4- Hydroxyphenyl acids

Although the presence of 3-hydroxyphenyl acids had been detected previously in urine, a widespread occurrence of such compounds had not been suspected before the work of Armstrong et al. (A12, A15). These acids probably arise from precursors found in the diet, as is shown by the influence of prolonged administration of chemically well-defined diets (A12), as well as by the big increase in the elimination of m-hydroxyhippuric and m-hydroxyphenylhydracrylic acids after ingestion of coffee (B22, S14). 

Fig. 9. 3-Hydroxyphenyl acids found in normal human urine.

A12. Armstrong, M. D., and Shaw, K. N. F, Origin of the 3-hydroxyphenyl acids ill human urine. Proc. Intern. Congr. Biochem. 4th Congr. Vienna p. 152 (1958). 

Figure 2. Linear regression plot of root growth inhibition of tomato and radish seedlings by o and -hydroxyphenyl) acids. o-Hydroxycinnamic acid, (o-hydroxyphenyl) acetic acid ( ) melilotic acid, 2-(o-hydroxyphenyl) butanoic acid ( ) o-hydroxy-benzoic acid, ( -hydroxypheny 1 )acetic acid (0) -hydroxycinnamic acid, =hydroxybenzoic acid, 3-( -hydroxyphenyl) propanoic acid (X) o-coumaryl glucoside, water control (----) (1 ). ...

The origin of the 4-hydroxyphenyl acids of urine was studied very... 

Three 2-hydroxyphenyl acids occur in normal urine (A14) o-hydroxy-hippuric (salicyluric) acid, which is present almost constantly o-hy-droxyphenylacetic acid, which is found frequently in normal urine and whose daily elimination is about 1 mg (A13) and o-hydroxybenzoic (salicylic) acid, which is found far less frequently. 

The probable precursors of these 2-hydroxyphenyl acids is o-tyrosine, which could be formed itself from phenylalanine (AlO) phenylalanine would be transformed first into activated phenylalanine, which would give rise mainly to tyrosine, but also, by a side reaction, to o-tyrosine. 

Methoxy-4-hydroxyphenyl Acids The following 3-methoxy-4-hydroxyphenyl acids have been found in normal human urine (A14, A16, S14) (Fig. 11) 3-methoxy-4-hydroxy-... 

The other 3-methoxy-4-hydroxyphenyl acids, as well as a part of the urinary vanillylmandelic acid, arise from dietary precursors their elimination increases markedly, for instance, after ingestion of coflEee (S16). 

Apart from the increased excretion of nonphenolic aromatic acids, there is a large excretion of 2-hydroxyphenyl and 4-hydroxyphenyl acids, whereas the 3-hydroxyphenyI acids present in normal urine are reduced or absent (B27). 

The elevated 4-hydroxyphenyl acids are represented mainly by p-hydroxyphenyllactic and p-hydroxyphenylacetic acids due to its instability, p-hydroxyphenylpyruvic acid is less regularly found (B26). 

In addition to para hydroxylation evidence for an ortho and meta hydroxylation of phenylalanine has acciunulated through the isolation of various m- and o-hydroxyphenyl acids in the urine of phenylketonurics and of normal man and animals 196,196). 

Thus o-hydroxyphenyl-llthium cannot be obtained from o-bromophenol and lithium but, under proper conditions, o-bromophenol reacts with n-butyl-lithium to give a good yield of the lithium salt of o-hydroxyphenyl-hthium. An interesting application is to the preparation from m-bromochlorobenzene and M-butyl-lithlum of w-chlorobenzoic acid—an expensive chemical ... 

Reaction of one mole of acetaldehyde and excess phenol in the presence of a mineral acid catalyst gives l,l-bis(p-hydroxyphenyl)ethane [2081-08-5], acid catalysts, acetaldehyde, and three moles or less of phenol yield soluble resins. Hardenable resins are difficult to produce by alkaline condensation of acetaldehyde and phenol because the acetaldehyde tends to undergo aldol condensation and self-resinification (see Phenolic resins). 

