Tuesday, 16 September 2014

Multi-step synthesis using modular flow reactors: the preparation of yne-ones and their use in heterocycle synthesis

Multi-step synthesis using modular flow reactors: the preparation of yne-ones and their use in heterocycle synthesis 

I.R. Baxendale, S.C. Schou, J. Sedelmeier, S.V. Ley, Chem. Eur. J. 2010, 16, 89-94.


 Thumbnail image of graphical abstract

Multi-step in flow: The palladium-catalysed acylation of terminal alkynes for the synthesis of yne[BOND]ones as well as their further transformation to various heterocycles in a continuous-flow mode is presented. Furthermore, an extension of the simple flow configuration that allows for easy batch splitting and the generation of a heterocyclic library is described (see scheme).

Wednesday, 10 September 2014

CH2 Adds Something to Fullerenes

CH2 Adds Something to Fullerenes

Methylene addends in fullerene electron acceptors increase solar-cell efficiency
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 Fullerene derivatives are used as electron acceptors in organic solar cells. CH2 addends can effectively raise fullerene lowest unoccupied molecular orbital (LUMO) energy levels, which leads to high open-circuit voltage (Voc). As the smallest addend, CH2 does not affect fullerene packing in the solid state, thus keeping good electron mobility for the acceptors.


Carbohydrate Orientation

 thumbnail image: Carbohydrate Orientation


Carbohydrate Orientation

Incorporation of a photosensitive azobenzene linker for controllable carbohydrate orientation
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 Carbohydrate recognition is an important biological process that is essential for the communication between cells, such as cellular adhesion and recognition. A control of the spatial orientation of these carbohydrate units could potentially be used to modify this recognition event.


Remold Crystals with Vapor

Remold Crystals with Vapor

Halogen bonding drives the conversion from surface-confined crystals to co-crystals without the use of solvent
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 The ultimate application of functional materials requires successful fabrication of devices. For organic molecules, this usually involves the deposition of organic thin films on surfaces, which often limits the options for subsequent modification and optimization.


Monday, 8 September 2014

Mechanism for pyrrole synthesis

This shows the tradtional mechanism for forming a pyrrole ring using a 1,4-diketone and ammonia. The hydroxyl groups are removed as water in two separate dehydration steps, forming enamines in two of the intermediates.
A new mechanism, which does not require enamine formation, has been proposed based on a study using Density Functional Theory.

This shows the mechanism for pyrrole synthesis based on recent DFT study. Instead of the formation and cyclisation of a enamine intermediate, a hemiaminal intermediate in formed, followed by the consecutive dehydrations of the two hydroxyl groups. The dehydration steps may look familiar: it is just the formation of an enamine

A more traditional approach to the mechanism, which appears in some text books and taught courses, can be found here.

This mechanism was based on the paper: B. Mothana, R. J. Boyd, J. Mol. Struct.: THEOCHEM, 2007, 811, 97-107

Saturday, 6 September 2014

Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride

Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride


Cyclohexanone+Paraformaldehyde+Dimethylammonium chloride
reacts to
2-Dimethylaminomethyl cyclohexanone hydrochloride

Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride

Reaction type:reaction of the carbonyl group in aldehydes, Mannich reaction
Substance classes:ketone, aldehyde, amine
Techniques:heating under reflux, stirring with magnetic stir bar, evaporating with rotary evaporator, filtering, recrystallizing, heating with oil bath
Degree of difficulty:Easy


round bottom flask 25 mLround bottom flask 25 mLreflux condenserreflux condenser
suction filtersuction filtersuction flasksuction flask
heatable magnetic stirrer with magnetic stir barheatable magnetic stirrer with magnetic stir barrotary evaporatorrotary evaporator
exsiccator with drying agentexsiccator with drying agentoil bathoil bath

Operating scheme

Inline image 1

Instruction (batch scale 100 mmol) 
100 mL round bottom flask, reflux condenser, Buechner funnel (Ø 5.5 cm), suction flask, 
heatable magnetic stirrer, magnetic stir bar, rotary evaporator, desiccator, oil bath 
cyclohexanone (bp 156 °C) 9.82 g (10.3 mL, 100 mmol) 
paraformaldehyde (mp 120-170 °C) 3.60 g (120 mmol) 
dimethylammonium chloride 8.16 g (100 mmol) 
hydrochloric acid (conc.) 0.4 mL 
ethanol (bp 78 °C) 64 mL 
acetone (bp 56 °C) 180 mL 

9.82 g (10.3 mL, 100 mmol) cyclohexanone, 3.60 g (120 mmol) paraformaldehyde, 8.16 g 
(100 mmol) dimethylammonium chloride and 4 mL ethanol are filled in a 100 mL round 
bottom flask with reflux condenser and magnetic stir bar. 0.4 mL conc. hydrochloric acid are 
added and the mixture is heated under stirring for 4 hours under reflux. 
Work up 
The hot solution is filtered in a round-bottom flask and the solvent is evaporated at the rotary 
evaporator. The residue is dissolved in 20 mL ethanol under heating. At room temperature 
70 mL acetone are added to the solution. For complete crystallization the solution is stored 
over night in the freezer compartment. The crystallized crude product is sucked off over a 
Buechner funnel (Ø = 5.5 cm) and dried in the desiccator over silica gel. 
Crude yield: 15.6 g; mp 149-150 °C 
For further purification the crude product is again dissolved in about 40 mL ethanol under 
reflux and at room temperature 110 mL acetone are added. The crystallization is completed in 
the freezer compartment. The product is sucked off and dried in the desiccator. 
Yield: 14.7 g (76.7 mmol, 77%,); mp 156-157 °C 
To verify a complete crystallization, the mother liquor is stored in the freezer compartment. 
No product should crystallize any further.

Simple evaluation indices

Atom economynot defined
Target product mass1.45g
Sum of input masses54g
Mass efficiency27mg/g
Mass index37g input / g product
E factor36g waste / g product


Inline image 2

Inline image 3

1H-NMR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
500 MHz, CDCl3
delta [ppm]mult.atomsassignment
1.35m1 H
1.54m1 H
1.73m1 H
1.82m1 H
2.05m1 H
2.37m2 H6-H (ring)
2.41m1 H
2.67d3 HN-CH3
2.74m1 H
2.77d3 HN-CH3
3.09m1 HN-CH2
3.57m1 HN-CH2
11.88m1 HN-H

Inline image 4
Inline image 5

13C-NMR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
125 MHz, CDCl3
delta [ppm]assignment
209.58C1 (C=O)


Inline image 6

IR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
[Film, T%, cm-1]
3068, 3020N-H valence
2932, 2858C-H valence
1698C=O valence, ketone