Phosphorus acid derivatives, substitution reactions with

Because of the structural requirements of the bielectrophile, fully aromatized heterocycles are usually not readily available by this procedure. The dithiocarbamate (159) reacted with oxalyl chloride to give the substituted thiazolidine-4,5-dione (160) (see Chapter 4.19), and the same reagent reacted with iV-alkylbenzamidine (161) at 100-140 °C to give the 1 -alkyl-2-phenylimidazole-4,5-dione (162) (see Chapter 4.08). Iminochlorides of oxalic acid also react with iV,iV-disubstituted thioureas in this case the 2-dialkylaminothiazolidine-2,4-dione bis-imides are obtained. Thiobenzamide generally forms linear adducts, but 2-thiazolines will form under suitable conditions (70TL3781). Phenyliminooxalic acid dichloride, prepared from oxalic acid, phosphorus pentachloride and aniline in benzene, likewise yielded thiazolidine derivatives on reaction with thioureas (71KGS471). 

A review on the reaction of tervalent phosphorus acid derivatives with halogens has appeared. Alkylbis(diisopropyl-amino) phosphines (41) react with carbon tetrachloride or bromotrichloromethane to give the P-halogeno ylides (42) below 0 The ylides rearrange to the substituted phosphines (43)... 

In a search for tervalent phosphorus acid derivatives with better phosphitylation properties than usual aminophosphines or phosphoramidites Nifant ev et al. have prepared several new reagents. These include pyrazole derivatives, e.g. (51), 2-aminopyridine derivatives, e.g. (52), amidine derivatives, e.g. (53), and hydrazine derivatives, e.g. (54). They were prepared by standard methods and examined for their reactivity towards alcohols and, in the case of the amidine derivatives, for their tendency to isomerize by migration of the phosphorus group to the other nitrogen atom. Another type of reactive tervalent phosphorus acid derivative is phosphites derived from hydroxylamine. Several stable derivatives, e.g. (55) and (56), have been prepared and substitution reactions with alcohols studied. ... 

The reactions of bis(phosphoryl) disulphides with a variety of tervalent phosphorus acid derivatives or triphenylphosphine have been studied by means of low-temperature n.m.r. Intermediates were detected which indicated initial attack on one sulphur atom followed by substitution reactions at one of the phosphorus atoms, Arbuzov dealkylations, or phosphorane formation. An example is shown for the reaction of tributyl phosphite with bis(diethoxyphosphoryl) disulphide (25). In order to obtain solely thiophosphate products it is necessary to use bis(thiophosphoryl) disulphides, and one such compound (26) has been proposed as a highly effective reagent for the oxidation of oligonucleoside phosphites to phosphorothioates. A comparison of the efficiency of (26) with that of four other sulphurizing agents for use in... 

Triazanaphthalenes (446) substituted with a single leaving group have been little studied. 4-Aminopyrido[3,2-d]pyrimidine and its 6-methyl derivative have been hydrolyzed with 5N acid (100°, 30 min) and lOA alkali (95°, 3 hr, 10% yield).Attempted replacement of the 4-oxo group (via acyloxy intermediates) with phosphorus oxychloride or pentasulfide failed,in contrast to the successful replacement in the more activated 4-oxo-l,3,8-triaza analog discussed below. Similarly, the 2,4-dioxo derivative could not be thionated with the pentasulfide, and its reaction with the oxychloride was less facile than that of the 2,4-dioxo-l,3,8-triaza compound. 

Detailed investigations of the chemical reactivity of the diketiminato-stabilized phosphenium cations like 28 (Scheme 17) are to date rare and include only two reports dealing with the substitution and reduction of P-halogen-derivatives. Thus, reaction of 28 (X=Br) with sodium hydroxide in toluene was reported to proceed with displacement of the halide substituent at phosphorus and conservation of the heterocyclic ring to give a mixture of bromide and triflate salts containing a P-hydroxy-substituted cation, both of which were isolated in small yields [89], The products are remarkable as they represent one of very few examples of a stable phosphinous acid which does not rearrange to the tautomeric secondary phosphine oxide. Potassium reduction of the P-chloro-substituted derivative 34 produced the... 