Pharmaceuticals. -Hydroxybenzaldehyde is often a convenient intermediate in the manufacture of pharmaceuticals (qv). For example, 2-(p-hydroxyphenyl)glycine can be prepared in a two-step synthesis starting with -hydroxybenzaldehyde (86). This amino acid is an important commercial intermediate in the preparation of the semisynthetic penicillin, amoxicillin (see ANTIBIOTICS, P-LACTAMs). Many cephalosporin-type antibiotics can be made by this route as well (87). The antiemetic trimethobenzamide [138-56-7] is convenientiy prepared from -hydroxybenzaldehyde (88) (see Gastrointestinal agents). 

Chemical off—on switching of the chemiluminescence of a 1,2-dioxetane (9-benzyhdene-10-methylacridan-l,2-dioxetane [66762-83-2] (9)) was first described in 1980 (33). No chemiluminescence was observed when excess acetic acid was added to (9) but chemiluminescence was recovered when triethylamine was added. The off—on switching was attributed to reversible protonation of the nitrogen lone pair and modulation of chemically induced electron-exchange luminescence (CIEEL). Base-induced decomposition of a 1,2-dioxetane of 2-phen5l-3-(4 -hydroxyphenyl)-l,4-dioxetane (10) by deprotonation of the phenoHc hydroxy group has also been described (34). 

Methylphenol is converted to 6-/ f2 -butyl-2-methylphenol [2219-82-1] by alkylation with isobutylene under aluminum catalysis. A number of phenoHc anti-oxidants used to stabilize mbber and plastics against thermal oxidative degradation are based on this compound. The condensation of 6-/ f2 -butyl-2-methylphenol with formaldehyde yields 4,4 -methylenebis(2-methyl-6-/ f2 butylphenol) [96-65-17, reaction with sulfur dichloride yields 4,4 -thiobis(2-methyl-6-/ f2 butylphenol) [96-66-2] and reaction with methyl acrylate under base catalysis yields the corresponding hydrocinnamate. Transesterification of the hydrocinnamate with triethylene glycol yields triethylene glycol-bis[3-(3-/ f2 -butyl-5-methyl-4-hydroxyphenyl)propionate] [36443-68-2] (39). 2-Methylphenol is also a component of cresyHc acids, blends of phenol, cresols, and xylenols. CresyHc acids are used as solvents in a number of coating appHcations (see Table 3). 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

Acetarsone. Acetarsone (3-acetamido-4-hydroxyphenyl arsonic acid) (13), also known as acetarsol, stovarsol, and Ehrlich 594, forms white prisms from water. 

A (4-Hydroxyphenyl)glycine. This derivative (23) forms aggregate spheres or shiny leaflets from water. It turns brown at 200°C, begins to melt at 220°C, and melts completely with decomposition at 245 —247°C. The compound is soluble in alkaU and mineral acid and sparingly soluble in water, glacial acetic acid, ethyl acetate, ethanol, diethyl ether, acetone, chloroform, and benzene. 

A/-(4-Hydroxyphenyl)glycine can be prepared from 4-aminophenol and chloracetic acid (199,200) or by alkaline hydrolysis of the corresponding nitrile with subsequent elimination of ammonia (201). 

The Chemicaly3.bstractIndexis 2,7-naphthalene-disulfonic acid, 4-amino-5-hydroxy-3-[[4 -[(4-hydroxyphenyl)azo] [l,l -biphenyl]-4-yl]azo]-6-(phenylazo)-, disodium salt. 

This group was developed for protection of the 5 -OH group in nucleosides. The derivative is prepared from the corresponding triaiylmethyl chloride, and is cleaved by reductive cleavage (Zn/AcOH) of the phenacyl ether to the p-hydroxyphenyl-diphenylmethyl ether followed by acidic hydrolysis with formic acid. ... 

N-methyltyrosine ((3-p-hydroxyphenyl-a-methylaminopropionic acid) under the names angeline, andirine, geoffroyine, surinamine and rhatanine has been isolated from Ferreira sj ciabilis, Audit a retusa, A. inermis, Geqffroea sumamensis and Krameria triandra. ... 

Triazine 4-oxides 55 react with phenols (phenol, 2,6-dimethylphenol, resorcinol, 4-hexyh esorcinol) in trifluoroacetic acid in a similar way, yielding intermediate (T -adducts 5-hydroxyphenyl-4-hydroxy-4,5-dihydro-l,2,4-triazines 61. Subsequent oxidation leads to the corresponding 5-hydroxyphenyl-l,2,4-triazine 4-oxides 62 (97MC116). 

---