Pyridinols

The pyridinols (synonym: hydroxypyridines ) are a group of chemical compounds . They are positionally isomeric hydroxyl-substituted pyridines ; consequently they belong to the nitrogen heterocycles .

The tautomeric equilibrium between 2- and 4-pyridinol is on the side of the associated pyridine ketones ( pyridones , pyridinones ), the systematic names of the corresponding derivatives contain -pyridone- as part of the name.

Representative

Pyridinols
Surname	2-pyridinol 2-pyridone	3-pyridinol	4-pyridinol 4-pyridone
Structural formula
other names	2-hydroxypyridin pyridin-2-one	Pyridin-3-ol	4-hydroxypyridin pyridin-4-one
CAS number	142-08-5	109-00-2	626-64-2
PubChem	8871	7971	12290
Molecular formula	C 5 H 5 NO
Molar mass	95.10 g mol −1
Physical state	firmly
Melting point	104-107 ° C	123-126 ° C	150-151 ° C
solubility	450 g l −1 (water, 20 ° C)	33 g l −1 (water, 20 ° C)	soluble in water
GHS labeling	danger	Caution	Caution
H and P phrases	301	315-319-335	315-319-335
	309 + 310	302 + 352-304 + 340-305 + 351 + 338	261-305 + 351 + 338

Occurrence

A number of natural products with a pyridinol partial structure are known:

• Partial structures of 2-pyridinol have been found in various quinolizidine alkaloids , for example in anagyrine or baptifoline , as well as in lycopodium alkaloids such as huperzine A and B ; in camptothecin , a cytostatic , as well as in mappicin and in fungal pigments such as tenellin .
• 3-pyridinol is a structural element of the pyridoxines and thus of vitamin B6 .
• 4-pyridinol forms the basic structure of mimopudine and is found in the milk hydrolysis product pyridosine or the non-proteinogenic amino acid mimosine .

synthesis

The pyridinols are accessible by diazotization of the aminopyridines and subsequent boiling . 2-pyridinol can also be prepared starting from pyridine- N oxide by reaction with acid anhydrides can be obtained and subsequent hydrolysis. 2- and 4-pyridinol can also be obtained by reacting the corresponding pyrones with ammonia .

properties

Tautomerism

2- and 4-pyridinol are in tautomeric equilibrium with the corresponding pyridine ketone, the 2- or 4-pyridone. The balance is on the side of the keto connection with both. 2-Pyridinol can be understood as the lactime form of the lactam 2-pyridone, it is a lactam-lactime tautomerism .

On the other hand, no pyridine ketone form is known of 3-pyridinol; instead, the hydroxyl group reacts phenolically , i. H. a pyridinium phenolate boundary structure can be formulated.

Reactivity

2- and 4-pyridinols can be converted into the corresponding halopyridines with phosphorus pentachloride . Electrophilic substitution reactions proceed easily because the hydroxyl group has properties as an electron donor. The substitution products ortho and para to the OH group are preferably formed analogously to phenol . In the case of 2- and 4-pyridinols, alkylations with alkyl halides lead to mixtures of O- and N -alkylated products, whereas in the case of 3-pyridinol, selectively to the O -alkylated product.

use

2-pyridinol is used as an intermediate in the synthesis of amphenidone . 3-Pyridinol is used for the synthesis of the cholinesterase inhibitors pyridostigmine bromide and distigmine bromide . 4-Pyridinol is a precursor of the X-ray contrast agent propyliodone . Hydrogenation leads to 4-piperidinol , which is used for the synthesis of pericyazine .

literature

• Shinkichi Shimizu, Nanao Watanabe, Toshiaki Kataoka, Takayuki Shoji, Nobuyuki Abe, Sinji Morishita, Hisao Ichimura: Pyridine and Pyridine Derivatives. In: Ullmann's Encyclopedia of Industrial Chemistry . Wiley-VCH, Weinheim 2006. doi : 10.1002 / 14356007.a22_399 . Chapter 3.9: Pyridinols .
• Entry to pyridinols. In: Römpp Online . Georg Thieme Verlag, accessed on December 25, 2017.

Individual evidence

1. ↑ ^{a b c d e f} Shinkichi Shimizu, Nanao Watanabe, Toshiaki Kataoka, Takayuki Shoji, Nobuyuki Abe, Sinji Morishita, Hisao Ichimura: Pyridine and Pyridine Derivatives. In: Ullmann's Encyclopedia of Industrial Chemistry . Wiley-VCH, Weinheim 2006. doi : 10.1002 / 14356007.a22_399 . Chapter 3.9: Pyridinols .
2. ↑ ^{a b c d} data sheet 2-hydroxypyridine (PDF) from Merck , accessed on December 25, 2017.
3. ↑ ^{a b c d} Data sheet 3-Pyridinol (PDF) from Merck , accessed on December 25, 2017.
4. ↑ ^{a b c} Data sheet 4-Hydroxypyridine from Sigma-Aldrich , accessed on December 25, 2017 ( PDF ).
5. ↑ Data sheet 4-Hydroxypyridine at AlfaAesar, accessed on December 25, 2017 ( PDF )(JavaScript required) .
6. ↑ ^{a b} entry on pyridinols. In: Römpp Online . Georg Thieme Verlag, accessed on December 25, 2017.