Dehydration reactions pyridine

Pyrrolizidine amino-alcohols are readily dehydrated for example, hydroxyheliotridane and retronecanol, when treated with sulfuric acid, afford heliotridene (see e.g., refs. 105 to 107). A more complicated dehydration reaction is the transformation of the alkaloid rosmarinine into the alkaloid senecionine.83 Dehydration of 1-hydroxy-l-carbethoxypyrrolizidine53 in the presence of phosphorus oxychloride in pyridine results mainly in the formation of the A1,8-unsaturated ester (see Section II, E). The authors61,62 claimed that the dehydration product of l-carbethoxy-2-hydroxy-3-oxopyrrolizidine contained a A1,2-double bond (159). Later, however, the UV, IR, and NMR spectra67 revealed that the double bond had migrated the... 

Dehydration of pyridine-3-carboxylic acid amide (Nicotinamide) Dehydration of nicotinamide was carried out at different temperatures using conditions similar to those employed for benzamide. The results are shown in Fig.4. The reaction followed zero order kinetics and rate of reaction is very comparable to that of dehydration of benzamide. The kinetic constants are given in Table 2. In contrast with benzamide dehydration of nicotinamide in the absence of catalyst was negligible. 

Antecedent dehydration reactions can be complicated by acid-base reactions, for different protonated forms show different rates of dehydration. In all the systems studied so far — pyridine aldehydes (77, 78—80) quinazoline 81, 82) and glyoxalic acid (83) — either the dehydration of the conjugate base is faster than that of the conjugate acid, or the conjugate base is less hydrated. This is shown by the increase of current at pH > 2 in Fig. 22. The increase of current in acidic media corresponds... 

Another system in which ring-formation has been considered to be manifested on polarographic curves is the reduction of pyridoxal (77, 80). The reduction wave of this compound changes with pH and the observed plot is similar to that shown in Fig. 22. This dependence can be explained either by hydration (as for other pyridine carboxaldehydes), or by hemiacetal formation. The same two interpretations can be applied to electronic spectra. A comparison with the behaviour of pyridoxal-5-phosphate can contribute to the solution of this problem. With this ester the formation of the hemiacetal form is impossible and practically no current decrease in acidic solutions can be observed. Hence it can be concluded that the decrease in the limiting current of pyridoxal is due to ring formation. Nevertheless, the possibility of some participation by a dehydration reaction cannot be completely excluded, for it is possible to assume that the introduction of a phosphoric acid residue into position 5 either shifts the equilibrium towards the dehydrated form or increases the rate of dehydration. 

Acid chlorides react rapidly with alcohols to give esters in a strongly exothermic reaction. This reaction requires caution to keep the temperature low to avoid dehydration of the alcohol, because acid chlorides are powerful dehydrating agents. Pyridine (or another base) is often added to the solution to neutralize the HC1 by-product. 

The reaction does not occur on heating at 310°C for 2 h in the gas phase or in basic medium (e.g., pyridine, aqueous sodium hydroxide) suggesting that the reaction involves the protonation of the double bond. When the hydroxyl group is tertiary, it appears impossible to avoid the competitive dehydration reaction. However, after standing at room temperature for 7 years in a sealed tube, 2-isopropylidene-l-methylcyclobutanol (253) has undergone ring contraction to the extent of 60% (equation 173) " . ... 

Aldehydes are usually more easily reduced than carboxylic acids, but as in the previous case the aldehyde may exist in aqueous solution predominantly as the hydrate [Eq. (2)]. The hydrates are reduced at more negative potentials than carboxylic acids. Several other systems have been found to behave similarly [16,17] pyridine-2- and -4-carboxylic acid, imidazole-2-carboxylic acid, and thiazole-2-carboxylic acid. In the last case the yield is low due to competing reduction of the ring. Yields of aldehyde are better at low temperatures due to the slowing of the dehydration reaction. In neutral or basic solution there is electroanalytical evidence for dimerization in the reduction of pyridine-4-carboxylic acid [18]. 

Then the hydroxyl at C-5 is protected by means of acetylation carried out with acetic anhydride in pyridine affording conq>ound 13g. The analysis of the H-NMR spectrum of acetyl derivative 13g allows to claim surely the regiospecificity of the dehydration reaction in fact in the acetylation reaction fi om 13f to 13g, it is showed the usual deshielding of about 1 ppm of proton whose chemical shift (6 5.15) is, of course, attributable to a not allyhc position. 

Although the Hemetsberger reaction is clearly a powerful synthesis of indole-2-carboxylates, some problems are encountered in addition to the occasional mixture of nitrene cyclization products. Indeed, often the aldoliza-tion route to the 2-azidocinnamates proceeds poorly. This can be obviated at lower temperatures (-30 °C) to stop the reaction at the azido alcohol stage. Subsequent dehydration with thionyl chloride in pyridine or triethylamine afforded the 2-azidocinnamates. This two-step process was superior to the conventional one-step aldolization/ dehydration reaction, as found by Murakami and coworkers [67]. Tercel s group also observed that a low temperature (-78 °C) aldol condensation, isolation of the azido... 

