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.

 http://onlinelibrary.wiley.com/doi/10.1002/chem.200902906/abstract

 

Multi-step in flow: The palladium-catalysed acylation of terminal alkynes for the synthesis of yneones 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).

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 (V_oc). As the smallest addend, CH₂ does not affect fullerene packing in the solid state, thus keeping good electron mobility for the acceptors.


 http://www.chemistryviews.org/details/ezine/6508231/CH2_Adds_Something_to_Fullerenes.html

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.

 http://www.chemistryviews.org/details/ezine/6533751/Carbohydrate_Orientation.html

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
Read more



 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.


 http://www.chemistryviews.org/details/news/6543561/Remold_Crystals_with_Vapor.html

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

Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride

Synthesis of 2-dimethylaminomethyl-cyclohexanone hydrochloride

http://orgspectroscopyint.blogspot.in/2014/09/synthesis-of-2-dimethylaminomethyl.html




++

EtOH, HCl

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

Equipment

	round bottom flask 25 mL			reflux condenser
	suction filter			suction flask
	heatable magnetic stirrer with magnetic stir bar			rotary evaporator
	exsiccator with drying agent			oil bath

Instruction (batch scale 100 mmol) 

Equipment 

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 

Substances 

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 

Reaction 

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 

Comments 

To verify a complete crystallization, the mother liquor is stored in the freezer compartment. 

No product should crystallize any further.

Simple evaluation indices

Atom economy		not defined
Yield		76	%
Target product mass		1.45	g
Sum of input masses		54	g
Mass efficiency		27	mg/g
Mass index		37	g input / g product
E factor		36	g waste / g product

1H-NMR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
500 MHz, CDCl3
delta [ppm]	mult.	atoms	assignment
1.35	m	1 H
1.54	m	1 H
1.73	m	1 H
1.82	m	1 H
2.05	m	1 H
2.37	m	2 H	6-H (ring)
2.41	m	1 H
2.67	d	3 H	N-CH3
2.74	m	1 H
2.77	d	3 H	N-CH3
3.09	m	1 H	N-CH2
3.57	m	1 H	N-CH2
11.88	m	1 H	N-H
7.26			CHCl3

13C-NMR: 2-Dimethylaminomethyl cyclohexanone hydrochloride
125 MHz, CDCl3
delta [ppm]	assignment
24.70	C5
27.70	C3
33.88	C4
41.75	CH3
42.26	CH3
44.99	C6
46.69	C2
56.80	-CH2-N-
209.58	C1 (C=O)
76.5-77.5	CDCl3

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

http://kriemhild.uft.uni-bremen.de/nop/en/instructions/pdf/4008_en.pdf

Synthesis of gamma-decalactone from 1-octene and iodoacetic acid ethyl ester

Synthesis of gamma-decalactone from 1-octene and iodoacetic acid ethyl ester

+

Cu

+

Synthesis of gamma-decalactone from 1-octene and iodoacetic acid ethyl ester

(batch scale 10 mmol)

Substances
1-octen (bp 121 °C) 1.12 g (1.56 mL, 10.0 mmol)
iodoacetic acid ethyl ester (bp 73-74 °C/ 21 hPa) 2.78 g (1.54 mL, 13.0 mmol)
copper powder (finely powdered, > 230 mesh ASTM) 1.53 g (24.0 mmol)
tert-butyl methyl ether (bp 55 °C) 35 mL
Reaction
In a 50 mL two-neck flask with magnetic stir bar and a reflux condenser connected with a
protective gas piping 1.12 g (1.56 mL, 10.0 mmol) 1-octen are mixed with 2.78 g (1.54 mL,
13.0 mmol) iodoacetic acid ethyl ester and 1.53 g (24.0 mmol) copper powder under a
protective gas atmosphere. Afterwards the reaction mixture is stirred at 130 °C oil bath
temperature under protective gas for 2 hours under reflux. NOP http://www.oc-praktikum.de


Work up
The reaction mixture is cooled down to room temperature, diluted with 20 mL tert-butyl
methyl ether, stirred for 5 minutes and filtered off. The copper powder on the filter is washed
three times with 5 mL tert-butyl methyl ether each. Filtrate and wash solutions are combined,
the solvent is evaporated at the rotary evaporator. A liquid residue remains as crude product.
Crude yield: 1.5 g
The crude product is fractional distilled in a half-micro distillation apparatus under reduced
pressure.
Yield: 1.30 g ( 7.63 mmol, 77%); head temperature 85 °C (4.8·10-2 hPa, oil bath temperature
120 °C), colourless liquid; 20 nD = 1.4508

1H-NMR: gamma-Decalactone
500 MHz, CDCl3
delta [ppm]	mult.	atoms	assignment
0.74	t	3 H	10-H
1.12-1.20	m	8 H	6-H, 7-H, 8-H, 9-H
1.39-1.77	m	3 H	3-H, 5-Hb
2.18	m	1 H	5-Ha
2.36	dd	2 H	2-H
4.33	tt	1 H	4-H
7.26			CHCl3

13C-NMR: gamma-Decalactone
125.7 MHz, CDCl3
delta [ppm]	assignment
13.9	C10
22.4	C9
25.0	C5
27.9-29.0	C6, C7, C8
31.5	C3
35.4	C2
80.9	C4
177.1	C1 (O-C(=O)-)
76.5-77.5	CDCl3

IR: gamma-Decalactone[Film, T%, cm^-1][cm^-1]assignment

Instruction (batch scale 100 mmol)
Equipment
100 mL two-neck flask, protective gas supply, reflux condenser, heatable magnetic stirrer,
magnetic stir bar, rotatory evaporator, high vacuum pump, distillation apparatus, oil bath
Substances
1-octen (bp 121 °C) 11.2 g (15.6 mL, 100 mmol)
iodoacetic acid ethyl ester (bp 73-74 °C/ 21 hPa) 27.8 g (15.4 mL, 130 mmol)
copper powder (finely powdered, > 230 mesh ASTM) 15.3 g (240 mmol)
tert-butyl methyl ether (bp 55 °C) 130 mL
 NOP http://www.oc-praktikum.de


Reaction
In a 100 mL two-neck flask with magnetic stir bar and a reflux condenser connected with a
protective gas piping 11.2 g (15.6 mL, 100 mmol) 1-octen are mixed with 27.8 g (15.4 mL,
130 mmol) iodoacetic acid ethyl ester and 15.1 g (240 mmol) copper powder under a protectiv
gas atmosphere. Afterwards the reaction mixture is stirred at 130 °C oil bath temperature
under protective gas for 6 hours under reflux.
Work up
The reaction mixture is cooled down to room temperature, diluted with 30 mL tert-butyl
methyl ether, stirred for 5 minutes and filtered off. The copper powder on the filter is washed
4 times with 25 mL tert-butyl methyl ether each. Filtrate and wash solutions are combined,
the solvent is evaporated at the rotary evaporator. A liquid residue remains as crude product.
Crude yield: 15.9 g
The crude product is fractional distilled under reduced pressure.
Yield: 13.5 g (79.3 mmol, 79%); head temperature 70 °C (1.7·10-2 hPa, oil bath temperature
120 °C), colourless liquid; 20 nD = 1.4508 

http://kriemhild.uft.uni-bremen.de/nop/en/instructions/pdf/4004_en.pdf

Equipment

Batch scale:

0.01 mol

0.1 mol

1-Octene

	two-necked flask 50 mL			protective gas piping
	reflux condenser			heatable magnetic stirrer with magnetic stir bar
	rotary evaporator			vacuum pump
	semi-micro distillation apparatus			oil bath