Formamide hydrolysis

The study of formamide hydrolysis performed at Nancy (Rivail et al., 1994 Antonczack et al., 1994) can be here accompanied by studies on other reactions (hydration of oxoaldehydes and aldol condensation) performed at Pisa (Coitino et al., 1994, 1995b, 1995c). In all cases the calculations have been performed at a good level, MP2 over an extended basis set, taking into account solvation effects in all their contributions and with cavities of appropriate shape. To simplify the discussion we shall confine ourselves to neutral reactions the quoted papers also consider proton assisted reactions. The nominal reactions are reported below ... 

These polymers are useful for reacting with alkylamine (/ = 8, 12) to formamides. Hydrolysis of the remaining anhydride groups gives water soluble polymeric amides. 

The 2-[2-thienyl]selenazole is formylated in the 5-position by action of n-butyllithium. dimethyl formamide. and hydrolysis (106). 

Formic acid is currently produced iadustriaHy by three main processes (/) acidolysis of formate salts, which are ia turn by-products of other processes (2) as a coproduct with acetic acid ia the Hquid-phase oxidation of hydrocarbons or (3) carbonylation of methanol to methyl formate, followed either by direct hydrolysis of the ester or by the iatermediacy of formamide. 

Coproductioa of ammonium sulfate is a disadvantage of the formamide route, and it has largely been supplanted by processes based on the direct hydrolysis of methyl formate. If the methanol is recycled to the carbonylation step the stoichiometry corresponds to the production of formic acid by hydration of carbon monoxide, a reaction which is too thermodynamicaHy unfavorable to be carried out directly on an iadustrial scale. 

Formamide is hydroly2ed very slowly at room temperature. The rate of hydrolysis increases rapidly in the presence of acids or bases and is further accelerated at elevated temperatures. 

Cycloahphatics capable of tertiary carbocation formation are candidates for nucleophilic addition of nitriles. HCN in strong sulfuric acid transforms 1-methyl-1-cyclohexanol to 1-methyl-1-cyclohexylamine through the formamide (47). The terpenes pinene (14) [2437-95-8] and limonene [5989-27-5] (15) each undergo a double addition of HCN to provide, after hydrolysis, the cycloahphatic diamine 1,8-menthanediamine (16) (48). 

Hydrolysis of TEOS in various solvents is such that for a particular system increases directiy with the concentration of H" or H O" in acidic media and with the concentration of OH in basic media. The dominant factor in controlling the hydrolysis rate is pH (21). However, the nature of the acid plays an important role, so that a small addition of HCl induces a 1500-fold increase in whereas acetic acid has Httie effect. Hydrolysis is also temperature-dependent. The reaction rate increases 10-fold when the temperature is varied from 20 to 45°C. Nmr experiments show that varies in different solvents as foUows acetonitrile > methanol > dimethylformamide > dioxane > formamide, where the k in acetonitrile is about 20 times larger than the k in formamide. The nature of the alkoxy groups on the siHcon atom also influences the rate constant. The longer and the bulkier the alkoxide group, the lower the (3). 

The utility of 2,2 -biindolyl derivatives as indolocarbazole precursors has also been exploited extensively by Somei and co-workers, who reported the first syntheses of the naturally occurring indolo[2,3-a]carbazoles 16 and 17 (Scheme 9). A chloroacetylation of 2,2 -biindolyl (46) followed by treatment of the resulting product 58 with sodium cyanide in formamide-methanol provided 59. Transformation of 59 into the acetoxy derivative 60, followed by hydrolysis to 61, finally led to the target compounds after subsequent sequential melhylations [97H(45)1647]. 

In a departure from the prototype molecule, the benzylpiperi-done is first converted to the corresponding aminonitrile (a derivative closely akin to a cyanohydrin) by treatment with aniline hydrochloride and potassium cyanide (126). Acid hydrolysis of the nitrile affords the corresponding amide (127). Treatment with formamide followed by reduction affords the spiro oxazinone... 

Condensation of hydrazine with ethoxymethylenemalononitrile (22) gives 3-amino-4-cyanopyrazole (23). Hydrolysis with sulfuric acid leads to the amide, 24 heating with formamide inserts... 

Aminotrimethanephosphonic acid is formed from formamide, acetamide, urea, or alkanenitriles with phosphorous acid [296]. By reaction of monoalkyl phosphite or P406 with glacial acetic acid or the corresponding anhydride ethane-1 -hydroxy-1,1-diphosphonic acid is formed after hydrolysis [297,298]. P406 can be obtained from P4 and 02 in a high yield of 85-90% [299]. 

Formylation of alkenes can be accomplished with N-disubstituted formamides and POCl3. ° This is an aliphatic Vilsmeier reaction (see 11-15). Vilsmeier formylation can also be performed on the ot position of acetals and ketals, so that hydrolysis of the products gives keto aldehydes or dialdehydes ... 

The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

The Jacobsen group has also shown that the recycling of the resin-bounded catalyst can be successfully performed [152,154]. Moreover, they have developed an efficient method for the hydrolysis of the aminonitrile into the corresponding amino acid. This method was apphed for the commercial production of optically active K-amino acids at Rhodia ChiRex (e.g. tert-leucine) the catalyst was immobihsed on a resin support (4 mol %, 10 cycles) and the intermediate hydrocyanation adduct was trapped by simply replacing TFAA with HCOOH/AC2O, for example. Highly crystalhne formamide derivatives were thus obtained in excellent yields (97-98% per cycle) with very high enantioselectivities (92-93% per cycle) [158]. 

Noncyanogenic fungi can degrade cyanide to formamide followed by hydrolysis by a hydratase to formate and ammonia (Dumestre et al. 1997). This pathway is also used by some bacteria (Jandyala et al. 2003). Bacteria also use a number of reactions for the detoxification of cyanide, including monooxygenation to COj and ammonia (Wang et al. 1996). 

British Biotech has described co-crystal structures of both BB-3497 and actinonin bound in the active site of E. coli PDF [24]. The metal centre (Ni ) in both complexes adopts a pentacoordinate geometry, bound by the two oxygen atoms of the hydroxamate along with Cys-90, His-132 and His-136. This coordination pattern is consistent with the mechanism of de-formylation proposed by Becker et al. [56] and Jain et al. [67], in which a pentacoordinated metal centre stabilises the transition state during hydrolysis of the formamide bond. When compared to the co-crystal structure of a substrate hydrolysis product, Met-Ala-Ser, it is clear that the side chains of these two inhibitors bind into the active site pockets similarly to the substrate [56]. 

Aldehydes can also be obtained from Grignard reagents by reaction with formamides, such as A-formylpiperidine. In this case, the initial adducts are stable and the aldehyde is not formed until hydrolysis during workup. 

Ring D inversion seems to be a crucial step in biogenetic transformations of protoberberines to related alkaloids such as rhoeadine, retroprotoberberine, spirobenzylisoquinoline, and indenobenzazepine alkaloids. 8,14-Cyclober-bin-13-ol 478 derived from berberine (15) was successively treated with ethyl chloroformate, silver nitrate, and pyridinium dichromate (PDC) in dimethyl-formamide to give the keto oxazolidinone 479 (Scheme 98). Heating of 479 with 10% aqueous sodium hydroxide in ethanol effected hydrolysis, retro-aldol reaction, cyclization, and dehydration to provide successfully the... 

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