Aldehyde Modification

Figure 20.9 Polysaccharide groups on antibody molecules may be oxidized with periodate to create aldehydes. Modification with biotin-hydrazide results in hydrazone linkages. The sites of modification using this technique often are away from the antibody-antigen binding regions, thus preserving antibody activity.

The concentration of HOCl was measured by using a molar extinction coefficient of 350 M cm at 290 nm at pH 12. One milliliter solution contained 10 pM HOCl, 250 pM DTPA and 500 pM luminol in the absence or presence of 10 nM of aldehyde-modifed HSA. Chemiluminescent intensity was recorded continuously for 5 min using Mini Lumat LB 9506 luminometer (EG G Berthold, Germany). 

Figure 3. Antioxidant activity of aldehyde-modified HSA against hypochlorous acid (HOCl). One milliliter solution contained 10 /llM HOCl, 250 juM DTP A, 500 fiM luminol and 10 nM of aldehyde-modifed HSA. Chemiluminescent intensity was recorded as described MATERIALS AND METHODS. Antioxidant activities of aldehyde-modified HSA against HOCl were shown as Vo of native HSA.

This reaction, applicable only to the preparation of hydroxy-aldehydee, is alternative to the Gattermann aldehyde reaction (or the Adams modification of it) given under 4. The yields are usually smaller, but a large quantity of the phenol may be recovered. The following mechanism is consistent with the known facts ... 

The Doebner condensation (or reaction) is a slight modification of the Knoevenagel reaction and consists in warming a solution of the aldehyde and... 

In a modification of the original method. Read (60) replaced a-amino acids with a-amino nitriles. This reaction is sometimes known as Strecker hydantoin synthesis, the term referring to the reaction employed for the synthesis of the a-amino nitrile from an aldehyde or ketone. The cycli2ation intermediate (18) has been isolated in some cases (61), and is involved in a pH-controUed equiUbrium with the corresponding ureide. 

Synthesis from Thiohydantoins. A modification (71) of the Bucherer-Bergs reaction consisting of treatment of an aldehyde or ketone with carbon disulfide, ammonium chloride, and sodium cyanide affords 2,4-dithiohydantoias (19). 4-Thiohydantoias (20) are available from reaction of amino nitriles with carbon disulfide (72). Compounds (19) and (20) can be transformed iato hydantoias. 

Other modifications of the polyamines include limited addition of alkylene oxide to yield the corresponding hydroxyalkyl derivatives (225) and cyanoethylation of DETA or TETA, usuaHy by reaction with acrylonitrile [107-13-1/, to give derivatives providing longer pot Hfe and better wetting of glass (226). Also included are ketimines, made by the reaction of EDA with acetone for example. These derivatives can also be hydrogenated, as in the case of the equimolar adducts of DETA and methyl isobutyl ketone [108-10-1] or methyl isoamyl ketone [110-12-3] (221 or used as is to provide moisture cure performance. Mannich bases prepared from a phenol, formaldehyde and a polyamine are also used, such as the hardener prepared from cresol, DETA, and formaldehyde (228). Other modifications of polyamines for use as epoxy hardeners include reaction with aldehydes (229), epoxidized fatty nitriles (230), aromatic monoisocyanates (231), or propylene sulfide [1072-43-1] (232). 

Methylfurfural may be prepared by a modification of this method, which is more rapid but gives lower yiddsd A solution of 800 g. of sucrose in i 1. of hot water is allowed to flow slowly into a boiling solution of 500 g. of stannous chloride crystals, 2 kg. of sodium chloride, and 4 1. of 12 per cent sulfuric acid in a 12-I. flask. The aldehyde distils ofl as rapidly as it is formed and is steam-distilled from the original distillate after rendering it alkaline witlr sodium carbonate. The product is isolated by benzene extraction of the second distillate and distillation under reduced pressure. The yield is 27-35 g- (10-13 per cent of the theoretical amount). 

Tribromobenzoic acid has been prepared by the deamination of 2,4,6-tribromo-3-aminobenzoic acid (reagents not specified), by hydrolysis of 2,4,6-tribromobenzonitrile, " and by oxidation of the tribromotoluene, the benzyl chloride, the aldehyde,and the glyoxylic acid.i The present method is a modification of that of Bunnett, Robison, and Pennington.i ... 

Tetrahydroharman, m.p. 179-80°, has been prepared by a number of workers by a modification of this reaction, viz., by the interaction of tryptamine (3-)5-aminoethylindole) with acetaldehyde or paraldehyde and Hahn et al. have obtained a series of derivatives of tetrahydronorharman by the use of other aldehydes and a-ketonic acids under biological conditions of pH and temperature, while Asahina and Osada, by the action of aromatic acid chlorides on the same amine, have prepared a series of amides from which the corresponding substituted dihydronorharmans have been made by effecting ring closure with phosphorus pentoxide in xylene solution. 

The Borsche modification describes the protection of the aldehyde as an imine ... 

Toward the end of the 19 century both Pomeranz and Fritsch independently reported the preparation of isoquinolines by the reaction of aminoacetaldehyde dimethyl acetal 2 (R = Me) with aromatic aldehydes 1 followed by cyclisation in acidic media. " Unfortunately yields were often poor and not always reproducible. This has prompted the search for various improvements and modifications on the original theme, including the use of reagents other than strong mineral acid which tends to destroy the intermediate imine. ... 

The AFO reaction has seen very few variations since it was first reported in 1934. However, the most significant modification was reported in 1958 by Ozawa and further elaborated by Smith and others. Prior to this modification the intermediate chalcones were purified and then subjected to hydrogen peroxide in a basic medium. With the modification, the chalcone was generated in situ, from an aldehyde and a hydroxyacetophenone, and then allowed to react with aqueous hydrogen peroxide in the presence of sodium hydroxide to deliver the flavonol. Smith and coworkers conducted a limited study to examine the scope and limitations of this modification.Flavonols were delivered in 51-67% however, no flavonols were isolated with highly reactive aldehydes such as p-nitrobenzaldehyde and when 2-hydroxy-4-methoxyacetophenone was used. 

Reaction of tryptamine with simple ketones has not been widely explored. Acetone in the presence of benzoyl chloride has been reported to yield 2-benzoyl-1,1 -dimethyl-1,2,3,4-tetrahydro-j8-carbo-line. That the keto group is much less reactive than the aldehyde group is indicated by the fact that j8-keto aldehydes, in the form of their acetals or sodium salts, react with tryptamine at the aldehyde function to yield the conjugated enamine 24, which undergoes ring closure via an intramolecular Michael addition. The potentialities of this interesting modification of the Pictet-Spengler reaction have not yet been fuUy explored. 

In this method the nitro group in the aliphatic nitro compound is usually present on a carbon atom, which is also activated by CO-functioiiality (aldehyde, ester, arylketoiie). A successful application of this method is the Borsche modification of the Friedlander synthesis, involving condensation of A-(3-amino-4-picolylidene)-p-toluidine (17) with [Pg.289]

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

The term Knoevenagel reaction however is used also for analogous reactions of aldehydes and ketones with various types of CH-acidic methylene compounds. The reaction belongs to a class of carbonyl reactions, that are related to the aldol reaction. The mechanism is formulated by analogy to the latter. The initial step is the deprotonation of the CH-acidic methylene compound 2. Organic bases like amines can be used for this purpose a catalytic amount of amine usually suffices. A common procedure, that uses pyridine as base as well as solvent, together with a catalytic amount of piperidine, is called the Doebner modification of the Knoevenagel reaction. 

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