Синтез 3,4-Dihydroxy-2,5-dimethoxytetrahydrofuran

[Clor]

Подскажите, где я неправ? Вроде бы так, но слишком просто!

[Cherep]

ЕМНИП, боргидрид натрия восстанавливает циклические ангидриды в лактоны.

[pH<7]

Диметоксидигидрофуран можно получить оксилением фурана бромом в метаноле.

[Phobos]

Двойная хеми-ацеталь в реакции с борогидридом не образуется. Представляется соединением весьма неустойчивым. Существует ли такое вообще?

[Cherep]

2,5-диметокси-2,5-дигидрофуран относительно устойчив. И получается, ЕМНИП, как pH<7 говорит.

[pH<7]

Диметокси вроде даже продаётся.

Если честно, за диметокси не уверен, но диацетокси точно так получается (бром в уксусу).

[ChemNavigator]

Это задача InnoCentive.
3 дня назад начал аналогичную тему здесь -
http://chemnavigator.fastbb.ru/index.pl ... 1146770406

[Phobos]

Ацеталь всегда устойчивее, чем хемиацеталь. Насчет диметокси все нормально. Вот дигидрокси структура у меня сомнения вызывает.

[Clor]

Ацеталь всегда устойчивее, чем хемиацеталь. Насчет диметокси все нормально. Вот дигидрокси структура у меня сомнения вызывает.

*** Physical Property Report Generated By CS ChemProp ***

************************************************************************
Estimation of the Boiling and Freezing points.
************************************************************************

Normal Boiling Point [p=1atm]: 544.99 [K]
Standard Error: 20.400 [K]
Joback fragmentation method modified by S.E. Stein


Normal Boiling Point [p=1atm]: 594.30 [K]
Standard Error: Error was not estimated.
Joback fragmentation method


Freezing Point [p=1atm]: 347.73 [K]
Standard Error: 25.000 [K]
Joback fragmentation method

************************************************************************
Estimation of the Critical properties.
************************************************************************

Critical Temperature: 706.81 [K]
Standard Error: Error was not estimated.
Joback fragmentation method


Critical Pressure: 40.466 [bar]
Standard Error: Error was not estimated.
Joback fragmentation method


Critical Volume: 404.50 [cm.cm.cm/mol]
Standard Error: Error was not estimated.
Joback fragmentation method

************************************************************************
Estimation of the Thermodynamics properties
************************************************************************

Heat of Formation [T=298.15K, p=1atm]: -868.61 [kJ/mol]
Standard Error: Error was not estimated.
Joback fragmentation method


Gibbs Energy [T=298.15K, p=1atm]: -556.70 [kJ/mol]
Standard Error: Error was not estimated.
Joback fragmentation method


Ideal gas thermal capacity for T= 298.15 [K] and p=1atm: 191.89 [J/(mol.K)]
Standard Error: Error was not estimated.
Joback fragmentation method

[eukar]

Вторично на подобный пост -

И?

[Cherep]

Это задача InnoCentive.
3 дня назад начал аналогичную тему здесь -
http://chemnavigator.fastbb.ru/index.pl ... 1146770406

А в соединении 2 какая стереохимия метокси-групп?

Upd: Может им нужна технология без брома?

[ChemNavigator]

А в соединении 2 какая стереохимия метокси-групп?

Upd: Может им нужна технология без брома?

Им нужна технология именно второй стадии, к первой вопросов нет.
Это вещество - синтетический эквивалент диальдегида, и при гидролизе вся стереохимия метокси-групп всё равно будет потеряна. Видимо, поэтому стереохимия указана только для OH-групп (цис-положение).

Вот что ещё там пишут:

An efficient synthesis of cis-3,4-Dihydroxy-2,5-dimethoxytetrahydrofuran is desired.

Cis-3,4-Dihydroxy-2,5-dimethoxytetrahydrofuran has been synthesized in the literature by the following scheme (see references below):

The Seeker Client had explored these literature methods and other oxidation methods for preparing the desired target material from 2,5-dimethoxy dihydrofuran.
Unfortunately, all methods tested proved unsatisfactory for various reasons:

- Preparations which use potassium permanganate showed low volume yields in all cases. Mostly water with a co-solvent (THF, Acetone, Ethanol e.g.) was used as a solvent. For example, US 5,681,945 uses a total of almost 3 liters of solvent to oxidize 50 grams of the dihydrofuran. The chemical yields were poor to moderate. The water solubility of the product requires the removal of a large quantity of water from the reaction medium. Attempts by the Seeker Client to reduce the quantity of water were unsuccessful.

- Osmium catalyzed hydroxylation has been considered but is viewed as an expensive alternative.

- Ruthenium catalyzed hydroxylation was unsuccessful.

- Epoxidation followed by ring opening was not successful. The epoxide of the dihydrofuran is known but uses hypochlorous acid (explosive under certain conditions) or t-butylhypochlorite. Both methods give the halohydrin which is treated with base to give the epoxide. Peracids did not work. These routes are viewed as too long anyway.

The Seeker would like to explore alternative synthetic approaches. A one step procedure would be preferable though not critical. A chemical yield of 80% or more is desired with particular attention to volume yield. Both catalytic and stoichiometric oxidation methods are of interest to the Seeker.

Solvers are requested to propose an experimentally validated method which meets the following Technical Requirements:
Produces the target material 3,4-dihydroxy-2,5-dimethoxytetrahydrofuran in an overall isolated yield of > 80% in preferably one step from 2,5-dimethoxy dihydrofuran. The use of starting materials other than 2,5-dimethoxy dihydrofuran is acceptable if cost for materials and process are comparable. Both preparations of a single stereoisomer or a mixture of stereoisomers of the target material are acceptable. The volume yield should be significantly better than the one referred to in the patent preparation above and should be ideally around 150-200g per liter of solvent used.

The reaction and work-up must be compatible with a large scale process (tons). The pure cis-isomer and the pure trans-isomer are most likely solids and crystallization is preferred. If the proposed process produces a mixture of isomers the product material will most likely be an oil. Extraction is preferred. Chromatography is not allowed. No time-consuming work-up steps should be used.

Avoids the use of carcinogenic, pyrophoric, explosive or highly volatile toxic reagents.
The proposed synthesis should offer the Seeker Client "freedom to practice" or be available for potential licensing. There should be no patent art preventing the use of the proposed synthesis for commercial application. Methods lifted from the public domain are acceptable.

References:
McLean, Michael Joseph; Garman, Andrew John. Support for oligonucleotide synthesis. US5,681,945.

Villacampa, Mercedes; Martinez, Manuel; Gonzalez-Trigo, Gregorio; Sollhuber, Monica M. Synthesis and stereochemistry of (3α)-6β ,7β -dihydroxy- and 6β -hydroxy-8-alkyl-8-azabicyclo[3.2.1]octane-3-spiro-5'-imidazoline-2',4'-diones. Journal of Heterocyclic Chemistry (1992), 29(6), 1541-4.

Honel, Michael; Mosher, Harry S. Selective permanganate oxidation of cis- vs. trans-2,5-dihydro-2,5-dimethoxyfuran. Journal of Organic Chemistry (1985), 50(22), 4386-8.

[Cherep]

тады ой