Several reports have been made of a successful catalyzed addition/ substitution reaction resulting in direct attachment of phosphorus to aromatic rings. The preparation of mixed triarylphosphines has been accomplished by the reaction of tin- or silicon-substituted diphe-nylphosphines with aryl halides catalyzed by palladium reagents.74 A similar transformation has also been reported using nickel catalysis.75 The addition/substitution of diphenylphosphine to triflate functionalized phenolic linkages has been of use for the preparation of substances as analogues of tyrosine-related amino acid derivatives, accomplished with catalysis by palladium acetate (Equation 4.29).76... 

Note that the reaction at the phosphorus atom is postulated to occur by an SN2 (no intermediate formed) rather than by an addition mechanism such as we encountered with carboxylic acid derivatives (Kirby and Warren, 1967). As we learned in Section 13.2, for attack at a saturated carbon atom, OH- is a better nucleophile than H20 by about a factor of 104 (Table 13.2). Toward phosphorus, which is a harder electrophilic center (see Box 13.1), however, the relative nucleophilicity increases dramatically. For triphenyl phosphate, for example, OH- is about 108 times stronger than H20 as a nucleophile (Barnard et al., 1961). Note that in the case of triphenyl phosphate, no substitution may occur at the carbon bound to the oxygen of the alcohol moiety, and therefore, neutral hydrolysis is much less important as compared to the other cases (see /NB values in Table 13.12). Consequently, the base-catalyzed reaction generally occurs at the phosphorus atom leading to the dissociation of the alcohol moiety that is the best leaving group (P-0 cleavage), as is illustrated by the reaction of parathion with OH ... 

In the synthesis of specially substituted methylene diphosphines, made from secondary phosphines and carbonyl derivatives (7), a carbenium ion adjacent to trivalent phosphorus as the transition state has been discussed. The transfer of this reaction principle to primary phosphines and suitable carbonyl compound revealed a further pathway to derivatives of dicoordinated phosphorus (8). Aromatic phosphines react with carboxylic acid amide acetals under elimination of alcohol giving dialkylamino-alkylidene phosphines (Scheme 5). A modification of the synthesis... 

Ethane occurs in natural gas, from which it is isolated. Ethane is among the chemically less reactive organic substances. However, ethane reacts with chlorine and bromine to form substitution compounds. Ethyl iodide, bromide, or chlorides are preferably made by reaction with ethyl alcohol and the appropriate phosphorus halide. Important ethane derivatives, by successive oxidation, are ethyl alcohol, acetaldehyde, and acetic acid. Ethane can also be used for the production of aromatics by pyrolysis (Fig. 1). 

Since sulfonation of pyridine iV-oxide is about as difficult as is that of pyridine itself and takes place at the 3-position,17 it has been assumed18 that, in fuming sulfuric acid, pyridine iV-oxide reacts only in the salt form (3), when the prediction is that substitution at C-3 would take place. It is, however, difficult to account for the fact that bromination, even at 110° in the presence of iron powder, does not occur.17 Bromination in chloroform solution in the presence of acetic anhydride and sodium acetate (when the O-acetate is the the probable substrate) take place readily, however, to give 3,5-dibromopyridine JV-oxide.19 The predicted order of nucleophilic reactivity, on the basis of both atom localization energies and ground-state v-electron density calculations, is 4 > 2 > 3. The same order is predicted for the nucleophilic substitution reactions of the salts of pyridine JV-oxide. In actual practice, iV-alkoxypyridinium derivatives undergo nucleophilic attack preferentially at C-2.20-23 The reaction of some pyridine iV-oxides with phosphorus pentachloride may involve the formation... 

A reaction of rather less general application, but one which produces valuable intermediates, is the treatment of dithiosalicylamide and its A-substituted derivatives with phosphorus pentachloride. Thus, A.A-diethyldithiosalicylamide (20) yields 3-chloro-2-ethyl-l,2-benz-isothiazolium chloride (21).14-16 This salt (21) is a versatile compound for example, heating it with diethylamine gives 3-diethylamino-l,2-benzisothiazole (22)16, treatment with base yields 2-ethyl-l,2-benzisothiazolinone (23), and reaction with ammonia, followed by hydrochloric acid, affords 3-ethylamino-l,2-benzisothiazole (24).14 This final reaction involves an interesting rearrangement which will be discussed in more detail in Sections II, C, 2 and II, C, 3. 

Step 1 Reaction of the diphosphate oxygen of GDP with the phosphorus of the acyl phosphate to produce an intermediate similar to the intermediates formed in nucleophilic acyl substitutions of carboxylic acid derivatives. 

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