 -phenyl-J 4-1,3,4-oxadiazoline-2-thione (LXXXI11), 3 -phenyl-4-ben z-amido-J2"I>2,4-triazoline-5-thione (LXXXV), probably from the intermediately formed t,5-dibenzoylthiocarbohdrazide (LXXXIV). 

Proton Transfer Reactions in Doped Benzoic Acid. Benzoic acid, doped with different guest molecules, has emerged as a particularly well-suited model system for high-resolution optical spectroscopic studies of proton tunneling reactions at low temperatures. In these crystals, a variety of... 

---