The syntheses of other hydroxyalkyl pyridines and their dehydration reactions are described in Refs. [557-559]. As catalysts, alkali hydroxide, H2SO4, KHSO4, and P2O5 are used for liquid-phase reactions. For gas-phase dehydration, AI2O3 is applied. 

In 2008, our group disclosed a novel method that involved the one-pot synthesis of multisubstituted pyridines 92 by Rh-catalyzed oxime-assisted alkenyl C-H bond functionalization of a, -unsaturated oximes with alkynes [48]. The scope includes a variety of a, -unsaturated oximes and symmetrical alkynes. This report is one of a few examples of Rh(I)-catalyzed alkenyl C-H bond functionalization. The mechanism is thought to occur by oxime-directed oxidative insertion of the Rh catalyst into the alkenyl C-H bond to form the hydrometalacycle LI. Hydrorhodation onto the alkyne then occurs to give L2, followed by reductive elimination to provide L3. Intermediate L3 can undergo a 6. r-electrocyclization and then a dehydration reaction to form pyridine (Eq. (5.89)). Overall, this Rh(I)-catalyzed reaction is a redox neutral. 

Reaction with Ammonia. Although the Hquid-phase reaction of acrolein with ammonia produces polymers of Htde interest, the vapor-phase reaction, in the presence of a dehydration catalyst, produces high yields of [ -picoline [108-99-6] and pyridine [110-86-4] n.2L mXio of approximately 2/1. 

The reactions of primary amines and maleic anhydride yield amic acids that can be dehydrated to imides, polyimides (qv), or isoimides depending on the reaction conditions (35—37). However, these products require multistep processes. Pathways with favorable economics are difficult to achieve. Amines and pyridines decompose maleic anhydride, often ia a violent reaction. Carbon dioxide [124-38-9] is a typical end product for this exothermic reaction (38). 

Oxa2oles react with dienophiles to give pyridines after dehydration or other aromatization reactions (69,70). A commercially important example is the reaction of a 5-aLkoxy-4-methyloxa2ole with 1,4-butenediol to yield pyridoxine (55), which is vitamin... 

These reactions can be cataly2ed by bases, eg, pyridine, or by Lewis acids, eg, 2inc chloride. In the case of asymmetric alcohols, steric control, ie, inversion, racemi2ation, or retention of configuration at the reaction site, can be achieved by the choice of reaction conditions (173,174). Some alcohols dehydrate to olefins when treated with thionyl chloride and pyridine. 

Thus, Mathis et al. [1, 2] investigated oxidation reactions with 4-nitroperbenzoic acid, sodium hypobromite, osmium tetroxide and ruthenium tetroxide. Hamann et al. [3] employed phosphorus oxychloride in pyridine for dehydration. However, this method is accompanied by the disadvantages that the volume applied is increased because reagent has been added and that water is sometimes produced in the reaction and has to be removed before the chromatographic separation. 

If homolytic reaction conditions (heat and nonpolar solvents) can be avoided and if the reaction is conducted in the presence of a weak base, lead tetraacetate is an efficient oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. The yield of product is in many cases better than that obtained by oxidation with chromium trioxide. The reaction in pyridine is moderately slow the intial red pyridine complex turns to a yellow solution as the reaction progresses, the color change thus serving as an indicator. The method is surprisingly mild and free of side reactions. Thus 17a-ethinyl-17jS-hydroxy steroids are not attacked and 5a-hydroxy-3-ket-ones are not dehydrated. 

Acetonides are quite stable to base, and to oxidation, dehydration and acylation reactions carried out in pyridine. They are cleaved by acid hydrolysis. The 17,21-acetonides of 17a,21-dihydroxy-20-keto steroids and related acetals are split by very mild acid conditions. ... 

The reaction can be carried out in any inert solvent, but using a base such as pyridine has an additional advantage in the subsequent dehydration step... 

Sorm" " found that when cholesterol acetate (67) is oxidized by chromic acid in acetic acid-water at 55°, crystalline keto seco-acid (69) is obtained in 25-30 % yield from the mother liquors after removal of successive crops of 7-ketocholesterol acetate (68). Reaction of keto acid (69) with benzoyl chloride in pyridine gives a dehydration product, shown" to be the )5-lactone... 

The reaction of diketosulfides with 1,2-dicarbonyl compounds other than glyoxal is often not efficient for the direct preparation of thiophenes. For example, the reaction of diketothiophene 24 and benzil or biacetyl reportedly gave only glycols as products. The elimination of water from the P-hydroxy ketones was not as efficient as in the case of the glyoxal series. Fortunately, the mixture of diastereomers of compounds 25 and 26 could be converted to their corresponding thiophenes by an additional dehydration step with thionyl chloride and pyridine. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

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