Pyridine acid chloride synthesis

Furthermore, oxazoles of type 9-82 bearing a secondary amino functionality can be converted into pyrrolo[3,4-b]pyridines 9-86 by reaction with appropriate acid chlorides 9-83 in a triple domino process consisting of amide formation/hetero Diels-Alder reaction and retro-Michael cycloreversion via 9-84 and 9-85 (Scheme 9.17). The pyrrolo[3,4-fc]pyridines can be obtained in even higher yields when the whole sequence is carried out as a four-component synthesis in toluene. Here, 1.5 equiv. NH4C1 must be added for the formation of the now intermediate oxazoles [56b]. 

In 1972 Wright prepared 3-chlorothieno[3,2-6]thiophene-2-carbonyl chloride (94) in 11-13% yield by heating 3-(2-thienyl)acrylic acid, thionyl chloride, and pyridine, a method of synthesis of benzo[6]-thiophene-2-carbonyl chloride derivatives. " Methyl 3,5-dichloro-thieno[3,2-6]thiophene-2-carboxylate (95) and methyl 2-chloro-3-(5-chloro-2-thienyl)acrylate were also isolated. When fte reaction was carried out in refluxing toluene or chlorobenzene, the acid chloride (94)... 

Hydrolytic reactions can also be applied in the synthesis of aldehydes or ketones via the corresponding 1,3-oxazine derivatives. The anion formed from 3-methyl-2-(4-pyridyl)tetrahydro-l,3-oxazine 155 on treatment with BuLi proved to react with various electrophiles (alkyl halides, carboxylic esters, acid chlorides, or aldehydes) exclusively at position 2 of the 1,3-oxazine ring and not at the pyridine nitrogen atom. The readily formed 2,2-disubstituted-l,3-oxazine... 

Optically active namral and unnamral amino acids as well as various cyclic amino alcohols have been utilized in the synthesis of a wide variety of bis(oxazo-line) ligands. As previously mentioned, the first bis(oxazoline) ligands, py-box la-d, were synthesized by Nishiyama and co-workers in 1989. The common material for their syntheses was pyridine 2,6-dicarboxylic acid 19. Conversion of 19 to the acid chloride was achieved by treatment with thionyl chloride, as illustrated in Figure 9.4. This was followed by condensation with (5)-valinol in the presence of triethylamine. Conversion of the resulting bis(amidodiol) 20 to py-box-ip lb was achieved by sequential treatment of 20 with thionyl chloride at 50 °C followed by cyclization with aqueous sodium hydroxide in methanol to afford py-box-/p lb in 60% overall yield. The same synthetic scheme can be used to obtain the other... 

Imidazo[4,5- ]pyridines can be synthesized by a large number of routes, from which condensation of the appropriate carboxylic acid or acid chloride with the corresponding diaminopyridine, sometimes requiring cyclization of the intermediate amide with strong acid, appears to be the most widely used method <1996CHEC-II(7)283>. A recent example has been reported for the synthesis of pyridoimidazole C-nucleosides, and although the yield in this particular case was low, no epimerization at the C-1 stereocenter was observed (Equation 29) <2003TL5807>. 

Synthesis of the sulfonamides is accomplished with the camphorsulfonic acid chloride in a 1 1 ratio with the chiral primary amine in pyridine (2 h, 60 °C). 

We have described (88TL4855) a simple synthesis of pyridin-2-ones by a two-step annulation of 2 with aliphatic acid chlorides (Scheme 27). The acylation of aminoazadienes 2 in pyridine furnished 4-amidoyl-l-azabutadienes 107 in high yields (85JOC802) lithium diisopropylamide-catalyzed aldol-type cyclization of 107 afforded pyridin-2-ones 108 in 83-94% yield. Extension of this reaction to methanesulfonyl chloride permitted preparation of open-chain derivatives 109 in 88-90% yield, which in turn cyclized in the presence of lithium diisopropylamide to 2//-l,2-thiazines 110 in 82-92% yield (89TL4705). Earlier work by the Komatsu-Ohshiro group showed that the reaction of simple 1-azadienes... 

One of the first compounds to be introduced to the clinic, aztreonam (40-9), has been produced by total synthesis. Constmction of the chiral azetidone starts with amide formation of L-threonine (40-1) via its acid chloride treatment with ammonia leads to the corresponding amide (40-2). The primary amino group in that product is then protected as its carbobenzyloxy derivative (40-3). Reaction of that product with methanesulfonyl chloride affords the mesylate (40-4). Treatment of that intermediate with the pyridine sulfur trioxide complex leads to the formation of the A -sulfonated amide (40-5). Potassium bicarbonate is sufficiently basic to ionize the very acidic proton on the amide the resulting anion then displaces the adjacent mesylate to form the desired azetidone the product is isolated as its tetrabutyl ammonium salt (40-6). Catalytic hydrogenation over palladium removes the carbobenzyloxy protecting group to afford the free primary amine (40-7). The... 

Treatment of an a-amino acid with an anhydride in the presence of pyridine, known as the Dakin-West reaction,[1431 gives access to a racemic a-amido ketone.1 44 1451 The mechanism involves formation of an oxazolinone (98)J146 In the modified Dakin-West reaction, the oxazolinone is reacted with an acid chloride (Scheme 33)J136 139] Due to the rapid epimer-ization of the oxazolinones, a diastereomeric mixture of product 99 is obtained. No detailed protocol has been published so far for the modified Dakin-West synthesis applied to (oxomethyleneamino) peptides, but the procedure is adapted from that already reported for (oxomethylene) peptides containing the tp[CO-CH2] link.1147 ... 

Acyl chlorides. Acyl chlorides are formed rapidly by reaction of carboxylic acids with SOCl2 and pyridine in CH2C12 at 25°. The dicyclohexylammonium salts of carboxylic acids react particularly rapidly (ca. 1 minute). The acid chlorides prepared in situ in this way react with amines in the presence of DMAP or DBU to form amides in >85% yield. This SOCl2-Py method is also useful for peptide synthesis with slight racemization. 

Phosphoric acid chloride and thiophosphoric acid chloride pyrididium betaines (I) which are easily prepared by reacting P401Qt P OgS. and P4S1Q, respectively, with phosphorus oxychldride or phdspnorus thio-chloride in the presence of pyridine (1.), are of interest for the synthesis of substituted phosphates and thiophosphates. 

There are various ways wherein esters can be synthesised. An effective method is to react an acid chloride with an alcohol in the presence of pyridine yield. Acid anhydrides also react with alcohols to esters, but are less reactive. Moreover, the reaction is wasteful because half of the acyl content on the acid anhydride is wasted as the leaving group (i.e. the carboxylate ion). If the acid anhydride is cheap and readily available, this method can be used, e.g., acetic anhydride is useful for the synthesis of a range of acetate esters ... 

Chlorination of aldoximes. NCS converts aryl aldoximes to hydroxamic acid chlorides without significant chlorination of the aryl group. This reaction has been used for a novel synthesis of nitrile oxides. Thus reaction of salicylaldoxime (1) with NCS followed by dehydrochlorination with pyridine generates a nitrile oxide, which is trapped by styrene to give the isoxazoline 2. The N-O bond can be cleaved by catalytic hydrogenation to 3, which is converted into the chalcone 4 on elimination of water. This product can be converted by classical methods to the flavanone 5 and the flavone 6. An analogous route can be used to synthesize 2-... 

In many cases, the trimethoxybenzoyl group has been introduced into synthetic methyl reserpate as the last or second-to-last step. An optimal yield of 72% of reserpine is reported if a 50% excess of the acid chloride is used (190, 193), the yield diminishing as the amount of acylating agent is increased. In the French synthesis, acylation is carried out with tri-methoxybenzoic anhydride in triethylamine and pyridine (185). 

When 2-chloro-6-phenyl-phenolmethylether is transfered into the Grignard compound and then reacted with cyclohexanone, dehydrated and finally dehydrogenated, 2,6-diphenylphenolmethylether is formed61). The synthesis is versatile since a variety of cyclohexanone-derivatives can be used. This and other phenolethers can then easily be demethylated. One of the mildest demethylations is to react the methylether with borontribromide at low temperatures °21. Hydroiodine acid, Lewis acids, such as aluminium-chloride 63 , pyridine/pyridinium chloride, or sodium in pyridine 64) are also valuable tools in ether demethylations. 

Anhydride Synthesis. A wide variety of pyridine 1-oxides are highly selective catalysts for the conversion of acid chlorides and sodium carbox-... 

For reactions carried out in homogeneous solution or under solid-phase conditions the use of Fmoc amino acid chlorides is limited by the competition between their aminolysis and the formation of the less reactive oxazol-5(4//)-ones in the presence of tertiary amines, which are essential components of such reaction systems. To improve the results under these conditions a hindered base, e.g. 2,6-di-/er/-butylpyridine, can be used as a hydrogen chloride acceptor since conversion to oxazol-5(4//)-one is slow with such bases. Although shown to be advantageous in certain cases, Fmoc amino acid chlorides are used in homogeneous solution synthesis only in particular cases. They react efficiently in the presence of pyridine with weak nucleophiles such as imine 2P l (Scheme 2) where other activated species such as an active ester, anhydride, acyl fluoride, and acyl imidazolide fail. 

A synthesis of electrochemically amphoteric TTFAQ-ct-A derivatives 917 and 918 (TTFAQ = 9,10-bis(l,3-dithiol-2-ylidene)-9,10-dihydroanthracene, ct = saturated spacer, A = polynitrofluorene acceptor) involved esterification of the acid chloride 916 with the hydroxymethyl-substituted TTFAQ derivative 915 in pyridine. To increase acceptor properties, 917 was converted into the dicyanomethylene derivative 918 by reaction with malononitrile in DMF (Scheme 138) <2002JA14227>. 

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